Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Review of
Physiology
1st
edition
By: REBAND AHMED
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Part A
1. Structure and function of cell membranes
Structure
Lipid bilayer
The cell membrane consists primarily of a thin layer of amphipathic
phospholipids which are arranged so that the hydrophobic "tail"
regions are shielded from the surrounding polar fluid, causing the
more hydrophilic "head" regions to associate with the cytosolic and
extracellular faces of the resulting bilayer. This forms a continuous,
spherical lipid bilayer.
The arrangement of hydrophilic heads and hydrophobic tails of the lipid bilayer prevent polar solutes
(e.g. amino acids, nucleic acids, carbohydrates, proteins, and ions) from diffusing across the
membrane, but generally allows for the passive diffusion of hydrophobic molecules.
Integral membrane proteins
The cell membrane contains many integral membrane proteins. These structures, which can be
visualized by electron microscopy or fluorescence microscopy, can be found on the inside of the
membrane, the outside, or membrane spanning. These may include integrins, cadherins,
desmosomes, clathrin-coated pits, caveolaes, and different structures involved in cell adhesion.
Function
The cell membrane surrounds the protoplasm of a cell and, in animal cells, physically separates the
intracellular components from the extracellular space, thereby serving a function similar to that of
skin. In fungi, some bacteria, and plants, an additional cell wall forms the outermost boundary;
however, the cell wall plays mostly a mechanical support role rather than a role as a selective
boundary. The cell membrane also plays a role in anchoring the cytoskeleton to provide shape to the
cell, and in attaching to the extracellular matrix and other cells to help group cells together to form
tissues. The barrier is differentially permeable and able to regulate what enters and exits the cell,
thus facilitating the transport of materials needed for survival. The movement of substances across
the membrane can be either passive, occurring without the input of cellular energy, or active,
requiring the cell to expend energy in moving it. The membrane also maintains the cell potential.
Specific proteins embedded in the cell membrane can act as molecular signals that allow cells to
communicate with each other. Protein receptors are found ubiquitously and function to receive
signals from both the environment and other cells
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
2. Structure and functions of cell organelles
Chromosomes
- Usually in the form of chromatin
- Contains genetic information
- Composed of DNA
- Set number per species (i.e. 23 pairs for human)
Nuclear membrane
- Surrounds nucleus
- Composed of two layers
- Numerous openings for nuclear traffic
Nucleolus
- Spherical shape
- Visible when cell is not dividing
- Contains RNA for protein manufacture
Centrioles
- Paired cylindrical organelles near nucleus
- Composed of nine tubes, each with three tubules
- Involved in cellular division
- Lie at right angles to each other
Chloroplasts
- A plastid usually found in plant cells
- Contain green chlorophyll where photosynthesis takes place
Cytoskeleton
- Composed of microtubules
- Supports cell and provides shape
- Aids movement of materials in and out of cells
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Endoplasmic reticulum
- Tubular network fused to nuclear membrane
- Goes through cytoplasm onto cell membrane
- Stores, separates, and serves as cell's transport system
- Smooth type: lacks ribosomes
- Rough type (pictured): ribosomes embedded in surface
Golgi apparatus
- Protein 'packaging plant'
- A membrane structure found near nucleus
- Composed of numerous layers forming a sac
Lysosome
- Digestive 'plant' for proteins, lipids, and carbohydrates
- Transports undigested material to cell membrane for removal
- Vary in shape depending on process being carried out
- Cell breaks down if lysosome explodes
Mitochondria
- Second largest organelle with unique genetic structure
- Double-layered outer membrane with inner folds called cristae
- Energy-producing chemical reactions take place on cristae
- Controls level of water and other materials in cell
- Recycles and decomposes proteins, fats, and carbohydrates, and forms urea
Ribosomes
- Each cell contains thousands
- Miniature 'protein factories'
- Composes 25% of cell's mass
- Stationary type: embedded in rough endoplasmic reticulum
- Mobile type: injects proteins directly into cytoplasm
Vacuoles
- Membrane-bound sacs for storage, digestion, and waste removal
- Contains water solution
- Contractile vacuoles for water removal (in unicellular organisms)
Cell wall
- Most commonly found in plant cells
- Controls turgity
- Extracellular structure surrounding plasma membrane
- Primary cell wall: extremely elastic
- Secondary cell wall: forms around primary cell wall after growth is complete
Plasma membrane
- Outer membrane of cell that controls cellular traffic
- Contains proteins (left, gray) that span through the membrane and allow passage of materials
- Proteins are surrounded by a phospholipid bi-layer.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
3. Passive transport across membranes. Cotransport.
Passive transport means moving biochemicals and atomic or molecular substances across the cell
membrane. Unlike active transport, this process does not involve chemical energy.
The four main kinds of passive transport are diffusion, facilitated diffusion, filtration and osmosis.
I. Diffusion is a process by which there is a net flow of matter from a region of high
concentration to one of low concentration. It is driven by a conc. gradient. It can be
measured using the following equation: J = -PA (C1 – C2)
where: J = flux (flow) [mmol/sec], P = permeability (cm/sec), A = area (cm2
), C1 = conc.1
(mmol/L), C2 = conc.2 (mmol/L)
II. Facilitated diffusion is the spontaneous
passage of molecules or ions across a
biological membrane passing through
specific transmembrane transport proteins.
It occurs down an electrochemical gradient
(“downhill”), similar to simple diffusion.
Glucose transport in muscle an adipose cells is
“downhill”, is carrier-mediated, and is inhibited by
sugars as galactose; therefore, it is categorized as facilitated diffusion.
III. Filtration is a mechanical or physical operation which is
used for the separation of solids from fluids (liquids or
gases) by interposing a medium through which only the
fluid can pass. Oversize solids in the fluid are retained,
but the separation is not complete; solids will be
contaminated with some fluid and filtrate will contain
fine particles (depending on the pore size and filter
thickness).
IV. Osmosis is the diffusion of water molecules across a
selectively permeable membrane. The net movement of water
molecules through a partially permeable membrane from a
solution of high water potential to an area of low water
potential.
Co-transport
Also known as coupled transport, refers to the simultaneous or sequential passive transfer of
molecules or ions across biological membranes in a fixed ratio. Cotransporters can be classified as
symporters and antiporters depending on whether the substances move in the same or opposite
directions.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
4. Compartmentalization of body fluids
The total body fluid is distributed mainly between two compartments: the extracellular fluid
and the intracellular fluid. The extracellular fluid is divided into the interstitial fluid and the
blood plasma.
. There is another small compartment of fluid that is referred to as transcellular fluid. This
compartment includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as
well as the cerebrospinal fluid; it is usually considered to be a specialized type of extracellular
fluid, although in some cases, its composition may differ markedly from that of the plasma
or interstitial fluid. All the transcellular fluids together constitute about 1 to 2 liters.
In the average 70-kilogram adult human, the total body water is about 60 per cent of the
body weight, or about 42 liters. This percentage can change, depending on age, gender, and
degree of obesity. As a person grows older, the percentage of total body weight that is fluid
gradually decreases. This is due in part to the fact that aging is usually associated with an
increased percentage of the body weight being fat, which decreases the percentage of water
in the body. Because women normally have more body fat than men, they contain slightly
less water than men in proportion to their body weight.
Intracellular Fluid Compartment
About 28 of the 42 liters of fluid in the body are inside the 75 trillion cells and are collectively
called the intracellular fluid. Thus, the intracellular fluid constitutes about 40 per cent of the
total body weight in an “average” person.
Extracellular Fluid Compartment
All the fluids outside the cells are collectively called the extracellular fluid. Together these
fluids account for about 20 per cent of the body weight, or about 14 liters in a normal 70kilogram
adult. The two largest compartments of the extracellular fluid are the interstitial
fluid, which makes up more than three fourths of the extracellular fluid, and the plasma,
which makes up almost one fourth of the extracellular fluid, or about 3 liters. The plasma is
the noncellular part of the blood; it exchanges substances continuously with the interstitial
fluid through the pores of the capillary membranes. These pores are highly permeable to
almost all solutes in the extracellular fluid except the proteins. Therefore, the extracellular
fluids are constantly mixing, so that the plasma and interstitial fluids have about the same
composition except for proteins, which have a higher concentration in the plasma.
Measurement
The volume of a fluid compartment in the body can be measured by placing an indicator
substance in the compartment, allowing it to disperse evenly throughout the compartment’s
fluid, and then analyzing the extent to which the substance becomes diluted.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
5. Differences between intra- and extracellular fluids
Ionic Composition of Plasma and
Interstitial Fluid Is Similar
Because the plasma and interstitial fluid are separated
only by highly permeable capillary membranes, their
ionic composition is similar. The most important difference
between these two compartments is the higher
concentration of protein in the plasma; because the
capillaries have a low permeability to the plasma proteins,
only small amounts of proteins are leaked into
the interstitial spaces in most tissues.
Because of the Donnan effect, the concentration of
positively charged ions (cations) is slightly greater
(about 2 per cent) in the plasma than in the interstitial fluid.
Important Constituents of the
Intracellular Fluid
The intracellular fluid is separated from the extracellular fluid by a cell membrane that is highly
permeable to water but not to most of the electrolytes in the body.
In contrast to the extracellular fluid, the intracellular fluid contains only small quantities of sodium
and chloride ions and almost no calcium ions. Instead, it contains large amounts of potassium and
phosphate ions plus moderate quantities of magnesium and sulfate ions, all of which have low
concentrations in the extracellular fluid. Also, cells contain large amounts of protein, almost four
times as much as in the plasma.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
6. Production and resorption of interstitial fluid (Starling forces)
Interstitial fluid is a solution that bathes and surrounds the cells of
multicellular animals. It is the main component of the extracellular
fluid, which also includes plasma and transcellular fluid.
The interstitial fluid is found in the interstitial spaces, also known as
the tissue spaces.
. On average, a person has about 11 litres (2.4 imperial gallons) of
interstitial fluid, providing the cells of the body with nutrients and a
means of waste removal.
Formation of interstitial fluid
Hydrostatic pressure is generated by the systolic force of the heart. It pushes water out of the
capillaries (Starling forces).
The water potential is created due to the ability of small solutes to pass through the walls of
capillaries. This buildup of solutes induces osmosis. The water passes from a high concentration (of
water) outside of the vessels to a low concentration inside of the vessels, in an attempt to reach an
equilibrium. The osmotic pressure drives water back into the vessels. Because the blood in the
capillaries is constantly flowing, equilibrium is always reached.
The balance between the two forces differs at different points on the capillaries. At the arterial end
of a vessel, the hydrostatic pressure is greater than the osmotic pressure, so the net movement
favors water and other solutes being passed into the tissue fluid. At the venous end, the osmotic
pressure is greater, so the net movement favors substances being passed back into the capillary. This
difference is created by the direction of the flow of blood and the imbalance in solutes created by the
net movement of water favoring the interstitial fluid.
Removal of interstitial fluid
To prevent a build-up of interstitial fluid surrounding the cells in the tissue, the lymphatic system
plays a part in the transport of interstitial fluid. Interstitial can pass into the surrounding lymph
vessels, and eventually ends up rejoining the blood.
Sometimes the removal of tissue fluid does not function correctly, and there is a build-up. This
causes swelling, and can often be seen around the feet and ankles, for example Elephantiasis. The
position of swelling is due to the effects of gravity.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
7. Ion channels
Ion channels are integral proteins that span the membrane and, when open, permit the passage of
certain ions.
1. Ion channels are selective; they permit the passage of some ions, but not others. Selectively
is based on the size of the channel and the distribution of charges that line it.
2. Ions channels may be opened or closed. When the channel is open, the ion(s) for which it is
selective can flow through it. When the channel is closed, ions cannot flow through them.
3. The conductance of a channel depends on the probability that the channel is open. The
higher the probability that a channel is open, the higher the conductance, or permeability.
Opening and closing of channels are controlled by gates.
a. Voltage-gated channels are open or closed by changes in membrane potential.
 The activation gate of the Na+
channel in nerve is opened by depolarization;
when open, the nerve membrane is permeable to Na+ (e.g., during the
upstroke of the nerve action potential).
 The inactivation gate of the Na+ channel in nerve is closed by
depolarization; when closed, the nerve membrane is impermeable to Na+
(e.g., during the repolarization phase of the nerve action potential).
b. Ligand-gated channels are opened or closed by hormones, second messengers, or
neurotransmitters.
 For example, the nicotinic receptor for acetylcholine (ACh) at the motor end
plate is an ion channel that opens when Ach binds to it. When open, it is
permeable to Na+ and K+, causing the motor end plate to depolarize.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
8. Intercellular communication
Cells communicate with each other via direct contact (juxtacrine signaling), over short distances
(paracrine signaling), or over large distances and/or scales (endocrine signaling).
Cells receive information from their environment through a class of proteins known as receptors.
Molecules that activate (or, in some cases, inhibit) receptors can be classified as hormones,
neurotransmitters, cytokines, growth factors but all of these are called receptor ligands.
For several types of intercellular signaling molecules that are unable to permeate the hydrophobic
cell membrane due to their hydrophilic nature, the target receptor is expressed on the membrane.
When such signaling molecule activates its receptor, the signal is carried into the cell usually by
means of a second messenger such as cAMP.
Within endocrinology (the study of intercellular signalling in animals) and the endocrine system,
intercellular signalling is subdivided into the following classifications:
 Endocrine signals are produced by endocrine cells and travel through the blood to reach all
parts of the body.
 Paracrine signals target only cells in the vicinity of the emitting cell. Neurotransmitters
represent an example.
 Autocrine signals affect only cells that are of the same cell type as the emitting cell. An
example for autocrine signals is found in immune cells.
 Juxtacrine signals are transmitted along cell membranes via protein or lipid components
integral to the membrane and are capable of affecting either the emitting cell or cells
immediately adjacent.
Intercellular connections
1. Tightjunctions (zonula occludens)
- are the attachments between cells (often epithelial cells).
- may be an intercellular pathway for solutes, depending on the size, charge, and
characteristics of the tight junction.
- may be “tight” (impermeable), as in the renal distal tubule, or “leaky” (permeable),
as in the renal proximal tubule and gallbladder.
2. Gap junctions
- are the attachments between cells that permit intercellular communication.
- for example, permit current flow and electrical coupling between myocardial cells.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
9. Second messengers
Second messengers are molecules that relay signals from receptors on the cell surface to target
molecules inside the cell, in the cytoplasm or nucleus. They relay the signals of hormones like
epinephrine (adrenalin), growth factors, and others, and cause some kind of change in the activity of
the cell. They greatly amplify the strength of the signal.
Types of secondary messenger molecules
There are three basic types of secondary messenger molecules:
 Hydrophobic molecules: water-insoluble molecules, like diacylglycerol, and
phosphatidylinositols, which are membrane-associated and diffuse from the plasma
membrane into the intermembrane space where they can reach and regulate membraneassociated
effector proteins
 Hydrophilic molecules: water-soluble molecules, like cAMP, cGMP, IP3, and Ca2+
, that are
located within the cytosol
 Gases: nitric oxide (NO) and carbon monoxide (CO), which can diffuse both through cytosol
and across cellular membranes.
These intracellular messengers have some properties in common:
 They can be synthesized/released and broken down again in specific reactions by enzymes or
ion channels.
 Some (like Ca2+
) can be stored in special organelles and quickly released when needed.
 Their production/release and destruction can be localized, enabling the cell to limit space
and time of signal activity.
Common mechanism of second messenger systems
There are several different secondary messenger systems (cAMP system, phosphoinositol system,
and arachidonic acid system), but they all are quite similar in overall mechanism, though the
substances involved in those mechanisms and effects are different.
In all of these cases, a neurotransmitter binds to a membrane-spanning receptor protein molecule.
The binding of the neurotransmitter to the receptor changes the receptor and causes it to expose a
binding site for a G-protein. The G-protein (named for the GDP and GTP molecules that bind to it) is
bound to the inner membrane of the cell and consists of three subunits: alpha, beta and gamma. The
G-protein is known as the "transducer."
When the G-protein binds to the receptor, it becomes able to exchange a GDP (guanosine
diphosphate) molecule on its alpha subunit for a GTP (guanosine triphosphate) molecule. Once this
exchange takes place, the alpha subunit of the G-protein transducer breaks free from the beta and
gamma subunits, all parts remaining membrane-bound. The alpha subunit, now free to move along
the inner membrane, eventually contacts another membrane-bound protein - the "primary effector."
The primary effector then has an action, which creates a signal that can diffuse within the cell. This
signal is called the "secondary messenger." (The neurotransmitter is the first messenger.) The
secondary messenger may then activate a "secondary effector" whose effects depend on the
particular secondary messenger system.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
10. Functions of the nerve cell
The nervous tissue consists of two principal types of cells: the
nerve cells or neurons, and special supporting cells called
neuroglia.
. The functional units of nervous tissue are neurons in which
two properties of protoplasm are developed to a great degree:
irritability (the capacity for response to physical and chemical
agents with the initiation of an impulse), and conductivity (the
ability to transmit such an impulse from one locality to
another).
Functional Morphology
Each neuron consists of three parts: the cell body or perikaryon (contains the nucleus and the main
conc. of organelles), the dendrites (their number varies in a great range, theoretically from one to
several hundred; they are usually short and conduct impulses to the perikaryon), and the axon or
neurite (it is mostly very long and always single, it conducts the impulses away from respective cell.
Terminally, each axon ends in twiglike branching or arborizations – the telodendria, which touch the
perikarya, dendrites or axons of one or more neurons. The sites of contact between neurons are
called synapses.
1. The cell body or perikaryon contains round nucleus with a prominent nucleolus in the centre. By
electron microscopy, numerous mitochondria, large Golgi apparatus, lysosomes, microtubules,
neurofilaments and inclusions are detectable in the cytoplasm.
. Free ribosomes and RER are often clustered and form areas known as Nissl bodies. Nissl bodies
are considered as morphological indicator of protein synthesis.
2. Dendrites are always present near the cell body and they tend to branch, forming arborizations.
Many dendrites have short, spinous processes that touch the axon endings of other neurons.
Dendrites contain the same organelles as the cell body proper, except the Golgi network.
3. Axon is only for each neuron and may be often extremely long. The part of the axon that joins to
the cell body is cone-shaped and it is called axon hillock. The initial segment is a portion of the axon
between the axon hillock and the point at which myelination begins. The initial segment is the site
where the nerve impulses are generated.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
11. Functional morphology of synapses
A synapse is defined as the site of junction of neurons or site of junction between neuron and the
effector cell. The synapse itself consists of three distinct parts:
1. A presynaptic knob or axonal ending of on neuron, it contains besides mitochondria and
neurofilaments a great number of synaptic vesicles, in which transmitters are stored.
2. A postsynaptic membrane – is the membrane of the second neuron and/or effector cell.
3. A synaptic cleft – is a narrow space, about 20nm, separating above mentioned parts of each
synapse.
Types of synapses: axosomatic, axodendritic, acosomatodendritic, axoaxonal (they are rare).
In addition to the chemical synapses, in which a chemical substance mediates the transmission of
the nerve impulse, there are also the electrical synapses. Here the nerve cells are linked through a
gap junction. Electrical synapses are less numerous then chemical synapses.
Principle of transmission of impulses:
When an impulse reaches the axonal ending
(presynaptic knob), Ca2+
enter the ending.
The action of calcium causes the vesicles
to migrate to and fuse with the presynaptic
membrane and then discharge the transmitter
into the synaptic cleft by exocytosis.
. The transmitter diffuses across the synaptic
cleft and binds to receptors in the postsynaptic
membrane (membrane of dendrite or
perikaryon).
. This process results in depolarization of the
postsynaptic membrane which is propagated to the
initial segment – the site where nerve impulses are generated.
Examples of transmitters:
- acetylcholine (ACh)
- noradrenaline (norepinephrine, NE)
- dopamine (DA)
- serotonine (5-hydroxytryptamine)
- gamma amino butyric acid (GABA)
- glutamic acid and glycine
- some of peptides
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
12. Synthesis and break down of neurotransmitters
Examples of transmitters:
- acetylcholine (ACh)
- noradrenaline (norepinephrine, NE)
- dopamine (DA)
- serotonine (5-hydroxytryptamine)
- gamma amino butyric acid (GABA)
- glutamic acid and glycine
- some of peptides
Synthesis of cathecholamines
Dopamine is the first catecholamine to be synthesized from steps shown. Norepinephrine and
epinephrine, in turn, are derived from further modifications of dopamine. Synthesis of
norepinephrine begins in the axoplasm of the terminal nerve endings of adrenergic nerve fibers but
is completed inside the secretory vesicles. It is important to note that the enzyme dopamine
hydroxylase requires copper as a cofactor and DOPA decarboxylase requires PLP . The rate limiting
step in the biosynthesis is hydroxylation of tyrosine.
Degradation and elimination
Neurotransmitter must be broken down once it reaches the post-synaptic cell to prevent further
excitatory or inhibitory signal transduction. For example, acetylcholine (ACh), an excitatory
neurotransmitter, is broken down by acetylcholinesterase (AChE). Choline is taken up and recycled
by the pre-synaptic neuron to synthesize more ACh. Other neurotransmitters such as dopamine are
able to diffuse away from their targeted synaptic junctions and are eliminated from the body via the
kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at
regulatory points, which may be the target of the body's own regulatory system or recreational
drugs.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
15. Local Response of membrane potential
Although the subthreshold stimuli do not produce an action potential, they do have an effect on the
membrane potential. This can be demonstrated by placing recording electrodes within a few
millimeters of a stimulating electrode and applying subthreshold stimuli of fixed duration.
Application of such currents with a cathode leads to a localized depolarizing potential change that
rises sharply and decays exponentially with time. Conversely, an anodal current produces a
hyperpolarizing potential change of similar duration.
. These potentials are called electronic potentials.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
16. Action potential
An action potential is a short-lasting event in which the electrical membrane potential of a cell
rapidly rises and falls, following a stereotyped trajectory. Action potentials occur in several types of
excitable cells, including neurons, muscle cells, and endocrine cells.
Definitions
Depolarization makes the membrane potential less negative (the cell interior becomes less
negative)
 Hyperpolarization makes the membrane potential more negative (the cell interior becomes more
negative)
 Inward current is the flow of positive charge into the cell. Inward current depolarizes the
membrane potential.
 Outward current is the flow of positive charge out of the cell. Outward current hyperpolarizes the
membrane potential.
 Action potential is a property of excitable cells (i.e., nerve, muscle) that consists of a rapid
depolarization, or upstroke, followed by repolarization of the membrane potential. Action potentials
have stereotypical size and shape, are propagating, and are all-or-none.
 Threshold is the membrane potential at which the action potential is inevitable. At threshold
potential, net inward current becomes larger than net outward current. The resulting depolarization
becomes self-sustained and gives rise to the upstroke of the action potential. If the net inward
current is less than outward current, no action potential will occur (i.e., all-or-none response).
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
17. Receptor potential
The change in membrane potential produced by the stimulus is the receptor potential, or generator
potential.
 If the receptor potential is depolarizing, it brings the membrane potential closer to threshold. If
the receptor potential is large enough, the membrane potential will exceed threshold and an action
potential will fire in the sensory neuron.
 Receptor potentials are graded in size depending on the size of the stimulus.
Receptor (generator) potential and how
it may led to an action potential.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
19. Up- and down regulation of receptors
 Hormones determine the sensitivity of the target tissue by regulating the number of or sensitivity of
receptors.
1. Down-regulation of receptor
. – A hormone decreases the number or affinity of receptors for itself or for another hormone.
. – For example, in the uterus, progesterone down-regulates its own receptor and the receptor for
. estrogen.
2. Up-regulation of receptors
. – A hormone increases the number or affinity of receptors for itself or for another hormone.
. – For example, in the ovary, estrogen up-regulates its own receptor and the receptor of LH.
20. Excitability and refrectoriness
Excitability (of cardiac cells)
– is the ability of cardiac cells to initiate action potentials in response to inward, depolarizing current.
– reflects the recovery of channels that carry the inward currents for the upstroke of the action .
. potential.
– changes over the course of the action potential. These changes in excitability are described by refractory
. periods (se figure).
1. Absolute refractory period (ARP)
. – begins with the upstroke of the action potential and ends after the plateau. .
. – reflects the time during which no action potential can be initiated, regardless of how much
. inward current is supplied.
2. Effective refractory period (ERP) .
. – is slightly longer than the ARP. .
. – is the period during which a conducted action potential cannot be elicited.
3. Relative refractory period (RRP) .
. – is the period immediately after the ARP when repolarization is almost complete. .
. – is the period during which an action potential can be elicited, but more than usual inward .
. current is required.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
21. Excitation-contraction coupling
Excitation-contraction coupling is a term that describes the physiological process of converting an
electrical stimulus to a mechanical response.
Steps in excitation-contraction coupling in skeletal muscle:
1. Action potentials in the muscle cell membrane initiate depolarization of the T tubules.
2. Depolarization of the T tubules causes a conformational change in its dihydropyridine receptor,
which opens Ca2+
release channels (ryanodine receptors) in the nearby SR, causing release of Ca2+
from the SR into the intracellular fluid.
3. Intracellular [Ca2+] increases.
4. Ca2+
binds to troponin C on the thin filaments, causing a conformational change in troponin that
moves tropomyosin out of the way. The cross-bridge cycle begins:
. a. At first, no ATP is bound to myosin (A), and myosin is tightly attached to actin. In rapidly
. contracting muscle, this stage is brief. In the absence of ATP, this state is permanent (i.e., rigor).
. b. ATP then binds to myosin (B), producing a conformational change in the myosin that causes
. myosin to be released from actin.
. c. Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and
. inorganic phosphate (Pi). ADP remains attached to myosin (C).
. d. Myosin attaches to a new site on actin, which constitutes the power (force generating) stroke
. (D). ADP is then released, returning myosin to its rigor state.
. e. The cycle repeats as long as Ca
2+
is bound to troponin C. Each cross-bridge cycle “walks” myosin
. further along the actin filament.
! Steps in excitation-contraction coupling in smooth muscle  Costanzo 4th
ed. page 22
! Steps in excitation-contraction coupling in cardiac muscle  Costanzo 4th
ed. page 79
Masaryk University Faculty of Medicine Physiology Exam
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23. Electrical and mechanical behavior of skeletal muscle
Steps in excitation-contraction coupling in skeletal muscle:
1. Action potentials in the muscle cell membrane initiate depolarization of the T tubules.
2. Depolarization of the T tubules causes a conformational change in its dihydropyridine receptor,
which opens Ca2+
release channels (ryanodine receptors) in the nearby SR, causing release of Ca2+
from the SR into the intracellular fluid.
3. Intracellular [Ca2+] increases.
4. Ca2+
binds to troponin C on the thin filaments, causing a conformational change in troponin that
moves tropomyosin out of the way. The cross-bridge cycle begins:
. a. At first, no ATP is bound to myosin (A), and myosin is tightly attached to actin. In rapidly
. contracting muscle, this stage is brief. In the absence of ATP, this state is permanent (i.e., rigor).
. b. ATP then binds to myosin (B), producing a conformational change in the myosin that causes
. myosin to be released from actin.
. c. Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and
. inorganic phosphate (Pi). ADP remains attached to myosin (C).
. d. Myosin attaches to a new site on actin, which constitutes the power (force generating) stroke
. (D). ADP is then released, returning myosin to its rigor state.
. e. The cycle repeats as long as Ca
2+
is bound to troponin C. Each cross-bridge cycle “walks” myosin
. further along the actin filament.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
24. Electrical and mechanical behavior of smooth muscle
Smooth muscle - Contraction
• source of Ca
2+
: ECF (VOC, ROC), SR
• there is no troponine C, but two other regulatory proteins binding calcium – calmodulin + caldesmon
• calcium-calmodulin complex (Ca
2+
-CM) activates MLCK (myosin light chain kinase)
• activated MLCK catalyzes the phosphorylation of myosin
• phosphorylated myosin is capable to make complex with actin  contraction
Smooth muscle - Relaxation
Two relaxing processes occur:
1. Removing intracellular Ca
2+
from ICF (like in cardiac m.)
2. MLC-phosphatase catalyzes the hydrolysis of phosphorylated myosin:
MLC-P + H2O  Pi + MLC
MLC does not bind to actin  relaxation
The influence of cAMP on smooth muscles
• cAMP activates protein kinase A (PK-A)
• PK-A phosphorylates MLC-kinase:
MLCK  MLCK-P
• MLCK-P is inactive, does not phosphorylates MLC  no interaction between actin and myosin
 relaxation
Smooth muscle cells are characterized by the instability of its membrane potential and the fact that it
shows continuous, irregular contractions that are independent on nerve supply => Tonus
To maintain organ dimensions against force, cells are fastened to one another by adherent junctions.
As a consequence, cells are mechanically coupled to one another such that contraction of one cell
invokes some degree of contraction in an adjoining cell.
Smooth muscle may contract spontaneously (via ionic channel dynamics) or as in the gut special
pacemakers cells interstitial cells of Cajal produce rhythmic contractions
Specialized smooth muscle cells within the afferent arteriole of the juxtaglomerular apparatus of
kidney produces renin which activates the angiotensin II system.
Masaryk University Faculty of Medicine Physiology Exam
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25. Electrical and mechanical behavior of cardiac muscle
Cardiac muscle – contraction
Cardiac muscle - relaxation
• Ca
2+
ions are liberated from troponin C and removed from sarcoplasm
1. Ca
2+
-ATPase in SR
2. Ca
2+
-ATPase in sarcolemma
3. Na
+
/Ca
2+
antiport in sarcolemma
4. Ca
2+
re-entry to mitochondria
Excitation – contraction coupling
- Contraction of the heart is called systole whilst relaxation of the heart is called diastole.
- As the function of the heart is that of a pump, both actions are important - a pump has to fill up with fluid before it can
pump it out. The filling process occurs during diastole.
- One systole and its following diastole are called one cardiac cycle.
- In the normal heart, beating at a rate of 75 beats/min, the duration of ventricular systole is around 0.3 sec while diastole is
around 0.5 sec (total length of cycle 0.8 sec)
Mechanism
The key role = Ca
2+
(T-tubules & sarcoplasmic reticulum)
During the action potential of cardiac muscle the plateau phase is the result of slow sodium/calcium channels
that remain open for several hundred milliseconds.
Ca
2+
 diffuses to the cytosol, it catalyses sliding of actin and myosin (similar to the mechanism in skeletal
muscle):
 Ca
2+
binds to troponin and removes it from the actin binding site
 Exposed actin binding site is available for attachment of myosin heads to produce actin myosin
bridges.
 Myosin heads detach and attach to the next binding site, causing both filaments to slide against each
other causing contraction.
Autoregualtion in cardiac muscle
- intracellular calcium is in the complex with protein calmodulin: CM-4Ca
2+
- Ca
2+
-CM stimulates all Ca
2+
-pumps (some by phosphorylation) which decrease the Ca
2+
concentration in sarcoplasm
- the increase of intracellular [Ca
2+
] triggers contraction but, at the same time, stimulates
relaxation processes
Masaryk University Faculty of Medicine Physiology Exam
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26. Isometric and isotonic contraction. Length-tension relation
Isometric contractions => are measured when length is held constant. Muscle length (preload) is
fixed, the muscle is stimulated to contract, and the developed tension is measured. There is no
shortening.
Isotonic contractions => are measured when load is held constant. The load against which the
muscle contracts (afterload) is fixed, the muscle is stimulated to contract, and shortening is
measured.
Length-tension relationship
- measures tension developed during isometric contractions when the muscle is set to fixed lengths
(preload).
 Passive tension is the tension developed by stretching the muscle to different
lengths.
 Total tension is the tension developed when the muscle is stimulated to contract at
different lengths.
 Active tension is the difference between total tension and passive tension.
 Active tension represents the active force developed from contraction of the
muscle. It can be explained by the cross-bridge cycle model.
 Active tension is proportional to the number of cross-bridges formed.
Tension will be maximum when there is overlap of thick and thin filaments.
When the muscle is stretched to greater lengths, the number of crossbridges
is reduced because there is less overlap. When muscle length is
decreased, the thin filaments collide and tension is reduced.
Length-tension relationship in
skeletal muscle
Masaryk University Faculty of Medicine Physiology Exam
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27. Neuromuscular junction
– is the synapse between axons of motoneurons and skeletal muscle.
– The neurotransmitter released from the presynaptic terminal is Ach, and the postsynaptic membrane
contains a nicotinic receptor.
1. Synthesis and storage of Ach in the presynaptic terminal
- Choline acetyltransferase catalyzes the formation of Ach from acetyl coenzyme A (CoA) and
choline in the presynaptic terminal.
- Ach is stored in the synaptic vesicles with ATP and proteoglycan for later release.
2. Depolarization of the presynaptic terminal and Ca
2+
uptake
- Action potentials are conducted down the motoneurons. Depolarization of the presynaptic
terminal opens Ca
2+
channels.
- When Ca
2+
permeability increases, Ca
2+
rushes into the presynaptic terminal down its
electrochemical gradient.
3. Ca
2+
uptake causes release of Ach into the synaptic cleft
- The synaptic vesicles fuse with the plasma membrane and empty their contents into the cleft
by exocytosis.
4. Diffusion of Ach to the postsynaptic membrane (muscle end plate) and binding of Ach to nicotinic
receptors
- The nicotinic ACh receptor is also a Na
+
and K
+
ion channel.
- Binding of Ach to α subunits of the receptor causes a conformational change that opens the
central core of the channel and increases its conductance to Na
+
and K
+
. These are examples
of ligand-gated channels.
5. End plate potential (EEP) in the postsynaptic membrane
- Because the channels opened by ACh conduct both Na
+
and K+ ions, the postsynaptic
membrane potential is depolarized to a value halfway between the Na
+
and K
+
equilibrium
potential (approx. 0 mV).
- The contents of one synaptic vesicle produce a miniature end plate potential (MEPP), the
smallest possible EPP.
- MEPPs summate to produce a full-fledged EPP. The EEP is not an action potential, but simply
a depolarization of the specialized muscle end plate.
6. Depolarization of adjacent muscle membrane to threshold
- Once the end plate region is depolarized, local currents cause depolarization and action
potentials in the adjacent muscle tissue. Action potentials in the muscle are followed by
contraction.
7. Degradation of ACh
- The EPP is transient because ACh is degraded to acetyl CoA and choline by
acetylcholinesterase (AChE).
- One-half of the choline is taken back into the presynaptic ending by Na
+
-choline cotransport
and used to synthesize new ACh.
- AChE inhibitors (neostigmine) block the degradation of ACh, prolong its action at the muscle
end plate, and increase the size of the EPP.
- Hemicholinium blocks choline reuptake and depletes the presynaptic endings of ACh stores.
Masaryk University Faculty of Medicine Physiology Exam
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28. Temporal and space summation (summation and recruitment) in skeletal
muscle
See PRACTICALS page 75 + resp. protocol
29. Energy production and conservation
Coupled Reactions
All the energy foods—carbohydrates, fats, and proteins—can be oxidized in the cells, and during this process,
large amounts of energy are released. To provide energy needed by the physiologic processes of the cells, the
chemical reactions must be “coupled” with the systems responsible for these physiologic functions. This
coupling is accomplished by special cellular enzyme and energy transfer systems.
“Free Energy”
The amount of energy liberated by complete oxidation of a food is called the free energy of oxidation of the food, and this is
generally represented by the symbol DG. Free energy is usually expressed in terms of calories per mole of substance. For
instance, the amount of free energy liberated by complete oxidation of 1 mole (180 grams) of glucose is 686,000 calories.
Role of Adenosine Triphosphate in Metabolism
Adenosine triphosphate (ATP) is an essential link between energy-utilizing and energy-producing functions of
the body. For this reason, ATP has been called the energy currency of the body, and it can be gained and spent
repeatedly.
Energy derived from the oxidation of carbohydrates, proteins, and fats is used to convert adenosine
diphosphate (ADP) to ATP, which is then consumed by the various reactions of the body that are necessary for
(1) active transport of molecules across cell membranes; (2) contraction of muscles and performance of
mechanical work; (3) various synthetic reactions that create hormones, cell membranes, and many other
essential molecules of the body; (4) conduction of nerve impulses; (5) cell division and growth; and (6) many
other physiologic functions that are necessary to maintain and propagate life.
ATP is a combination of adenine, ribose, and three phosphate radicals. The last two phosphate radicals are
connected with the remainder of the molecule by high-energy bonds.
The amount of free energy in each of these highenergy bonds per mole of ATP is about 7300 calories under
standard conditions and about 12,000 calories under the usual conditions of temperature and concentrations
of the reactants in the body. Therefore, in the body, removal of each of the last two phosphate radicals
liberates about 12,000 calories of energy. After loss of one phosphate radical from ATP, the compound
becomes ADP, and after loss of the second phosphate radical, it becomes adenosine monophosphate (AMP).
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
30. Caloric content of food. Direct calorimetry.
Energy Available in Foods
The energy liberated from each gram of carbohydrate as it is oxidized to carbon dioxide and water is
4.1 Calories (1 Calorie equals 1 kilocalorie), and that liberated from fat is 9.3 Calories. The energy
liberated from metabolism of the average dietary protein as each gram is oxidized to carbon dioxide,
water, and urea is 4.35 Calories.
. Also, these substances vary in the average percentages that are absorbed from the gastrointestinal
tract: about 98 per cent of carbohydrate, 95 per cent of fat, and 92 per cent of protein. Therefore,
the average physiologically available energy in each gram of these three foodstuffs is as follows:
1 gram of Calories
Carbonhydrate 4
Fat 9
Protein 4
Direct Calorimetry
Direct Calorimetry Measures Heat Liberated from the Body.
In determining the metabolic rate by direct calorimetry, one measures the quantity of heat liberated
from the body in a large, specially constructed calorimeter. The subject is placed in an air chamber
that is so well insulated that no heat can leak through the walls of the chamber. Heat formed by the
subject’s body warms the air of the chamber. However, the air temperature within the chamber is
maintained at a constant level by forcing the air through pipes in a cool water bath. The rate of
heat gain by the water bath, which can be measured with an accurate thermometer, is equal to the
rate at which heat is liberated by the subject’s body.
Masaryk University Faculty of Medicine Physiology Exam
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31. Energy balance. Indirect calorimetry.
If the caloric content of the food ingested is less than the energy output – ie, if the balance is
negative – endogenous stores are utilized. Glycogen, body protein, and fat are catabolized, and the
individual loses weight. The caloric value of the food intake exceeds energy loss due to heat and work
and the food is properly digested and absorbed – ie, if the balance is positive – energy is stored, and
the individual gains weight.
To balance basal output so that the energy-consuming tasks essential for life can be performed, the
average adult must take in about 2000 kcal/d. Caloric requirements above the basal level depend on
the individual’s activity.
Indirect Calorimetry—The “Energy Equivalent” of Oxygen
Because more than 95 per cent of the energy expended in the body is derived from reactions of
oxygen with the different foods, the whole-body metabolic rate can also be calculated with a high
degree of accuracy from the rate of oxygen utilization. When 1 liter of oxygen is metabolized with
glucose, 5.01 Calories of energy are released; when metabolized with starches, 5.06 Calories
are released; with fat, 4.70 Calories; and with protein, 4.60 Calories.
For the average diet, the quantity of energy liberated per liter of oxygen used in the body averages
about 4.825 Calories. This is called the energy equivalent of oxygen; using this energy equivalent, one
can calculate with a high degree of precision the rate of heat liberation in the body from the quantity
of oxygen used in a given period of time.
32. Physiological role of calcium
It plays an important role in signal transduction pathways, where it acts as a second messenger, in
neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many
enzymes require calcium ions as a cofactor; those of the blood-clotting cascade being notable
examples. Extracellular calcium is also important for maintaining the potential difference across
excitable cell membranes, as well as proper bone formation.
ECC in skeletal muscle & myocardium: Ca2+
binds to troponin C on the thin filaments, causing a
conformational change in troponin that moves tropomyosin out of the way; the cross-bridge cycle
beings.
EEC in smooth muscle: Ca2+
binds to calmodulin. The Ca2+
-calmodulin complex binds to and activate
myosin light-chain kinase. When activated, myosin light-chain phosphorylates myosin and allows it to
bind to actin. Contraction then occurs.
In neuromuscular junction: Ca2+
triggers a marked increase in exocytosis of ACh containing vesicles.
Blood coagulation: Activation of Factor X
In myocardial contractility: is related to the intracellular Ca2+
concentration. The magnitude of the
tension that develops is proportional to the intracellular [Ca2+
].
Decrease in extracellular Ca2+
causes typical spasm in muscles of extremities.
Masaryk University Faculty of Medicine Physiology Exam
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33. Vitamins – overview
Daily Requirements of Vitamins
A vitamin is an organic compound needed in small
quantities for normal metabolism that cannot be
manufactured in the cells of the body. Lack of
vitamins in the diet can cause important metabolic
deficits. The requirements vary considerably,
depending on such factors as body size, rate of
growth, amount of exercise, and pregnancy.
Storage of Vitamins in the Body
Vitamins are stored to a slight extent in all cells.
Some vitamins are stored to a major extent in the
liver. For instance, the quantity of vitamin A stored in the liver may be sufficient to maintain a person
for 5 to 10 months without any intake of vitamin A. The quantity of vitamin D stored in the liver is
usually sufficient to maintain a person for 2 to 4 months without any additional intake of vitamin D.
Absence of vitamin C, one of the water-soluble vitamins, can cause symptoms within a few weeks
and can cause death from scurvy in 20 to 30 weeks.
Vitamin A
Vitamin A occurs in animal tissues as retinol. Vitamin A is needed to form the visual pigments and,
therefore, to prevent night blindness. Vitamin A is also necessary for normal growth of most cells of
the body and especially for normal growth and proliferation of the different types of epithelial cells.
Main food sources are liver, butter, egg yolk, coloured vegetables and fruits.
Thiamine (Vitamin B1)
Thiamine operates in the metabolic systems of the body principally as thiamine pyrophosphate; this
compound functions as a cocarboxylase, operating mainly in conjunction with a protein
decarboxylase for decarboxylation of pyruvic acid and other α-keto acids.
Thiamine deficiency (beriberi) causes decreased utilization of pyruvic acid and some amino acids by
the tissues, but increased utilization of fats. Thus, thiamine is specifically needed for the final
metabolism of carbohydrates and many amino acids.
Niacin
Niacin, also called nicotinic acid, functions in the body as coenzymes in the form of nicotinamide
adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These
coenzymes are hydrogen acceptors; they combine with hydrogen atoms as they are removed from
food substrates by many types of dehydrogenases. Its mainly found in meat and liver.
Riboflavin (Vitamin B2)
Riboflavin normally combines in the tissues with phosphoric acid to form two coenzymes, flavin
mononucleotide (FMN) and flavin adenine dinucleotide (FAD). They operate as hydrogen carriers in
important oxidative systems of the mitochondria. It is found in eggs, milk liver, yeast and cereals.
Cobalamin (Vitamin B12)
Vitamin B12 performs several metabolic functions, acting as a hydrogen acceptor coenzyme.
Its most important function is to act as a coenzyme for reducing ribonucleotides to
deoxyribonucleotides, a step that is necessary in the replication of genes. This could explain the
major functions of vitamin B12: (1) promotion of growth and (2) promotion of red blood cell
formation and maturation. It is only found in animal products.
Folic Acid (Vitamin B11)
Masaryk University Faculty of Medicine Physiology Exam
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Folic acid functions as a carrier of hydroxymethyl and formyl groups. Perhaps it’s most important
use in the body is in the synthesis of purines and thymine, which are required for formation of DNA.
Therefore, folic acid, like vitamin B12, is required for replication of the cellular genes. This may
explain one of the most important functions of folic acid—to promote growth.
Main food sources are leafy vegetables and liver.
Pyridoxine (Vitamin B6)
Pyridoxine exists in the form of pyridoxal phosphate in the cells and functions as a coenzyme for
many chemical reactions related to amino acid and protein metabolism. Its most important role is
that of coenzyme in the transamination process for the synthesis of amino acids.
As a result, pyridoxine plays many key roles in metabolism, especially protein metabolism.
Main food sources are meat, liver, cereal germs and yeast.
Pantothenic Acid
Pantothenic acid mainly is incorporated in the body into coenzyme A (CoA), which has many
metabolic roles in the cells. Two of these are (1) conversion of decarboxylated pyruvic acid into
acetyl-CoA before its entry into the citric acid cycle, and (2) degradation of fatty acid molecules into
multiple molecules of acetyl-CoA. Thus, lack of pantothenic acid can lead to depressed metabolism of
both carbohydrates and fats. Main food sources are liver, milk and eggs.
Ascorbic Acid (Vitamin C)
Ascorbic Acid Deficiency Weakens Collagen Fibers Throughout the Body.
Ascorbic acid is essential for activating the enzyme prolyl hydroxylase, which promotes the
hydroxylation step in the formation of hydroxyproline, an integral constituent of collagen. Without
ascorbic acid, the collagen fibers that are formed in virtually all tissues of the body are defective and
weak. Therefore, this vitamin is essential for the growth and strength of the fibers in subcutaneous
tissue, cartilage, bone, and teeth. Main food sources are fresh fruits, vegetables and potatoes.
Vitamin D
Vitamin D increases calcium absorption from the gastrointestinal tract and helps control calcium
deposition in the bone. The mechanism by which vitamin D increases calcium absorption is mainly to
promote active transport of calcium through the epithelium of the ileum. In particular, it increases
the formation of a calcium binding protein in the intestinal epithelial cells that aids in calcium
absorption. Main food sources are butter, fish, oil and eggs. It is partly formed in skin.
Vitamin E
Vitamin E is a name for a group of natural antioxidants.
Deficiency of vitamin E prevents normal growth and sometimes causes degeneration of the renal
tubular cells and the muscle cells. Vitamin E is believed to play a protective role in the prevention of
oxidation of unsaturated fats. Main food sources are plant oils, nuts, seeds and germ oil.
Vitamin K
Vitamin K is necessary for the formation by the liver of prothrombin, Factor VII (proconvertin), Factor
IX, and Factor X, all of which are important in blood coagulation. Therefore, when vitamin K
deficiency occurs, blood clotting is retarded. Main food sources are vegetables and liver. It is partly
formed by intestinal bacteria.
Masaryk University Faculty of Medicine Physiology Exam
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34. Hypovitaminoses and hypervitaminoses
Hypovitaminoses
Avitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect
in metabolic conversion, such as tryptophan to niacin. They are designated by the same letter as the
vitamin.
Avitaminosis includes:
 vitamin A deficiency causes xerophthalmia or night blindness
 thiamine deficiency causes beriberi
 niacin deficiency causes pellagra
 vitamin B12 deficiency leads to megaloblastic anemia
 vitamin C deficiency leads to scurvy
 vitamin D deficiency causes rickets
 vitamin K deficiency causes impaired coagulation
Hypervitaminoses
Vitamin poisoning, hypervitaminosis or vitamin overdose refers to a condition of high storage levels
of vitamins, which can lead to toxic symptoms. The medical names of the different conditions are
derived from the vitamin involved: an excess of vitamin A, for example, is called hypervitaminosis A.
. Generally, toxic levels of vitamins are achieved through high supplement intake and not from
dietary sources. Toxicities of fat-soluble vitamins result also can be caused by a large intake of highly
fortified foods, but foods rarely deliver dangerous levels of water-soluble vitamins.
 Hypervitaminosis A is characterized by anorexia, headache, hepatosplenomegaly,
irritability, scaly dermatitis, patchy loss of hair, bone pain, and hyperostosis.
 Hypervitaminosis D is associated with weight loss, calcification of many soft tissues,
and eventual renal failure.
 Hypervitaminosis K is characterized by gastrointestinal disturbance and anemia.
 Large doses of water-soluble vitamins have been thought to be less likely to cause problems
because they can be rapidly cleared from the body.
Masaryk University Faculty of Medicine Physiology Exam
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35. Basal Metabolism
Basal metabolic rate
- the energy necessary to maintain essential processes in basal conditions
- the BMR of men (70 kg) is 6300 – 7350 kJ/day
- BMR is about 10% lower in women
- Factors affecting BMR:
o Surface area
 BMR is standardised to the surface of the body and expressed as kJ/m2/h
 Increase in weight and height will lead to increase in BMR
 s = W0.425
 H0.725
 0.007184 where s = surface area in m2
 the formula is derived from nomograms
 and is used to determine the surface area of the body
 standard value for BMR  167 kJ/m2/h  surface in m2
(men)
 150 kJ/m2/h  surface in m2
(women)
 using Harris-Benedict formula
 BMR man = 66.5 + (13.8  b.w.) + 5  hight (cm) - 6.8  age
 BMR woman = 66.5 + (9.5  b.w.) + 1.8  hight (cm) - 4.7  age
o Sex – man = 167 kJ/m2/h (40 kcal/ m2/h)
women = 150 kJ/ m2/h (36 kcal/m2/h)
o Age – newborn  low BMR which increases during childhood and puberty
Old age  decreasing BMR
o Hormones
 Catecholamines
 Thyroid hormones
 Insulin
 Growth hormone
o Body temperature
 BMR increases by 10% every increase in 1◦
C
o Climate – higher temperatures  lower BMR
lower temperatures  higher BMR
o Nutritional status – fasting and undernutrition  decrease in BMR
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
36. Principle of balanced nutrition
- diet should provide
- sufficient amount of energy
- right proportion of lipids, carbohydrates and proteins
- minerals and vitamins
- Biological value of proteins = measure of the proportion of absorbed protein from a food
which becomes incorporated into the proteins of the organism's body
- An adult male (70kg) would require
carbohydrates 400 g 6.8 MJ 55 %
protein 100 g 1.7 MJ 15 %
fat 100 g 3.9 MJ 30 %
Total 12.4 MJ
- Caloric value of the diet should approximate the ratio of energy expenditure
o Insufficient caloric intake  fat and protein stores of the body are catabolized
o Excessive intake over a long period of time  obesity
Man (70 kg) kcal/m2/h
rest 40 (lying awake)
light activity 70 (clerical work)
moderate activity 120 (walking, housework)
heavy activity 300-600 (bicycling, running)
- Food restriction is believed to extend the life span
o Maybe due to protection from damage caused by radicals
Most foods contain a mix of some or all of the nutrient classes, together with other substances such
as toxins or various sorts. Some nutrients can be stored internally (e.g., the fat soluble vitamins),
while others are required more or less continuously. Poor health can be caused by a lack of required
nutrients or, in extreme cases, too much of a required nutrient. For example, both salt and water
(both absolutely required) will cause illness or even death in too large amounts.
In general, eating a wide variety of fresh, whole (unprocessed), foods have proven favorable
compared to monotonous diets based on processed foods.In particular, the consumption of wholeplant
foods slows digestion and allows better absorption, and a more favorable balance of essential
nutrients per Calorie, resulting in better management of cell growth, maintenance, and mitosis (cell
division), as well as better regulation of appetite and blood sugar. Regularly scheduled meals (every
few hours) have also proven more wholesome than infrequent or haphazard ones.
Masaryk University Faculty of Medicine Physiology Exam
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37. Glycaemia
Glycemia means the presence, or the level, of glucose in one's blood. Normally, in mammals the
body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mmol/L.
Hypoglycemia
Is the medical term for a state produced by a lower than normal level of blood glucose.
The most common forms of moderate and severe hypoglycemia occur as a complication of treatment
of diabetes mellitus with insulin or oral medications.
Symptoms: sweating, double vision, headache, heart palpation, tremor, fatigue and more.
Hyperglycemia
High blood sugar is a condition in which an excessive amount of glucose circulates in the blood
plasma. This is generally a blood glucose level higher than 10 mmol/L, but symptoms may not start to
become noticeable until even higher values such as 15-20 mmol/L. However, chronic levels
exceeding 7 mmol/L can produce organ damage.
Causes:
> Diabetes mellitus - usually caused by low insulin levels.
> Drugs – i.e. beta blockers, epinephrine, thiazide diuretics, corticosteroids, niacin.
> Critical illness - patients suffering an acute stress such as stroke or myocardial infarction.
> Physiological stress - When the body is stressed, endogenous catecholamines are released that amongst
other things - serve to raise the blood glucose levels.
Symptoms: polyphagia, polydipsia, polyuria, blurred vision, fatigue (sleepiness), weight loss, dry
mouth, dry or itchy skin, cardiac arrhythmia
Masaryk University Faculty of Medicine Physiology Exam
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38. Acid-base balance
Acid-base homeostasis is the part of human homeostasis concerning the proper balance between acids and
bases, in other words, the pH.
Buffers
– prevent a change in pH when H
+
ions are added to or removed from a solution.
– are most effective within 1.0 pH unit of the pK of the buffer (i.e., in the linear portion of the titration curve).
1. Extracellular buffers
. a. The major extracellular buffer is HCO3
,
which is produced from CO2 and H2O.
. – The pK of the CO2 /HCO3
buffer
pair is 6.1.
. b. Phosphate is a minor extracellular buffer.
. – The pK of the H2PO4
-
/HPO4
2buffer
pair is 6.8.
. – Phosphate is most important as urinary buffer; excretion of H
+
as H2PO4
is
called titratable acid.
2. Intracellular buffers
. a. Organic phosphates [e.g., AMP, ADP, ATP, 2,3-diphosphoglycerate (DPG)].
. b. Proteins
. – Imidazole and α-amino groups on proteins have pKs that are within the physiological pH range.
. – Hemoglobin is a major intracellular buffer.
. – In the physiological pH range, deoxyhemoglobin is a better buffer than oxyhemoglobin.
3. Using the Henderson-Hasselbalch equation to calculate pH
where:
pH = - log10 [H
+
] (pH units)
pK = - log10 equilibrium constant (pH units)
[A
]
= base form of buffer (mM)
[HA] = acid form of buffer (mM)
- A
,
the base form of the buffer, is the H
+
acceptor.
- HA, the acid form of the buffer, is the H
+
donor.
- When the concentrations of A
and
HA are equal, the pH of the solution equals the pK of the buffer, as calculate
by the Henderson-Hasselbalch equation.
Renal acid-base
1. Reabsorption of filtered HCO3
.
- occurs primarily in the proximal tubule.
. a. Key features of reabsorption of filtered HCO3
.
(1) H
+
and HCO3
are
produced in the proximal tubule cells from CO2 and H2O. CO2 and H2O combine to
. form H2CO3, catalyzed by intracellular carbonic anhydrase; H2CO3 dissociates into H
+
and HCO3
.
H+ is
. secreted into the lumen via the Na
+
-H
+
exchange mechanism in the luminal membrane.
. The HCO3
is
reabsorbed.
. (2) In the lumen, the secreted H+ concentration combines with filtered HCO3
to
form H2CO, which
. dissociates into CO2 and H20 catalyzed by brush border carbonic anhydrase. CO2 and H2O diffuse into
. cell to start the cycle again.
. (3) The process results in net reabsorption of filtered HCO3
.
However, it does not result in net secretion
. of H
+
.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
b. Regulation of reabsorption of filtered HCO3
.
(1) Filtered load
. – Increases in the filtered load of HCO3
result
in increased rates of HCO3
.
However, if the plasma HCO3
.
conc. becomes very high (e.g., metabolic alkalosis), the filtered load will exceed the reabsorptive
. capacity, and HCO3
will
be excreted in the urine.
. (2) PCO2
. – Increases in PCO2 result in increased rates of HCO3
reabsorption
because the supply of intracellular H
+
. for secretion is increased. This mechanism is the basis of the renal compensation for respiratory
. acidosis.
. – Decrease in PCO2 result in decreased rates of HCO3
reabsorption
because the supply of intracellular H
+
. for secretion is decreased. This mechanism is the basis of the renal compensation for respiratory
. alkalosis.
. (3) ECF volume
. – ECF volume expansion results in decreased HCO3
-
reabsorption.
. – ECF volume contraction results in increased HCO3
reabsorption
(contraction alkalosis).
. (4) Angiotensin II
. – stimulates Na
+
-H
+
exchange and thus increases HCO3
reabsorption,
contributing to the contraction
. alkalosis that occurs secondary to ECF volume contraction.
2. Excretion of fixed H
+
. – Fixed H
+
produced from the catabolism of protein and phospholipid is excreted by two mechanism,
. titratable acid (H2PO4
)
and NH4
+
.
I.
II.
L
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
39. Hypoxia and ischemia
Hypoxia.
An abnormally reduced O2 supply to tissue is classified as follows:
1. Hypoxic hypoxia: an insufficient O2 supply reaches the blood due, for example, to decreased
atmospheric PO2 at high altitudes, reduced alveolar ventilation, or impaired alveolar gas exchange.
2. Anemic hypoxia : reduced O2-carrying capacity of blood, e.g., due to decreased total Hb in iron
deficiency anemia.
3. Stagnant or ischemic hypoxia: insufficient O2 reaches the tissue due to reduced blood flow. The
cause can be systemic (e.g., heart failure) or local (e.g., obstructed artery). The reduction of blood
flow must be compensated for by a rise in ([O2]a – [O2]y) to maintain an adequate O2 delivery.
This is not the case in hypoxic and anemic hypoxia. The influx and efflux of substrates and
metabolites is also impaired in stagnant hypoxia. Anaerobic glycolysis is therefore of little help.
4. Hypoxia can also occur when the diffusion distance is increased due to tissue thickening without a
corresponding increase in the number of blood capillaries. This results in an insufficient blood supply
to cells lying outside the O2 supply radius (R) of the Krogh cylinde.
5. Histotoxic or cytotoxic hypoxia occurs due to impaired utilization of O2 by the tissues despite a
sufficient supply of O2 in the mitochondria, as observed in cyanide poisoning. Cyanide (HCN) blocks
oxidative cellular metabolism by inhibiting
cytochromoxidase.
Ischemia
Is a restriction in blood supply, generally due to factors in
the blood vessels, with resultant damage or dysfunction of
tissue.
. Rather than hypoxia, ischemia is an absolute or relative
shortage of the blood supply to an organ, i.e. a shortage of
oxygen, glucose and other blood-borne fuels. A relative
shortage means the mismatch of blood supply (oxygen/fuel
delivery) and blood request for adequate metabolism of
tissue. Ischemia results in tissue damage because of a lack
of oxygen and nutrient. Ultimately, this can cause severe
damage because of the potential for a build-up of metabolic wastes.
Cardiac ischemia - may be asymptomatic or may cause chest pain, known as angina pectoris.
Bowel ischemia - Both large and small bowel can be affected by ischemia.
Brain ischemia -is insufficient blood flow to the brain, and can be acute (ie, rapid) or chronic (ie, long-
lasting).
Cutaneous ischemia - Reduced blood flow to the skin layers may result in mottling or uneven, patchy
discoloration of the skin.
Restoration of blood flow after a period of ischemia can actually be more damaging than the ischemia. Reintroduction of
oxygen causes a greater production of damaging free radicals as well as allowing, via removal of the extracellular acidotic
conditions, influx of calcium and thus calcium overloading. Overall this result in reperfusion injury which can result in
potentially fatal cardiac arrhythmias, also necrosis can be greatly accelerated. Low doses of hydrogen sulfide (H2S) have
been found to protect against regional myocardial ischemia–reperfusion injury.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
40. Heat production and heat loss
Heat production
The amount of heat produced is determined by energy metabolism. At rest, approximately 56% of
total heat production occurs in the internal organs and about 18% in the muscles and skin.
During physical exercise, heat production increases several-fold and the percentage of heat produced
by muscular work can rise to as much as 90%. To keep warm, the body may have to generate
additional voluntary (limb movement) and involuntary (shivering) muscle contractions.
Newborns also have tissue known as brown fat, which enables them to produce additional heat
without shivering. Cold stimulates a reflex pathway resulting in norepinephrine release
(β3-adrenergic receptors) in fatty tissues, which in turn stimulates (1) lipolysis and (2) the expression
of lipoprotein lipase (LPL) and thermogenin (UCP1). LPL increases the supply of free fatty acids.
Thermogenin localized in the inner mitochondrial membrane is an uncoupling protein that functions
as an H+ uniporter. It short-circuits the H+ gradient across the inner mitochondrial membrane
thereby uncoupling the (heat-producing) respiratory chain of ATP production.
Heat produced in the body is absorbed by the bloodstream and conveyed to the body surface.
In order for this internal flow of heat to occur, the temperature of the body surface must be lower
than that of the body interior. The blood supply to the skin is the chief determinant of heat transport
to the skin.
Heat loss
Heat loss occurs by the physical processes of
radiation, conduction, convection, and evaporation.
1. Radiation - The amount of heat lost by radiation
from the skin is chiefly determined by the
temperature of the radiator (fourth power of its
absolute temperature). Heat net–radiates from the
body surface to objects or individuals when they are
cooler than the skin, and net–radiates to the body
from objects (sun) that are warmer than the skin.
Heat radiates from the body into the environment when no radiating object is present (night sky).
Heat radiation does not require the aid of any vehicle and is hardly affected by the air temperature
(air itself is a poor radiator).
2. Conduction and convection – These processes involve the transfer of heat from the skin to cooler
air or a cooler object (e.g. sitting on rock) in contact with the body (conduction). The amount of heat
lost by conduction to air increases greatly when the warmed air moves away from the body by
natural convection (heated air rises) or forced convection (wind).
3. Evaporation - The first two mechanisms alone are unable to maintain adequate temperature
homeostasis at high environmental temperatures or during strenuous physical activity. Evaporation
is the means by which the body copes with the additional heat. The water lost by evaporation
reaches the skin surface by diffusion (insensible perspiration) and by neuron-activated sweat glands.
About 2428 kJ (580 kcal) of heat are lost for each liter of water evaporating and thereby cooling the
skin. At temperatures above 36 °C or so, heat loss occurs by evaporation only. At even higher
environmental temperatures, heat is absorbed by radiation and conduction/convection.
The body must lose larger amounts of heat by evaporation to make up for this. The surrounding air
must be relatively dry in order for heat loss by evaporation to occur. Humid air retards evaporation.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
41. Hormone-receptor complex
Hormones are messenger substances that convey information signals relevant to cell function.
 Endocrine hormones, i.e., those transported in the bloodstream, are produced in endocrine glands
such as the hypothalamus, thyroid, parathyroid glands, adrenal medulla, pancreatic islets, ovaries and
testes. They are also synthesized in diffusely scattered endocrine cells of the CNS, in C cells of the
thyroid, and in the thymus, atria, kidneys, liver, gastrointestinal tract, etc.
 Paracrine hormones, i.e., those that affect nearby cells only (tissue hormones or mediators; see
below) are secreted by cells widely distributed throughout the body.
Types of hormone
1. Peptide hormones and glycoprotein hormones are hydrophilic hormones stored in secretory granules and
released by exocytosis as required. Multiple hormones can be produced from a single gene (e.g., POMC
gene) by variable splicing and posttranslational modification.
2. Steroid hormones and calcitriol are chemically related lipophilic hormones metabolized from cholesterol.
They are not stored, but are synthesized as needed.
3. Tyrosine derivatives include (a) the hydrophilic catecholamines dopamine, epinephrine and norepinephrine
and (b) lipophilic thyroid hormones (T3, T4).
The lipophilic hormones are transported in the blood while bound to plasma proteins. Corticosteroids are
carried bound to globulin and albumin, testosterone and estrogen to sex hormone-binding globulin and T3 and
T4 to albumin and two other plasma proteins.
Hormone receptors
The receptors (docking sites) for glycoprotein hormones, peptide hormones and catecholamines are
transmembrane proteins that bind to their specific hormone on the outer cell surface.
Many of these hormones induce the release of intracellular second messengers that transmit the hormone
signal inside the cell.
Some peptide hormones like insulin, prolactin, atriopeptin and numerous growth factors bind to cell surface
receptors with cytosolic domains with enzymatic activity. Steroid hormones, on the other hand, enter the cells
themselves. Once they bind to cytosolic receptor proteins, steroid hormones (as well as calcitriol, T3 and T4)
are transported to the cell nucleus, where they influence transcription (genomic action).
. A target cell can have different receptors for different hormones (e.g., insulin and glucagon) or different
receptors for a single hormone (e.g., α1 and β2 adrenoceptors for epinephrine).
Masaryk University Faculty of Medicine Physiology Exam
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Ptm = T/r (or Ptm = 2 T/r, resp.)
Laplace Law
42. Physiological applications of law of Laplace
According to Laplace’s law for cylindrical (or spherical) hollow bodies,
Here, T is the total mural tension, regardless how thick the wall is.
Application in medicine
In medicine it is often referred to as the Law of Laplace, and it is used in the context of respiratory physiology,
in particular alveoli in the lung, where a single alveolus is modeled as being a perfect sphere.
In this context, the pressure differential is a force pushing inwards on the surface of the alveolus. The law of
Laplace states that there is an inverse relationship between surface tension and alveolar radius. It follows from
this that a small alveolus will experience a greater inward force than a large alveolus, if their surface tensions
are equal. In that case, if both alveoli are connected to the same airway, the small alveolus will be more likely
to collapse, expelling its contents into the large alveolus.
This explains why the presence of surfactant lining the alveoli is of vital importance. Surfactant reduces the
surface tension on all alveoli, but its effect is greater on small alveoli than on large alveoli. Thus, surfactant
compensates for the size differences between alveoli, and ensures that smaller alveoli do not collapse.
The Law of Laplace also explains various phenomena encountered in the pathology of vascular or
gastrointestinal walls. The "surface tension" in this case represents the muscular tension on the wall of the
vessel. For example, if an aneurysm forms in a blood vessel wall, the radius of the vessel has increased. This
means that the inward force on the vessel decreases, and therefore the aneurysm will continue to expand until
it ruptures. A similar logic applies to the formation of diverticuli in the gut.
43. Invasive assessment of blood pressure
Arterial blood pressure (BP) is most accurately measured invasively through an arterial line. Invasive arterial
pressure measurement with intravascular cannulae involves direct measurement of arterial pressure by placing
a cannula needle in an artery (usually radial, femoral, dorsalis pedis or brachial).
. The cannula must be connected to a sterile, fluid-filled system, which is connected to an electronic pressure
transducer. The advantage of this system is that pressure is constantly monitored beat-by-beat, and a
waveform (a graph of pressure against time) can be displayed.
. Cannulation for invasive vascular pressure monitoring is infrequently associated with complications such as
thrombosis, infection, and bleeding. It is generally reserved for patients where rapid variations in arterial
pressure are anticipated.
. Invasive vascular pressure monitors are pressure monitoring systems designed to acquire pressure
information for display and processing. There are a variety of invasive vascular pressure monitors for trauma,
critical care, and operating room applications. These include single pressure, dual pressure, and multiparameter
(i.e. pressure / temperature). The monitors can be used for measurement and follow-up of arterial,
central venous, pulmonary arterial, left atrial, right atrial, femoral arterial, umbilical venous, umbilical arterial,
and intracranial pressures.
Masaryk University Faculty of Medicine Physiology Exam
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44. Non-invasive assessment of blood pressure
1. Riva Rocci (auscultatory) method
- Using sphygmomanometer - Cuff wrapped around the
arm
- Stethoscope is placed over the brachial artery at the
ant cubital fossa
- Cuff is inflated until the pressure is well above
expected systolic pressure
- The artery is occluded by the cuff and there will be no
pulse sound
- The pressure in the cuff is lowered using the valve
- At the point where systole pressure exceeds the cuff, a sharp sound can be heard as
blood forces its way through the vessel – this first sound is systole
- As the cuff pressure is lowered further, the sounds become louder, then dull and
weaker and gradually fades to a point – this last sound is diastole
- These sounds (kortikoff sounds) can be heard due to turbulent flow in the brachial
artery, because when the artery is narrowed, the velocity of flow through the
constriction exceeds the critical velocity  turbulent flow
2. Oscillometric method
Involves the observation of oscillations in the sphygmomanometer cuff pressure which are caused by
the oscillations of blood flow, i.e. the pulse. The electronic version of this method is sometimes used
in long-term measurements and general practice. It uses a sphygmomanometer cuff like the
auscultatory method, but with an electronic pressure sensor (transducer) to observe cuff pressure
oscillations, electronics to automatically interpret them, and automatic inflation and deflation of the
cuff. The pressure sensor should be calibrated periodically to maintain accuracy.
Oscillometric measurement requires less skill than the auscultatory technique, and may be suitable
for use by untrained staff and for automated patient home monitoring.
The cuff is inflated to a pressure initially in excess of the systolic arterial pressure, and then reduces
to below diastolic pressure over a period of about 30 seconds. When blood flow is zero (cuff pressure
exceeding systolic pressure) or unimpeded (cuff pressure below diastolic pressure), cuff pressure will
be essentially constant. When blood flow is present, but restricted, the cuff pressure, which is
monitored by the pressure sensor, will vary periodically in synchrony with the cyclic expansion and
contraction of the brachial artery, i.e., it will oscillate. The values of systolic and diastolic pressure are
computed, not actually measured from the raw data, using an algorithm; the computed results are
displayed.
Oscillometric monitors may produce inaccurate readings in patients with heart and circulation
problems, that include arterial sclerosis, arrhythmia, preeclampsia, pulsus alternans, and pulsus
paradoxus.
The term NIBP, for Non-Invasive Blood Pressure, is often used to describe oscillometric monitoring
equipment.
Masaryk University Faculty of Medicine Physiology Exam
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3. Palpation
- inflate arm cuff until radial pulse is no longer detectable
- let pressure fall and determine the pressure at which the radial pulse first becomes
palpable => systolic pressure
- due to difficulty in measuring – pressures are usually 2-3mmHg lower than measured
in riva rocci method.
NOTE
When arterial pressure is measured using a sphygmomanometer (i.e., blood pressure cuff) on the upper arm,
the systolic and diastolic pressures that are measured represent the pressure within the brachial artery, which
is slightly different than the pressure found in the aorta or the pressure found in other distributing arteries. As
the aortic pressure pulse travels down the aorta and into distributing arteries, there are characteristic changes
in the systolic and diastolic pressures, as well as in the mean pressure. The systolic pressure rises and the
diastolic pressure falls, therefore the pulse pressure increases, as the pressure pulse travels away from the
aorta. This occurs because of reflective waves from vessel branching, and from decreased arterial compliance
(increased vessel stiffness) as the pressure pulse waves travels from the aorta into systemic arteries. There is
only a small decline in mean arterial pressure as the pressure pulse travels down distributing arteries due to
the relatively low resistance of large distributing arteries.
Finapres (method of Prof. Jan Peñáz)
The Finapres non-invasive blood pressure (BP) monitor uses the method of Peñáz to indirectly record
the arterial waveform.
Volume clamp with physiocal technology
The volume-clamp method was first introduced by Czech physiologist Prof. J Peñáz in 1967. With this
method, finger arterial pressure is measured using a finger cuff and an inflatable bladder in
combination with an infrared plethysmograph, which consists of an infrared light source and
detector. The infrared light is absorbed by the blood, and the pulsation of arterial diameter during a
heart beat causes a pulsation in the light detector signal.
The first step in this method is determining the proper unloaded diameter of the finger arteries, the
point at which finger cuff pressure and intra-arterial pressure are equal and at which the transmural
pressure across the finger arterial walls is zero. Then the arteries are clamped (kept at this unloaded
diameter) by varying the pressure of the finger cuff inflatable bladder using the fast cuff pressure
control system.
A servo-controller system usually defines a target value or setpoint and a measured value that is
compared with this setpoint. In the servo-controller the setpoint is the signal of the plethysmograph
(unloaded diameter of the arteries) that must be clamped. The measured value comes from the light
detector. The amplified difference between the setpoint and measured value, "the error signal," is
used to control a fast pneumatic proportional valve in the frontend unit. This proportional valve
modulates the air pressure generated by the air compressor, thus causing changes in the finger cuff
pressure in parallel with intra-arterial pressure in the finger so as to dynamically unload the arterial
walls in the finger. The cuff pressure thus provides an indirect measure of intra-arterial pressure.
Physiocal is the automatic algorithm that calibrates the finger arterial size at which finger cuff air
pressure equals finger arterial blood pressure.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
45. Measurement of cardiac output
In the human, except in rare instances, cardiac output is measured by indirect methods that do not
require surgery. Two of the methods commonly used are the oxygen Fick method and the indicator
dilution method.
Oxygen Fick Principle
The Fick principle is explained by the figure to the
right. This figure shows that 200 ml of oxygen are
being absorbed from the lungs into the pulmonary
blood each minute. It also shows that the blood
entering the right heart has an oxygen concentration
of 160 ml per liter of blood, whereas that leaving the
left heart has an oxygen concentration of 200 ml per
liter of blood. From this data, one can calculate that
each liter of blood passing through the lungs absorbs
40 ml of oxygen.
Because the total quantity of oxygen absorbed into
the blood from the lungs each minute is 200 ml,
dividing 200 by 40 calculates a total of five 1-liter portions of blood that must pass through the
pulmonary circulation each minute to absorb this amount of oxygen. Therefore, the quantity of blood
flowing through the lungs each minute is 5 liters, which is also a measure of the cardiac output.
Thus, the cardiac output can be calculated by the following formula:
In applying this Fick procedure for measuring cardiac output in the human being, mixed venous blood
is usually obtained through a catheter inserted up the brachial vein of the forearm, through the
subclavian vein, down to the right atrium, and, finally, into the right ventricle or pulmonary artery.
And systemic arterial blood can then be obtained from any systemic artery in the body. The rate of
oxygen absorption by the lungs is measured by the rate of disappearance of oxygen from the
respired air, using any type of oxygen meter.
Indicator Dilution Method
The method measures the concentration of a dye at different points in the circulation, usually from
an intravenous injection and then at a downstream sampling site, usually in a systemic artery.
A small amount of indicator, such as a dye, is injected into a large systemic vein or, preferably, into a
large systemic vein or, preferably, into right atrium. This passes through the right side of the heart,
then through the blood vessels of the lungs, through the left side of the heart and, finally, into the
systemic arterial system. The concentration of the dye is recorded as the dye passes though one of
the peripheral arteries, giving a curve.
The cardiac output can be determined using the following formula:
Cardiac output = ml of dye injected x 60
Average concentration of dye
in each ml of blood x
for the duration of the curve
Duration of
the curve
in seconds
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
46. Measurement of blood flow
Electromagnetic Flowmeter
A blood vessel is placed between the poles of a strong
magnet, and electrodes are placed on the two sides of the
vessel perpendicular to the magnetic lines of force. When
blood flows through the vessel, an electrical voltage
proportional to the rate of the blood flow is generated
between the two electrodes, and this is recorded using an
appropriate voltmeter or electronic recording apparatus.
A special advantage of the electromagnetic flowmeter is
that it can record changes in flow in less than 1/100 of a
second, allowing accurate recording of pulsatile changes in
flow as well as steady flow.
Ultrasonic Doppler Flowmeter
A microscopic piezoelectric crystal is mounted at one end in the wall of the device. This crystal, when
energized with an appropriate electronic apparatus, transmits ultrasound at a frequency of several
hundred thousand cycles per second downstream along the flowing blood. A portion of the sound is
reflected by the red blood cells in the flowing blood. The reflected sound waves then travel backward
from the blood cells toward the crystal. These reflected waves have a lower frequency than the
transmitted wave because the red blood cells are moving away from the transmitter crystal.
This is called Doppler effect.
47. Phonocardiography
A Phonocardiogram or PCG is a plot of high fidelity recording of
the sounds and murmurs made by the heart with the help of the
machine called phonocardiograph, or "Recording of the sounds
made by the heart during a cardiac cycle." The sounds are
thought to result from vibrations created by closure of the heart
valves. There are at least two: the first when the atrioventricular
valves close at the beginning of systole and the second when the
aortic valve closes at the end of systole. It allows the detection
of subaudible sounds and murmurs, and makes a permanent
record of these events. In contrast, the ordinary stethoscope
cannot detect such sounds or murmurs, and provides no record
of their occurrence.
The ability to quantitate the sounds made by the heart provides
information not readily available from more sophisticated tests,
and provides vital information about the effects of certain cardiac drugs upon the heart. It is also an
effective method for tracking the progress of the patient's disease.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
48. ECG leads
There are several ways in which the ECG can be connected to electrodes placed on the body. These are
referred to as leads, and they fall into 2 categories:
a) bipolar – when the ECG is connected between 2 electrodes on the surface of the body
b) unipolar – when ECG is connected between one electrode and an indifferent point representing the
body as whole
12 Leads used for routine purposes are:
Standard limb leads – (BIPOLAR)
These leads measure the difference in electric potential between 2 points. The leads are bipolar (1 –ve 1 +ve).
Electrodes are placed on right arm (red), left arm (yellow), left leg (green) and a ground electrode on the right
leg (black).
Note – Einthovens triangle is used to represent the heart in the middle of
a isosceles triangle with the 2 upper corners representing the shoulders
and the bottom corner representing the symphysis pubis.
Unipolar leads
Is based on recording potential difference between an exploring electrode
and an indifferent electrode.
There are 4 types of unipolar leads:
a) Unipolar limb leads – VR, VL, VF. The indifferent electrode is
Wilson electrode (5k) (NOT USED AS OFTEN. AUGMENTED IS USED)
b) Augmented limb leads (goldberger) – aVR = +ve terminal on right arm
– aVL = +ve terminal on the left arm
. – aVF = +ve terminal on the left leg
c) unipolar chest leads (precordial leads)
d) Esophageal electrode (extra)
This is used to study atrial activity. This electrode is inserted in
. a catheter and swallowed. Each esophageal electrode is identified .
. by the letter E + number (cm from teeth to electrode)
Relationship between direction of the lead and amplitude of ECG
In the unipolar leads
 if the depolarization is travelling towards the explorating electrode  positive deflection
 if the depolarization is travelling outwards explorating electrode  negative deflection
In the bipolar leads
 in direction from the negative to the positive electrode  positive deflection
 in direction from the positive to the negative electrode  negative deflection
 If no potential at all is recorded in the ECG when the ventricular muscle is either completely polarized or
completely depolarized.
Lead I = Right arm (negative) – Left arm (positive)
Lead II = Right arm (negative) – Left leg (positive)
Leads III = Left arm (negative) – Left leg (positive)
Exploring electrodes:
V1 - Rt, 4th
intercostal space
V2 - Lt, 4th
intercostal space
V3 - Lt, midway between V2 and V4
V4 - Lt, 5th
intercostal space, mid-clavicular line
V5 - Lt, 5th
intercostal space, anterior axillary line
V6 - Lt, 5th
intercostal space, mid-axillary line
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
49. ECG recording in different leads
Electrocardiographic Leads Three Bipolar Limb Leads
The figure to the right demonstrates electrical connections between the
patient’s limbs and the electrocardiograph for recording
electrocardiograms from the so-called standard bipolar limb leads.
The term “bipolar” means that the electrocardiogram is recorded from
two electrodes located on different sides of the heart, in this case, on
the limbs.
Lead I. In recording limb lead I, the negative terminal of the electrocardiograph is
connected to the right arm and the positive terminal to the left arm. Therefore,
when the point where the right arm connects to the chest is electronegative with
respect to the point where the left arm connects, the electrocardiograph records
positively, that is, above the zero voltage line in the electrocardiogram. When the
opposite is true, the electrocardiograph records below the line.
Lead II. To record limb lead II, the negative terminal of the electrocardiograph is
connected to the right arm and the positive terminal to the left leg. Therefore,
when the right arm is negative with respect to the left leg, the electrocardiograph
records positively.
Lead III. To record limb lead III, the negative terminal of the electrocardiograph
is connected to the left arm and the positive terminal to the left leg.
This means that the electrocardiograph records positively when the left arm
is negative with respect to the left leg.
Chest Leads (Precordial Leads)
Often electrocardiograms are recorded with one electrode placed on
the anterior surface of the chest directly over the heart at one of the
points shown in the figure (right). This electrode is connected to the
positive terminal of the electrocardiograph, and the negative
electrode, called the indifferent electrode, is connected through
equal electrical resistances to the right arm, left arm, and left leg all
at the same time. Usually six standard chest leads are recorded, one
at a time, from the anterior chest wall, the chest electrode being
placed sequentially at the six points shown in the diagram. The
different recordings are known as leads V1, V2, V3, V4, V5, and V6.
Because the heart surfaces are close to the chest wall, each chest
lead records mainly the electrical potential of the cardiac
musculature immediately beneath the electrode. Therefore,
relatively minute abnormalities in the ventricles, particularly in the
anterior ventricular wall, can cause marked changes in the
electrocardiograms recorded from individual chest leads.
In leads V1 and V2, the QRS recordings of the normal heart are mainly
negative because the chest electrode in these leads is nearer to the
base of the heart than to the apex, and the base of the heart is the
direction of electronegativity during most of the ventricular
depolarization process. Conversely, the QRS complexes in leads
V4,V5, and V6 are mainly positive because the chest electrode in these
leads is nearer the heart apex, which is the direction of electropositivity during most of depolarization.
Augmented Unipolar Limb Leads
Another system of leads in wide use is the augmented unipolar limb lead. In this type of recording, two of the limbs are
connected through electrical resistances to the negative terminal of the electrocardiograph, and the third limb is connected
to the positive terminal.
When the positive terminal is on the right arm, the lead is known as the aVR lead; when on the left arm, the aVL lead; and
when on the left leg, the aVF lead.
Einthoven’s Law. Einthoven’s law states that if the
electrical potentials of any two of the three bipolar
limb electrocardiographic leads are known at any
given instant, the third one can be determined
mathematically by simply summing the first two (but
note that the positive and negative signs of the
different leads must be observed when making this
summation).
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Vectorial Analysis of Potentials in the Three
Standard Bipolar Limb Leads
50. Estimation of electric axis of the heart (Guyton chap. 12)
Use of Vectors to Represent Electrical Potentials
A vector is an arrow that points in the direction of the electrical potential generated by the current flow, with
the arrowhead in the positive direction. Also, by convention, the length of
the arrow is drawn proportional to the voltage of the potential.
Electrical current flows between the depolarized areas inside the heart and
the nondepolarized areas on the outside of the heart. Some current also
flows inside the heart chambers directly from the depolarized areas
toward the still polarized areas. Overall, considerably more current flows
downward from the base of the ventricles toward the apex than in the
upward direction. Therefore, the summated vector of the generated
potential at this particular instant, called the instantaneous mean vector, is
represented by the long black arrow drawn through the center of the
ventricles in a direction from base toward apex.
In a normal heart, the average direction of the vector during spread of the
depolarization wave through the ventricles, called the mean QRS vector, is
about +59 degrees, which is shown by vector A drawn through the center of
figure on the right in the +59-degree direction. This means that during most
of the depolarization wave, the apex of the heart remains positive with
respect to the base of the heart.
Vectocardigram
The so-called vectorcardiogram depicts these changes at different times
during the cardiac cycle, as shown in Figure 12–10.
Masaryk University Faculty of Medicine Physiology Exam
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51. Cardiac contractility, ejection fraction, heart failure
Contractility
– is the intrinsic ability of cardiac muscle to develop a force at a given muscle length.
– is also called inotropism.
– is related to the intracellular Ca
2+
concentration.
– can be estimated by the ejection fraction (stoke volume/ end-diastolic volume), which is normally 0.55 (55%).
– Positive inotropic agents produce an increase in contractility.
– Negative inotropic agents produce a decrease in contractility.
1. Factors that increase contractility (positive inotropism)
. a. Increases heart rate
. – When more action potentials occur per unit time, more Ca
2+
enters the myocardial cells during the
. action potential plateaus, more Ca
2+
is released from the SR, and greater tension is produced during
. contraction.
. b. Sympathetic stimulation (cathecholamines) via β1 receptors
. – increases the force of contraction by two mechanisms:
. (1) It increases the inward Ca
2+
current during the platue of each cardiac action potential.
. (2) It increases the activity of the Ca
2+
pump of the SR (by phosphorylation of phospholamban); as a result
. more Ca
2+
is available for release in subsequent beats.
. c. Cardiac glycosides (digitialis)
. – increase the force of contraction by inhibiting Na
+
, K
+
-ATPase in the myocardial cell membrane (figure).
. – As a result of this inhibition, the intracellular [Na
+
], diminishing the Na
+
gradient across the cell
. membrane.
. – Na
+
-Ca
2+
exchange (a mechanism that extrudes Ca
2+
from the cell) depends on the size of the Na
+
gradient
. and thus is diminished, producing increase in intracellular [Ca
2+
].
2. Factors that decrease contractility (negative inotropism)
. – Parasympathetic stimulation (ACh) via muscarinic receptors decrease the force of contraction in the atria
. by decreasing the inward Ca
2+
current during the platue of the cardiac action potential.
Ejection fraction
– is the fraction of the end-diastolic volume ejected in each stroke volume.
– is related to contractility.
– is normally 0.55, or 55%.
– is expressed by the following equation:
Stepwise explanation how ouabain (digitalis9
causes an increase in intracellular [Ca2+] and
myocardial contractility.
Ejection fraction = Stroke volume / End-diastolic volume
Masaryk University Faculty of Medicine Physiology Exam
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Cardiac failure (“Heart failure”)
The term “cardiac failure” means simply failure of the heart to pump enough blood to satisfy the
needs of the body. It can be acute and associated with sudden death, or chronic. The failure may
involve primarily the right ventricle, but much more commonly it involves the larger, thicker left
ventricle or both ventricles. .
. In chronic heart failure (congestive heart failure), cardiac output is initially inadequate during
exercise but adequate at rest. As the disease progresses, the output at rest also becomes
inadequate.
There are two types of failure, systolic and diastolic. In systolic failure, stroke volume is reduced
because ventricular contraction is weak. This causes an increase in the end-systolic ventricular
volume, so that the ejection fraction – the fraction of the blood in the ventricles that is ejected
during systole – falls from 65% to as low as 20%. The initial response to failure is activation of the
genes that cause cardiac myocytes to hypertrophy, and thicken of the ventricular wall (cardiac
remodeling). The incomplete filling of the arterial system leads to increased discharge of the
sympathetic nervous system and increased secretion of renin and aldosterone, so Na+
and water is
retained. The responses are initially compensatory, but eventually the failure worsens and the
ventricles dilate.
. In diastolic failure, the ejection fraction is initially maintained but the elasticity of the myocardium
is reduced so filling during diastole is reduced. This lead to inadequate stroke volume and the same
cardiac remodeling and Na+ and water retention that occur in systolic failure.
. It should be noted that the inadequate cardiac output in failure may be relative rather than
absolute. When a larger arterior venous fistula is present, in thyrotoxicosis, and in thiamine
deficiency, cardiac output may be elevated in absolute terms but still be inadequate to meet the
needs of the tissues (high-output failure).
Treatment
Treatment of congestive heart failure is aimed at improving cardiac contractility, treating the
symptoms, and decreasing the load on the heart. Currently, the most effective treatment in general
use is inhibition of the production of angiotensin II with angiotensin-converting enzyme inhibitors.
Blocking the production of angiotensin II or its effects also reduces the circulating aldosterone level
and decreases blood pressure, reducing the afterload against which the heart pumps. Digitalis
derivatives such as dioxin have classically been used to treat congestive heart failure because of their
ability to increase intracellular Ca2+
and hence exert a positively inotropic effect, but they are now
used in a secondary role to treat systolic dysfunction and slow the ventricular rate in patients with
atrial fibrillation.
Masaryk University Faculty of Medicine Physiology Exam
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52. Cardiac catheterization
Cardiac catheterization (heart cath) is the insertion of a catheter into a chamber or vessel of the
heart. This is done for both investigational and interventional purposes. Coronary catheterization is a
subset of this technique, involving the catheterization of the coronary arteries.
Procedure:
Local anaesthetic is injected into the skin to numb the area. A small puncture is then made with a
needle in either the femoral artery in the groin or the radial artery in the wrist, before a guidewire is
inserted into the arterial puncture. A plastic sheath (with a stiffer plastic introducer inside it) is then
threaded over the wire and pushed into the artery (Seldinger technique). The wire is then removed
and the side-port of the sheath is aspirated to ensure arterial blood flows back. It is then flushed with
saline.
Catheters are inserted using a long guidwire and moved towards the heart. Once in position above
the aortic valve the guidewire is then removed. The catheter is then engaged with the origin of the
coronary artery (either left main stem or right coronary artery) and x-ray opaque iodine-based
contrast is injected to make the coronary vessels show up on the x-ray fluoroscopy image.
When the necessary procedures are complete, the catheter is removed. Firm pressure is applied to
the site to prevent bleeding. If the femoral artery was used, the patient will probably be asked to lie
flat for several hours to prevent bleeding or the development of a hematoma.
A cardiac catheterization is a general term for a group of procedures that are performed using this
method, such as coronary angiography, as well as left ventrical angiography. Once the catheter is in
place, it can be used to perform a number of procedures including angioplasty, angiography, balloon
septostomy, and an Electrophysiology study.
Indications for investigational use
This technique has several goals:
 confirm the presence of a suspected heart ailment
 quantify the severity of the disease and its effect on the heart
 seek out the cause of a symptom such as shortness of breath or signs of cardiac insufficiency
 make a patient assessment prior to heart surgery
Investigative techniques used with cardiac catheterization
A probe that is opaque to X-rays is inserted into the left or right chambers of the heart for the
following reasons:
 to measure intracardiac and intravascular blood pressures
 to take tissue samples for biopsy
 to inject various agents for measuring blood flow in the heart; also to detect and quantify the
presence of an intracardiac shunt
 to inject contrast agents in order to study the shape of the heart vessels and chambers and
how they change as the heart beats
Masaryk University Faculty of Medicine Physiology Exam
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53. Polygraphic methods
A polygraph (or “lie detector”) is an instrument that measures and
records several physiological indices such as blood pressure, pulse,
respiration, breathing rhythms/ratios, and skin conductivity while the
subject is asked and answers a series of questions, in the belief that
deceptive answers will produce physiological responses that can be
differentiated from those associated with non-deceptive answers.
Polygraphs are in some countries used as an interrogation tool. Within
the US federal government, a polygraph examination is also referred to
as a psycho physiological detection of deception (PDD) examination.
This method was in the past used in clinical practice, nowadays it is replaced by other methods. In practicals, it
will help us to demonstrate interrelationships of particular processes of cardiac action.
(Masaryk Uni. Phys. Prac.): Evaluation Systolic Time Interval using Polygraph Recording
3 parameters will be registered simultaneously; electrical activity of the heart by means of electrocardiography
(ECG; I. lead), pulse wave on a. carotis by means of infrared sensor, sfygmography (SFG) and heart sounds by
means of phonocardiography (FCG).
Measured parameters (from figure):
RR interval: cardiac cycle duration (time between two successive R on ECG recording)
LVET: Ejection phase duration (time from the onset of the sphygmographic curve to the dicrotic incisure, it
corresponds to the time interval between the opening and closure of the aortic valves)
QS2: electromechanical systole – time from electrical activation of septum to closure of aortic valve (time from
Q ton ECG recording to the 2
nd
heart sound on FCG or FCG* recording)
S1S2: duration of mechanical systole (time between 1
st
and 2
nd
heart sound on FCG or FCG* recording)
Calculated parameters:
S2S1: mechanical diastole duration (S2S1= RR interval - S1S2)
PEP: preejection period – time from electrical activation of septum to opening of seminlunar valves (PEP = QS2 – LVET)
IVC: isovolumic contraction duration (IVC = S1S2 – LVET) EML: electromechanical latency – time from electrical
activation of septum to closing of atrioventricular valves and beginning of systole of ventricles (EML=QS2 - S1S2)
Indexes:
∆P/∆t = average speed of pressure increase in isovolumic phase of systole
PEP/LVET =it is index of cardiac contractility
Systolic intervals depend on the heart rate. In order to compare various recordings the interval must be
corrected. The easiest and most often used correction is done according to Bazett’s formula:
Ic = Im / , where Ic is corrected interval, Im is measured interval in milliseconds and RR is cycle length in
. seconds
Masaryk University Faculty of Medicine Physiology Exam
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Electromyographic tracings from human
biceps and triceps muscles during
alternate flexion and extension of elbow
54. Electromyography
Electromyography (EMG) is a technique for evaluating and recording
the electrical activity produced by skeletal muscles. EMG is performed
using an instrument called an electromyograph, to produce a record
called an electromyogram. An electromyograph detects the electrical
potential generated by muscle cellswhen these cells are electrically or
neurologically activated. The signals can be analyzed to detect
medical abnormalities, activation level, and recruitment order or to
analyze the biomechanics of human or animal movement.
Procedure
There are two kinds of EMG in widespread use: surface EMG
and intramuscular (needle and fine-wire) EMG.
1. To perform intramuscular EMG, a needle electrode or a needle containing two fine-wire
electrodes is inserted through the skin into the muscle tissue. A trained professional observes the
electrical activity while inserting the electrode. The insertional activity provides valuable information
about the state of the muscle and its innervating nerve. Normal muscles at rest make certain, normal
electrical sounds when the needle is inserted into them. Then the electrical activity when the muscle
is at rest is studied. Abnormal spontaneous activity might indicate some nerve and/or muscle
damage. Then the patient is asked to contract the muscle smoothly. The shape, size, and frequency
of the resulting motor unit potentials are judged. Then the electrode is retracted a few millimeters,
and again the activity is analyzed until at least 10–20 units have been collected. Each electrode track
gives only a very local picture of the activity of the whole muscle. Because skeletal muscles differ in
the inner structure, the electrode has to be placed at various locations to obtain an accurate study.
2. Intramuscular EMG may be considered too invasive or unnecessary in some cases. Instead, a
surface electrode may be used to monitor the general picture of muscle activation, as opposed to
the activity of only a few fibers as observed using an intramuscular EMG. This technique is used in a
number of settings; for example, in the physiotherapy clinic, muscle activation is monitored using
surface EMG and patients have an auditory or visual stimulus to help them know when they are
activating the muscle (biofeedback).
A motor unit is defined as one motor neuron and all of the muscle fibers it innervates. When a motor
unit fires, the impulse is carried down the motor neuron to the muscle. The area where the nerve
contacts the muscle is called the neuromuscular junction, or the motor end plate. After the action
potential is transmitted across the neuromuscular junction, an action potential is elicited in all of the
innervated muscle fibers of that particular motor unit. The sum of all this electrical activity is known
as a motor unit action potential (MUAP). This electrophysiologic activity from multiple motor units is
the signal typically evaluated during an EMG. The composition of the motor unit, the number of
muscle fibers per motor unit, the metabolic type of muscle fibers and many other factors affect the
shape of the motor unit potentials in the myogram.
Normal results
Muscle tissue at rest is normally electrically inactive. After the electrical activity caused by the irritation of
needle insertion subsides, the electromyograph should detect no abnormal spontaneous activity (i.e., a muscle
at rest should be electrically silent, with the exception of the area of the neuromuscular junction, which is,
under normal circumstances, very spontaneously active). When the muscle is voluntarily contracted, action
potentials begin to appear. As the strength of the muscle contraction is increased, more and more muscle
fibers produce action potentials. When the muscle is fully contracted, there should appear a disorderly group
of action potentials of varying rates and amplitudes (a complete recruitment and interference pattern).
Masaryk University Faculty of Medicine Physiology Exam
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55. Registration of membrane potential and currents
Electrodes for Active Biosignals
Masaryk University Faculty of Medicine Physiology Exam
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56. External signs of breathing
Check for Breathing
 Look for signs of breathing. Watch the victim’s chest to see if it is rising and falling, which would
indicate breathing is occurring.
 Listen for signs of breathing by placing your ear near the victim's nose. Weak breathing may not
produce obvious rising and falling of the chest, but you may still be able to hear the breathing.
 Place your hand in front of the victim's nose and mouth to see if you can feel warm air being expelled
during breathing. If you have a mirror, such as one from a cosmetic case, hold it under the victim's
nose and see if it fogs with expelled breath.
 Smell of breath
Examination of the chest
The physical examination of the chest consists of inspection, palpation, percussion, and auscultation.
Inspection – one looks at the shape of the chest, deformities; checks the respiratory movements and soft parts.
– Respiratory movements: During respiratory movements we watch the type of respiration and check whether
both sides of the chest participate in the air exchange equally and with the same force; we also check the
respiratory rate (frequency).
. The “abdominal type” of respiration is common in men: breathing movements are accomplished mostly by
the diaphragm with a rhythmic protrusion of the abdominal wall.
. In women the “costal type” of respiration is common, mainly with elevation and lowering of the ribcage.
In diseases of the pleura, in pleuropneumonic adhesion, pleural effusion or pneumothorax, the movements of
the chest on the affected side may be diminished or absent. Respiratory rate in resting adult is approx. 16-20
beats per minute. This normal respiration is called eupnea. During exercise and under pathologic conditions
respiration may greatly change in the number of breaths per minute, as well as in depth and regularity.
Tachypnea is and increased breathing rate (frequency); it may be an important sign of lung disease.
Bradypnea is a decreased number of breaths per minute.
Apnea is a temporary cessation of respiration (e.g. the apneic phase of Cheyne-Stokes periodic respiration).
Hyperpnea is a deepened respiration (increases minute volume if air in lungs).
Dyspnea is “shortness of breath”.
Palpation of the Chest: by Vocal Fremitus; the perception of vibration of the chest wall caused by phonation
(talking) of the patient. The patient loudly pronounces certain words to cause resonance (for instance, “onetwo-three,
or ninety-nine”) of the chest wall. The voice is transmitted from the vocal cords through the trachea
and bronchi into the lung tissue, and from there the voice is transferred to the chest wall, which acts as a
resonator. One places the palms of both hands (bilaterally) over corresponding areas on the hemithoraces and
compares the vibrations evoked by the spoken sounds.
Percussion of the Chest: The percussion sound over normal lungs is sonorous, resonant, and clear, with a
slightly hyperresonant character toward the lung bases. It may change under pathological conditions to:
1. Hypersonorous (hyperresonant)- if the lungs become more expanded and filled with air: this is found in
emphysema, or if there is some air in the pleural cavity (pneumothorax).
2. dull to flat: e.g., if the lung tissue loses its air content and becomes consolidated, dense (e.g. in pneumonia).
Auscultation of the Lungs: One may utilize the direct method by placing one’s ear directly on the chest wall – or
the preferred indirect method – with the aid of a stethoscope.
Breath Sounds: vesicular breathing and bronchial (tubular) breathing
Masaryk University Faculty of Medicine Physiology Exam
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57. Lung ventilation, volumes, measurement
Mechanism of Breathing
The lungs can be expanded and contracted in two ways: (1) by
downward and upward movement of the diaphragm to lengthen
or shorten the chest cavity, and (2) by elevation and depression of
the ribs to increase and decrease the anteroposterior diameter of
the chest cavity.
Muscles of inspiration
1. Diaphragm – when it contracts, the abdominal contents are
pushed downward, and the ribs are lifted upward and outward, increasing the volume of the thoracic cavity.
2. External intercostals and accessory muscles – are used during exercise and in respiratory distress.
Muscles of expiration
– expiration is normally passive. Because the lung-chest wall system is elastic, it returns to its resting position
after inspiration.
– Expiratory muscles are used during exercise or when airway resistance is increased because of disease (e.g.,
asthma).
1. Abdominal muscles – compress the abdominal cavity, push the diaphragm up, and push air put of the lungs.
2. Internal intercostals – pull the ribs downward and inward.
Pulmonary Volumes
1. The tidal volume is the volume of air inspired or
expired with each normal breath; it amounts to
about 500 milliliters in the adult male.
2. The inspiratory reserve volume is the extra
volume of air that can be inspired over and above
the normal tidal volume when the person inspires
with full force; it is usually equal to about 3000
milliliters.
3. The expiratory reserve volume is the maximum
extra volume of air that can be expired by forceful
expiration after the end of a normal tidal
expiration; this normally amounts to about
1100 milliliters.
4. The residual volume is the volume of air
remaining in the lungs after the most forceful
expiration; this volume averages about
1200 milliliters.
Recording Changes in Pulmonary Volume -
Spirometry
A simple method for studying pulmonary ventilation
is to record the volume movement of air into and out
of the lungs, a process called spirometry.
It consists of a drum inverted over a chamber of water, with
the drum counterbalanced by a weight. In the drum is a
breathing gas, usually air or oxygen; a tube connects
the mouth with the gas chamber. When one breathes
into and out of the chamber, the drum rises and falls,
and an appropriate recording is made on a moving
sheet of paper.
Masaryk University Faculty of Medicine Physiology Exam
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58. Dead space, measurement
Some of the air a person breathes never reaches the gas exchange areas but simply fills respiratory
passages where gas exchange does not occur, such as the nose, pharynx, and trachea. This air is
called dead space air because it is not useful for gas exchange.
On expiration, the air in the dead space is expired first, before any of the air from the alveoli
reaches the atmosphere. Therefore, the dead space is very disadvantageous for removing the
expiratory gases from the lungs.
a. Anatomic dead space
. – is the volume of the conducting airways.
. – is normally approximately 150 mL.
b. Physiological dead space
. – is a functional measurement.
. – is defined as the volume of the lungs that does not participate in gas exchange.
. – is approx. equal to the anatomic dead space in normal lungs.
. – may be greater than the anatomic dead space in lung diseases in which there are
. ventilation/perfusion (V/Q) defects.
. – is calculated by the following equation:
VD = VT x
where:
VD = physiological dead space (mL)
VT = tidal volume (mL)
P
ACO2
= PCO2 of alveolar gas (mm Hg) = PCO2 of arterial blood
P
ECO2
= PCO2 of expired air (mm Hg)
 In word, the equation states that physiological dead space is tidal volume multiplied by a
fraction. The fraction represents the dilution of alveolar PCO2 by dead-space air, which does
not participate in gas exchange and does not therefore contribute CO2 to expired air.
P
ACO2 –
P
ECO2
P
ACO2
Masaryk University Faculty of Medicine Physiology Exam
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59. Resistance of airways, measurement
Calculating resistance of the airways
 Resistance can be calculated using Ohm's law or Poiseuille's law.
Ohm's law
 R = resistance
 P = pressure
 = airflow (the dot over the letter is used to denote rate in respiratory physiology.)
Poiseuille's law
 R = resistance
 n = viscosity
 l = length
 r = radius
 Because of the fourth power in the denominator, resistance increases rapidly as diameter
decreases.
Factors that change airway resistance
a. Contraction or relaxation of bronchial smooth muscle
– changes airway resistance by altering the radius of the airways.
(1) Parasympathetic stimulation, irritants, and the slow-reacting substance of anaphylaxis
(asthma) constrict the airways, decrease the radius, and increase the resistance to airflow.
(2) Sympathetic stimulation and sympathetic agonists (isoproterenol) dilate the airways via
β2 receptors, increase the radius, and decrease the resistance to airflow.
b. Lung volumes
(1) High lung volumes are associated with greater traction and decreased airway resistance.
(2) Low lung volumes are associated with less traction and increased airway resistance.
c. Viscosity or density of inspired gas
– During a deep-sea dive, both air density and resistance to airflow are increased.
– Breathing a low-density gas, such as helium, reduces the resistance to airflow.
Masaryk University Faculty of Medicine Physiology Exam
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Pneumography –recording, the way of evaluation
60. Pneumography and pneumotachography
Pneumography
Pneumography is a method of recording the respiratory movements. Sensor – respiratory belt
- works on piezoelectric principle (mechanical stimuli – increase or decrease of chest circumference
are converted to electrical signal). The signal is then amplified and recorded.
Pneumotachography
The pneumotachograph is an instrument consisting of parallel tubes of equal diameter that ensure
laminar flow during breathing. One of the tubes has two side-branches near its both ends that are
connected to a differential manometer by rubber tubing. The differential manometer measures the
difference in air pressure of the inspired air or expired air. The pressure at the end of the
pneumotachograph corresponds approximately to atmospheric pressure and is taken as zero.
Pressure in the alveoli is estimated by closing the outer end of the pneumotachograph by a special
device (valve) for a fraction of second during normal breathing. The alveolar and airway pressure
equilibrate at this moment and the alveolar pressure is recorded. Estimation of airway resistance is
important for diagnosis of bronchial asthma where it is increased.
During breathing trough the pneumotachograph, two resistances are connected in series: that of the
pneumotachograph (Rp) and the airway resistance (Ra). If the alveolar pressure (Palv), pressure at
proximal end of the pneumotachograph (Pp), and resistance of the pneumotachograph (Rp) are
known, then:
- duration of inspiration (Ti)
- duration of expiration (Te)
- respiratory intervals (BI=breathing interval)
- amplitude Vt
Principle of pneumotachography
The formula for calculation of airway
resistance is:
Rd = Rp x (∆ Palv/∆Pp – 1)
Masaryk University Faculty of Medicine Physiology Exam
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61. Maximum respiratory flow – volume curve (spirogram)
1. The inspiratory capacity equals the tidal volume
plus the inspiratory reserve volume. This is the
amount of air (about 3500 milliliters) a person can
breathe in, beginning at the normal expiratory
level and distending the lungs to the maximum
amount.
2. The functional residual capacity equals the
expiratory reserve volume plus the residual
volume. This is the amount of air that remains in
the lungs at the end of normal expiration (about
2300 milliliters).
3. The vital capacity equals the inspiratory reserve
volume plus the tidal volume plus the expiratory
reserve volume. This is the maximum amount of
air a person can expel from the lungs after first
filling the lungs to their maximum extent and then
expiring to the maximum extent (about 4600
milliliters).
4. The total lung capacity is the maximum volume
to which the lungs can be expanded with the
greatest possible effort (about 5800 milliliters); it is equal
to the vital capacity plus the residual volume.
COMPLETE .. . specify !!
62. pH measurement (Astrup method)
The Astrup method for determination of arterial pH, pCO2, and “base excess” provides a simple and
accurate means for quantitation of acid-base disorders. The “base excess” value, a measure of
metabolic acidosis or alkalosis, gives the clinician a valuable tool with which to estimate electrolyte
replacement. The pCO2 is a measure of respiratory acidosis or alkalosis. The pH is used as a measure
of the adequacy of compensation. Several representative cases illustrate the use and interpretation
of the test.
“Base excess”:
1. Metabolic acidosis – patients have a “base excess” less than zero (minus “base excess”).
2. Metabolic alkalosis – the diagnostic feature seen is an elevated “base excess”.
pCO2: is a measure of respiratory acidosis/alkalosis.
pH: is used as a measure of the adequacy of compensation.
Astrup recommended that electrolyte deficits in the extracellular space be calculated using the
formula: Total deficit mEq = “Base excess” X 0.3 X body weight Kg
The advantages of the Astrup system are its technical simplicity and speed and the ability to
graphically clarify complex chemical relationships.
Masaryk University Faculty of Medicine Physiology Exam
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63. Clearance
– indicates the volume of plasma cleared of a substance per unit time.
– The units of clearance are mL/min and mL/24 hr.
C = UV/P
where:
C = clearance (mL/min or mL/24 hr)
U = urine concentration (mg/mL)
V = urine volume/time (mg/min)
P = plasma concentration (mg/mL)
The expression on the right of equation represents clearance, regardless of which substance is being
investigated. Therefore, the inulin or creatinine clearance represents the GFR. (Although the plasma
concentration of creatinine, Pcr, rises as the GFR falls, Pcr alone is a quite unreliable measure of GFR.)
Fractional excretion (FE) is the ratio of clearance of a given substance X to inulin clearance (CX/CIn) and defines
which fraction of the filtered quantity of X was excreted. FE>1 if the substance is removed from the tubule by
reabsorption (e.g. Na
+
, Cl
–
, amino acids, glucose, etc.), and FE<1 if the substance is subject to filtration plus
tubular secretion. For PAH, tubular secretion is so effective that FEPAH ≈5 (500%).
Masaryk University Faculty of Medicine Physiology Exam
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64. Audiometry
Subjective hearing tests are performed using an audiometer. The patient is presented sounds of various
frequencies and routes of conduction (bone, air). The sound pressure is initially set at a level under the
threshold of hearing and is raised in increments until the patient is able to hear the presented sound (threshold
audiogram). If the patient is unable to hear the sounds at normal levels, he or she has an hearing loss, which is
quantitated in decibels (dB). In audiometry, all frequencies at the normal threshold of hearing are assigned the
value of 0 dB. Hearing loss can be caused by presbycusis, middle ear infection (impaired air conduction), and
damage to the internal ear (impaired air and bone conduction) caused, for example, by prolonged exposure to
excessive sound pressure, by ototoxic medication (blockage of stria vascularis by loop diuretics), or by defects
of the KCNQ4 or KCC4 genes.
Audiogram
In performing a hearing test using an audiometer, one
tests about 8 to 10 frequencies covering the auditory
spectrum, and the hearing loss is determined for each of
these frequencies. Then the so-called audiogram is
plotted, depicting hearing loss at each of the frequencies
in the auditory spectrum.
. The audiometer, in addition to being
equipped with an earphone for testing air conduction
by the ear, is equipped with a mechanical vibrator for
testing bone conduction from the mastoid process of the
skull into the cochlea.
65. Cardiovascular response to Valsalva manoeuvre
The integrity of the baroreceptor mechanism can be tested with the Valsalva maneuver (i.e., expiring against a
closed epiglottis).
It is performed by forcible exhalation against a closed airway, usually done by closing one's mouth and pinching
one's nose shut.
Physiological response:
 Expiring against a closed glottis causes an increase in intrathoracic pressure, which decreases venous
return.
 The decrease in venous return causes a decrease in cardiac output and arterial pressure.
 If the baroreceptor reflex is intact, the decrease in arterial pressure is sensed by the baroreceptors,
leading to an increase in sympathetic outflow to the heart and blood vessels. In the test, an increase
in heart rate would be noted.
 When the person stops the maneuver, there is a rebound increase in venous return, cardiac output,
and arterial pressure. The increase in arterial pressure is sensed by the baroreceptors, which direct a
decrease in heart rate.
Recordings of blood pressure (systolic) and pulse rate during a normal response to Valsalva’s maneuver is
studied; deviation from this response pattern signifies either abnormal heart function or abnormal autonomic
nervous control of the heart.
The maneuver can sometimes be used to diagnose
heart abnormalities, especially when used in
conjunction with echocardiogram.
Masaryk University Faculty of Medicine Physiology Exam
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66. Examination of baroreflex sensitivity
The integrity of the baroreceptor mechanism can be tested with the Valsalva maneuver (i.e., expiring against a
closed epiglottis).
is performed by forcible exhalation against a closed airway, usually done by closing one's mouth and pinching
one's nose shut.
Physiological response:
 Expiring against a closed causes an increase in intrathoracic pressure, which decreases venous return.
 The decrease in venous return causes a decrease in cardiac output and arterial pressure.
 If the baroreceptor reflex is intact, the decrease in arterial pressure is sensed by the baroreceptors,
leadin to an increase in sympathetic outflow to the heart and blood vessels. In the test, an increase in
heart rate would be noted.
 When the person stops the maneuver, there is a rebound increase in venous return, cardiac output,
and arterial pressure. The increase in arterial pressure is sensed by the baroreceptors, which direct a
decrease in heart rate.
67. Examination of heart rate and blood pressure variability
See Q. 43-45, 52, 68
Masaryk University Faculty of Medicine Physiology Exam
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68. Special methods of ECG and blood pressure examination (24-hourmonitoring,
late potentials, invasive electrophysiological studies)
24-hour-monitoring (Holter Monitoring)
Holter Monitoring - To detect irregular heart rhythms, patients wear
a Walkman-size recording box attached to their chest by five
adhesive electrode patches for 24-48 hours.
Event Recorder - Patients carry a pager-sized event recording box so
they can make a one- to two-minute recording of their heart rhythm
when they actually experience symptoms. This is useful for patients
with relatively infrequent and brief symptoms.
Late potentials (Signal-averaged electrocardiography (SAECG))
A resting electrocardiogram (ECG) is recorded in the supine position using an ECG machine equipped with
SAECG software. Unlike standard basal ECG recording, which requires only a few seconds, SAECG recording
requires a few minutes (usually about 7-10 minutes), as the machine must record multiple subsequent QRS
potentials to remove interference due to skeletal muscle and to obtain a statistically significant average trace.
Results
SAECG recording yields a single, averaged QRS potential, usually printed in a much larger scale than standard
ECGs, upon which the SAECG software performs calculations to reveal small variations (typically 1-25 mV) in
the final portion of the QRS complex (the so-called "late potentials, or more accurately, "late ventricular
potentials"). These can be immediately interpreted by comparing results with cut-off values.
. Late potentials are taken to represent delayed and fragmented depolarisation of the ventricular
myocardium, which may be the substrate for a micro-re-entry mechanism, implying a higher risk of potentially
dangerous ventricular tachyarrhythmias. This has been used for the risk stratification of sudden cardiac death
in people who have had a myocardial infarction, as well as in people with known coronary heart disease,
cardiomyopathies, or unexplained syncope.
Invasive electrophysiological studies
The procedure involves inserting a catheter – a narrow, flexible tube – attached to electricity monitoring
electrodes, into a blood vessel, often through a site in the groin or neck, and winding the catheter wire up into
the heart. The journey from entry point to heart muscle is navigated by images created by a fluoroscope,
an x-ray-like machine that provides continuous, “live” images of the catheter and heart muscle. Once the
catheter reaches the heart, electrodes at its tip gather data and a variety of electrical measurements are made.
These data pinpoint the location of the faulty electrical site. During this “electrical mapping,” the cardiac
arrhythmia specialist may instigate, through pacing (the use of tiny electrical impulses), some of the very
arrhythmias that are the crux of the problem.
Once the damaged site or sites are confirmed, the specialist may administer different medications or electrical
impulses to determine their ability to halt the arrhythmia and restore normal heart rhythm. Based on this data,
as well as information garnered before the study, sometimes the specialist will proceed to place an implantable
cardioverter device (ICD) or a pacemaker or will perform radiofrequency ablation. In any case, the information
proves useful for diagnosis and treatment.
Masaryk University Faculty of Medicine Physiology Exam
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69. Examination methods in endocrinology (historical and biological methods,
RIA, enzyme-imuno-analysis)
Radioimmunoassay (RIA)
Is a method of clinical biochemistry and haematology. It is used for determination of low
concentrated substances, e.g. hormones in blood.
. To perform a radioimmunoassay, a known quantity of an antigen is made radioactive, frequently by
labeling it with gamma-radioactive isotopes of iodine attached to tyrosine. This radiolabeled antigen
is then mixed with a known amount of antibody for that antigen, and as a result, the two chemically
bind to one another. Then, a sample of serum from a patient containing an unknown quantity of that
same antigen is added. This causes the unlabeled (or "cold") antigen from the serum to compete with
the radiolabeled antigen ("hot") for antibody binding sites.
. As the concentration of "cold" antigen is increased, more of it binds to the antibody, displacing the
radiolabeled variant, and reducing the ratio of antibody-bound radiolabeled antigen to free
radiolabeled antigen. The bound antigens are then separated from the unbound ones, and the
radioactivity of the free antigen remaining in the supernatant is measured. Using known standards, a
binding curve can then be generated which allows the amount of antigen in the patient's serum to be
derived.
In RIA, mainly β-emitters are used (tritium, iodine-125, iron-59 etc.), because the detector can be
very close to the radioactive sample.
Enzyme immunoassay (EIA)
Also known as Enzyme-Linked Immunosorbent Assay
(ELISA) can be used to measure almost any protein,
including hormones. This test combines the specificity of
antibodies with the sensitivity of simple enzyme assays.
The figure on the right shows the basic elements of this
method, which is often performed on plastic plates that
each have 96 small wells. Each well is coated with an
antibody (AB1) that is specific for the hormone being
assayed. Samples or standards are added to each of the
wells, followed by a second antibody (AB2) that is also
specific for the hormone but binds to a different site of the
hormone molecule. A third antibody (AB3) is added that
recognizes AB2 and is coupled to an enzyme that converts a
suitable substrate to a product that can be easily detected
by colorimetric or fluorescent optical methods.
In contrast to competitive radioimmunoassay methods,
ELISA methods use excess antibodies so that all hormone
molecules are captured in antibody-hormone complexes.
Therefore, the amount of hormone present in the sample
or in the standard is proportional to the amount of product formed.
Masaryk University Faculty of Medicine Physiology Exam
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70. Reaction of circulatory system on bleeding
Masaryk University Faculty of Medicine Physiology Exam
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71. Reflex reactions of circulatory system (diving reflex, Valsalva manouvre,
Mϋller manouvre)
Diving reflex
Upon initiation of the reflex, three changes happen to the body, in this order:
1. Bradycardia is the first response to submersion. Immediately upon facial contact with cold water, the
human heart rate slows down ten to twenty-five percent. Slowing the heart rate lessens the need for
bloodstream oxygen, leaving more to be used by other organs.
2. Next, peripheral vasoconstriction sets in. When under high pressure induced by deep diving, capillaries in
the extremities start closing off, stopping blood circulation to those areas. Note that vasoconstriction
usually applies to arterioles, but in this case is completely an effect of the capillaries. Toes and fingers close
off first, then hands and feet, and ultimately arms and legs stop allowing blood circulation, leaving more
blood for use by the heart and brain. Human musculature accounts for only 12% of the body's total oxygen
storage, and the body's muscles tend to suffer cramping during this phase.
3. Finally is the blood shift that occurs only during very deep dives. Organ and circulatory walls allow
plasma/water to pass freely throughout the thoracic cavity, so its pressure stays constant and the organs
aren't crushed. In this stage, the lungs' alveoli fill up with blood plasma, which is reabsorbed when the
animal leaves the pressurized environment. This stage of the diving reflex has been observed in humans
(such as world champion freediver Martin Štěpánek) during extremely deep (over 90 m or 300 ft)
freedives.
Müller's manoeuvre
After a forced expiration, an attempt at inspiration is made with closed mouth and nose, whereby the negative
pressure in the chest and lungs is made very subatmospheric; the reverse of Valsalva manoeuvre.
. Breathe in with mouth and nose closed
. Generation of a negative pressure in upper airway
. Results are monitored by echocardiogram of left ventricle
. End diastolic and end systolic dimension increases
. Obtained results show that lung volume affects left ventricle response due to reduced intrathoracic
. pressure changing afterload and filing.
Valsalva manouvre
 Expiring against a closed glottis causes an increase in intrathoracic pressure, which decreases venous
return.
 The decrease in venous return causes a decrease in cardiac output and arterial pressure.
 If the baroreceptor reflex is intact, the decrease in arterial pressure is sensed by the baroreceptors,
leading to an increase in sympathetic outflow to the heart and blood vessels. In the test, an increase
in heart rate would be noted.
 When the person stops the maneuver, there is a rebound increase in venous return, cardiac output,
and arterial pressure. The increase in arterial pressure is sensed by the baroreceptors, which direct a
decrease in heart rate.
Recordings of blood pressure (systolic) and pulse rate during a normal response to Valsalva’s maneuver is
studied; deviation from this response pattern signifies either abnormal heart function or abnormal autonomic
nervous control of the heart.
The maneuver can sometimes be used to diagnose
heart abnormalities, especially when used in
conjunction with echocardiogram.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
72. Respiratory quotient
“Respiratory Quotient” Is the Ratio of CO2 Production to O2 Utilization and Can Be Used to
Estimate Fat and Carbohydrate Utilization
When carbohydrates are metabolized with oxygen, exactly one carbon dioxide molecule is formed
for each molecule of oxygen consumed. This ratio of carbon dioxide output to oxygen usage is called
the respiratory quotient, so the respiratory quotient for carbohydrates is 1.0.
When fat is oxidized in the body’s cells, an average of 70 carbon dioxide molecules are formed for
each 100 molecules of oxygen consumed. The respiratory quotient for the metabolism of fat
averages 0.70.When proteins are oxidized by the cells, the average respiratory quotient is 0.80.
The reason that the respiratory quotients for fats and proteins are lower than that for carbohydrates
is that a large share of the oxygen metabolized with these foods is required to combine with the
excess hydrogen atoms present in their molecules, so that less carbon dioxide is formed in relation to
the oxygen used.
Using of the respiratory quotient to determine the relative utilization of different foods by the
body: First, one knows that the output of carbon dioxide by the lungs divided by the uptake of
oxygen during the same period is called the respiratory exchange ratio. Over a period of 1 hour or
more, the respiratory exchange ratio exactly equals the average respiratory quotient of the
metabolic reactions throughout the body. If a person has a respiratory quotient of 1.0, he or she is
metabolizing almost entirely carbohydrates, because the respiratory quotients for both fat and
protein metabolism are considerably less than 1.0. Likewise, when the respiratory quotient is about
0.70, the body is metabolizing almost entirely fats, to the exclusion of carbohydrates and proteins.
And, finally, if we ignore the normally small amount of protein metabolism, respiratory quotients
between 0.70 and 1.0 describe the approximate ratios of carbohydrate to fat metabolism.
To be more exact, one can first determine the protein utilization by measuring nitrogen excretion
and then, using the appropriate mathematical formula, calculate almost exactly the utilization of the
three foodstuffs.
Some of the important findings from studies of respiratory quotients are the following:
1. Immediately after a meal, almost all the food
that is metabolized is carbohydrates, so that the
respiratory quotient at that time approaches 1.0.
2. About 8 to 10 hours after a meal, the body has
already used up most of its readily available
carbohydrates, and the respiratory quotient
approaches that for fat metabolism, about 0.70.
3. In untreated diabetes mellitus, little carbohydrate
can be used by the body’s cells under any
conditions, because insulin is required for this.
Therefore, when diabetes is severe, most of the
time the respiratory quotient remains near that for
fat metabolism, 0.70.
Masaryk University Faculty of Medicine Physiology Exam
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73. Cardiopulmonary response to exercise
Cardiovascular response
Respiratory response
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
74. Autocrine, paracrine, and endocrine regulation
Autocrine signaling
– Is a form of signaling in which a cell secretes a hormone or chemical messenger (called the
autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cells.
– An example of an autocrine agent is the cytokine interleukin-1 in monocytes. When this is
produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that
produced it.
Paracrine signaling
– Is a form of cell signaling in which the target cell is near the signal-releasing cell.
– Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor
signaling plays an especially important role in the development of tissues. In insects, Allatostatin
controls growth through paracrine action on the corpora allata.
Endocrine signaling
– Is a system of glands, each of which secretes a type of hormone into the bloodstream to regulate
the body. A number of glands that signal each other in sequence is usually referred to as an axis, for
example, the hypothalamic-pituitary-adrenal axis.
– Typical endocrine glands are the pituitary, thyroid, and adrenal glands.
– In addition to the specialized endocrine organs mentioned above, many other organs that are part
of other body systems, such as the kidney, liver, heart and gonads, have secondary endocrine
functions. For example the kidney secretes endocrine hormones such as erythropoietin and renin.
Masaryk University Faculty of Medicine Physiology Exam
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75. Chemical characteristics of hormones
Hormones are messenger substances that convey information signals relevant to cell function.
 Endocrine hormones, i.e., those transported in the bloodstream, are produced in endocrine glands
such as the hypothalamus, thyroid, parathyroid glands, adrenal medulla, pancreatic islets, ovaries and
testes. They are also synthesized in diffusely scattered endocrine cells of the CNS, in C cells of the
thyroid, and in the thymus, atria, kidneys, liver, gastrointestinal tract, etc.
 Paracrine hormones, i.e., those that affect nearby cells only (tissue hormones or mediators; see
below) are secreted by cells widely distributed throughout the body.
Types of hormone
1. Peptide hormones and glycoprotein hormones are hydrophilic hormones stored in secretory granules and
released by exocytosis as required. Multiple hormones can be produced from a single gene (e.g., POMC
gene) by variable splicing and posttranslational modification.
2. Steroid hormones and calcitriol are chemically related lipophilic hormones metabolized from cholesterol.
They are not stored, but are synthesized as needed.
3. Tyrosine derivatives include (a) the hydrophilic catecholamines dopamine, epinephrine and norepinephrine
and (b) lipophilic thyroid hormones (T3, T4).
The lipophilic hormones are transported in the blood while bound to plasma proteins. Corticosteroids are
carried bound to globulin and albumin, testosterone and estrogen to sex hormone-binding globulin and T3 and
T4 to albumin and two other plasma proteins.
Hormone receptors
The receptors (docking sites) for glycoprotein hormones, peptide hormones and catecholamines are
transmembrane proteins that bind to their specific hormone on the outer cell surface.
Many of these hormones induce the release of intracellular second messengers that transmit the hormone
signal inside the cell.
Some peptide hormones like insulin, prolactin, atriopeptin and numerous growth factors bind to cell surface
receptors with cytosolic domains with enzymatic activity. Steroid hormones, on the other hand, enter the cells
themselves. Once they bind to cytosolic receptor proteins, steroid hormones (as well as calcitriol, T3 and T4)
are transported to the cell nucleus, where they influence transcription (genomic action).
. A target cell can have different receptors for different hormones (e.g., insulin and glucagon) or different
receptors for a single hormone (e.g., α1 and β2 adrenoceptors for epinephrine).
The secretion of hormones is often triggered by neural impulses from the CNS. The hypothalamus is the main
neurohormonal control center. Hypothalamic neurons extend to the posterior pituitary (neurohypophysis). The
hormones are secreted either by the hypothalamus itself or by the posterior pituitary. Hypothalamic hormones
also control hormone release from the anterior pituitary (adenohypophysis). Anterior pituitary Glandotropic
hormones control peripheral endocrine glands, which release the endhormone. The original signal can be
amplified or modulated at these relay sites.
Masaryk University Faculty of Medicine Physiology Exam
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76. Sympathetic alpha- and beta-receptors
Adrenergic receptors (adrenoreceptors)
α1 Receptors
 are located on vascular smooth muscle of then skin and splanchnic regions, the
gastrointestinal (GI) and bladder sphincters, and the radial muscle of the iris.
 produce excitation (e.g., contraction or constriction).
 Are equally sensitive to norepinephrine and epinephrine. However, only norepinephrine
released from adrenergic neurons is present in high enough conc. to activate α1 receptors.
 Mechanism of action: Gq protein; stimulation of phospholipase C, and increase in inositol
1,4,5-triphosphate (IP3) and intracellular [Ca2+
].
α2 Receptors
 are located in presynaptic nerve terminals, platelets, fat cell, and the walls of the GI tract.
 often produce inhibition (e.g., relaxation or dilation).
 Mechanism of action: Gi protein inhibition of adenylate cyclase and decrease in cyclic
adenosine monophosphate (cAMP).
β1 Receptors
 are located in the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular muscle of
the heart.
 produce excitation (e.g., increased heart rate, increased conduction velocity, increased
contractility).
 are sensitive to both norepinephrine and epinephrine, and are more sensitive than the α1
receptors.
 Mechanism of action: Gs protein, stimulation of adenylate cyclase and increas in cAMP.
β2 Receptors
 are located on vascular smooth muscle of skeletal muscle, bronchial smooth muscle, and in
the walls of the GI tract and bladder.
 produce relaxation (e.g., dilation of vascular smooth muscle, dilation of bronchioles,
relaxation of the bladder wall).
 are more sensitive to epinephrine than to norepinephrine.
 are more sensitive to epinephrine than α1 receptors.
 Mechanism of action: Gs protein, stimulation of adenylate cyclase and increas in cAMP.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
77. Sex differentiation
 Genetic sex is defined by the chromosome, XY in males and XX in females.
 Gonadal sex is defined by the presence of testes in males and ovaries in females.
 Phenotypic sex is defined by the characteristics of the internal genital tract and the external
genitalia.
Male phenotype
 The testes of gonodal males secrete antimϋllerian hormone and testosterone.
 Testosterone stimulates the growth and differentiation of the wolffian ducts, which develop
into male internal genital tract.
 Antimϋllerian hormone causes atrophy of the mϋllerian ducts (which would have become
the female internal genital tract).
Female phenotype
 The ovaries of gonodal females secrete estrogen, but not antimϋllerian hormone or
testosterone.
 Without testosterone, wolffian ducts do not differentiate.
 Without antimϋllerian hormone, the mϋllerian ducts are not suppressed and therefore
develop into the female internal genital tract.
78. Oogenesis
The development of the female gametes (ova) extends from the oogonium stage to the primary
oocyte stage (in the primordial follicle), starting long before birth. Oogenesis therefore occurs much
sooner than the corresponding stages of spermatogenesis. The fetal phase of oogenesis is completed
by the first week of gestation; these oocytes remain latent until puberty. In the sexually mature
female, a fertilizable ovum develops in the graafian follicles approximately every28 days.
2 phases: oocytogenesis
Meiosis
oocytogenesis - mitotic division of oogonia - begins during the fetal period
the oogonia enlarge to form primary oocytes, they enter the first meiotic division that is stopped in
the prophase, the cell nucleus is then transformed into the interphase form in which is to stay to the
beginning of reproductive life of females
the first meiotic division is completed shortly before the ovulation - the primary oocyte divides
unequal and gives rise to large secondary oocyte and the first polar body (polar body is
nonfunctional and soon degenerates)
in time of ovulation the secondary oocyte enters the second meiotic division that progresses only to
metaphase, in which division is arrested
completion of the second meiotic division is closely connected with penetration of the sperm into
the oocyte: the division becomes again to continue and developed daughter cells are the mature
ovum and the secondary polar body
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
79. Hormonal contraception
Hormonal contraception
The term refers to birth control methods that act on the endocrine system.
. There are two main types of hormonal contraceptive formulations: combined methods which contain both an
estrogen and a progestin, and progestin-only methods which contain only progesterone or one of its synthetic
analogues (progestins). Combined methods work by suppressing ovulation; while progestin-only methods
reduce the frequency of ovulation, most of them rely heavily on secondary mechanisms such as changes in
cervical mucus.
Combined
The most popular form of hormonal contraception is the combined oral contraceptive pill. It is taken once a
day, most commonly for 21 days followed by a seven-day break. The contraceptive patch is applied to the skin
and worn continuously. A combined injectable contraceptive is a shot given once per month.
Progestin-only
The progestin only pill (POP) is taken once per day within the same three-hour window. For women not using
ongoing hormonal contraception, progestin-only pills may be taken after intercourse as emergency
contraception. Two types of progestin-only contraceptive implants are available. Both are inserted under the
skin of the upper arm.
Mechanism of action
Combined hormonal contraceptives
Prevent ovulation by suppressing the release of gonadotropins. They inhibit follicular development and prevent
ovulation as their primary mechanism of action.
. Progestin negative feedback decreases the pulse frequency of gonadotropin-releasing hormone (GnRH)
release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and greatly
decreases the release of luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit
follicular development, preventing an increase in estradiol levels. Progestin negative feedback and the lack of
estrogen positive feedback on LH release prevent a mid-cycle LH surge. Inhibition of follicular development and
the absence of a LH surge prevent ovulation.
. Estrogen was originally included in oral contraceptives for better cycle control (to stabilize the endometrium
and thereby reduce the incidence of breakthrough bleeding), but was also found to inhibit follicular
development and help prevent ovulation. Estrogen negative feedback on the anterior pituitary greatly
decreases the release of FSH, which inhibits follicular development and helps prevent ovulation.
A secondary mechanism of action of all progestin-containing contraceptives is inhibition of sperm penetration
through the cervix into the upper genital tract, by decreasing the amount of and increasing the viscosity of the
cervical mucus.
Progestin-only
The mechanism of action of progestogen-only contraceptives depends on the progestogen activity and dose.
Low dose progestin-only contraceptives inhibit ovulation in ~50% of cycles and rely mainly on their progestin
effect of thickening the cervical mucus and thereby reducing sperm viability and penetration.
Intermediate dose progestogen-only allow some follicular development but much more consistently inhibit
ovulation in 97–99% of cycles.
High dose progestogen-only contraceptives, such as the injectables Depo-Provera and Noristerat, completely
inhibit follicular development and ovulation.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
80. Spermatogenesis
Maturation process of male gametes is called spermatogenesis. It includes the series of events by
which spermatogonia are transformed into haploid spermatids. These are then gradually developed
into mature sperms by the process known as spermiogenesis (histological differentiation of
spermatids). Seminiferous tubules of the testis are the site where both differentiation events occur.
Spermatogenesis
It begins with a primitive germ cell, the spermatogonium. At sexual maturity, spermatogonia begin
dividing by mitosis, producing successive generations of cells. The newly formed cells can follow one
or two paths: they can continue dividing as stem cells, also called type A spermatogonia, or they can
differentiate during progressive mitotic cycles to become type B spermatogonia. Type B
spermatogonia are progenitor cells that will differentiate into primary spermatocytes (44 + XY and
4N of DNA).
. From this first meiotic division arise smaller cells called secondary spermatocytes. Division of each
secondary spermatocytes results in two cells that contain 23 chromosomes, the spermatids.
Spermiogenesis
It is the final stage of production of spermatozoids. During spermiogenesis the spermatids are
transformed into spermatozoa.
Masaryk University Faculty of Medicine Physiology Exam
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81. Puberty and menopause
Puberty and Menarche
Puberty means the onset of adult sexual life, and menarche means the beginning of the cycle of
menstruation. The period of puberty is caused by a gradual increase in gonadotropic hormone
secretion by the pituitary, beginning in about the eighth year of life, as shown in figure below, and
usually culminating in the onset of puberty and menstruation between ages 11 and 16 years in girls
(average, 13 years).
In the female, as in the male, the infantile pituitary gland and ovaries are capable of full function if
appropriately stimulated. However, as is also true in the male, and for reasons not understood, the
hypothalamus does not secrete significant quantities of GnRH during childhood. Experiments have
shown that the hypothalamus itself is capable of secreting this hormone, but the appropriate signal
from some other area of brain to cause the secretion is lacking. Therefore, it is now believed that the
onset of puberty is initiated by some maturation process that occurs elsewhere in the brain, perhaps
somewhere in the limbic system.
Menopause
The period during which the cycle ceases and the female sex hormones diminish to almost none is
called menopause.
. The cause of menopause is “burning out” of the ovaries. Throughout a woman’s reproductive life,
about 400 of the primordial follicles grow into mature follicles and ovulate, and hundreds of
thousands of ova degenerate. At about age 45 years, only a few primordial follicles remain to be
stimulated by FSH and LH, and, as shown in the figure below, the production of estrogens by the
ovaries decreases as the number of primordial follicles approaches zero. When estrogen production
falls below a critical value, the estrogens can no longer inhibit the production of the gonadotropins
FSH and LH. Instead the gonadotropins FSH and LH (mainly FSH) are produced after menopause in
large and continuous quantities, but as the remaining primordial follicles become atretic, the
production of estrogens by the ovaries falls virtually to zero.
Masaryk University Faculty of Medicine Physiology Exam
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82. Physiological significance of positive and negative feed-back
Negative Feedback Nature of Most Control Systems
Most control systems of the body act by negative feedback. In the regulation of carbon dioxide concentration,
a high concentration of carbon dioxide in the extracellular fluid increases pulmonary ventilation.
This, in turn, decreases the extracellular fluid carbon dioxide concentration because the lungs expire greater
amounts of carbon dioxide from the body. In other words, the high concentration of carbon dioxide initiates
events that decrease the concentration toward normal, which is negative to the initiating stimulus.
Conversely, if the carbon dioxide concentration falls too low, this causes feedback to increase the
concentration. This response also is negative to the initiating stimulus.
In the arterial pressure–regulating mechanisms, a high pressure causes a series of reactions that promote a
lowered pressure, or a low pressure causes a series of reactions that promote an elevated pressure. In both
instances, these effects are negative with respect to the initiating stimulus.
Therefore, in general, if some factor becomes excessive or deficient, a control system initiates negative
feedback, which consists of a series of changes that return the factor toward a certain mean value, thus
maintaining homeostasis.
Positive Feedback
If one considers the nature of positive feedback, one immediately sees that positive feedback does not lead to
stability but to instability and often death. For example, if a healthy person with a heart that pumps about 5
liters of blood per minute, suddenly bled 2 liters, the amount of blood in the body is decreased to such a low
level that not enough blood is available for the heart to pump effectively. As a result, the arterial pressure falls,
and the flow of blood to the heart muscle through the coronary vessels diminishes. This results in weakening of
the heart, further diminished pumping, a further decrease in coronary blood flow, and still more weakness of
the heart; the cycle repeats itself again and again until death occurs. Note that each cycle in the feedback
results in further weakening of the heart. In other words, the initiating stimulus causes more of the same,
which is positive feedback.
Positive Feedback Can Sometimes Be Useful. In some instances, the body uses positive feedback to its
advantage. Blood clotting is an example of a valuable use of positive feedback. When a blood vessel is ruptured
and a clot begins to form, multiple enzymes called clotting factors are activated within the clot itself. Some
of these enzymes act on other unactivated enzymes of the immediately adjacent blood, thus causing more
blood clotting. This process continues until the hole in the vessel is plugged and bleeding no longer occurs.
Childbirth is another instance in which positive feedback plays a valuable role.When uterine contractions
become strong enough for the baby’s head to begin pushing through the cervix, stretch of the cervix sends
signals through the uterine muscle back to the body of the uterus, causing even more powerful contractions.
Thus, the uterine contractions stretch the cervix, and the cervical stretch causes stronger contractions. When
this process becomes powerful enough, the baby is born. If it is not powerful enough, the contractions usually
die out, and a few days pass before they begin again.
Another important use of positive feedback is for the generation of nerve signals. That is, when the
membrane of a nerve fiber is stimulated, this causes slight leakage of sodium ions through sodium channels in
the nerve membrane to the fiber’s interior. The sodium ions entering the fiber then change the membrane
potential, which in turn causes more opening of channels, more change of potential, still more opening of
channels, and so forth. Thus, a slight leak becomes an explosion of sodium entering the interior of the nerve
fiber, which creates the nerve action potential. This action potential in turn causes electrical current to flow
along both the outside and the inside of the fiber and initiates additional action potentials. This process
continues again and again until the nerve signal goes all the way to the end of the fiber.
83. Physiological regulations (overview) see Q. 84 (94, 74, 82, 100)
Masaryk University Faculty of Medicine Physiology Exam
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84. Homeostasis
The term homeostasis is used by physiologists to mean maintenance of nearly constant conditions in the
internal environment. Essentially all organs and tissues of the body perform functions that help maintain these
constant conditions. For instance, the lungs provide oxygen to the extracellular fluid to replenish the oxygen
used by the cells, the liver is responsible for metabolizing toxic substances and maintaining carbohydrate
metabolism, the kidneys are responsible for regulating blood water levels, re-absorption of substances into the
blood, maintenance of salt and ion levels in the blood, regulation of blood pH, and excretion of urea and other
wastes.
An inability to maintain homeostasis may lead to death or a disease, a condition known as homeostatic
imbalance. For instance, heart failure may occur when negative feedback mechanisms become overwhelmed
and destructive positive feedback mechanisms take over. Other diseases which result from a homeostatic
imbalance include diabetes, dehydration, hypoglycemia, hyperglycemia, gout and any disease caused by the
presence of a toxin in the bloodstream. Medical intervention can help restore homeostasis and possibly
prevent permanent damage to the organs.
Temperature
Thermoregulation is an important aspect of human homeostasis. The control center for body temperature and
central thermosensors are located in the hypothalamus. Additional thermosensors are located in the spinal
cord and skin.
. Temperature may enter a circle of positive feedback, when temperature reaches extremes of 45°C (113°F), at
which cellular proteins denature, causing the active site in proteins to change, thus causing metabolism stop
and ultimately death.
Iron
Is an essential element for human beings. The control of this necessary but potentially toxic substance is an
important part of many aspects of human health and disease.
. When body levels of iron are too low, then hepcidin in the duodenal epithelium is decreased. This causes an
increase in ferroportin activity, stimulating iron uptake in the digestive system. An iron surplus will stimulate
the reverse of this process.
. In individual cells, an iron deficiency causes responsive element binding protein (IRE-BP) to bind to iron
responsive elements (IRE) on mRNAs for transferrin receptors, resulting in increased production of transferrin
receptors. These receptors increase binding of transferrin to cells, and therefore stimulating iron uptake.
Sugar
Blood glucose is regulated with two hormones, insulin and glucagon, both released from the pancreas.
. When blood sugar levels become too high, insulin is released from the pancreas. Glucose, or sugar, is stored
in body cells as glycogen, lowering the blood sugar levels. On the other hand, when blood sugar levels become
too low, glucagon is released. It promotes the release of glycogen, converted back into glucose. This increases
blood sugar levels.
Osmoregulation
Osmoregulation is the active regulation of the osmotic pressure of bodily fluids to maintain the homeostasis of
the body's water content; that is it keeps the body's fluids from becoming too dilute or too concentrated.
. The cell’s plasma membrane contains mechanosensors that stimulate balancing ion flow accompanied by
water.
Pressure
The renin-angiotensin system (RAS) is a hormone system that helps regulate long-term blood pressure and
extracellular volume in the body.
Calcium
When blood calcium becomes too low, calcium-sensing receptors in the parathyroid gland become activated.
This results in the release of PTH, which acts to increase blood calcium, e.g. by release from bones.
Masaryk University Faculty of Medicine Physiology Exam
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85. Regulation of constant pH
The pH of different cellular compartments, body fluids, and organs is usually tightly regulated in a
process called acid-base homeostasis.
The pH of blood is usually slightly basic with a value of pH 7.4. This value is often referred to as
physiological pH in biology and medicine.
Buffers
– prevent a change in pH when H
+
ions are added to or removed from a solution.
– are most effective within 1.0 pH unit of the pK of the buffer (i.e., in the linear portion of the titration curve).
1. Extracellular buffers
. a. The major extracellular buffer is HCO3
,
which is produced from CO2 and H2O.
. – The pK of the CO2 /HCO3
buffer
pair is 6.1.
. b. Phosphate is a minor extracellular buffer.
. – The pK of the H2PO4
-
/HPO4
2buffer
pair is 6.8.
. – Phosphate is most important as urinary buffer; excretion of H
+
as H2PO4
is
called titratable acid.
2. Intracellular buffers
. a. Organic phosphates [e.g., AMP, ADP, ATP, 2,3-diphosphoglycerate (DPG)].
. b. Proteins
. – Imidazole and α-amino groups on proteins have pKs that are within the physiological pH range.
. – Hemoglobin is a major intracellular buffer.
. – In the physiological pH range, deoxyhemoglobin is a better buffer than oxyhemoglobin.
Masaryk University Faculty of Medicine Physiology Exam
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86. Kidney in regulation of homeostasis
The kidneys “clear” unwanted substances from the filtrate (and therefore from the blood) by
excreting them in the urine while returning substances that are needed back to the blood.
The kidneys serve multiple functions, including the following:
 Excretion of metabolic waste products and foreign chemicals
 Regulation of water and electrolyte balances
 Regulation of body fluid osmolality and electrolyte concentrations
 Regulation of arterial pressure
 Regulation of acid-base balance
 Secretion, metabolism, and excretion of hormones
 Gluconeogenesis
Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites.
The kidneys are the primary means for eliminating waste products of metabolism that are no longer needed by
the body. These products include urea (from the metabolism of amino acids), creatinine (from muscle
creatine), uric acid (from nucleic acids), end products of hemoglobin breakdown (such as bilirubin), and
metabolites of various hormones. These waste products must be eliminated from the body as rapidly as they
are produced. The kidneys also eliminate most toxins and other foreign substances that are either produced by
the body or ingested, such as pesticides, drugs, and food additives.
Regulation of Water and Electrolyte Balances.
For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. If intake
exceeds excretion, the amount of that substance in the body will increase. If intake is less than excretion, the
amount of that substance in the body will decrease.
Intake of water and many electrolytes is governed mainly by a person’s eating and drinking habits, requiring
the kidneys to adjust their excretion rates to match the intake of various substances.
Regulation of Arterial Pressure.
The kidneys play a dominant role in long-term regulation of arterial pressure by excreting variable amounts of
sodium and water. The kidneys also contribute to short-term arterial pressure regulation by secreting
vasoactive factors or substances, such as renin, that lead to the formation of vasoactive products (e.g.,
angiotensin II).
Regulation of Acid-Base Balance. The kidneys contribute to acid-base regulation, along with the lungs and
body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. The kidneys are the only
means of eliminating from the body certain types of acids, such as sulfuric acid and phosphoric acid, generated
by the metabolism of proteins.
Regulation of Erythrocyte Production. The kidneys secrete erythropoietin, which stimulates the production of
red blood cells. One important stimulus for erythropoietin secretion by the kidneys is hypoxia. The kidneys
normally account for almost all the erythropoietin secreted into the circulation.
Regulation of 1,25–Dihydroxyvitamin D3 Production. The kidneys produce the active form of vitamin D, 1,25dihydroxyvitamin
D3 (calcitriol), by hydroxylating this vitamin at the “number 1” position. Calcitriol is essential
for normal calcium deposition in bone and calcium reabsorption by the gastrointestinal tract. Calcitriol plays an
important role in calcium and phosphate regulation.
Glucose Synthesis. The kidneys synthesize glucose from amino acids and other precursors during prolonged
fasting, a process referred to as gluconeogenesis. The kidneys’ capacity to add glucose to the blood during
prolonged periods of fasting rivals that of the liver. With chronic kidney disease or acute failure of the kidneys,
these homeostatic functions are disrupted, and severe abnormalities of body fluid volumes and composition
rapidly occur.
With complete renal failure, enough potassium, acids, fluid, and other substances accumulate in the body to
cause death within a few days, unless clinical interventions such as hemodialysis are initiated to restore, at
least partially, the body fluid and electrolyte balances.
Masaryk University Faculty of Medicine Physiology Exam
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87. Regulation of cardiac output
The following factors, among others, directly affect the cardiac output: (1) the basic level of body
metabolism, (2) whether the person is exercising, (3) the person’s age, and (4) size of the body.
For young, healthy men, resting cardiac output averages about 5.6 L/min. For women, this value is
about 4.9 L/min.
Control of Heart Rate
The SA node of the heart is enervated by both
sympathetic and parasympathetic nerve
fibers. Under conditions of rest the
parasympathetic fibers release acetylcholine,
which acts to slow the pacemaker potential of
the SA node and thus reduce heart rate.
Under conditions of physical or emotional
activity sympathetic nerve fibers release
norepinephrine, which acts to speed up the
pacemaker potential of the SA node thus
increasing heart rate. Sympathetic nervous
system activity also causes the release of
epinephrine from the adrenal medulla.
Epinephrine enters the blood stream, and is
delivered to the heart where it binds with SA
node receptors. Binding of epinephrine leads
to further increase in heart rate.
Control of Stroke Volume
Under conditions of rest, the heart does not fill to its maximum capacity. If the heart were to fill
more per beat then it could pump out more blood per beat, thus increasing stroke volume. Also,
the ventricles of the heart empty only about 50% of their volume during systole. If the heart were
to contract more strongly then the heart could pump out more blood per beat. In other words, a
stronger contraction would lead to a larger stroke volume. During periods of exercise, the stroke
volume increases because of both these mechanisms; the heart fills up with more blood and the
heart contracts more strongly.
Stroke volume is increased by 2 mechanisms:
1. increase in end-diastolic volume
2. increase in sympathetic system activity
End-diastolic Volume
An increase in venous return of blood to the heart will result in greater filling of the ventricles
during diastole. Consequently the volume of blood in the ventricles at the end of diastole, called
Masaryk University Faculty of Medicine Physiology Exam
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end-diastolic volume, will be increased. A larger end-diastolic volume will stretch the heart.
Stretching the muscles of the heart optimizes the length-strength relationship of the cardiac
muscle fibers, resulting in stronger contractility and greater stroke volume.
Starling's Law
Starling's Law describes the relationship between end-diastolic
volume and stroke volume. It states that the heart will pump
out whatever volume is delivered to it. If the end-diastolic
volume doubles then stroke volume will double.
An Increase in Sympathetic Activity Increases Stroke Volume
The cardiac muscle cells of the ventricular myocardium are richly enervated by sympathetic nerve
fibers. Release of norepinephrine by these fibers causes an increase in the strength of myocardiall
contraction, thus increasing stroke volume. Norepinephrine is thought to increase the intracellular
concentration of calcium in myocardial cells, thus facilitating faster actin/myosin cross bridging.
Also, a general sympathetic response by the body will induce the release of epinephrine from the
adrenal medulla. Epinephrine, like norepinephrine will stimulate an increase in the strength of
myocardial contraction and thus increase stroke volume.
Masaryk University Faculty of Medicine Physiology Exam
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88. Regulation of blood circulation upon orthostasis
Masaryk University Faculty of Medicine Physiology Exam
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89. Regulation of ventilation
Innervations and control centres
The respiratory muscles are innervated by nerve fibers extending from the cervical and thoracic medulla (C4 –
C8 and T1 –T7). The most important control centers are located in the medulla oblongata and cervical medulla
(C1–C2), where interactive inspiratory and expiratory neurons exist on different levels. The network of these
spatially separate neuron groups form a rhythm generator (respiratory “center”) where respiratory rhythm
originates. The neuron groups are triggered alternately, resulting in rhythmic inspiration and expiration.
They are activated in a tonic (nonrhythm- dependent) manner by the formation reticularis, which receives
signals from respiratory stimulants in the periphery and higher centers of the brain.
Respiratory sensors or receptors are involved in respiratory control circuits
Central and peripheral chemosensors on the medulla oblongata and in the arterial circulation continuously
register gas partial pressures in cerebrospinal fluid (CSF) and blood, respectively, and mechanosensors in the
chestwall respond to stretch of intercostal muscles to modulate the depth of breathing. Pulmonary stretch
sensors in the tracheal and bronchial walls respond to marked increases in lung volume, thereby limiting the
depth of respiration in humans (Hering–Breuer reflex). Muscle spindles in the respiratory muscles also respond
to changes in airway resistance in the lung and chest wall.
The extent of involuntary ventilation is mainly determined by the partial pressures of O2 and CO2
and the pH of blood and CSF. Chemosensors respond to any changes in these variables.
 Peripheral chemosensors in the glomera aortica and carotica register changes in the arterial PO2. If it
falls, they stimulate an increase in ventilation via the vagus (X) and glossopharyngeal nerves (IX) until
the arterial PO2 rises again. This occurs, for example, at high altitudes. The impulse frequency of the
sensors increases sharply when the PO2 drops below 13 kPa or 97mmHg (peripheral ventilatory drive).
These changes are even stronger when PCO2 and/or the H
+
concentration in blood also increase.
 The central chemosensors, in particular, in the medulla react to CO2 and H
+
increases (=pH decrease)
in the CSF. Ventilation is then increased until PCO2 and the H
+
concentration in blood and CSF decrease
to normal values. This mostly central respiratory drive is very effective in responding to acute
changes. An increase in arterial PCO2 from, say, 5 to 9 kPa increases the total ventilation VE by a factor
often.
Exercise
During physical work, the total ventilation increases due to (a) co-innervation of the respiratory centers (by
collaterals of cortical efferent motor fibers) and (b) through impulses transmitted by proprioceptive fibers from
the muscles.
Non-feedback sensors and stimulants
Also play an important role in modulating the basic rhythm of respiration. They include:
 Irritant sensors in the bronchial mucosa, which quickly respond to lung volume decreases by
increasing the respiratory rate (deflation reflex or Head’s reflex), and to dust particles or irritating
gases by triggering the cough reflex.
 J sensors of free C fiber endings on alveolar and bronchial walls; these are stimulated in pulmonary
edema, triggering symptoms such as apnea and lowering the blood pressure.
 Higher central nervous centers such as the cortex, limbic system, hypothalamus or pons. They are
involved in the expression of emotions like fear, pain and joy; in reflexes such as sneezing, coughing,
yawning and swallowing; and in voluntary control of respiration while speaking, singing, etc.
 Pressosensors, which are responsible for increasing respiration when the blood pressure decreases.
 Heat and cold sensors in the skin and thermoregulatory center. Increases (fever) and decreases in
body temperature lead to increased respiration.
 Certain hormones also help to regulate respiration. Progesterone, for example, increases respiration
in the second half of the menstrual cycle and during pregnancy.
Masaryk University Faculty of Medicine Physiology Exam
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90. Regulation of gastric and pancreatic secretion
Stimulation of Gastric Acid Secretion
The parietal cells, located deep in the oxyntic glands of the main body of the stomach, are the only cells that
secrete hydrochloric acid. As noted earlier in the chapter, the acidity of the fluid secreted by these cells can be
very great, with pH as low as 0.8. However, secretion of this acid is under continuous control by both endocrine
and nervous signals. Furthermore, the parietal cells operate in close association with another type of cell called
enterochromaffin-like cells (ECL cells), the primary function of which is to secrete histamine.
. The rate of formation and secretion of hydrochloric acid by the parietal cells is directly related to the amount
of histamine secreted by the ECL cells. In turn, the ECL cells can be stimulated to secrete histamine in several
different ways: (1) Probably the most potent mechanism for stimulating histamine secretion is by the hormonal
substance gastrin, which is formed almost entirely in the antral portion of the stomach mucosa in response to
proteins in the foods being digested. (2) In addition, the ECL cells can be stimulated by (a) acetylcholine
released from stomach vagal nerve endings and (b) probably also by hormonal substances secreted by the
enteric nervous system of the stomach wall.
Stimulation of Acid Secretion by Gastrin. Gastrin is itself a
hormone secreted by gastrin cells, also called G cells. These
cells are located in the pyloric glands in the distal end of the
stomach.
When meats or other protein-containing foods reach the
antral end of the stomach, some of the proteins from these
foods have a special stimulatory effect on the gastrin cells in the
pyloric glands to cause release of gastrin into the digestive
juices of the stomach. The vigorous mixing of the gastric juices
transports the gastrin rapidly to the ECL cells in the body of the
stomach, causing release of histamine directly into the deep
oxyntic glands. The histamine then acts quickly to stimulate
gastric hydrochloric acid secretion.
Regulation of Pepsinogen Secretion
Pepsinogen secretion by the peptic cells in the oxyntic glands occurs in response to two types of signals:
(1) stimulation of the peptic cells by acetylcholine released from the vagus nerves or from the gastric enteric
nervous plexus, and (2) stimulation of peptic cell secretion in response to acid in the stomach. The acid elicits
additional enteric nervous reflexes that support the original nervous signals to the peptic cells. Therefore, the
rate of secretion of pepsinogen, the precursor of the enzyme pepsin that causes protein digestion, is strongly
influenced by the amount of acid in the stomach.
Regulation of Pancreatic Secretion
Three basic stimuli are important in causing pancreatic secretion:
1. Acetylcholine, which is released from the parasympathetic vagus
nerve endings and from other cholinergic nerves in the enteric nervous
system
2. Cholecystokinin, which is secreted by the duodenal and upper jejunal
mucosa when food enters the small intestine
3. Secretin, which is also secreted by the duodenal and jejunal mucosa
when highly acid food enters the small intestine
The first two of these stimuli, acetylcholine and cholecystokinin,
stimulate the acinar cells of the pancreas, causing production of large
quantities of pancreatic digestive enzymes but relatively small quantities
of water and electrolytes to go with the enzymes. Without the water,
most of the enzymes remain temporarily stored in the acini and ducts
until more fluid secretion comes along to wash them into the duodenum.
Secretin, in contrast to the first two basic stimuli, stimulates secretion of
large quantities of water solution of sodium bicarbonate by the pancreatic ductal epithelium.
Masaryk University Faculty of Medicine Physiology Exam
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92. Thermoregulation
Thermoregulation maintains the core temperature at a constant set point (≈37°C) despite
fluctuations in heat absorption, production, and loss. The core temperature exhibits circadian
variation. It fluctuates by about 0.6 °C and is lowest around 3 a.m., and highest around 6 p.m..
The set point changes are controlled by an intrinsic biological clock. Extended set-point fluctuations
happen during the menstrual cycle and fever.
The control center for body temperature and central thermosensors are located in the
hypothalamus. Additional thermosensors are located in the spinal cord and skin. The control center
compares the actual core temperature with the set-point value and initiates measures to counteract
any deviations.
When the core temperature rises above the set point (e.g., during exercise), the body increases
the internal heat flow by dilating the blood vessels of the skin. Moreover, arteriovenous anastomoses
open in the periphery, especially in the fingers. The blood volume transported per unit time then not
only conveys more heat, but also reduces the countercurrent exchange of heat between the arteries
and their accompanying veins. In addition, venous return in the extremities is re-routed from the
deep, accompanying veins to the superficial veins. Sweat secretion also increases. The evaporation
of sweat cools the skin, thereby creating the core/skin temperature gradient needed for the internal
heat flow. Centralwarm sensors emit the signals that activate the sweat glands. The efferent nerve
fibers to the sweat glands are cholinergic fibers of the sympathetic nervous system.
When the core temperature falls below set point, the body checks heat loss by constricting
the blood vessels in the shell and increases heat production by generating voluntary and involuntary
(shivering) muscle activity. Although infants can quickly become hypothermic because of their high
surface/volume ratio, their brown fat allows them to produce additional heat (non-shivering
thermogenesis). Upon exposure to low ambient temperatures, these three mechanisms are activated
by the cold receptors of the skin before the core temperature falls.
Masaryk University Faculty of Medicine Physiology Exam
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93. Regulation of renal functions
Nervous and Hormonal Factors Increase the Effectiveness
of Renal-Body Fluid Feedback Control
Sympathetic Nervous System Control of Renal Excretion: Arterial Baroreceptor and Low-Pressure
Stretch Receptor Reflexes
Because the kidneys receive extensive sympathetic innervation, changes in sympathetic activity can alter
renal sodium and water excretion as well as regulation of extracellular fluid volume under some conditions.
For example, when blood volume is reduced by hemorrhage, the pressures in the pulmonary blood vessels and
other low-pressure regions of the thorax decrease, causing reflex activation of the sympathetic nervous
system. This in turn increases renal sympathetic nerve activity, which has several effects to decrease sodium
and water excretion: (1) constriction of the renal arterioles, with resultant decreased GFR; (2) increased tubular
reabsorption of salt and water; and (3) stimulation of renin release and increased angiotensin II and
aldosterone formation, both of which further increase tubular reabsorption.
Also, reflex inhibition of renal sympathetic activity may contribute to the rapid elimination of excess fluid in the
circulation that occurs after eating a meal that contains large amounts of salt and water.
Role of Angiotensin II in Controlling Renal Excretion
When sodium intake is elevated above normal, renin secretion is decreased, causing decreased angiotensin II
formation. Because angiotensin II has several important effects in increasing tubular reabsorption of sodium, a
reduced level of angiotensin II decreases tubular reabsorption of sodium and water, thus increasing the
kidneys’ excretion of sodium and water.
Conversely, when sodium intake is reduced below normal, increased levels of angiotensin II cause sodium
and water retention and oppose reductions in arterial blood pressure that would otherwise occur.
Thus, changes in activity of the renin-angiotensin system act as a powerful amplifier of the pressure natriuresis
mechanism for maintaining stable blood pressures and body fluid volumes.
Role of Aldosterone in Controlling Renal Excretion
Aldosterone increases sodium reabsorption, especially in the cortical collecting tubules. The increased sodium
reabsorption is also associated with increased water reabsorption and potassium secretion. Therefore, the net
effect of aldosterone is to make the kidneys retain sodium and water but to increase potassium excretion in
the urine.
The function of aldosterone in regulating sodium balance is closely related to that described for angiotensin
II. That is, with reduction in sodium intake, the increased angiotensin II levels that occur stimulate aldosterone
secretion, which in turn contributes to the reduction in urinary sodium excretion and, therefore, to the
maintenance of sodium balance.
Role of ADH in Controlling Renal Water Excretion
ADH plays an important role in allowing the kidneys to form a small volume of concentrated urine while
excreting normal amounts of salt. This effect is especially important during water deprivation, which strongly
elevates plasma levels of ADH that in turn increase water reabsorption by the kidneys and help to minimize the
decreases in extracellular fluid volume and arterial pressure that would otherwise occur.
Role of Atrial Natriuretic Peptide in Controlling Renal Excretion
Once released by the cardiac atria, ANP enters the circulation and acts on the kidneys to cause small increases
in GFR and decreases in sodium reabsorption by the collecting ducts.
Masaryk University Faculty of Medicine Physiology Exam
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94. General principle of endocrine regulation
Endocrine signaling
– Is a system of glands, each of which secretes a type of hormone into the bloodstream to regulate
the body. A number of glands that signal each other in sequence is usually referred to as an axis, for
example, the hypothalamic-pituitary-adrenal axis.
– Typical endocrine glands are the pituitary, thyroid, and adrenal glands.
– In addition to the specialized endocrine organs mentioned above, many other organs that are part
of other body systems, such as the kidney, liver, heart and gonads, have secondary endocrine
functions. For example the kidney secretes endocrine hormones such as erythropoietin and renin.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
95. Sympathetic nervous system (overview)
 Part of the autonomic nervous system
The vegetative or autonomic nervous system supplies the internal organs and their coverings.
The main function of the autonomic nervous system is to stabilize the internal environment of the
organism and to regulate the function of the organs in accordance with the changing requirements of
the surroundings. This regulation is achieved by interaction of two antagonistic parts of the
autonomic system, the sympathetic nervous system (yellow, below) and the parasympathetic
nervous system (green below). The sympathetic nervous system is stimulated by increased physical
activity, resulting in elevated blood pressure, accelerated heart rate and respiratory rate, dilated
pupils, raised hair, and increased perspiration. At the same time, the peristaltic activity of the
gastrointestinal tract is suppressed and secretion by intestinal glands is reduced.
The sympathetic nervous system is responsible for increased performance under stress and in
states of emergency.
We distinguish between a peripheral and a central
autonomic nervous system.
. The sympathetic neurons occupy the lateral horn
in the thoracic and upper lumbar segments of the spinal
cord.
Sympathetic Nervous System
The sympathetic neurons in the thoracic and lumbar
lateral horn send their axons via the communicating
branches to the sympathetic trunk. The latter consists of
a chain of sympathetic ganglia which lie on each side of
the vertebral column, in front of the transverse processes
of each vertebra, and extend from the base of the skull to
the coccyx. They are interconnected by interganglionic
branches.
There are three ganglia in the cervical segment, namely,
the superior cervical ganglion, the variable middle cervical
ganglion, and the stellate ganglion (cervicothoracic
ganglion). The thoracic segment contains 10 – 11 ganglia,
the lumbar segment usually four, and the sacral segment
also four ganglia. The chain is completed by the small
unpaired ganglion which lies in the middle in front of the
coccyx. The sacral ganglia receive their preganglionic
fibers via interganglionic branches from spinal cord levels
T12 – L2.
From the thoracic and lumbar sympathetic trunk ganglia, nerves extend to ganglia that lie within
dense nervous plexuses on both sides of the abdominal aorta. The upper group of ganglia are the
celiac ganglia to which the greater splanchnic nerve extends from the fifth to the ninth sympathetic
trunk ganglia. Below it lies the superior mesenteric ganglion and the inferior mesenteric ganglion. The
superior hypogastric plexus and the inferior hypogastric plexus expand in the pelvis.
The middle cervical ganglion may be absent, and the inferior cervical ganglion has in most cases fused with the first thoracic
ganglion to form the stellate ganglion. Its postganglionic fibers form plexuses around the subclavian artery and around the
vertebral artery. Fiber bundles connecting the stellate ganglion with the middle cervical ganglion extend across the
subclavian artery and form the subclavian ansa. Nerves from the cervical ganglia and nerves from the upper thoracic
ganglia extend to the heart and to the hila of the lungs, where they participate together with the parasympathetic fibers of
the vagus nerve in the formation of the cardiac plexus.
Masaryk University Faculty of Medicine Physiology Exam
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96. Parasympathetic nervous system (overview)
 Part of the autonomic nervous system
The vegetative or autonomic nervous system supplies the internal organs and their coverings.
The main function of the autonomic nervous system is to stabilize the internal environment of the
organism and to regulate the function of the organs in accordance with the changing requirements of
the surroundings. This regulation is achieved by interaction of two antagonistic parts of the
autonomic system, the sympathetic nervous system (yellow, below) and the parasympathetic
nervous system (green below. When the parasympathetic system predominates, it increases
peristaltic activity and intestinal secretion, stimulates defecation and urination, and reduces the heart
rate and respiratory rate, while the pupils constrict.
We distinguish between a peripheral and a central
autonomic nervous system.
. Parasympathetic neurons form nuclei in the brain stem:
 The Edinger-Westphal nucleus (3)
 The salivatory nuclei (4)
 The dorsal nucleus of the vagus nerve (5)
The sacral spinal cord also contains parasympathetic
neurons (6).
Parasympathetic Nervous System
The fibers of the central parasympathetic neurons run
within various cranial nerves to the parasympathetic
ganglia in the head region where they synapse;
the postganglionic fibers extend to the effector organs.
The vagus nerve, which is the principal nerve of the
parasympathetic nervous system, descends together with
the large cerebral vessels (neurovascular trunk
of the neck); after passing through the superior thoracic
aperture, it divides into plexuses in the regions of the
thoracic and abdominal viscera.
The cells lying in the intermediolateral nucleus and
intermediomedial nucleus of the sacral spinal cord send
their axons through the third and fourth sacral root to the
pudendal nerve; from here the fibers pass as pelvic nerves
into the inferior hypogastric plexus and to the pelvic organs (urinary bladder, rectum, and genitals).
Synapses with postganglionic neurons are formed in the inferior hypogastric plexus or in small
ganglia of the various organ plexuses. As is the case with the sympathetic nervous system, the
peripheral supply is provided by two neurons: the first neuron (preganglionic neuron) in the spinal
cord, and the second neuron (postganglionic neuron) in the ganglia.
Masaryk University Faculty of Medicine Physiology Exam
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97. Adaptations to extreme environmental conditions
Respiratory system
Diving reflex
Upon initiation of the reflex, three changes happen to the body, in this order:
4. Bradycardia is the first response to submersion. Immediately upon facial contact with cold water, the human heart
rate slows down ten to twenty-five percent. Slowing the heart rate lessens the need for bloodstream oxygen, leaving
more to be used by other organs.
5. Next, peripheral vasoconstriction sets in. When under high pressure induced by deep diving, capillaries in the
extremities start closing off, stopping blood circulation to those areas. Note that vasoconstriction usually applies to
arterioles, but in this case is completely an effect of the capillaries. Toes and fingers close off first, then hands and feet,
and ultimately arms and legs stop allowing blood circulation, leaving more blood for use by the heart and brain.
Human musculature accounts for only 12% of the body's total oxygen storage, and the body's muscles tend to suffer
cramping during this phase.
6. Finally is the blood shift that occurs only during very deep dives. Organ and circulatory walls allow plasma/water to
pass freely throughout the thoracic cavity, so its pressure stays constant and the organs aren't crushed. In this stage,
the lungs' alveoli fill up with blood plasma, which is reabsorbed when the animal leaves the pressurized environment.
This stage of the diving reflex has been observed in humans (such as world champion freediver Martin Štěpánek)
during extremely deep (over 90 m or 300 ft) freedives.
Thermorgulation
The control center for body temperature and central thermosensors are located in the hypothalamus.
Additional thermosensors are located in the spinal cord and skin. The control center compares the actual core
temperature with the set-point value and initiates measures to counteract any deviations.
When the core temperature rises above the set point (e.g., during exercise), the body increases
the internal heat flow by dilating the blood vessels of the skin. Moreover, arteriovenous anastomoses open in the
periphery, especially in the fingers. The blood volume transported per unit time then not
only conveys more heat, but also reduces the countercurrent exchange of heat between the arteries and their
accompanying veins. In addition, venous return in the extremities is re-routed from the deep, accompanying veins to the
superficial veins. Sweat secretion also increases. The evaporation of sweat cools the skin, thereby creating the core/skin
temperature gradient needed for the internal heat flow. Centralwarm sensors emit the signals that activate the sweat
glands. The efferent nerve fibers to the sweat glands are cholinergic fibers of the sympathetic nervous system.
When the core temperature falls below set point, the body checks heat loss by constricting
the blood vessels in the shell and increases heat production by generating voluntary and involuntary (shivering) muscle
activity. Although infants can quickly become hypothermic because of their high surface/volume ratio, their brown fat
allows them to produce additional heat (non-shivering thermogenesis). Upon exposure to low ambient temperatures, these
three mechanisms are activated by the cold receptors of the skin before the core temperature falls.
1.
2.
3.
Masaryk University Faculty of Medicine Physiology Exam
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98. Adaption to exercise
Cardiovascular response
Respiratory response
Sources of ATP during muscular work
Masaryk University Faculty of Medicine Physiology Exam
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99. Integration of nervous and hormonal regulation
Unlike unicellular organisms, multicellular organisms have numerous specialized groups of cells and organs, the
many different functions of which must be expediently integrated and coordinated. In mammals, the nervous
system and endocrine system are chiefly responsible for control and integration, while the immune system
serves as an information system for corporal immune defense. These systems communicate by way of electrical
and/or chemical signals.
Nerve impulses and hormonal signals serve to control and regulate the metabolism and internal milieu
(blood pressure, pH, water and electrolyte balance, temperature, etc.), physical growth and maturation,
reproductive functions, sexual response, and responses to the social environment. The signals received by
sensors (= sensory receptors) in the inner organs, musculoskeletal system, skin and the sensory organs, as well
as psychological factors, skeletal muscles and other factors also play a part in regulation and control. The
signals are used by many feedback mechanisms in the body.
Nerve fibers are specifically adapted for rapid transmission of finely graded signals.
The nervous system consists of the central nervous system (CNS) and peripheral nervous system . The latter
consists of:
 The somatic nervous system, which conducts impulses from non-visceral sensors to a center (afferent
neurons) and controls the skeletal musculature (efferent neurons).
 The peripheral autonomic nervous system, which consists of efferent neurons and mainly functions
to control the circulatory system, inner organs and sexual functions. It is supplemented by:
 Visceral afferent neurons, i.e., nerve fibers that conduct signals from inner organs to a
center. They are usually located in the same nerves as autonomous fibers (e.g., in vagus
nerve); and the
 Enteric nervous system, which integrates the local functions of the esophagus,
stomach and gut.
Hormones
Like neurotransmitters and the immune system’s cytokines and
chemokines, hormones serve as messenger substances that are
mainly utilized for slower, long-term transmission of signals.
- Endocrine hormones are carried by the blood to target
structures great distances away.
- Paracrine hormones (and other paracrine transmitters)
only act on cells in the immediate vicinity of the cells
from which they are released.
- Hormones that act on the cells that produced the
messenger substance are referred to as autocrine
hormones.
Hormones work closely with the nervous system to regulate
digestion, metabolism, growth, maturation, physical and mental
development, maturation, reproduction, adaptation, and the
internal milieu of the body
(homeostasis). Most of these actions are predominately
autonomous functions subject to central control by the
hypothalamus, which is controlled by higher centers of the brain
Neurotransmitters
Are released at chemical synapses of nerve endings transmit
signals to postsynaptic nerve fibers, muscles or glands. Some
neuropeptides released by presynaptic neurons also exert their
effects in neighboring synapses, resulting in a kind of “paracrine”
action.
Neurons can also secrete hormones, e.g., epinephrine,
oxytocin and antidiuretic hormone. Some transmitter substances
of the immune system, e.g. thymosin and various cytokines, also
have endocrine effects.
Masaryk University Faculty of Medicine Physiology Exam
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Part B
1. Blood composition – values.
The blood consists of a suspension of special cells in liquid called plasma. In an adult man, the blood
is about 1/12th of the body weight and this corresponds to 5-6 liters. Blood consists of 55 % plasma,
and 45 % by cells called formed elements.
THE PLASMA
Cells free serum or plasma, can be obtained by centrifugation. The plasma is a slightly alkaline fluid, with a
typical yellowish color. It consists of 90 % water and 10% dry matter. Nine parts of it are made up by organic
substances, whereas one part is made up by minerals. These organic substances are composed of glycides
(glucose), lipids (cholesterol, triglycerides, phospholipids, lecithin, fats), proteins (globulins, albumins,
fibrinogen), glycoproteins, hormones (gonadotropins, erythropoietin, thrombopoietin), amino acids and
vitamins. The mineral substances are dissolved in ionic form, which is dissociated into positive and negative
ions.
20% of all WBCs
5 % of all WBCs
Masaryk University Faculty of Medicine Physiology Exam
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2. Red blood cell. Haemolysis.
Red Blood Cells (Erythrocytes)
The major function of red blood cells, also known as erythrocytes, is to transport hemoglobin, which
in turn carries oxygen from the lungs to the tissues. In some lower animals, hemoglobin circulates as
free protein in the plasma, not enclosed in red blood cells. When it is free in the plasma of the
human being, about 3 per cent of it leaks through the capillary membrane into the tissue spaces or
through the glomerular membrane of the kidney into the glomerular filtrate each time the blood
passes through the capillaries. Therefore, for hemoglobin to remain in the human blood stream, it
must exist inside red blood cells.
The red blood cells have other functions besides transport of hemoglobin. For instance, they
contain a large quantity of carbonic anhydrase, an enzyme that catalyzes the reversible reaction
between carbon dioxide (CO2) and water to form carbonic acid (H2CO3), increasing the rate of this
reaction several thousand fold. The rapidity of this reaction makes it possible for the water of the
blood to transport enormous quantities of CO2 in the form of bicarbonate ion (HCO3
–
) from the
tissues to the lungs, where it is reconverted to CO2 and expelled into the atmosphere as a body waste
product. The hemoglobin in the cells is an excellent acid-base buffer (as is true of most proteins), so
that the red blood cells are responsible for most of the acid-base buffering power of whole blood.
Shape and Size of Red Blood Cells.
Normal red blood cells are biconcave discs having a mean diameter of about 7.8 micrometers and a thickness
of 2.5 micrometers at the thickest point and 1 micrometer or less in the center. The average volume of the red
blood cell is 90 to 95 cubic micrometers.
The shapes of red blood cells can change remarkably as the cells squeeze through capillaries.
Concentration of Red Blood Cells in the Blood
In normal men, the average number of red blood cells per cubic millimeter is 5,200,000 (±300,000); in normal
women, it is 4,700,000 (±300,000). Persons living at high altitudes have greater numbers of red blood cells.
Quantity of Hemoglobin in the Cells
Red blood cells have the ability to concentrate hemoglobin in the cell fluid up to about 34 grams in each 100
milliliters of cells.
RETICULOCYTES are immature erythrocytes released from the bone marrow into the peripheral blood. They contain some
rests of organelles (mainly ribosomes, but not nucleus) which are loosed during maturation (24 – 48 hours) and
reticulocytes transform into mature erythrocytes. Reticulocytes represent 0.5 – 1.5 % of all erytrhocytes in peripheral
blood. Reticulocytosis – increased number of reticulocytes, a sign of increased releasing of these immature cells from bone
marrow. Anemia – decreased number of erythrocytes, polyglobulia or polycythemia – increased number of erythrocytes.
Haemolysis
Is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid
(plasma, in vivo).
In vivo (inside the body): hemolysis, which can be caused by a large number of conditions, can lead to anemia.
In vitro (outside the body): hemolysis can be an important unwanted effect in medical tests and can cause
inaccurate results, because the contents of hemolysed red blood cells are included with the plasma. The
concentration of potassium inside red blood cells is much higher than in the plasma and so an elevated
potassium is usually found in biochemistry tests of hemolysed blood. If as little as 0.5% of the red blood cells
are hemolysed the serum will have a visually obvious pinkish colour, due to hemoglobin.
Masaryk University Faculty of Medicine Physiology Exam
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3. Haemoglobin and its derivates
Minor hemoglobins
It is important to remember that human hemoglobin A (HbA)
is just one member of a functionally and structurally related
family of proteins, the hemoglobins (table on the right) Each
of these oxygen-carrying proteins is a tetramer composed of
two α-globulin-like polypeptides and two β-globulin-like
polypeptides. Certain hemoglobins, such as HbF, are normally
synthesized only during fetal development, whereas others,
such as HbA2, are synthesized in the adult, although at low
levels compared with HbA. HbA can also become modified by
the covalent addition of a hexose. For example, addition of
glucose forms the glucosylated hemoglobin derivative, HbA1c.
Masaryk University Faculty of Medicine Physiology Exam
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4. Erytropoesis
Erythropoesis
Proerythroblast
Basophilic erythroblast
Polychromatophilic erythroblast
Ortochromatic erythroblast
Reticulocyte
Process - during repeated mitoses:
 cell size decreases from 20 m to 8 m in diameter
 condensation of nuclear chromatin, nucleoli disappear, nucleus will be extruded - enucleation
 hemoglobin production
 transformation of cytoplasm staining – from basophilia (caused by ribosomes) to acidophilia (caused by
hemoglobin production)
Proerythroblast
 15 – 20 m
basophilic cytoplasm forms iregular, „ear-shaped“ projections from the surface of the cell
spherical nucleus contains 2 – 3 nucleoli
Basophilic erythroblast
 16 m
basophilic cytoplasm
condensation of nuclear chromatin begins
absence of nucleoli
Polychromatophilic erythroblast
 12 m
production of hemoglobin begins and causes irregular staining of cytoplasm – partly basophilic, partly
acidophilic
condensed chromatin
Ortochromatophilic erythroblast
 9 – 10 m
acidophilic cytoplasm with hemoglobin
pycnotic nucleus in excentric position before enucleation
Reticulocyte
 8 m
acidophilic cytoplasm with hemoglobin
without nucleus, but with the rests of some organelles – substantia reticulofilamentosa
Masaryk University Faculty of Medicine Physiology Exam
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5. Suspension stability of RBC (sedimentation rate)
Erythrocyte Sedimentation Rate (E.S.R.)
Estimation of E.S.R. is a non-specific laboratory method providing us with information on many
physiological and pathological processes in organism. Only in case of two diseases – temporal
arthritis and rheumatic polymyalgia – estimation of E.S.R. represents important diagnostic criterion.
Taking in consideration its low sensitivity, E.S.R. cannot be used as screening test in asymptomatic
persons. On the other hand, marked increase in sedimentation rate (above 100mm/h) is always
cause by pathological process – infection, tumors or cancer diseases.
The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those
factors resisting sedimentation, namely the negative charge of the erythrocytes (zeta potential).
When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red
blood cells to stick to each other. The red cells form stacks called 'rouleaux' which settle faster.
Rouleaux formation can also occur in association with some lymphoproliferative disorders in which
one or more immunoglobulins are secreted in high amounts. Rouleaux formation can, however, be a
normal physiological finding in horses, cats and pigs.
The ESR is increased by any cause or focus of inflammation. The ESR is increased in pregnancy or
rheumatoid arthritis, and decreased in polycythemia, sickle cell anemia, hereditary spherocytosis,
and congestive heart failure. The basal ESR is slightly higher in females.
Principle of method (Fahreus-Westergreen)
Red blood cells membranes are negatively charged. They float in the plasma although they are
specifically heavier (they are driven away from each other). Any factor decreasing or impairing their
surface charge causes their aggregation.
. Anti-coagulated blood is sucked up into a vertical glass tube fixed in a stand in such a way that it
cannot flow out. After 1, 2 (or even 24) hours, the height of the plasma column above the
sedimenting red cells is measured. When working with blood which has a high E.S.R. the readings are
made each 15 or 30 min during two hours.
Physiological (average) values:
Men: 2-8 mm/h, women: 7-12 mm/h, newborns: 2mm/h, infants: 4-8 mm/h
Masaryk University Faculty of Medicine Physiology Exam
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10. Blood groups antigens
A person’s blood group is determined by the type of antigen (certain glycolipids) present on the red
blood cells (RBCs).
In the AB0 system, the antigens are A and B. In blood type A, antigen A (on RBC) and anti-B antibody
(in serum) are present; in type B, B and anti-A are present; in type AB, A and B are present, no
antibody; in type 0 (zero), no antigen but anti-A and anti-B are present.
When giving a blood transfusion, it is important that the blood groups of donor and recipient
match, i.e. that the RBCs of the donor (e.g. A) do not come in contact with the respective antibodies
(e.g. anti-A) in the recipient. If the donor’s blood is the wrong type, agglutination (cross-linking by
IgM) and hemolysis (bursting) of the donor’s RBCs will occur. Donor and recipient blood types must
therefore be determined and cross-matched prior to a blood transfusion.
Since AB0 antibodies belong to the IgM class, they usually do not cross the placenta.
In the Rh system, antibodies against rhesus antigens (C, D, E) on RBCs do not develop unless prior
sensitization has occurred. D is by far the most antigenic. A person is Rh-positive (Rh+
) when D is
present on their RBCs (most people), and Rh-negative (Rh–
) when D is absent. Anti-D antibodies
belong to the IgG class of immunoglobulins, which are capable of crossing the placenta.
Rh–
individuals can form anti-Rh+
(= anti-D) antibodies, e.g., after sensitization by a mismatched
blood transfusion or of an Rh–
mother by an Rh+
fetus. Subsequent exposure to the mismatched blood
leads to a severe antigen-antibody reaction characterized by intravascular agglutination and
hemolysis.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
11. Function of platelets
Platelets, or thrombocytes are small, irregularly-shaped anuclear cell fragments which are derived
from fragmentation of precursor megakaryocytes. Platelets have many functional characteristics of
whole cells, even though they do not have nuclei and cannot reproduce. In their cytoplasm are such
active factors as (1) actin and myosin molecules, which are contractile proteins similar to those found
in muscle cells, and still another contractile protein, thrombosthenin, that can cause the platelets to
contract; (2) residuals of both the endoplasmic reticulum and the Golgi apparatus that synthesize
various enzymes and especially store large quantities of calcium ions; (3) mitochondria and enzyme
systems that are capable of forming adenosine triphosphate (ATP) and adenosine diphosphate (ADP);
(4) enzyme systems that synthesize prostaglandins, which are local hormones that cause many
vascular and other local tissue reactions; (5) an important protein called fibrin-stabilizing factor,
which we discuss later in relation to blood coagulation; and (6) a growth factor that causes vascular
endothelial cells, vascular smooth muscle cells, and fibroblasts to multiply and grow, thus causing
cellular growth that eventually helps repair damaged vascular walls.
The cell membrane of the platelets is also important. On its surface is a coat of glycoproteins that
repulses adherence to normal endothelium and yet causes adherence to injured areas of the vessel
wall, especially to injured endothelial cells and even more so to any exposed collagen from deep
within the vessel wall. In addition, the platelet membrane contains large amounts of phospholipids
that activate multiple stages in the blood-clotting process.
When an endothelial injury occurs, platelets adhere to subendothelial collagen fibers bridged by von
Willebrand’s factor (vWF), which is formed by endothelial cells and circulates in the plasma
complexed with factor VIII. Glycoprotein complex GP Ib/IX on the platelets are vWF receptors.
This adhesion activates platelets. They begin to release substances, some of which promote platelet
adhesiveness (vWF). Others like serotonin, platelet-derived growth factor (PDGF) and thromboxane
A2 (TXA2) promote vasoconstriction. Vasoconstriction and platelet contraction slow the blood flow.
Mediators released by platelets enhance platelet activation and attract and activate more platelets:
ADP, TXA2, platelet-activating factor (PAF). The shape of activated platelets changes drastically.
Discoid platelets become spherical and exhibit pseudopodia that intertwine with those of other
platelets. This platelet aggregation is further enhanced by thrombin and stabilized by GP IIb/IIIa.
Once a platelet changes its shape, GP IIb/IIIa is expressed on the platelet surface, leading to
fibrinogen binding and platelet aggregation. GP IIb/IIIa also increases the adhesiveness of platelets,
which makes it easier for them to stick to subendothelial fibronectin.
Masaryk University Faculty of Medicine Physiology Exam
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12. Hemostasis
The term hemostasis means prevention of blood loss. Whenever a vessel is severed or ruptured, hemostasis is
achieved by several mechanisms: (1) vascular constriction, (2) formation of a platelet plug, (3) formation of a
blood clot as a result of blood coagulation, and (4) eventual growth of fibrous tissue into the blood clot to close
the hole in the vessel permanently.
Vascular Constriction
Immediately after a blood vessel has been cut or ruptured, the trauma to the vessel wall itself causes the
smooth muscle in the wall to contract; this instantaneously reduces the flow of blood from the ruptured vessel.
The contraction results from (1) local myogenic spasm, (2) local autacoid factors from the traumatized
tissues and blood platelets, and (3) nervous reflexes. The nervous reflexes are initiated by pain nerve impulses
or other sensory impulses that originate from the traumatized vessel or nearby tissues. However, even more
vasoconstriction probably results from local myogenic contraction of the blood vessels initiated by direct
damage to the vascular wall. And, for the smaller vessels, the platelets are responsible for much of the
vasoconstriction by releasing a vasoconstrictor substance, thromboxane A2.
Formation of the Platelet Plug
When an endothelial injury occurs, platelets adhere to subendothelial collagen fibers bridged by von
Willebrand’s factor (vWF), which is formed by endothelial cells and circulates in the plasma complexed with
factor VIII. Glycoprotein complex GP Ib/IX on the platelets are vWF receptors. This adhesion activates platelets.
They begin to release substances, some of which promote platelet adhesiveness (vWF). Others like serotonin,
platelet-derived growth factor (PDGF) and thromboxane A2 (TXA2) promote vasoconstriction. Vasoconstriction
and platelet contraction slow the blood flow. Mediators released by platelets enhance platelet activation and
attract and activate more platelets: ADP, TXA2, platelet-activating factor (PAF). The shape of activated
platelets changes drastically. Discoid platelets become spherical and exhibit pseudopodia that intertwine with
those of other platelets. This platelet aggregation is further enhanced by thrombin and stabilized by GP
IIb/IIIa. Once a platelet changes its shape, GP IIb/IIIa is expressed on the platelet surface, leading to fibrinogen
binding and platelet aggregation. GP IIb/IIIa also increases the adhesiveness of platelets, which makes it easier
for them to stick to subendothelial fibronectin.
Blood Coagulation in the Ruptured Vessel
The third mechanism for hemostasis is formation of the blood clot. The clot begins to develop in 15 to 20
seconds if the trauma to the vascular wall has been severe, and in 1 to 2 minutes if the trauma has been minor.
Activator substances from the traumatized vascular wall, from platelets, and from blood proteins adhering to
the traumatized vascular wall initiate the clotting process.
Within 3 to 6 minutes after rupture of a vessel, if the vessel opening is not too large, the entire opening or
broken end of the vessel is filled with clot. After 20 minutes to an hour, the clot retracts; this closes the vessel
still further. Platelets also play an important role in this clot retraction.
Fibrous Organization or Dissolution of the Blood Clot
Once a blood clot has formed, it can follow one of two courses: (1) It can become invaded by fibroblasts, which
subsequently form connective tissue all through the clot, or (2) it can dissolve. The usual course for a clot that
forms in a small hole of a vessel wall is invasion by fibroblasts, beginning within a few hours after the clot is
formed (which is promoted at least partially by growth factor secreted by platelets). This continues to complete
organization of the clot into fibrous tissue within about 1 to 2 weeks.
Conversely, when excess blood has leaked into the tissues and tissue clots have occurred where they are not
needed, special substances within the clot itself usually become activated. These function as enzymes to
dissolve the clot.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
13. Anticlotting mechanism
The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting
inside the blood vessels and to break down any clots that do form. These reactions include the
interaction between the platelet-aggregation effect of thromboxane A2 and the antiaggregation
effect of prostacyclin, which causes clots to form at the site when a blood vessel is injured but keeps
the vessel lumen free of clot.
. Antithrombin III is a circulating protease inhibitor that binds to the serine proteases in the
coagulation system, blocking their activity as clotting factors. This binding is facilitated by heparin, a
naturally occurring anticoagulant that is a mixture of sulfated polysaccharides. The clotting factors
that are inhibited are the active forms of factors IX, X, XI, and XII.
. The endothelium of the blood vessels also plays an active role in preventing the extension of clots
into blood vessels. All endothelial cells except those in the cerebral microcirculation produce
thrombomodulin, a thrombin-binding protein, and express it on their surface. In the circulating
blood, thrombin is a procoagulant that activates factors V and VIII, but when it binds to
thrombomodulin, it becomes an anticoagulant in that the thrombomodulin-thrombin complex
activates protein C. Activated protein C (APC), along with its cofactor protein S, inactivates factor V
and VII and inactivates an inhibitor of tissue plasminogen activator, increasing the formation of
plasmin.
. Plasmin (fibrinolysis) is the active component of the plasminogen (fibrinolytic) system. This
enzyme lyses fibrin and fibrinogen, with the production of fibrinogen degradation products (FDP)
that inhibit thrombin. Plasmin is formed from its inactive precursor, plasminogen, by the action of
thrombin and tissue-type plasminogen activator (t-PA). It is also activated by urokinase-type
plasminogen activator (u-PA).
. Plasminogen receptors are located on the surface of many different types of cells and are
plentiful on endothelial cells. When plasminogen binds to its receptors, it becomes activated, so
intact blood vessel walls are provided with a mechanism that discourages clot formation.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
14. Conducting system of the heart
Specialized Excitatory and Conductive System of the Heart (figure on the right)
Sinus (Sinoatrial) Node
It is located in the superior posterolateral wall of the right atrium immediately
below and slightly lateral to the opening of the superior vena cava.
The sinus nodal fibers connect directly with the atrial muscle fibers, so that any
action potential that begins in the sinus node spreads immediately into the
atrial muscle wall.
Automatic Electrical Rhythmicity of the Sinus Fibers
Some cardiac fibers have the capability of self-excitation. For this
reason, the sinus node ordinarily controls the rate of beat of the entire
heart. Note (figure to the right) that the “resting membrane potential”
of the sinus nodal fiber between discharges has a negativity of about -
55 to -60 millivolts, in comparison with -85 to -90 millivolts for the
ventricular muscle fiber. The cause of this lesser negativity is that the
cell membranes of the sinus fibers are naturally leaky to sodium and
calcium ions, and positive charges of the entering sodium and calcium
ions neutralize much of the intracellular negativity.
That cardiac muscle has three types of membrane ion channels that
play important roles in causing the voltage changes of the action
potential. They are (1) fast sodium channels, (2) slow sodiumcalcium
channels, and (3) potassium channels. Opening of the fast sodium
channels for a few 10,000ths of a second is responsible for the rapid
upstroke spike of the action potential observed in ventricular muscle,
because of rapid influx of positive sodium ions to the interior of the fiber. Then the “plateau” of the ventricular
action potential is caused primarily by slower opening of the slow sodium-calcium channels, which lasts for
about 0.3 second. Finally, opening of potassium channels allows diffusion of large amounts of positive
potassium ions in the outward direction through the fiber membrane and returns the membrane potential to
its resting level.
But there is a difference in the function of these channels in the sinus nodal fiber because the “resting”
potential is much less negative—only -55 millivolts in the nodal fiber instead of the -90 millivolts in the
ventricular muscle fiber. At this level of -55 millivolts, the fast sodium channels mainly have already become
“inactivated,” which means that they have become blocked. The cause of this is that any time the membrane
potential remains less negative than about -55 millivolts for more than a few milliseconds, the inactivation
gates on the inside of the cell membrane that close the fast sodium channels become closed and remain so.
Therefore, only the slow sodium-calcium channels can open (i.e., can become “activated”) and thereby cause
the action potential. As a result, the atrial nodal action potential is slower to develop than the action potential
of the ventricular muscle.
Self-Excitation of Sinus Nodal Fibers
Because of the high sodium ion concentration in the extracellular fluid
outside the nodal fiber, as well as a moderate number of already open
sodium channels, positive sodium ions from outside the fibers normally
tend to leak to the inside. Therefore, between heartbeats, influx of
positively charged sodium ions causes a slow rise in the resting membrane
potential in the positive direction. Thus, the “resting” potential gradually
rises between each two heartbeats. When the potential reaches a
threshold voltage of about -40 millivolts, the sodium-calcium channels
become “activated,” thus causing the action potential. Therefore, basically,
the inherent leakiness of the sinus nodal fibers to sodium and calcium ions
causes their self-excitation.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
IMPORTANT!  Know by heart !!
Why does this leakiness to sodium and calcium ions not cause the sinus nodal fibers to remain depolarized
all the time? The answer is that two events occur during the course of the action potential to prevent this.
First, the sodium-calcium channels become inactivated (i.e., they close) within about 100 to 150 milliseconds
after opening, and second, at about the same time, greatly increased numbers of potassium channels open.
Therefore, influx of positive calcium and sodium ions through the sodium-calcium channels ceases, while at the
same time large quantities of positive potassium ions diffuse out of the fiber. Both of these effects reduce the
intracellular potential back to its negative resting level and therefore terminate the action potential.
Furthermore, the potassium channels remain open for another few tenths of a second, temporarily continuing
movement of positive charges out of the cell, with resultant excess negativity inside the fiber; this is called
hyperpolarization.
Last, we must explain why this new state of hyperpolarization is not maintained forever. The reason is that
during the next few tenths of a second after the action potential is over, progressively more and more
potassium channels close. The inward-leaking sodium and calcium ions once again overbalance the outward
flux of potassium ions, and this causes the “resting” potential to drift upward once more, finally reaching the
threshold level for discharge at a potential of about -40 millivolts. Then the entire process begins again.
15. Cardiac automaticity (prefer to q. 14)
Some cardiac fibers have the capability of self-excitation.
Self-Excitation of Sinus Nodal Fibers
Because of the high sodium ion concentration in the extracellular fluid
outside the nodal fiber, as well as a moderate number of already open
sodium channels, positive sodium ions from outside the fibers
normally tend to leak to the inside. Therefore, between heartbeats,
influx of positively charged sodium ions causes a slow rise in the
resting membrane potential in the positive direction. Thus, the
“resting” potential gradually rises between each two heartbeats.
When the potential reaches a threshold voltage of about -40 millivolts,
the sodium-calcium channels become “activated,” thus causing the
action potential. Therefore, basically, the inherent leakiness of the
sinus nodal fibers to sodium and calcium ions causes their self-
excitation.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Vectorial Analysis of Potentials in the Three
Standard Bipolar Limb Leads
16. Spread and retreat of excitation wavefront
17. Electric vector of the heart. Vectocardiography. (Guyton chap. 12)
Use of Vectors to Represent Electrical Potentials
A vector is an arrow that points in the direction of the electrical potential generated by the current flow, with
the arrowhead in the positive direction. Also, by convention, the length of
the arrow is drawn proportional to the voltage of the potential.
Electrical current flows between the depolarized areas inside the heart and
the nondepolarized areas on the outside of the heart. Some current also
flows inside the heart chambers directly from the depolarized areas
toward the still polarized areas. Overall, considerably more current flows
downward from the base of the ventricles toward the apex than in the
upward direction. Therefore, the summated vector of the generated
potential at this particular instant, called the instantaneous mean vector, is
represented by the long black arrow drawn through the center of the
ventricles in a direction from base toward apex.
In a normal heart, the average direction of the vector during spread of the
depolarization wave through the ventricles, called the mean QRS vector, is
about +59 degrees, which is shown by vector A drawn through the center of
figure on the right in the +59-degree direction. This means that during most
of the depolarization wave, the apex of the heart remains positive with
respect to the base of the heart.
Vectocardigram
The so-called vectorcardiogram depicts these changes at different times
during the cardiac cycle, as shown in Figure 12–10.
Masaryk University Faculty of Medicine Physiology Exam
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18. Specific features of cardiac metabolism
Most important, under resting conditions, cardiac muscle normally consumes fatty acids to supply most of its
energy instead of carbohydrates (about 70 per cent of the energy is derived from fatty acids). However, as is
also true of other tissues, under anaerobic or ischemic conditions, cardiac metabolism must call on anaerobic
glycolysis mechanisms for energy. Unfortunately, glycolysis consumes tremendous quantities of the blood
glucose and at the same time forms large amounts of lactic acid in the cardiac tissue, which is probably one of
the causes of cardiac pain in cardiac ischemic conditions.
As is true in other tissues, more than 95 per cent of the metabolic energy liberated from foods is used to
form ATP in the mitochondria. This ATP in turn acts as the conveyer of energy for cardiac muscular contraction
and other cellular functions. In severe coronary ischemia, the ATP degrades first to adenosine diphosphate,
then to adenosine monophosphate and adenosine. Because the cardiac muscle cell membrane is slightly
permeable to adenosine, much of this can diffuse from the muscle cells into the circulating blood.
The released adenosine is believed to be one of the substances that causes dilation of the coronary arterioles
during coronary hypoxia.
However, loss of adenosine also has a serious cellular consequence. Within as little as 30 minutes of severe
coronary ischemia, as occurs after a myocardial infarct, about one half of the adenine base can be lost from the
affected cardiac muscle cells. Furthermore, this loss can be replaced by new synthesis of adenine at a rate of
only 2 per cent per hour. Therefore, once a serious bout of coronary ischemia has persisted for 30 or more
minutes, relief of the ischemia may be too late to save the lives of the cardiac cells. This almost certainly is one
of the major causes of cardiac cellular death during myocardial ischemia.
19. Heart as a pump
The heart, is actually two separate pumps: a right heart that pumps blood through the lungs, and a left heart
that pumps blood through the peripheral organs. In turn, each of these hearts is a pulsatile two-chamber pump
composed of an atrium and a ventricle. Each atrium is a weak primer pump for the ventricle, helping to move
blood into the ventricle. The ventricles then supply the main pumping force that propels the blood either (1)
through the pulmonary circulation by the right ventricle or (2) through the peripheral circulation by the left
ventricle.
Physiology of Cardiac Muscle
The heart is composed of three major types of cardiac muscle: atrial muscle, ventricular muscle, and
specialized excitatory and conductive muscle fibers. The atrial and ventricular types of muscle contract in much
the same way as skeletal muscle, except that the duration of contraction is much longer. Conversely, the
specialized excitatory and conductive fibers contract only feebly because they contain few contractile fibrils;
instead, they exhibit either automatic rhythmical electrical discharge in the form of action potentials or
conduction of the action potentials through the heart, providing an excitatory system that controls the
rhythmical beating of the heart.
Cardiac Muscle as a Syncytium
At each intercalated disc the cell membranes fuse with one another in such a way that they form permeable
“communicating” junctions (gap junctions) that allow almost totally free diffusion of ions.
Thus, cardiac muscle is a syncytium of many heart muscle cells in which the cardiac cells are so
interconnected that when one of these cells becomes excited, the action potential spreads to all of them,
spreading from cell to cell throughout the latticework interconnections.
The heart actually is composed of two syncytiums: the atrial syncytium and the ventricular syncytium. This
division of the muscle of the heart into two functional syncytiums allows the atria to contract a short time
ahead of ventricular contraction, which is important for effectiveness of heart pumping.
! Action Potentials in Cardiac Muscle
The action potential recorded in a ventricular muscle fiber, averages about 105 millivolts, which means that the
intracellular potential rises from a very negative value, about -85 millivolts, between beats to a slightly positive
value, about +20 millivolts, during each beat. After the initial spike, the membrane remains depolarized for
about 0.2 second, exhibiting a plateau as shown in the figure, followed at the end of the plateau by abrupt
repolarization. The presence of this plateau in the action potential causes ventricular contraction to last as
much as 15 times as long in cardiac muscle as in skeletal muscle.
Masaryk University Faculty of Medicine Physiology Exam
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In cardiac muscle, the action potential is caused by opening of two
types of channels: (1) the same fast sodium channels as those in
skeletal muscle and (2) another entirely different population of slow
calcium channels, which are also called calcium-sodium channels.
This second population of channels differs from the fast sodium
channels in that they are slower to open and, even more important,
remain open for several tenths of a second. During this time, a large
quantity of both calcium and sodium ions flows through these
channels to the interior of the cardiac muscle fiber, and this
maintains a prolonged period of depolarization, causing the plateau
in the action potential.
Immediately after the onset of the action potential, the permeability
of the cardiac muscle membrane for potassium ions decreases about fivefold, an effect that does not occur in
skeletal muscle. The decreased potassium permeability greatly decreases the outflux of positively charged
potassium ions during the action potential plateau and thereby prevents early return of the action potential
voltage to its resting level. When
the slow calcium-sodium channels do close at the end of 0.2 to 0.3 second and the influx of calcium and sodium
ions ceases, the membrane permeability for potassium ions also increases rapidly; this rapid loss of potassium
from the fiber immediately returns the membrane potential to its resting level, thus ending the action
potential.
In addition to the calcium ions that are released into the sarcoplasm from the cisternae of the sarcoplasmic
reticulum, a large quantity of extra calcium ions also diffuses into the sarcoplasm from the T tubules
themselves at the time of the action potential. Indeed, without this extra calcium from the T tubules, the
strength of cardiac muscle contraction would be reduced considerably because the sarcoplasmic reticulum of
cardiac muscle is less well developed than that of skeletal muscle and does not store enough calcium to
provide full contraction. Also, inside the T tubules is a large quantity of mucopolysaccharides that are
electronegatively charged and bind an abundant store of calcium ions, keeping these always available for
diffusion to the interior of the cardiac muscle fiber when a T tubule action potential appears.
20. Difference between left and right heart
The difference between the two ventricles has to do with their related functions
Since the left ventricle has to pump blood much further (all the way around the body, including right up to the
top of the head and all the way to the toes) it has to do more work than the right does (which only has to pump
blood as far as the lungs and back to the heart). So the muscular walls of the left ventricle are much thicker to
produce the necessary force required for the more strenuous job it has to do. Another difference is seen in the
valves. The valves between the ventricles and the atria are called the atrioventricular valves. The one between
the right atria and ventricle has three parts, or cusps, and is called the tricuspid valve. The one in the left side of
the heart between the left atria and ventricle has two cusps and is called the bicuspid (or the mitral valve).
To sum it all up: The right ventricle pumps blood to both lungs, and the left ventricle pumps blood to all the
other body tissues.
Signs of.. .
Left-sided failure
Common respiratory signs are tachypnea (increased rate of breathing) and increased work of breathing (non-specific signs
of respiratory distress). Rales or crackles, heard initially in the lung bases, and when severe, throughout the lung fields
suggest the development of pulmonary edema (fluid in the alveoli).
Right-sided failure
Physical examination can reveal pitting peripheral edema, ascites, and hepatomegaly. Jugular venous pressure is frequently
assessed as a marker of fluid status, which can be accentuated by the hepatojugular reflux. If the right ventriclar pressure is
increased, a parasternal heave may be present, signifying the compensatory increase in contraction strength.
Masaryk University Faculty of Medicine Physiology Exam
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21. Determinants of cardiac performance: preload, afterload, inotropy
The heart autonomously responds to changes in ventricular volume load or aortic pressure load by adjusting
the stroke volume (SV) in accordance with the myocardial preload (resting tension). The FSM also functions to
maintain an equal SV in both ventricles to prevent congestion in the pulmonary or systemic circulation.
Preload change
When the volume load (preload) increases, the start of isovolumic
contraction shifts to the right along the passive P–V curve. This
increases end-diastolic volume (EDV), stroke volume (SV), cardiac
work and end-systolic
volume (ESV).
Afterload change
When the aortic pressure load (afterload) increases, the aortic valve
will not open until the pressure in the left ventricle has risen
accordingly. Thus, the SV in the short transitional phase (SVt) will
decrease, and ESV will rise (ESVt). Consequently, the start of the
isovolumic contraction shifts to the right along the passive P–V
curve. SV will then normalize despite the increased aortic pressure,
resulting in a relatively large increase in ESV.
Inotropism
Preload or afterload-independent changes in myocardial contraction force are referred to as contractility or
inotropism. It increases in response to norepinephrine (NE) and epinephrine (E) as well as to increases in heart
rate (β1-adrenoceptor-mediated, positive inotropic effect and frequency inotropism, respectively. This causes a
number of effects, particularly, an increase in isovolumic pressure peaks. The heart can therefore pump against
increased pressure levels and/or eject larger SVs (at the expense of the ESV).
While changes in the preload only affect the force of contraction, changes in contractility also affect the
velocity of contraction. The steepest increase in isovolumic pressure per unit time (maximum dP/dt) is
therefore used as a measure of contractility in clinical practice. dP/dt is increased E and NE and decreased by
bradycardia or heart failure.
Note - In the human heart, an abrupt
increase in afterload can cause a small
increase in inotropy (Anrep effect) by a
mechanism that is not fully understood.
Note #2 - Sympathetic inv, has a positive
inotropic affect on ventricles, however
parasympathetic inv, has a very little –
inotropic affect on ventricles but more
significant affect on the atria.
Masaryk University Faculty of Medicine Physiology Exam
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22. Cardiac reserve. Heart Failure.
Cardiac Reserve
The maximum percentage that the cardiac output can increase above normal is called the cardiac reserve.
Thus, in the healthy young adult, the cardiac reserve is 300 to 400 per cent. In athletically trained persons, it
is occasionally 500 to 600 per cent. But in heart failure, there is no cardiac reserve. As an example of normal
reserve, during severe exercise the cardiac output of a healthy young adult can rise to about five times
normal; this is an increase above normal of 400 per cent—that is, a cardiac reserve of 400 per cent.
Any factor that prevents the heart from pumping blood satisfactorily will decrease the cardiac reserve.
This can result from ischemic heart disease, primary myocardial disease, vitamin deficiency that affects cardiac
muscle, physical damage to the myocardium, valvular heart disease, and many other factors.
Diagnosis of Low Cardiac Reserve—Exercise Test
A diagnosis of low cardiac reserve usually can be easily made by requiring the person to exercise either on a
treadmill or by walking up and down steps, either of which requires greatly increased cardiac output. The
increased load on the heart rapidly uses up the small amount of reserve that is available, and the cardiac
output soon fails to rise high enough to sustain the body’s new level of activity.
Cardiac failure (“Heart failure”)
The term “cardiac failure” means simply failure of the heart to pump enough blood to satisfy the needs of the
body. It can be acute and associated with sudden death, or chronic. The failure may involve primarily the right
ventricle, but much more commonly it involves the larger, thicker left ventricle or both ventricles.
. In chronic heart failure (congestive heart failure), cardiac output is initially inadequate during exercise but
adequate at rest. As the disease progresses, the output at rest also becomes inadequate.
There are two types of failure, systolic and diastolic. In systolic failure, stroke volume is reduced because
ventricular contraction is weak. This causes an increase in the end-systolic ventricular volume, so that the
ejection fraction – the fraction of the blood in the ventricles that is ejected during systole – falls from 65% to as
low as 20%. The initial response to failure is activation of the genes that cause cardiac myocytes to
hypertrophy, and thicken of the ventricular wall (cardiac remodeling). The incomplete filling of the arterial
system leads to increased discharge of the sympathetic nervous system and increased secretion of renin and
aldosterone, so Na
+
and water is retained. The responses are initially compensatory, but eventually the failure
worsens and the ventricles dilate.
. In diastolic failure, the ejection fraction is initially maintained but the elasticity of the myocardium is reduced
so filling during diastole is reduced. This lead to inadequate stroke volume and the same cardiac remodeling
and Na+ and water retention that occur in systolic failure.
. It should be noted that the inadequate cardiac output in failure may be relative rather than absolute. When a
larger arterior venous fistula is present, in thyrotoxicosis, and in thiamine deficiency, cardiac output may be
elevated in absolute terms but still be inadequate to meet the needs of the tissues (high-output failure).
Treatment
Treatment of congestive heart failure is aimed at improving cardiac contractility, treating the symptoms, and
decreasing the load on the heart. Currently, the most effective treatment in general use is inhibition of the
production of angiotensin II with angiotensin-converting enzyme inhibitors. Blocking the production of
angiotensin II or its effects also reduces the circulating aldosterone level and decreases blood pressure,
reducing the afterload against which the heart pumps. Digitalis derivatives such as dioxin have classically been
used to treat congestive heart failure because of their ability to increase intracellular Ca
2+
and hence exert a
positively inotropic effect, but they are now used in a secondary role to treat systolic dysfunction and slow the
ventricular rate in patients with atrial fibrillation.
Masaryk University Faculty of Medicine Physiology Exam
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23. Cardiac cycle. Phases. Pressure-volume loop.
Cardiac Cycle
The cardiac events that occur from the beginning of one heartbeat to the beginning of the next are called the
cardiac cycle. Each cycle is initiated by spontaneous generation of an action potential in the sinus node. This
node is located in the superior lateral wall of the right atrium near the opening of the superior vena cava, and
the action potential travels from here rapidly through both atria and then through the A-V bundle into the
ventricles.
Because of this special arrangement of the conducting system from the atria into the ventricles, there is a delay
of more than 0.1 second during passage of the cardiac impulse from the atria into the ventricles. This allows
the atria to contract ahead of ventricular contraction, thereby pumping blood into the ventricles before the
strong ventricular contraction begins. Thus, the atria act as primer pumps for the ventricles, and the ventricles
in turn provide the major source of power for moving blood through the body’s vascular system.
Diastole and Systole
The cardiac cycle consists of a period of relaxation called diastole, during which the heart fills with blood,
followed by a period of contraction called systole.
The figure below (left) shows the different events during the cardiac cycle for the left side of the heart.
The top three curves show the pressure changes in the aorta, left ventricle, and left atrium, respectively.
The fourth curve depicts the changes in left ventricular volume, the fifth the electrocardiogram, and the sixth a
phonocardiogram, which is a recording of the sounds produced by the heart—mainly by the heart valves—as it
pumps.
Relationship of the Electrocardiogram to the Cardiac Cycle
The P wave is caused by spread of depolarization through the atria, and this is followed by atrial contraction,
which causes a slight rise in the atrial pressure curve immediately after the electrocardiographic P wave.
About 0.16 second after the onset of the P wave, the QRS waves appear as a result of electrical
depolarization of the ventricles, which initiates contraction of the ventricles and causes the ventricular
pressure to begin rising (as also shown in the figure). Therefore, the QRS complex begins slightly before the
onset of ventricular systole.
Finally, one observes the ventricular T wave in the electrocardiogram. This represents the stage of
repolarization of the ventricles when the ventricular muscle fibers begin to relax. Therefore, the T wave occurs
slightly before the end of ventricular contraction.
Pressure-volume loop
Masaryk University Faculty of Medicine Physiology Exam
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24. Stroke volume and cardiac output
Work Output of the Heart
The stroke work output of the heart is the amount of energy that the heart converts to work during each
heartbeat while pumping blood into the arteries. Minute work output is the total amount of energy converted
to work in 1 minute; this is equal to the stroke work output times the heart rate per minute.
Work output of the heart is in two forms. First, by far the major proportion is used to move the blood from
the low-pressure veins to the high-pressure arteries. This is called volume-pressure work or external work.
Second, a minor proportion of the energy is used to accelerate the blood to its velocity of ejection through the
aortic and pulmonary valves. This is the kinetic energy of blood flow component of the work output.
Right ventricular external work output is normally about one sixth the work output of the left ventricle
because of the sixfold difference in systolic pressures that the two ventricles pump. The additional work output
of each ventricle required to create kinetic energy of blood flow is proportional to the mass of blood ejected
times the square of velocity of ejection.
Ordinarily, the work output of the left ventricle required to create kinetic energy of blood flow is only about
1 per cent of the total work output of the ventricle and therefore is ignored in the calculation of the total
stroke work output. But in certain abnormal conditions, such as aortic stenosis, in which blood flows with great
velocity through the stenosed valve, more than 50 per cent of the total work output may be required to create
kinetic energy of blood flow.
Masaryk University Faculty of Medicine Physiology Exam
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25. Heart sounds. Diagnostic significance
Relationship of the Heart Sounds to Heart Pumping
When listening to the heart with a stethoscope, one does not hear the opening of the valves because this is a
relatively slow process that normally makes no noise. However, when the valves close, the vanes of the valves
and the surrounding fluids vibrate under the influence of sudden pressure changes, giving off sound that
travels in all directions through the chest.
When the ventricles contract, one first hears a sound caused by closure of the A-V valves. The vibration is low
in pitch and relatively long-lasting and is known as the first heart sound. When the aortic and pulmonary valves
close at the end of systole, one hears a rapid snap because these valves close rapidly, and the surroundings
vibrate for a short period. This sound is called the second heart sound.
Heart Sounds Normal Heart Sounds
Listening with a stethoscope to a normal heart, one hears a sound usually described as “lub, dub, lub, dub”. The
“lub” is associated with closure of the atrioventricular (A-V) valves at the beginning of systole, and the “dub” is
associated with closure of the semilunar (aortic and pulmonary) valves at the end of systole. The “lub” sound is
called the first heart sound, and the “dub” is called the second heart sound, because the normal pumping cycle
of the heart is considered to start when the A-V valves close at the onset of ventricular systole.
Causes of the First and Second Heart Sounds
The earliest explanation for the cause of the heart sounds was that the “slapping” together of the valve leaflets
sets up vibrations. However, this has been shown to cause little, if any, of the sound, because the blood
between the leaflets cushions the slapping effect and prevents significant sound. Instead, the cause is vibration
of the taut valves immediately after closure, along with vibration of the adjacent walls of the heart and major
vessels around the heart. That is, in generating the first heart sound, contraction of the ventricles first causes
sudden backflow of blood against the A-V valves (the tricuspid and mitral valves), causing them to close and
bulge toward the atria until the chordae tendineae abruptly stop the back bulging. The elastic tautness of the
chordae tendineae and of the valves then causes the back surging blood to bounce forward again into each
respective ventricle. This causes the blood and the ventricular walls, as well as the taut valves, to vibrate and
causes vibrating turbulence in the blood. The vibrations travel through the adjacent tissues to the chest wall,
where they can be heard as sound by using the stethoscope.
The second heart sound results from sudden closure of the semilunar valves at the end of systole. When the
semilunar valves close, they bulge backward toward the ventricles, and their elastic stretch recoils the blood
back into the arteries, which causes a short period of reverberation of blood back and forth between the walls
of the arteries and the semilunar valves, as well as between these valves and the ventricular walls. The
vibrations occurring in the arterial walls are then transmitted mainly along the arteries. When the vibrations of
the vessels or ventricles come into contact with a “sounding board,” such as the chest wall, they create sound
that can be heard.
Phonocardiogram
If a microphone specially designed to
detect low-frequency sound is placed on
the chest, the heart sounds can be
amplified and recorded by a high-speed
recording apparatus. The recording is
called a phonocardiogram, and the
heart sounds appear as waves.
Masaryk University Faculty of Medicine Physiology Exam
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26. Autoregulation of cardiac contraction: Starling principle
Intrinsic Regulation of Heart Pumping—The Frank-Starling Mechanism
Each peripheral tissue of the body controls its own local blood flow, and all the local tissue flows combine and
return by way of the veins to the right atrium. The heart, in turn, automatically pumps this incoming blood into
the arteries, so that it can flow around the circuit again.
This intrinsic ability of the heart to adapt to increasing volumes of inflowing blood is called the Frank- Starling
mechanism of the heart. Basically, the Frank-Starling mechanism means that the greater the heart muscle is
stretched during filling, the greater is the force of contraction and the greater the quantity of blood pumped
into the aorta. Or, stated another way: Within physiologic limits, the heart pumps all the blood that returns to it
by the way of the veins.
What Is the Explanation of the Frank-Starling Mechanism?
When an extra amount of blood flows into the ventricles, the cardiac muscle itself is stretched to greater
length. This in turn causes the muscle to contract with increased force because the actin and myosin filaments
are brought to a more nearly optimal degree of overlap for force generation. Therefore, the ventricle, because
of its increased pumping, automatically pumps the extra blood into the arteries.
In addition to the important effect of lengthening the heart muscle, still another factor increases heart
pumping when its volume is increased. Stretch of the right atrial wall directly increases the heart rate by 10 to
20 per cent; this, too, helps increase the amount of blood pumped each minute, although its contribution is
much less than that of the Frank-Starling mechanism.
27. Autoregulation of cardiac contraction: frequency effect
Masaryk University Faculty of Medicine Physiology Exam
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28. Heart rate
Heart rate is the number of heartbeats per unit of time - typically expressed as beats per minute (bpm) - which
can vary as the body's need for oxygen changes, such as during exercise or sleep. The measurement of heart
rate is used by medical professionals to assist in the diagnosis and tracking of medical conditions. It is also used
by individuals, such as athletes, who are interested in monitoring their heart rate to gain maximum efficiency
from their training. The R wave to R wave interval (RR interval) is the inverse of the heart rate.
Heart rate is measured by finding the pulse of the body. This pulse rate can be measured at any point on the
body where an artery's pulsation is transmitted to the surface - often as it is compressed against an underlying
structure like bone - by pressuring it with the index and middle finger. The thumb should not be used for
measuring another person's heart rate, as its strong pulse may interfere with discriminating the site of
pulsation.
Possible points for measuring the heart rate are:
1. The ventral aspect of the wrist on the side of the thumb (radial artery)
2. The ulnar artery
3. The neck (carotid artery),
4. The inside of the elbow, or under the biceps muscle (brachial artery)
5. The groin (femoral artery)
6. Behind the medial malleolus on the feet (posterior tibial artery)
7. Middle of dorsum of the foot (dorsalis pedis).
8. Behind the knee (popliteal artery)
9. Over the abdomen (abdominal aorta)
10. The chest (apex of heart), which can be felt with one's hand or fingers. However, it is possible to auscultate the
heart using a stethoscope.
11. The temple
12. The lateral edge of the mandible
A more precise method of determining pulse involves the use of an electrocardiograph, or ECG (also
abbreviated EKG).
Resting heart rate (HRrest)
Is a person's heart rate when they are at rest: awake but lying down, and not having immediately
exerted themselves. Typical healthy resting heart rate in adults is 60–80 bpm, with rates below 60
bpm referred to as bradycardia and rates above 100 bpm referred to as tachycardia. Note however
that conditioned athletes often have resting heart rates below 60 bpm. Tour de France cyclist Lance
Armstrong has a resting HR around 32 bpm.
Rate of Heartbeat as Determined from the Electrocardiogram
The rate of heartbeat can be determined easily from an electrocardiogram because the heart rate is
the reciprocal of the time interval between two successive heartbeats. If the interval between two
beats as determined from the time calibration lines is 1 second, the heart rate is 60 beats per minute.
The normal interval between two successive QRS complexes in the adult person is about 0.83
second. This is a heart rate of 60/0.83 times per minute, or 72 beats per minute.
Masaryk University Faculty of Medicine Physiology Exam
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29. Arrythmias
Pathological changes in cardiac impulse generation or conduction that can be visualized by ECG.
Disturbances of impulse generation change the sinus rhythm.
 Sinus tachycardia: The sinus rhythm rises to 100 min
–1
or higher e.g., due to physical exertion, anxiety,
fever (rise of about 10 beats/min for each 1 °C) or hyperthyroidism.
 Sinus bradycardia: The heart rate falls below60 min
–1
(e.g., due to hypothyroidism).
In both cases the rhythm is regular whereas in sinus arrhythmias the rate varies. In adolescents, sinus
arrhythmias can be physiological and respiration-dependent (heart rate increases during inspiration
and decreases during expiration).
Ectopic pacemakers
Foci in the atrium, AV node or ventricles can initiate abnormal ectopic (heterotopic) impulses, even when
normal (nomotopic) stimulus generation by the SA node is taking place. The rapid discharge of impulses from
an atrial focus can induce atrial tachycardia (serrated baseline instead of normal P waves), which triggers a
ventricular response rate of up to 200 min
–1
. Fortunately, only every second or third stimulus is transmitted to
the ventricles because part of the impulses arrive at the Purkinje fibers (longest APs) during their refractory
period. Thus, Purkinje fibers act as impulse frequency filters. Elevated atrial contraction rates of up to 350 min
–1
are defined as atrial flutter, and all higher rates are defined as atrial fibrillation (up to 500 min–1).
Ventricular tachycardia is a rapid train of impulses originating from a ventricular (ectopic) focus, starting
with an extrasystole (ES). The heart therefore fails to fill adequately, and the stroke volume decreases. A
ventricular ES can lead to ventricular fibrillation (extremely frequent and uncoordinated contractions).
Because of failure of the ventricle to transport blood, ventricular fibrillation can be fatal.
Disturbances of impulse conduction  AV block
 First-degree AV block: prolonged but otherwise normal impulse conduction in the AV node (PQ
interval >0.2 sec).
 Second-degree AV block: only every second (2:1 block) or third (3:1 block) impulse is conducted.
 Third-degree AV block: no impulses are conducted; sudden cardiac arrest may occur (Adam–Stokes
attack or syncope). Ventricular atopic pacemakers then take over (ventricular bradycardia with normal
atrial excitation rate), resulting in partial or total disjunction of QRS complexes and P waves. The heart
rate drops to 40 to 55 min
–1
when the AV node acts as the pacemaker, and to a mere 25 to 40 min
–1
when tertiary (ventricular) pacemakers take over. Artificial pacemakers are then used.
Bundle branch block
Disturbance of conduction in a branch of the bundle of His. Severe QRS changes occur because the affected
side of the myocardium is activated by the healthy side via abnormal pathways.
Masaryk University Faculty of Medicine Physiology Exam
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30. Mechanism of re-entry
When the normal cardiac impulse in the normal heart has traveled through the extent of the
ventricles, it has no place to go because all the ventricular muscle is refractory and cannot conduct
the impulse farther. Therefore, that impulse dies, and the heart awaits a new action potential to
begin in the atrial sinus node.
Under some circumstances, however, this normal sequence of events does not occur. Therefore,
let us explain more fully the background conditions that can initiate re-entry and lead to “circus
movements,” which in turn cause ventricular fibrillation.
A common cause of paroxysmal arrhythmias is a defect in conduction that permits a wave of
excitation to propagate continuously within a closed circuit (circus movement).
For example, if a transient block is present on one side of a portion of the conducting system, the
impulse can go down the other side. If the block then wears off, the impulse may conduct in a
retrograde direction in the previously blocked side back to the origin and then descend again,
establishing a circus movement.
. If the reentry is in the AV node, the reentrant activity depolarizes the atrium, and the resulting
atrial beat is called en echo beat. In addition, the reentrant activity in the node propagates back
down to the ventricle, producing paroxysmal nodal tachycardia.
31. Athlete’s heart
An Athletic Heart is known in sports medicine as a non-pathological condition of a sportsman's heart.
The heart enlarges through (extreme) physical training (aerobic exercise, especially endurance
sports) and the resting pulse lowers.
A larger heart results in higher cardiac output, or, in other words, more blood is being pumped out
with each beat. With high cardiac output, the heart can allow itself to beat less, thus the bradycardia
occurs.
Among the differences between untrained individuals and trained athletes it that the athletes have
lower heart rates, greater end-systolic volumes, and greater stroke volumes in rest. Therefore, they
can potentially achieve a given increase in cardiac output by further increase in stroke volume
without increasing their heart rate to as great a degree as an untrained individual.
When one is diagnosed with Athlete’s Heart, there are usually three characteristics that accompany
the condition:
 Bradycardia is a slower than normal heartbeat around 40-60 beats per minute.
 Cardiomegaly is the state of an enlarged heart.
 Cardiac hypertrophy is the thickening of the muscular wall of the heart, specifically the left ventricle
Masaryk University Faculty of Medicine Physiology Exam
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32. Coronary circulation
Coronary blood supply
The blood flow to the myocardium is supplied by the two coronary
arteries that arise from the aortic root. The right coronary artery
(approx. 1/7th of the blood) usually supplies the greater portion of the
right ventricle, while the left coronary artery (6/7th of the blood)
supplies the left ventricle.
. Most of the coronary venous blood flow from the left ventricular
muscle returns to the right atrium of the heart by way of the coronary
sinus—which is about 75 per cent of the total coronary blood flow. And
most of the coronary venous blood from the right ventricular muscle
returns through small anterior cardiac veins that flow directly into the
right atrium, not by way of the coronary sinus. A very small amount of
coronary venous blood also flows back into the heart through very
minute thebesian veins, which empty directly into all chambers of the heart.
Coronary blood flow (Qcor)
Is phasic, i.e., the amount of blood in the coronary arteries fluctuates during the cardiac cycle due to extremely
high rises in extravascular tissue pressure during systole. The blood flow in the epicardial coronary artery
branches and subepicardial vessels remains largely unaffected by these pressure fluctuations.
However, the subendocardial vessels of the left ventricle are compressed during systole when the extravascular
pressure in that region (≈pressure in left ventricle, PLV) exceeds the pressure in the lumen of the vessels.
Consequently, the left ventricle is mainly supplied during diastole. The fluctuations in right ventricular blood
flow are much less distinct because right ventricular pressure (PRV) is lower.
Control of Coronary Blood Flow
Local Muscle Metabolism Is the Primary Controller of Coronary Flow
Blood flow through the coronary system is regulated mostly by local arteriolar vasodilation in response to
cardiac muscle need for nutrition. That is, whenever the vigor of cardiac contraction is increased, regardless of
cause, the rate of coronary blood flow also increases. Conversely, decreased heart activity is accompanied by
decreased coronary flow.
– exhibits autoregulation.
– exhibits active and reactive hyperemia.
– The most important local metabolic factors are hypoxia and adenosine.
– For example, increases in myocardial contractility are accompanied by an increased demand for O2. To meet
. this demand, compensatory vasodilation of coronary vessels occurs and, accordingly, both blood flow and O2
. delivery to the contracting heart increase (active hyperemia).
– During systole, mechanical compression of the coronary vessels reduces blood flow. After the period of
. occlusion, blood flow increases to repay the O2 debt (reactive hyperemia).
– Sympathetic nerves play a minor role.
Masaryk University Faculty of Medicine Physiology Exam
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33. Coronary reserve. Ischaemic heart disease.
Coronary reserve
Myocardial O2 consumption
Is defined as Qcor times the arteriovenous O2 concentration difference, (Ca–Cv)O2.
The myocardial (Ca–Cv)O2 is relatively high (0.12 L/L blood), and oxygen extraction at rest
([Ca–Cv]O2/CaO2 = 0.12/0.21) is almost 60% and, thus, not able to rise much further. Therefore, an
increase in Qcor is practically the only way to increase myocardial VO2 when the O2 demand rises.
Adaptation of the myocardial O2 supply
According to need is therefore primarily achieved by adjusting vascular resistance.
The (distal) coronary vessel resistance can normally be reduced to about 1/4 the resting value
(coronary reserve). The coronary blood flow Qcor (approx. 250 mL/min at rest) can therefore be
increased as much as 4–5 fold. In other words, approx. 4 to 5 times more O2 can be supplied during
maximum physical exertion.
Ischemic heart disease
Ischemic heart disease, is a disease characterized by reduced blood supply to the heart muscle, usually due to
coronary artery disease (atherosclerosis of the coronary arteries).
Ischaemic heart disease may present with any of the following problems:
– Angina pectoris (chest pain on exertion, in cold weather or emotional situations)
– Acute chest pain: acute coronary syndrome, unstable angina or myocardial infarction ("heart attack", severe
. chest pain unrelieved by rest associated with evidence of acute heart damage)
– Heart failure (difficulty in breathing or swelling of the extremities due to weakness of the heart muscle)
Stable angina
In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of
cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography
(using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide
by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography
may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.
. ECGs show elevation of the "ST segment", which in the context of severe typical chest pain is strongly
indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-elevation MI), and is treated as an
emergency with either urgent coronary angiography and percutaneous coronary intervention (angioplasty with
or without stent insertion) or with thrombolysis ("clot buster" medication), whichever is available.
. In the absence of ST-segment elevation, heart damage is detected by cardiac markers (blood tests that
identify heart muscle damage)..
Pathogenesis
The disease process underlying most ischemic heart disease is atherosclerosis of the coronary arteries. The
arteries become "furred up" by fat-rich deposits in the vessel wall (plaques).
. Stable angina is due to inability to supply the myocardium (heart muscle) with sufficient blood in situations
of increased demand for oxygen, such as exsertion.
. Unstable angina, STEMI and NSTEMI are attributed to "plaque rupture", where one of the plaques gets
weakened, develops a tear, and forms an adherent blood clot that either obstructs blood flow or floats further
down the blood vessel, causing obstruction there.
Treatment
In stable IHD, antianginal drugs may be used to reduce the rate of occurrence and severity of angina attacks.
Treatment of coronary artery disease includes addressing "modifiable" risk factors. This includes suppression of
cholesterol (usually with statins), even in those with statistically normal cholesterol levels, control of blood
pressure, blood sugars (if diabetic), regular exercise and a healthy diet. Smokers are encouraged to stop
smoking.
Masaryk University Faculty of Medicine Physiology Exam
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34. Cardiovascular system – general principles
Functional Parts of the Circulation
 The function of the arteries is to transport blood under high pressure to the tissues. For this reason,
the arteries have strong vascular walls, and blood flows at a high velocity in the arteries.
 The arterioles are the last small branches of the arterial system; they act as control conduits through
which blood is released into the capillaries. The arteriole has a strong muscular wall that can close the
arteriole completely or can, by relaxing, dilate it severalfold, thus having the capability of vastly
altering blood flow in each tissue bed in response to the need of the tissue.
 The function of the capillaries is to exchange fluid, nutrients, electrolytes, hormones, and other
substances between the blood and the interstitial fluid.
 The venules collect blood from the capillaries, and they gradually coalesce into progressively larger
veins.
 The veins function as conduits for transport of blood from the venules back to the heart; equally
important, they serve as a major reservoir of extra blood.
Volumes of Blood in the Different Parts of the Circulation
About 84 per cent of the entire blood volume of the body is
in the systemic circulation, and 16 per cent in heart and lungs.
Of the 84 per cent in the systemic circulation, 64 per cent is in the veins,
13 per cent in the arteries, and 7 per cent in the systemic arterioles and
capillaries. The heart contains 7 per cent of the blood,
and the pulmonary vessels, 9 per cent.
Pressures in the Various Portions of the Circulation
Because the heart pumps blood continually into the aorta, the mean pressure
in the aorta is high, averaging about 100 mm Hg. Also, because heart pumping
is pulsatile, the arterial pressure alternates between a systolic pressure
level of 120 mm Hg and a diastolic pressure level of 80 mm Hg.
As the blood flows through the systemic circulation, its mean pressure
falls progressively to about 0 mm Hg by the time it reaches the termination
of the venae cavae where they empty into the right atrium of the heart.
The pressure in the systemic capillaries varies from as high as 35 mm Hg
near the arteriolar ends to as low as 10 mm Hg near the venous ends,
but their average “functional” pressure in most vascular beds is about 17 mm Hg.
In the pulmonary arteries, the pressure is pulsatile, just as in the aorta, but the pressure level is far less:
pulmonary artery systolic pressure averages about 25 mm Hg and diastolic pressure 8 mm Hg, with a mean
pulmonary arterial pressure of only 16 mm Hg. The mean pulmonary capillary pressure averages only 7 mm Hg.
Yet the total blood flow through the lungs each minute is the same as through the systemic circulation.
The low pressures of the pulmonary system are in accord with the needs of the lungs, because all that is
required is to expose the blood in the pulmonary capillaries to oxygen and other gases in the
pulmonary alveoli.
Basic Theory of Circulatory Function
There are three basic principles that underlie all functions of the system.
1. The rate of blood flow to each tissue of the body is almost always
precisely controlled in relation to the tissue need.
2. The cardiac output is controlled mainly by the sum of all the local tissue flows.
3. In general the arterial pressure is controlled independently of either local blood flow control
or cardiac output control
Masaryk University Faculty of Medicine Physiology Exam
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35. Significance of Poiseuille-Hagen formula for blood flow
In the Hagen–Poiseuille equation the flow resistance (R) in a tube of known length (l) is dependent
on the viscosity (η) of the fluid in the tube and the fourth power of the inner radius of the tube (r4
).
Decreasing the radius by only about 16% will therefore suffice to double the resistance.
Very Slight Changes in Diameter of a Vessel Can Change Its Conductance Tremendously!
The cause of this great increase in conductance when the
diameter increases can be explained by referring to Figure
to the right, which shows cross sections of a large and a
small vessel. The concentric rings inside the vessels indicate
that the velocity of flow in each ring is different from that
in the adjacent rings because of laminar flow.
That is, the blood in the ring touching the wall of the
vessel is barely flowing because of its adherence to
the vascular endothelium. The next ring of blood toward
the center of the vessel slips past the first ring and,
therefore, flows more rapidly. The third, fourth, fifth, and
sixth rings likewise flow at progressively increasing
velocities. Thus, the blood that is near the wall of the
vessel flows extremely slowly, whereas that in the
middle of the vessel flows extremely rapidly.
In the small vessel, essentially all the blood is near the wall, so that the extremely rapidly flowing
central stream of blood simply does not exist.
By integrating the velocities of all the concentric rings of flowing blood and multiplying them by the
areas of the rings, one can derive the following formula, known as Poiseuille’s law:
in which F is the rate of blood flow, ∆P is the pressure difference between the ends of the vessel, r is
the radius of the vessel, l is length of the vessel, and h is viscosity of the blood.
Note particularly in this equation that the rate of blood flow is directly proportional to the fourth
power of the radius of the vessel, which demonstrates once again that the diameter of a blood vessel
(which is equal to twice the radius) plays by far the greatest role of all factors in determining the rate
of blood flow through a vessel.
Masaryk University Faculty of Medicine Physiology Exam
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36. Vascular resistance
Masaryk University Faculty of Medicine Physiology Exam
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37. Blood pressure. Hypertension.
Blood pressure (BP)
It is a force exerted by circulating blood on the walls of blood vessels, and is one of the principal vital signs.
During each heartbeat, BP varies between a maximum (systolic) and a minimum (diastolic) pressure. The mean
BP, due to pumping by the heart and resistance in blood vessels, decreases as the circulating blood moves
away from the heart through arteries.
. The term blood pressure usually refers to the pressure measured at a person's upper arm. It is measured on
the inside of an elbow at the brachial artery, which is the upper arm's major blood vessel that carries blood
away from the heart.
Measurement
Arterial pressure is most commonly measured via a sphygmomanometer,
which historically used the height of a column of mercury to reflect the
circulating pressure. BP values are reported in millimetres of mercury
(mmHg), though aneroid and electronic devices do not use mercury.
. For each heartbeat, BP varies between systolic and diastolic pressures.
Systolic pressure is peak pressure in the arteries, which occurs near the
end of the cardiac cycle when the ventricles are contracting. Diastolic
pressure is minimum pressure in the arteries, which occurs near the
beginning of the cardiac cycle when the ventricles are filled with blood. An
example of normal measured values for a resting, healthy adult human is
120 mmHg systolic and 80 mmHg diastolic (written as 120/80 mmHg).
! [Also see Q. 43 and 44 in part A]
Hypertension
Refers to arterial pressure being abnormally high, as opposed
to hypotension, when it is abnormally low. Hypertension has
several sub-classifications including, hypertension stage I,
hypertension stage II, and isolated systolic hypertension.
Isolated systolic hypertension refers to elevated systolic
pressure with normal diastolic pressure and is common in the
elderly.
Tests typically performed are classified as follows:
Masaryk University Faculty of Medicine Physiology Exam
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38. Arterial elasticity – significance
Vascular Distensibility
All blood vessels are distensible. When the pressure in blood vessels is increased, this dilates the
blood vessels and therefore decreases their resistance. The result is increased blood flow not only
because of increased pressure but also because of decreased resistance.
The distensible nature of the arteries allows them to accommodate the pulsatile output of the heart
and to average out the pressure pulsations. This provides smooth, continuous flow of blood through
the very small blood vessels of the tissues.
The most distensible by far of all the vessels are the veins. Even slight increases in venous pressure
cause the veins to store 0.5 to 1.0 liter of extra blood. Therefore, the veins provide a reservoir
function for storing large quantities of extra blood that can be called into use whenever required
elsewhere in the circulation.
Units of Vascular Distensibility
Vascular distensibility normally is expressed as the fractional increase in volume for each millimeter of mercury
rise in pressure, in accordance with the following formula:
That is, if 1 mm Hg causes a vessel that originally contained 10 millimeters of blood to increase its volume by 1
milliliter, the distensibility would be 0.1 per mm Hg, or 10 per cent per mm Hg.
Difference in Distensibility of the Arteries and the Veins
Anatomically, the walls of the arteries are far stronger than those of the veins. Consequently, the arteries, on
average, are about eight times less distensible than the veins. That is, a given increase in pressure causes about
eight times as much increase in blood in a vein as in an artery of comparable size.
In the pulmonary circulation, the pulmonary vein distensibilities are similar to those of the systemic
circulation. But, the pulmonary arteries normally operate under pressures about one sixth of those in the
systemic arterial system, and their distensibilities are correspondingly greater, about six times the distensibility
of systemic arteries.
Masaryk University Faculty of Medicine Physiology Exam
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39. Arterial pulse wave
A typical record of the pressure pulsations at the root of the aorta is
shown in figure to the right. In the healthy young adult, the pressure
at the top of each pulse, called the systolic pressure, is about 120
mm Hg. At the lowest point of each pulse, called the diastolic
pressure, it is about 80 mm Hg. The difference between these two
pressures, about 40 mm Hg, is called the pulse pressure.
Two major factors affect the pulse pressure: (1) the stroke volume
output of the heart and (2) the compliance (total distensibility) of the
arterial tree.
In general, the greater the stroke volume output, the greater the
amount of blood that must be accommodated in the arterial tree
with each heartbeat, and, therefore, the greater the pressure rise
and fall during systole and diastole, thus causing a greater pulse
pressure. Conversely, the less the compliance of the arterial system,
the greater the rise in pressure for a given stroke volume of blood
pumped into the arteries.
The pulse pressure in old age sometimes rises to as much as twice normal, because the arteries have become
hardened with arteriosclerosis and therefore are relatively noncompliant.
Transmission of Pressure Pulses to the Peripheral Arteries
The velocity of pressure pulse transmission in the normal aorta is 3 to 5
m/sec; in the large arterial branches, 7 to 10 m/sec; and in the small
arteries, 15 to 35 m/sec. In general, the greater the compliance of
each vascular segment, the slower the velocity, which explains the slow
transmission in the aorta and the much faster transmission in the much
less compliant small distal arteries.
Note especially in the three lower curves that the intensity of pulsation
becomes progressively less in the smaller arteries, the arterioles, and,
especially, the capillaries. In fact, only when the aortic pulsations are
extremely large or the arterioles are greatly dilated can pulsations be
observed in the capillaries.
This progressive diminution of the pulsations in the periphery is called
damping of the pressure pulses. The cause of this is twofold:
(1) resistance to blood movement in the vessels and (2) compliance of
the vessels. The resistance damps the pulsations because a small amount
of blood must flow forward at the pulse wave front to distend the next
segment of the vessel; the greater the resistance, the more difficult it is
for this to occur. The compliance damps the pulsations because the more
compliant a vessel, the greater the quantity of blood required at the
pulse wave front to cause an increase in pressure. Therefore, in effect, the degree of damping is almost directly
proportional to the product of resistance times compliance.
Masaryk University Faculty of Medicine Physiology Exam
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40. Physiological role of endothelium
The endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an
interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line
the entire circulatory system, from the heart to the smallest capillary. These cells reduce turbulence
of the flow of blood allowing the fluid to be pumped farther.
The endothelium normally provides a non-thrombogenic surface because it contains heparan
sulphate which acts as a cofactor for activating antithrombin III, a protease that cleaves several
factors in the coagulation cascade.
Endothelial cells are involved in many aspects of vascular biology, including:
 Vasoconstriction and vasodilation, and hence the control of blood pressure
 Blood clotting (thrombosis & fibrinolysis)
 Atherosclerosis
 Formation of new blood vessels (angiogenesis)
 Inflammation
 Barrier function - the endothelium acts as a selective barrier between the vessel lumen and
surrounding tissue, controlling the passage of materials and the transit of white blood cells
into and out of the bloodstream. Excessive or prolonged increases in permeability of the
endothelial monolayer, as in cases of chronic inflammation, may lead to tissue
oedema/swelling.
In some organs, there are highly differentiated endothelial cells to perform specialized 'filtering'
functions. Examples of such unique endothelial structures include the renal glomerulus and the
blood-brain barrier.
Endothelial exchange processes
Nutrients and waste products are exchanged across the walls of the capillaries and postpapillary
venules. Their endothelia can contain small (ca. 2–5 nm) or large (20–80 nm, especially in the kidneys
and liver) functional pores: permeable, intercellular fissures or endothelial fenestrae, respectively.
The degree of endothelial permeability varies greatly from one organ to another. Virtually all
endothelia allow water and inorganic ions to pass, but most are largely impermeable to blood cells
and large protein molecules. Transcytosis and carriers allow for passage of certain larger molecules.
Filtration and reabsorption. About 20 L/day of fluid is filtered (excluding the kidneys) into the
interstitium from the body’s exchange vessels. About 18 L/day of this fluid is thought to be
reabsorbed by the capillaries and venules. The remaining 2 L/day or so make up the lymph flow and
thereby return to the bloodstream. The filtration or reabsorption rate Qf is a factor of the endothelial
filtration coefficient Kf (=water permeability k · exchange area A) and the effective filtration
pressure Peff (Qf=Kf · Peff). Peff is calculated as the hydrostatic pressure difference ΔP minus the
oncotic pressure difference Δπ across the capillary wall (Starling’s relationship), where ΔP = capillary
pressure (Pcap) minus interstitial pressure (Pint, normally ≈ 0 mmHg).
In parts of the body below the heart, the effects of hydrostatic pressure from the blood column
increase the pressure in the capillary lumen (in the feet 90 mmHg). The filtration rate in these regions
therefore rise, especially when standing still. This is counteracted by two “self-regulatory”
mechanisms: (1) the outflow of water results in an increase in the luminal protein concentration (and
thus Δπ) along the capillaries (normally the case in glomerular capillaries); (2) increased filtration
results in an increase in Pint and a consequent decrease in ΔP.
Masaryk University Faculty of Medicine Physiology Exam
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41. Vasoactive substances
Vasoactive substances
Vasoactive hormones either have a direct effect on the vascular musculature (e.g., epinephrine) or lead to the
local release of vasoactive substances (e.g., nitric oxide, endothelin) that exert local paracrine effects.
 Nitric (mon) oxide (NO) acts as a vasodilatory agent. NO is released from the endothelium when
acetylcholine (M receptors), ATP, endothelin (ETB receptors), or histamine (H1 receptors) binds with an
endothelial cell. NO then diffuses to and relaxes vascular myocytes in the vicinity.
 Endothelin-1 can lead to vasodilatation by inducing the release of NO from the endothelium by way of
ETB receptors, or can cause vasoconstriction via ETA receptors in the vascular musculature. When
substances such as angiotensin II or ADH (= vasopressin; V1 receptor) bind to an endothelial cell, they
release endothelin-1, which diffuses to and constricts the adjacent vascular muscles with the aid of
ETA receptors.
 Epinephrine (E): High concentrations of E from the adrenal medulla have a vasoconstrictive effect
(α1 adrenoceptors), whereas low concentrations exert vasodilatory effects by way of β2 adrenoceptors
in the myocardium, skeletal muscle and live. The effect of E mainly depends on which type of
adrenoceptor is predominant in the organ. α1- adrenoceptors are predominant in the blood vessels of
the kidney and skin.
 Eicosanoids: Prostaglandin (PG) F2α and the thromboxanes A2 (released from platelets) and B2 have
vasoconstrictive effects, while PGI2 (= prostacyclin, e.g. released from endothelium) and PGE2 have
vasodilatory effects. Another vasodilator released from the endothelium (e.g., by bradykinin) opens K
+
channels in vascularmyocytes and hyperpolarizes them, leading to a drop in the cytosolic Ca
2+
concentration. This endothelium-derived hyperpolarizing factor (EDHF), has been identified as a
11,12-epoxyeicosatrienoic acid (11,12-EET).
 Bradykinin and kallidin are vasodilatory agents cleaved from kininogens in blood plasma by the
enzyme kallikrein. Histamine also acts as a vasodilator. All three substances influence also vessel
permeability (e.g., during infection) and blood clotting.
Masaryk University Faculty of Medicine Physiology Exam
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42. Micro-circulation
Structure of the Microcirculation and Capillary System
The microcirculation of each organ is organized specifically to serve that organ’s needs. In general, each
nutrient artery entering an organ branches six to eight times before the arteries become small enough to be
called arterioles, which generally have internal diameters of only 10 to 15 micrometers. Then the arterioles
themselves branch two to five times, reaching diameters of 5 to 9 micrometers at their ends where they supply
blood to the capillaries.
Structure of the Capillary beds
Passage of substances across the capillary wall
Fluid exchange across capillaries
Regulation of Vasomotion
The most important factor found thus far to affect the degree of opening and closing of the metarterioles and precapillary
sphincters is the concentration of oxygen in the tissues. When the rate of oxygen usage by the tissue is great so that tissue
oxygen concentration decreases below normal, the intermittent periods of capillary blood flow occur more often, and the
duration of each period of flow lasts longer, thereby allowing the capillary blood to carry increased quantities of oxygen (as
well as other nutrients) to the tissues.
Masaryk University Faculty of Medicine Physiology Exam
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43. Venous pressure
Masaryk University Faculty of Medicine Physiology Exam
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44. Venous return. Venous stasis and embolism.
Venous Return
Blood from the capillaries is collected in the veins and returned to the heart. The driving
forces for this venous return are:
(a) vis a tergo, i.e., the postcapillary blood pressure (BP) (ca. 15 mmHg);
(b) the suction that arises due to lowering of the cardiac valve plane in systole;
(c) the pressure exerted on the veins during skeletal muscle contraction (muscle pump); the valves of veins
prevent the blood from flowing in the wrong direction,
(d) the increased abdominal pressure together with the lowered intrathoracic pressure during inspiration,
which leads to thoracic venous dilatation and suction.
Venous statis
Is a condition of slow blood flow in the veins, usually of the legs. A patient with venous stasis might be more
vulnerable to the formation of blood clot, especially in the deep veins of the legs, called deep vein thrombosis
(DVT).
. Causes include long periods of immobility such as when driving for long distances. It has been called the
coach-class syndrome because of prevalence in long distance travel in cramped space. It also occurs in
prolonged bed rest with an illness or after surgery.
Deep vein thrombosis
The most serious complication of a DVT is that the clot could dislodge and travel to the lungs, which is called a
pulmonary embolism (PE).
According to Virchow's triad, venous thrombosis occurs via three mechanisms: (1) decreased flow rate of the
blood, (2) damage to the blood vessel wall and (3) an increased tendency of the blood to clot
(hypercoagulability).
There are several factors which can increase a person's risk for DVT, including surgery, hospitalization,
immobilization, smoking, obesity, age, certain drugs (such as estrogen or erythropoietin) and inborn tendencies
to form clots known as thrombophilia (for example, in carriers of factor V Leiden). Women have an increased
risk during pregnancy and in the postnatal period.
Masaryk University Faculty of Medicine Physiology Exam
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45. Lymphatic system
The lymphatic system represents an accessory route through which fluid can flow from the interstitial spaces
into the blood. Most important, the lymphatics can carry proteins and large particulate matter away from the
tissue spaces, neither of which can be removed by absorption directly into the blood capillaries. This return of
proteins to the blood from the interstitial spaces is an essential function without which we would die within
about 24 hours.
Lymphatic organs include: thymus, lymph nodes, spleen, tonsils, lymph nodules (in the wall of intestine
(lymphonoduli solitarii and Peyer's patches) and in the wall of respiratory and urinary passages).
Lymph channels of the body
Essentially all the lymph vessels from the lower part of the body eventually empty into the thoracic duct, which
in turn empties into the blood venous system at the juncture of the left internal jugular vein and left subclavian
vein (the venous angle).
Lymph from the left side of the head, the left arm, and parts of the chest region also enters the thoracic duct
before it empties into the veins.
Lymph from the right side of the neck and head, the right arm, and parts of the right thorax enters the right
lymph duct (much smaller than the thoracic duct), which empties into the blood venous system at the juncture
of the right subclavian vein and internal jugular vein.
Note: Normal drainage from breast is to anterior and posterior axillary, infraclavicular and internal thoracic
groups. With pathological blockage from disease the spread can be to opposite side, cervical, peritoneal cavity
and liver, and inguinal glands.
Function of the lymphatic system
The lymphatic system has four interrelated functions: it is responsible for the removal of interstitial fluid from
tissues; it absorbs and transports fatty acids and fats as chyle to the circulatory system; and to Nicklas cells and
it transports immune cells to and from the lymph nodes in to the sheppardian part of the bone. The lymph
transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune
response is stimulated. The lymph also carries lymphocytes from the efferent lymphatics exiting the lymph
nodes.
. The lymphatic system also plays a central role in controlling (1) the concentration of proteins in the
interstitial fluids, (2) the volume of interstitial fluid, and (3) the interstitial fluid pressure. Once the interstitial
fluid protein concentration reaches a certain level and causes a comparable increase in interstitial fluid volume
and interstitial fluid pressure, the return of protein and fluid by way of the lymphatic system becomes great
enough to balance exactly the rate of leakage of these into the interstitium from the blood capillaries.
The three major types of lymphocyte
NK cells are a part of innate immune system and play a major role in defending the host from both tumors and virally
infected cells. NK cells distinguish infected cells and tumors from normal and uninfected cells by recognizing level changes
of a surface molecule called MHC (major histocompatibility complex) class I. NK cells are activated in response to a family
of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered
cells. They were named "natural killer cells" because of the initial notion that they do not require prior activation in order to
kill cells which are missing MHC class I.
. T cells (Thymus cells) and B cells (bone cells) are the major cellular components of the adaptive immune response. T cells
are involved in cell-mediated immunity whereas B cells are primarily responsible for humoral immunity (relating to
antibodies). The function of T cells and B cells is to recognize specific “non-self” antigens, during a process known as antigen
presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally
eliminate specific pathogens or pathogen infected cells. B cells respond to pathogens by producing large quantities of
antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T
helper cells, produce cytokines that direct the immune response while other T cells, called cytotoxic T cells, produce toxic
granules that induce the death of pathogen infected cells. Following activation, B cells and T cells leave a lasting legacy of
the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal these memory cells
will “remember” each specific pathogen encountered, and are able to mount a strong response if the pathogen is detected
again.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
46. Pulmonary circulation
Physiologic Anatomy of the Pulmonary Circulatory System
Pulmonary Vessels
The pulmonary artery extends only 5 centimeters beyond the apex of the right ventricle and then
divides into right and left main branches that supply blood to the two respective lungs.
The pulmonary artery is thin, with a wall thickness one third that of the aorta. The pulmonary
arterial branches are very short, and all the pulmonary arteries, even the smaller arteries and
arterioles, have larger diameters than their counterpart systemic arteries. This, combined with the
fact that the vessels are thin and distensible, gives the pulmonary arterial tree a large compliance,
averaging almost 7 ml/mm Hg, which is similar to that of the entire systemic arterial tree. This large
compliance allows the pulmonary arteries to accommodate the stroke volume output of the right
ventricle.
The pulmonary veins, like the pulmonary arteries, are also short. They immediately empty their
effluent blood into the left atrium, to be pumped by the left heart through the systemic circulation.
Bronchial Vessels
Blood also flows to the lungs through small bronchial arteries that originate from the systemic
circulation, amounting to about 1 to 2 per cent of the total cardiac output. This bronchial arterial
blood is oxygenated blood, in contrast to the partially deoxygenated blood in the pulmonary arteries.
It supplies the supporting tissues of the lungs, including the connective tissue, septa, and large and
small bronchi. After this bronchial and arterial blood has passed through the supporting tissues, it
empties into the pulmonary veins and enters the left atrium, rather than passing back to the right
atrium. Therefore, the flow into the left atrium and the left ventricular output are about 1 to 2 per
cent greater than the right ventricular output.
Lymphatics
Lymph vessels are present in all the supportive tissues of the lung, beginning in the connective tissue
spaces that surround the terminal bronchioles, coursing to the hilum of the lung, and thence mainly
into the right thoracic lymph duct. Particulate matter entering the alveoli is partly removed by way of
these channels, and plasma protein leaking from the lung capillaries is also removed from the lung
tissues, thereby helping to prevent pulmonary edema.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
47. Cerebral circulation
Cranial arteries
There are two main pairs of arteries that supply the cerebral arteries and the cerebellum:
 Internal carotid arteries: These large arteries are the left and right branches of the common
carotid arteries in the neck which enter the skull, as opposed to the external carotid
branches which supply the facial tissues. The internal carotid artery branches into the
anterior cerebral artery and continues to form the middle cerebral artery
 Vertebral arteries. These smaller arteries branch from the subclavian arteries which
primarily supply the shoulders, lateral chest and arms. Within the cranium the two vertebral
arteries fuse into the basilar artery, which supplies the midbrain, cerebellum, and usually
branches into the posterior cerebral artery.
Both internal carotid arteries, within and along the floor of the cerebral vault, are interconnected via
the anterior communicating artery. Additionally, both internal carotid arteries are interconnected
with the basilar artery via bilateral posterior communicating arteries.
The circle of Willis, long considered to be an important anatomic vascular formation, provides
backup circulation to the brain. In case one of the supply arteries is occluded, the circle of Willis
provides interconnections between the internal carotid arteries and basilar artery along the floor of
the cerebral vault, providing blood to tissues that would otherwise become ischemic.
Cerebral venous drainage
The venous drainage of the cerebrum can be separated into two subdivisions: superficial and deep.
The superficial system is composed of dural venous sinuses, which have wall composed of dura
mater as opposed to a traditional vein. The dural sinuses are, therefore located on the surface of the
cerebrum. The most prominent of these sinuses is the superior sagittal sinus which flows in the
sagittal plane under the midline of the cerebral vault, posteriorly and inferiorly to the torcula,
forming the confluence of sinuses, where the superficial drainage joins with the sinus the primarily
drains the deep venous system. From here, two transverse sinuses bifurcate and travel laterally and
inferiorly in an S-shaped curve that form the sigmoid sinuses which go on to form the two jugular
veins. In the neck, the jugular veins parallel the upward course of the carotid arteries and drain blood
into the vena cava. The deep venous drainage is primarily composed of traditional veins inside the
deep structures of the brain, which join behind the midbrain to form the vein of Galen. This vein
merges with the inferior sagittal sinus to form the straight sinus which then joins the superficial
venous system mentioned above at the confluence of sinuses.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
48. Skin circulation
Skin Circulation
Skin is a complex organ that covers almost all of the body surface. It has many functions but, as far as
thread veins are concerned, its role as a regulator of body heat is important.
The skin has a blood supply from many small arterioles these
are small blood vessels that take blood at higher
pressure into the capillary networks.
The capillary networks are made up of a great many tiny
vessels with very thin walls.
From these networks the blood flows back into venules these
are small veins that take the blood back to the larger
veins and then ultimately the heart.
Blood flow in the capillary networks can be controlled by the body using both hormones and nerves
(the sympathetic nervous system).
When your body is too hot, more blood is allowed into the capillary networks and so more heat is
lost to the air around the body. When this happens, the skin goes pink or red (often called flushing or
blushing).
When your body is too cold, blood is not allowed into the capillary networks and so heat is kept in
the body and the skin acts as insulation - this makes the skin look very white.
Thread veins of the LEGS occur when the VENULES dilate (get bigger) and become big enough to be
visible through the skin. Thread veins of the FACE are usually more related to increased flow in the
feeding Arteriole end of the network.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
49. Muscle and splanchnic circulation
Circulation in skeletal muscle
- Resting blood flow through the muscles is ~4ml/min/100g
- This can increase 20 fold during exercise. Why? Higher blood flow is needed in order to meet with O2/nutrient
consumption and CO2 removal demands.
- Contraction of muscle will slightly decrease blood flow due to mechanical contraction of the vessel caused by the
surround contracting muscles, therefore blood flow increases between contractions. (temporary)
- During contraction, metabolic rate of tissue increase, and therefore O2 concentration decreases causing a vasodilative
reflex.
- Muscle exercise also releases vasodilators such as: adenosine, K
+
, H
+
, Lactic acid, and CO2.
- Sympathetic stimulation can vastly reduces blood flow e.g., in circulatory shock. This is due postganglionic nerve
release of NE/E and also adrenal release of NE/E in the blood acting on α1-adrenergenic receptors causing
vasoconstriction.
- During exercise, we know that there are massive cardiovascular changes caused by sympathetic discharge and
parasympathetic inhibition which results in: increase HR, increase heart strength, increase in heart conductance,
arteriole and venous constriction (exception to this is the VASODILATION in the vasculature of muscles, brain and coronary bed.
How? E can stimulate β2-adrenogenic receptors causing vasodilation)
- vasodilation  increases blood flow  more efficient rate of O2/CO2 exchange  increase mean systemic filling
pressure  increase venous return  increases EDV (starlings hypothesis)  increases CO up to 35L/min
- Exercise also increases mean arterial pressure (to 20-80mmHg) due to arteriolar and small artery constriction,
increased cardiac contractility, increase mean systemic filling pressure which helps to increase CO during exercise.
Splanchnic circulation
Intestinal circulation
o Intestine is supplied via branches of the superior and inferior mesenteric aa (colic, illeal, jejunal aa/vv)
o Intestinal circulation is capable of extensive auto-regulation. Thus the blood flow to the small intestine
can double after a meal to allow for sufficient exchange of nutrients - this can last up to 3 hours
Hepatic circulation
o The liver and viscera receive up to 30% of CO via celiac, superior & inferior mesenteric aa
o It receives 1L from the portal vein (blood from intestines, pancreas and spleen) and 0.5L from the
hepatic artery (branch of celiac a)
o Hepatic portal system:
 carries the blood from the GI tract and spleen to the liver before it enters the inferior vena
cava.
 This is needed because this blood has digestive end-products and absorbed toxins from the GI
tract and bilirubin from hemoglobin destruction in the spleen. The liver is in charge of
processing these substances.
 Blood in the splenic vein from the spleen receives blood from the inferior mesenteric vein
draining the large intestine, and then combines with the superior mesenteric vein coming
from the small intestine to form the portal vein (hepatic portal vein) which enters the liver.
 The liver also receives oxygenated blood through the hepatic artery and blood from these two
sources mixes in liver sinusoids which are lined with the hepatocytes (liver cells). Once
processed by these hepatocytes the blood returns to the circulation through the hepatic vein
 IVC
o The liver is known to have sympathetic fibers from T3-T12 spinal roots and splanchnic nerves, which
provides vasoconstriction of the intrahepatic portal veins. The hepatic artery receives symp. inv. from
the hepatic sympathetic plexus. A drop in systemic BP  diffuse noradrenergenic discharge 
intrahepatic portal vein constricts  increases portal pressure blood flow through liver decreases and
is usually bypassed/diverted (note – mesenteric vessels would also be constricted thus reducing portal
blood flow)
Reservoir function of splanchnic circulation
The whole visceral circulation is a reservoir of blood. For example, the liver consists of 25-30% blood, contraction of
capacitance vessels of the viscera can pump a litre of blood into the arterial circulation in less than 1 minute. During
exercise, vasoconstriction decreases the blood “storage” in the liver and splanchnic bed to allow for sufficient blood supply
to the exercising muscles.
Other organs which act as reservoirs are: skin (subdermal capillary system), lungs, and spleen
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
50. Placental and fetal circulation
Placenta
The maternal placenta acts as the “gut” (absorption of nutrients), “kidneys” (removal of waste products) and
“lungs” of the fetus (uptake of O2 and elimination of CO2). Although the fetal O2-hemoglobin dissociation
curve is shifted to the left compared to that of adults, only 60% (0.6) of placental hemoglobin is saturated with
O2.
In the fetus, not yet active or hardly active organs such as the lungs receive little blood.
The fetal cardiac output (from both ventricles) is about 0.2 L/min per kg body weight. The fetal heart rate rises
from an initial 65 min
–1
(week 5) to 130–160 min
–1
in later weeks. Approx. 50% of the blood ejected from the
heart flows through the placenta, the other half supplies the body (35%) and lungs (15%) of the fetus. This is
supplied by the left and right heart, which function essentially in parallel until after the birth (see below).
Fetal circulation
The blood flows through the fetal body as follows: After being arterialized in the placenta, the blood passes
into the fetus via the umbilical vein and part of it travels through the ductus venosus (Arantii), thereby
bypassing the liver. When entering the inferior vena cava, the blood mixes with venous blood from the lower
half of the body. Guided by special folds in the vena cava, the mixed blood passes directly from right atrium to
the left atrium through an opening in the atrial septum (foramen ovale). From the left atrium, it then proceeds
to the left ventricle. While in the right atrium, the blood mingles with venous blood from the superior vena
cava (only slight mixing), which is received by the right ventricle. Only about one-third of this blood reaches the
lungs (due to high flow resistance since the lungs are not yet expanded, and due to hypoxic vasoconstriction).
The other two-thirds of the blood travels through the ductus arteriosus (Botalli) to the aorta (right-to-left
shunt). Due to the low peripheral resistance (placenta), the blood pressure in the aorta is relatively low—only
about 65mmHg towards the end of pregnancy.
The arteries of the head and upper body are supplied with partly arterialized blood from the left ventricle.
This is important since brain tissue is susceptible to hypoxia. The remaining blood leaves the aorta and mixes
with venous blood from the ductus arteriosus. As a result, the blood supplied to the lower half of the body has
a relatively low O2 concentration (O2 saturation = 0.3). The majority of this blood returns via the umbilical
arteries to the placenta, where it is oxygenated again.
51. Circulatory adjustments at birth
Circulation during birth
The exchange of O2, CO2, nutrients, and waste materials through the placenta stops abruptly during birth. This
leads to a rise in blood PCO2, triggering chemosensors that induce a strong breathing reflex. The resultant
inspiratory movement causes negative pressure (suction) in the thoracic cavity, which removes the blood from
the placenta and umbilical vein (placental transfusion) and expands the lungs. The unfolding of the lungs and
the rise in alveolar PO2 reduce the resistance in the pulmonary circulation, and the blood flow increases while
the pressure decreases. Meanwhile, the resistance in the systemic circulation increases due to occlusion or
clamping of the umbilical cord. This changes the direction of blood flow in the ductus arteriosus, resulting in a
left-to-right shunt. The pulmonary circulation therefore receives aortic blood for a few days after birth. The
right atrial filling volume decreases due to the lack of placental blood, while that of the left atrium increases
due to the increased pulmonary blood flow. Due to the resultant pressure gradient from the left to right atrium
and to a decrease in vasodilatory prostaglandins, the foramen ovale closes after birth. The ductus arteriosus
and ductus venosus also close, and the systemic and pulmonary circulation now form serial circuits. The closure
of the ductus arteriosus is promoted by the rise in blood PO2 (a mitochondrial O2 sensor forms H2O2 K
+
channels blocked  depolarization  L-type Ca
2+
channels open vasoconstriction).
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
52. Intrapulmonary and pleural pressure. Pneumothorax.
Transpulmonary pressure is a term used to describe the difference between the alveolar pressure
and the pleural pressure in the lungs. During human ventilation, air flows because of pressure
gradients. Pressure in the respiratory system can be measured either in the air spaces of the lungs
(alveolar pressure) or in the pleural fluid (intrapleural pressure). Since atmospheric pressure is
relatively constant, pressure in the lungs must be higher or lower than atmospheric pressure for air
to flow between the atmosphere and the alveoli.
Where Ptp is transpulmonary pressure, Palv is alveolar pressure, and Ppl is pleural pressure.
At rest (before inspiration begins)
. – Alveolar pressure equals atmospheric pressure.
. – Intrapleural pressure is negative.
. – Intrapleural pressure can be measured by a balloon catheter in the esophagus
During inspiration
. – The inspiratory muscles contract and cause the volume of the thorax to increase.
.  decrease in alveolar pressure
.  the pressure gradient between the atmosphere and the alveoli now causes
. air to flow into the lungs.
. – Intrapleural pressure becomes more negative (because lung volume increases during .
. inspiration, the elastic recoil strength of the lungs also increases)
. – Changes in intrapleural pressure during inspiration are used to measure the dynamic compliance
. of the lungs.
During expiration
. – Alveolar pressure becomes greater than atmospheric pressure (this occurs because alveolar gas
. . is compressed by the elastic forces of the lung) , with the result that air flows out of the lungs.
. – Intrapleural pressure returns to its resting value during a normal (passive) expiration.
Pneumothorax
When air is admitted to the pleural space, through either a rupture in the lung or a hole in the chest
wall, the lung on the affected side collapses because of its elastic recoil. Side the intrapleural
pressure on the affected side is now atmospheric, the mediastinum shifts toward the normal side. If
the communication between the pleural space and the exterior remains open (open or sucking
pneumothorax), more air moves in and out of the pleural space each time the patient breathes.
. If there is a flap of tissue over the hole in the lungs or chest wall that acts as a flutter valve,
permitting air to enter during inspiration but preventing its exit during expiration, the pressure in the
pleural space rises above atmospheric pressure (tension pneumothorax). The hypoxic stimulus to
respiration causes deeper inspiratory efforts, which further increase the pressure in the pleural
cavity, kinking the great veins and cause further hypoxia and shock.
. If the hole through which air enters the pleural space seals off (closed pneumothorax) respiratory
distress is not great because, with each inspiration, air flows into the lung on the unaffected side
rather than into the pleural space.
Ptp = Palv - Ppl
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
53. Alveolar surface tension. Surfactant.
Alveolar Surface Tension
An important factor affecting the compliance of the lungs is the
surface tension of the film of fluid that lines the alveoli. The
magnitude of this component at various lung volumes can be
measured by removing the lungs from the body of an experimental
animal and distending them alternately with saline and with air
while measuring the intrapulmonary pressure. Because saline
reduces the surface tension to nearly zero, the pressure-volume
curve obtained with saline measures only the tissue elasticity,
whereas the curve obtained with air measure both tissue elasticity and surface tension.
Surfactant
The low surface when the alveoli are small is due to the presence in the fluid lining the alveoli of
surfactant. If the surface tension is not kept low when the alveoli become smaller during expiration,
they collapse in accordance with the law of Laplace. In spherical structures like the alveoli, the
distending pressure equals 2 times the tension divided by the radius (P= 2T/r); if T is not reduced as r
is reduced, the tension overcomes the distending pressure.
. Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein) formed by
type II alveolar cells. The proteins and lipids that surfactant comprises have both a hydrophilic region
and a hydrophobic region. By adsorbing to the air-water interface of alveoli with the hydrophilic
headgroups in the water and the hydrophobic tails facing towards the air, the main lipid component
of surfactant, dipalmitoylphosphatidylcholine, reduces surface tension.
. Surfactant is important at birth. The fetus makes respiratory movements in utero, but the lungs
remain collapsed until birth. After birth, the infant makes several strong inspiratory movements and
the lungs expand. Surfactant keeps them from collapsing again. Surfactant also help to prevent
pulmonary edema.
. Maturation of surfactant in the lungs is accelerated by glucocorticoid hormones.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
54. Compliance of lungs. Respiratory work.
Compliance
Pulmonary compliance (or lung compliance) is the ability of the lungs to stretch during a change in
volume relative to an applied change in pressure. Lung compliance is defined as the volume change
per unit of pressure change across the lung.
. Pulmonary surfactant increases compliance by decreasing the surface tension of water.
Functional significance of abnormally high or low compliance
 Low compliance indicates a stiff lung and means extra work is required to bring in a normal
volume of air. This occurs as the lungs in this case become fibrotic, lose their distensibility
and become stiffer.
 In a highly compliant lung, as in emphysema, the elastic tissue has been damaged, usually
due to their being overstretched by chronic coughing. Patients with emphysema have a very
high lung compliance due to the poor elastic recoil, they have no problem inflating the lungs
but have extreme difficulty exhaling air. In this condition extra work is required to get air out
of the lungs.
Calculation
Compliance is calculated using the following equation, where ΔV is the change in volume, and ΔP is
the change in pleural pressure:
Respiratory Work
The colored areas within
the loop (ARinsp and ARexp; C) represent the
inspiratory and expiratory PV work
exerted to overcome flow resistance. The
cross-hatched area (C) is the work required
to overcome the intrinsic elastic force of the
lungs and chest (Aelast). Inspiratory work is defined
as ARinsp + Aelast. The inspiratory muscles
must overcome the elastic force,
whereas the same elastic force provides the
(passive) driving force for expiration at rest
(sign reverses for Aelast). Thus, expiratory work
is ARexp – Aelast. Expiration can also require
muscle energy if ARexp becomes larger than
Aelast—e.g., during forced respiration or if RL is elevated.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
55. Composition of atmospheric and alveolar air
Air is mainly composed of nitrogen, oxygen, and argon, which together constitute the major gases of
the atmosphere. The remaining gases are often referred to as trace gases, among which are the
greenhouse gases such as water vapor, carbon dioxide, methane, nitrous oxide, and ozone. Filtered
air includes trace amounts of many other chemical compounds. Many natural substances may be
present in tiny amounts in an unfiltered air sample, including dust, pollen and spores, sea spray,
volcanic ash, and meteoroids. Various industrial pollutants also may be present, such as chlorine
(elementary or in compounds), fluorine compounds, elemental mercury, and sulfur compounds such
as sulfur dioxide [SO2].
Composition of alveolar air
Oxygen continuously diffuses out of the gas in the alveoli into the bloodstream, and CO2 continuously
diffuses into the alveoli from the blood. In the steady state, inspired air mixes with the alveolar gas,
replacing the O2 that has entered the blood and diluting the CO2 that has entered the alveoli. Part of
this mixture is expired. The O2 content of the alveolar gas then falls and its CO2 content rises until
next inspiration. Since the volume of gas in the alveoli is about 2L at the end of expiration, each
350mL increment of inspired and expired air has relativley little effect on PO2 and PCO2. Indeed, the
composition of alveolar gas remains remarkably constant, not only at rest but also under a variety of
other conditions.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
56. Gas exchange in lungs and tissues
Alveolar ventilation. Only the alveolar part
of the tidal volume reaches the alveoli.
The rest stays in the dead space.
The exchange of gases between the alveoli
and the blood occurs by diffusion, as described
by Fick’s law of diffusion. The driving “force” for
this diffusion is provided by the partial pressure
differences between alveolar space and
erythrocytes in pulmonary capillary blood (A).
The mean alveolar partial pressure of O2 (PAO2)
is about 13.3 kPa (100mmHg) and that of CO2
(PACO2) is about 5.3 kPa (40 mmHg).
The mean partial pressures in the “venous” blood
of the pulmonary artery are approx. 5.3 kPa
(40mmHg) for O2 (PVO2) and approx. 6.1 kPa (46mmHg) for CO2 (PVCO2).
Hence, the mean partial pressure difference between alveolus and capillary is
about 8 kPa (60mmHg) for O2 and about 0.8 kPa (6mmHg) for CO2.
Under normal resting conditions, the blood in the pulmonary
capillary is in contact with the alveolus for about 0.75 s. This contact time ( A) is long enough for the
blood to equilibrate with the partial pressure of alveolar gases.
CO2 diffuses much more rapidly than O2.
. During physical work (high cardiac output), the contact time falls to a third of the resting value.
Gas exchange in tissues
O2 diffuses from the periphereal blood to adjacent tissues and CO2 in the opposite direction.
Sufficient O2 delivery is ensured by a dense capillary network with a gas exchange area of about
1000m
2
. Diffusion distance is only about 10-25 µm. The driving force for diffusion is the difference in
partial pressures of oxygen (∆PO2) in the capillary blood and mitochondria where PO2 must not fall
below 0, 1 kPa. Using Fick’s principle oxygen consumption of a given organ is given by the following
formula: VO2= Q ([O2]a - [O2]v)
 consumption of O2 of an organ is calculated as the difference between the arterial supply ( where
Q is the rate of blood flow in the organ L/min) and non-utilized venous O2.
Oxygen supply varies according to the type and function of the organ.
EO2 = ([O2]a - [O2]v)/ [O2]a EO2 describes the O2
Under resting conditions: EO2 (brain) = 0, 04 (4%) EO2 (kidney) =0, 07 (7%)
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
57. Transport of O2. Oxygen-haemoglobin dissociation curve.
> O2 is carried to in the blood in two forms: dissolved or bound to hemoglobin (most important).
> Hemoglobin, at its normal conc., increases the O2-carrying capacity of blood seventyfold.
Hemoglobin
- is a globular protein of four subunits
- each subunit contains a heme portion, which is a
. complex of protoporphyrin IX and ferrous iron (Fe2+
).
- each subunit is a polypeptide chain. The hemoglobin
. tetramer can be envisioned as being composed of two
. identical dimers, (αβ)1 and (αβ)2.
Fetal hemoglobin [hemoglobin F (HbF)]
- in fetal hemoglobin, the B chains are replaced by ɣ
. chains.
- the O2 affinity of fetal hemoglobin is higher than the O2 affinity of adult hemoglobin
. (left-shift) because 2,3-diphosphoglycerate (DPG) binds less avidly.
- because the O2 affinity fo fetal hemoglobin is higher than the O2 affinity of adult hemoglobin,
. O2 movement from mother to fetus is facilitated.
Oxygen dissociation curve
 A plot of Y measured at different partial pressures of oxygen is called the oxygen dissociation
curve.
Hemoglobin: The oxygen dissociation curve for hemoglobin is
in shape, indicating that the subunits cooperate in binding
oxygen. Cooperative binding of oxygen by the four subunits of
hemoglobin means that the binding of an oxygen molecule at
one heme group increases the oxygen affinity of the remaining
heme groups in the same hemoglobin molecule. This effect is
referred to as heme-heme interaction . Although it is more
difficult for the first oxygen molecule to bind to hemoglobin, the
subsequent binding of oxygen occurs with high affinity, as
shown by the steep upward curve in the region near 20 to 30
mm Hg.
Shift of the oxygen-dissociation curve:
Hemoglobin from which 2,3-BPG has been removed has a high
affinity for oxygen. However, as seen in the red blood cell, the
presence of 2,3-BPG significantly reduces the affinity of
hemoglobin for oxygen, shifting the oxygen-dissociation curve
to the right (Figure This reduced affinity enables hemoglobin to
release oxygen efficiently at the partial pressures found in the
tissues.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
58. Transport of CO2
Forms of CO2 in blood
. > CO2 is produced in the tissues and carried to the lungs in the venous blood in three forms:
. 1. Disolved CO2 (small amount), which is free in solution
. 2. Carbaminohemoglocin (small amount), which is CO2 bound to hemoglobin
. 3. HCO3- [from hydration of CO2 in red blood cells], which is the major form (90%)
Transport of CO2 as HCO3
(figure
below)
1. CO2 is generated in the tissues and diffues freely into the venous plasma and then into the RBCs.
2. In the RBCs, CO2 combines with H2O to form H2CO3, a reaction that is catalyzed by carbonic
anhydrase. H2CO3 dissociates into H
+
and HCO3
-
.
3. HCO3
leaves
the TBCs in exchnage for Cl(chloride
shift) and is transported to the lungs in the
plasma. HCO3
is
the major form in which CO2 is transported to the lungs.
4. H+
is buffered inside the RBCs by deoxyhemoglobin.
5. In the lungs, all of the above reactions occur in reverse. HCO3
enters
the RBCs in exchange for Cl-
.
HCO3
recombines
with H
+
to form H2CO3, which decomposes into CO2 and H2O. Thus, CO2, originally
generated in the tissues, is expired.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
59. Herring-Breuer reflexes
In addition to the central nervous system respiratory control mechanisms operating entirely within
the brain stem, sensory nerve signals from the lungs alsohelp control respiration. Most important,
located in the muscular portions of the walls of the bronchi and bronchioles throughout the lungs are
stretch receptors that transmit signals through the vagi into the dorsal respiratory group of neurons
when the lungs become overstretched.These signals affect inspiration in much the same way as
signals from the pneumotaxic center; that is, when the lungs become overly inflated, the stretch
receptors activate an appropriate feedback response that “switches off” the inspiratory ramp and
thus stops further inspiration. This is called the Hering-Breuer inflation reflex. The Hering-Breuer
inflation reflex is an increase in the duration of expiration produced by steady lung inflation, and the
Hering-Breuer deflation reflex is a decrease in the duration of expiration produced by marked
deflation of the lung.
In human beings, the Hering-Breuer reflex probably is not activated until the tidal volume increases
to more than three times normal (greater than about 1.5 liters per breath). Therefore, this reflex
appears to be mainly a protective mechanism for preventing excess lung inflation rather than an
important ingredient in normal control of ventilation.
60. Respiratory responses to irritants.
Responses mediated by receptors in the Airways & Lungs
Receptors in the air ways and lungs are innervated by myelinated and unmyelinated vagal fibers. The
unmyelinated fibers are C fibers. The receptors innervated by myelinated fibers are commonly
divided into slowly adapting receptors and rapidly adapting receptors. Because the rapidly adapting
receptors are stimulated by chemicals such as histamine, they have been called irritant receptors.
Activation of rapidly adapting receptors in the trachea causes coughing, bronchoconstriction, and
mucus secretion, and activation of rapidly adapting receptors in the lung may produce hyperpnea.
Coughing & Sneezing
Coughing beings with a deep inspiration followed by forced expiration against a closed glottis.
This increases the intrapleural pressure to 100 mm Hg or more. The glottis is the suddenly opened,
producing an explosive outflow of air at velocities up to 965 km (600 miles) per hour.
Sneezing is a similar expiratory effect with a continuously open glottis. These reflexes help expel
irritants and keep airways clear.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
61. Artefecial ventilation
Mouth-to-mouth resuscitation is an emergency
measure performed when someone
stops breathing. The patient is placed flat on
the back. While pinching the patient’s nostrils
shut, the aid-giver places his or her mouth on
the patient’s mouth and blows forcefully into
the patient’s lungs (A3). This raises the alveolar
pressure in the patient’s lungs
relative to the atmospheric pressure outside
the chest and causes the lungs and chest to expand
(inspiration). The rescuer then removes
his or her mouth to allowthe patient to exhale.
Expulsion of the air blown into the lungs
(expiration) occurs due to the intrinsic elastic recoil
of the lungs and chest. This process can be
accelerated by pressing down on the chest.
The rescuer should ventilate the patient at a rate
of about 16 min–1. The expiratory O2 fraction
of the rescuer is high enough to adequately oxygenate the patient’s blood.
The color change in the patient’s skin from blue (cyanosis) to pink indicates
that a resuscitation attempt was successful.
Mechanical ventilation. Mechanical intermittent positive pressure ventilation (IPPV) works on the
same principle. This technique is used when the respiratory muscles are paralyzed due to disease,
anesthesia, etc. The pump of the respirator drives air into the patient’s lung during inspiration ( A1).
The external inspiratory and expiratory pathways are separated by a valve (close to the patient’s
mouth as possible) to prevent enlargement of dead space. Ventilation frequency, tidal volume,
inspiratory flow, as well as duration of inspiration and expiration can be preselected at the respirator.
The drawback of this type of ventilation is that venous return to the heart is impaired to some
extent. Today, the standard technique of mechanical respiration is continuous positive pressure
ventilation (CPPV). In contrast to IPPV, the endexpiratory pressure is kept positive (PEEP) in CPPV.
In any case, all ventilated patients should be continuously monitored (expiratory gas fraction; blood
gas composition, etc.).
The iron lung (Drinker respirator) makes use of negative-pressure respiration ( A2). The patient’s
body is enclosed from the neck down in a metal tank. To achieve inhalation, pressure in the tank is
decreased to a level below normal ambient pressure and, thus, below alveolar pressure.
This pressure difference causes the chest to expand (inspiratory phase), and the cessation of negative
pressure in the tank allows the patient to breathe out (expiratory phase).
This type of respirator is used to ventilate patients who require long-term mechanical ventilation due
to paralytic diseases, such as polio.
Masaryk University Faculty of Medicine Physiology Exam
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62. Formation, composition and functions of saliva
Secretion, Composition and Functions of Saliva
Saliva is produced in and secreted from the salivary glands. In the salivary glands, the secretory
(zymogen) granules containing the salivary enzymes are discharged from the acinar cells into the
ducts.
. About 1500 mL of saliva is secreted per day. The pH of saliva from resting glands is slightly less
than 7.0, but during active secretion, it approaches 8.0. Saliva contains two digestive enzymes:
lingual lipase, secreted by glands on the tongue, and salivary α-amylase, secreted by the salivary
glands. Saliva also contains mucins, glycoproteins that lubricate the food, bind bacteria, and protect
the oral mucosa. It also contains the secretory immune globulin IgA; lysozyme, which attacks the
walls of bacteria; lactoferin; which binds iron and is bacteriostatic; and prolinerich proteins that
protect tooth enamel and bind toxic tannins.
. Saliva performs a number of important functions. It facilitates swallowing, keeps the mouth moist,
serves as a solvent for the molecules that stimulate the taste buds, aids speech by facilitating
movements of the lips and tongue, and keeps the mouth and teeth clean. The saliva also has some
antibacterial action, and patients with deficient salivation (xerostomia) have a higher than normal
incidence of dental caries. The buffers in the saliva help maintain the oral pH at about 7.0. they also
help neutralize gastric acid and relieve heartburn when gastric juice is regurgitated into the
esophagus.
The ionic composition of saliva varies considerably from species to species and from gland to
gland. In general, however, saliva secreted in the acini is probably isotonic, with concentrations of
Na+
, K+
, Cl-, and HCO3
that
are close to those in plasma.
Control of Salivary Secretion
Salivary secretion is under neural control. Stimulation of the parasympathetic nerve supply causes
profuse secretion of watery saliva with a relatively low content of organic material. Associated with
this is a pronounced vasodilation in the gland, which appears to be due to the local release of VIP.
This polypeptide is a cotransmitter with acetylcholine in some of the postganglionic parasympathetic
neurons. Atropine and other cholinergic blocking agents reduce salivary secretion.
. Stimulation of the sympathetic nerve supply causes vasoconstriction and, in humans, secretion of
small amounts of saliva rich in organic constituents from the submandibular glands.
Food in the mouth causes reflex secretion of saliva, and so does stimulation of the vagal afferent
fibers at the gastric end of the esophagus.
Masaryk University Faculty of Medicine Physiology Exam
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63. Gastric production of HCL
Basic Mechanism of Hydrochloric Acid Secretion
When stimulated, the parietal cells secrete an acid solution
that contains about 160 millimoles of hydrochloric acid
per liter, which is almost exactly isotonic with the body
fluids. The pH of this acid is about 0.8, demonstrating
its extreme acidity. At this pH, the hydrogen ion
concentration is about 3 million times that of the arterial
blood. To concentrate the hydrogen ions this tremendous
amount requires more than 1500 calories of
energy per liter of gastric juice.
Secretion by parietal cells
HCL secretion by parietal cells in the stomach is
demonstrated in the figure on the right.
Active transport by ATPase is indicated by arrows
in circles. H+
is secreted into the gastric lumen in
exchange for K+
by H+
-K+
ATPase. HCO3- is
exchanged for CL
in
the interstitial fluid by an
antiport, and Na+
-K+
ATPase keeps intracellular
Na+
low. Dashed arrows indicate diffusion.
Regulation of Gastric Acid Secretion by the Parietal Cell.
Masaryk University Faculty of Medicine Physiology Exam
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64. Functions of the stomach
Bolus (masticated food) enters the stomach through the
esophagus via the esophageal sphincter. The stomach
releases proteases (protein-digesting enzymes such as
pepsin) and hydrochloric acid, which kills or inhibits bacteria
and provides the acidic pH for the proteases to work. Food is
churned by the stomach through muscular contractions of
the wall - reducing the volume of the fundus, before looping
around the fundus and the body of stomach as the boluses
are converted into chyme (partially-digested food). Chyme
slowly passes through the pyloric sphincter and into the duodenum,
where the extraction of nutrients begins. .
. In humans, the stomach has a relaxed, near empty volume of about 45 ml. It is a distensible organ.
It normally expands to hold about 1 liter of food, but will hold as much as 2-3 liters (whereas a
newborn baby will only be able to retain 30ml).
Control of Secretion and Motility
The movement and the flow of chemicals into the stomach are controlled by both the autonomic
nervous system and by the various digestive system hormones:
Other than gastrin, these hormones all act to turn off the stomach action.
Masaryk University Faculty of Medicine Physiology Exam
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65. Motility of the gastrointestinal tract
Two types of movements occur in the gastrointestinal tract: (1) propulsive movements, which cause
food to move forward along the tract at an appropriate rate to accommodate digestion and
absorption, and (2) mixing movements, which keep the intestinal contents thoroughly mixed at all
times.
Propulsive Movements—Peristalsis
The basic propulsive movement of the gastrointestinal
tract is peristalsis (illustrated in figure).
A contractile ring appears around the gut and then
moves forward. Any material in front of the contractile
ring is moved forward.
Peristalsis is an inherent property of many syncytial
smooth muscle tubes; stimulation at any point in the
gut can cause a contractile ring to appear in the circular
muscle, and this ring then spreads along the gut tube.
The usual stimulus for intestinal peristalsis is distention of the gut. That is, if a large amount of food
collects at any point in the gut, the stretching of the gut wall stimulates the enteric nervous system
to contract the gut wall 2 to 3 centimeters behind this point, and a contractile ring appears that
initiates a peristaltic movement. Other stimuli that can initiate peristalsis include chemical or physical
irritation of the epithelial lining in the gut. Also, strong parasympathetic nervous signals to the gut
will elicit strong peristalsis.
Effectual peristalsis requires an active myenteric plexus.
Mixing Movements
Mixing movements differ in different parts of the alimentary tract. In some areas, the peristaltic
contractions themselves cause most of the mixing.
Masaryk University Faculty of Medicine Physiology Exam
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66. Composition and function of pancreatic juice
The pancreatic juice contains enzymes that are of major importance in digestion (table below).
Its secretion is controlled in part by a reflex mechanism and in part by the gastrointestinal hormone
secretin and cholecystokinin (CCK).
Regulation of the Secretion of Pancreatic Juice
Secretion of pancreatic juice is primarily under hormonal control. Secretin acts on the pancreatic
ducts to cause secretion of a very alkaline pancreatic juice that is rich in HCO3- and poor in enzymes.
Cholecystokinin acts on the acinar cells to cause the release of zymogen granules and production of
pancreatic juice rich in enzymes but low in volume. Its effect is mediated by phospholipase C.
. Like CCK, acetylcholine acts on acinar cells via phospholipase C to cause discharge of zymogen
granules, and stimulation of the vagi causes secretion of a small amount of pancreatic juice rich in
enzymes.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
67. Liver functions
The various functions of the liver are carried out by the liver cells or hepatocytes. Currently, there is
no artificial organ or device capable of emulating all the functions of the liver.
Synthesis
 A large part of amino acid synthesis
 The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or
glycerol). Note that humans and some other mammals cannot synthesize glucose
from glycerol.
o Glycogenolysis (the breakdown of glycogen into glucose)
o Glycogenesis (the formation of glycogen from glucose)(muscle tissues can also do
this)
 The liver is responsible for the mainstay of protein metabolism, synthesis as well as
degradation
 The liver also performs several roles in lipid metabolism:
o Cholesterol synthesis
o Lipogenesis, the production of triglycerides (fats).
 The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as
well as protein C, protein S and antithrombin.
 In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd
week of gestation, the bone marrow has almost completely taken over that task.
 The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of
the bile drains directly into the duodenum, and some is stored in the gallbladder.
 The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone
that plays an important role in childhood growth and continues to have anabolic effects in
adults.
 The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein
hormone that regulates the production of platelets by the bone marrow.
Breakdown
 The breakdown of insulin and other hormones
 The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment
(bilirubin and biliverdin).
 The liver breaks down or modifies toxic substances (e.g., methylation) and most medicinal
products in a process called drug metabolism. This sometimes results in toxication, when the
metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail
excretion in bile or urine.
 The liver converts ammonia to urea. Review
Other functions
 The liver stores a multitude of substances, including glucose (in the form of glycogen),
vitamin A (1–2 years' supply), vitamin D (1–4 months' supply), vitamin B12 (1-3 years'
supply), iron, and copper.
Masaryk University Faculty of Medicine Physiology Exam
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 The liver is responsible for immunological effects- the reticuloendothelial system of the liver
contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the
portal system.
 The liver produces albumin, the major osmolar component of blood serum.
 The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood
pressure when activated by renin, an enzyme that is released when the kidney senses low
blood pressure.
68. Formation, composition and functions of bile
Production
Bile is produced by hepatocytes in the liver, draining through the many bile ducts that penetrate the
liver. During this process, the epithelial cells add a watery solution that is rich in bicarbonates that
dilutes and increases alkalinity of the solution. Bile then flows into the common hepatic duct, which
joins with the cystic duct from the gallbladder to form the common bile duct. The common bile duct
in turn joins with the pancreatic duct to empty into the duodenum. If the sphincter of Oddi is closed,
bile is prevented from draining into the intestine and instead flows into the gallbladder, where it is
stored and concentrated to up to five times its original potency between meals. This concentration
occurs through the absorption of water and small electrolytes, while retaining all the original organic
molecules. Cholesterol is also released with the bile, dissolved in the acids and fats found in the
concentrated solution. When food is released by the stomach into the duodenum in the form of
chyme, the duodenum releases cholecystokinin, which causes the gallbladder to release the
concentrated bile to complete digestion.
The human liver can produce close to one litre of bile per day (depending on body size). About 95%
of the salts secreted in bile are reabsorbed in the terminal ileum and re-used. Blood from the ileum
flows directly to the hepatic portal vein and returns to the liver where the hepatocytes reabsorb the
salts and return them to the bile ducts to be re-used, sometimes two to three times with each meal.
Composition of Bile
Masaryk University Faculty of Medicine Physiology Exam
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Physiological functions
Bile acts to some extent as a surfactant, helping to emulsify the
fats in the food. Bile salt anions have a hydrophilic side and a
hydrophobic side, and therefore tend to aggregate around
droplets of fat (triglycerides and phospholipids) to form micelles,
with the hydrophobic sides towards the fat and hydrophilic
towards the outside. The hydrophilic sides are positively charged
due to the lecithin and other phospholipids that compose bile,
and this charge prevents fat droplets coated with bile from reaggregating
into larger fat particles. Ordinarily, the micelles in
the duodenum have a diameter of around 14-33 μm.
The dispersion of food fat into micelles thus provides a largely increased surface area for the action
of the enzyme pancreatic lipase, which actually digests the triglycerides, and is able to reach the fatty
core through gaps between the bile salts. A triglyceride is broken down into two fatty acids and a
monoglyceride, which are absorbed by the villi on the intestine walls. After being transferred across
the intestinal membrane, fatty acids are reformed into triglycerides, and then absorbed into the
lymphatic system through lacteals. Without bile salts, most of the lipids in the food would be passed
out in feces, undigested.
Since bile increases the absorption of fats, it is an important part of the absorption of the fat-soluble
substances, such as the vitamins D, E, K and A.
Besides its digestive function, bile serves also as the route of excretion for bilirubin, a byproduct of
red blood cells recycled by the liver. Bilirubin derives from hemoglobin by glucuronidation.
The alkaline bile also has the function of neutralizing any excess stomach acid before it enters the
ileum, the final section of the small intestine. Bile salts also act as bactericides, destroying many of
the microbes that may be present in the food.
Masaryk University Faculty of Medicine Physiology Exam
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69. Digestion in the small intestine
The small intestine is where most chemical digestion takes place. Most of the digestive enzymes that
act in the small intestine are secreted by the pancreas and enter the small intestine via the
pancreatic duct. The enzymes enter the small intestine in response to the hormone cholecystokinin,
which is produced in the small intestine in response to the presence of nutrients. The hormone
secretin also causes bicarbonate to be released into the small intestine from the pancreas in order to
neutralize the potentially harmful acid coming from the stomach.
The three major classes of nutrients that undergo digestion are proteins, lipids (fats) and
carbohydrates:
 Proteins and peptides are degraded into amino acids. Chemical breakdown begins in the
stomach and continues in the small intestine. Proteolytic enzymes, including trypsin and
chymotrypsin, are secreted by the pancreas and cleave proteins into smaller peptides.
Carboxypeptidase, which is a pancreatic brush border enzyme, splits one amino acid at a
time. Aminopeptidase and dipeptidase free the end amino acid products.
 Lipids (fats) are degraded into fatty acids and glycerol. Pancreatic lipase breaks down
triglycerides into free fatty acids and monoglycerides. Pancreatic lipase works with the help
of the salts from the bile secreted by the liver and the gall bladder. Bile salts attach to
triglycerides to help emulsify them, which aids access by pancreatic lipase. This occurs
because the lipase is water-soluble but the fatty triglycerides are hydrophobic and tend to
orient towards each other and away from the watery intestinal surroundings. The bile salts
are the "middle man" that holds the triglycerides in the watery surroundings until the lipase
can break them into the smaller components that are able to enter the villi for absorption.
 Some carbohydrates are degraded into simple sugars, or monosaccharides (e.g., glucose).
Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides.
Other carbohydrates pass undigested into the large intestine and further handling by
intestinal bacteria. Brush border enzymes take over from there. The most important brush
border enzymes are dextrinase and glucoamylase which further break down
oligosaccharides. Other brush border enzymes are maltase, sucrase and lactase. Lactase is
absent in most adult humans and for them lactose, like most poly-saccharides are not
digested in the small intestine. Some carbohydrates, such as cellulose, are not digested at all,
despite being made of multiple glucose units.
Masaryk University Faculty of Medicine Physiology Exam
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70. Functions of colon
The large intestine comes after the small intestine in the digestive tract and measures approximately
1.5 meters in length. Although there are differences in the large intestine between different
organisms, the large intestine is mainly responsible for storing waste, reclaiming water, maintaining
the water balance, absorbing some vitamins, such as vitamin K, and providing a location for floraaided
fermentation.
By the time the chyme has reached this tube, most nutrients and 90% of the water have been
absorbed by the body. At this point some electrolytes like sodium, magnesium, and chloride are left
as well as indigestible parts of ingested food (e.g., a large part of ingested amylose, protein which has
been shielded from digestion heretofore, and dietary fiber, which is largely indigestible carbohydrate
in either soluble or insoluble form). As the chyme moves through the large intestine, most of the
remaining water is removed, while the chyme is mixed with mucus and bacteria (known as gut flora),
and becomes feces. The ascending colon receives fecal material as a liquid. The muscles of colon then
move the watery waste material forward and slowly absorb all the excess water. The stools get to
become semi solid as they move along into the descending colon. The bacteria break down some of
the fiber for their own nourishment and create acetate, propionate, and butyrate as waste products,
which in turn are used by the cell lining of the colon for nourishment. The large intestine produces
no digestive enzymes -— chemical digestion is completed in the small intestine before the chyme
reaches the large intestine. The pH in the colon varies between 5.5 and 7 (slightly acidic to neutral).
Most people can avoid problems in their colon simply by eating a diet which is high in fiber and fruits
and low in lean meat.
71. Resorption of lipids in the small intestine
Digestion of Lipids in Small Intestine
(1) Bile acids emulsify lipids in the small intestine, increasing the surface area for
digestion
(2) Pancreatic lipases hydrolyze lipids to fatty acids, monoglycerides, cholesterol, and
lysolecithin. The enzymes are pancreatic lipase, cholesterol ester hydrolase, and
phospholipase A2.
(3) The hydrophobic products of lipid digestion are solubilized in micelles by bile acids.
Absorption of lipids
a. Micelles bring the products of lipid digestion into contact with the absorptive surface of
intestinal cells. Then, fatty acids, monoglycerides, and cholesterol diffuse across the luminal
membranes into the cells. Glycerol is hydrophilic and is not contained in the micelles.
b. In the intestinal cells, the products of lipid digestion are re-esterified to triglycerides,
cholesterol ester, and phospholipids and, with apoproteins, form chylomicrons.
c. Chylomicrons are transported out of the intestinal cells by exocytosis. Because chylomicrons
are too large to enter the capillaries, they are transferred to lymph vessels and are added to
the bloodstream via the thoracic duct.
Masaryk University Faculty of Medicine Physiology Exam
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72. Resorption of minerals and water in small intestine
The average intake of water (in beverages and foodstuffs) is roughly 1.5 L per day.
An additional 7 L of fluid are secreted into the gastrointestinal (GI) tract (saliva, gastric juices, bile,
pancreatic juice and intestinal secretions), whereas only about 0.1 L/day is eliminated in the feces.
The digestive tract must therefore absorb a net volume of at least 8.4 L of water per day.
GI absorption of water occurs mainly in the jejunum and ileum, with smaller quantities
being absorbed by the colon. Water is driven through the intestinal epithelium by osmosis.
When solutes (Na+
, Cl–
, etc.) are absorbed in the intestine, water follows.
(The stool contains only small quantities of Na+
, Cl–
and water.) Conversely, the secretion of
substances into the lumen or the ingestion of non-absorbable substances leads to water
fluxes into the lumen. Poorly absorbable substances therefore act as laxatives (e.g. sulfate, sorbitol,
polyethylene glycol).
Water absorption is mainly driven by the absorption of Na+, Cl– and organic compounds.
The luminal concentration of Na+
and Cl–
steadily decreases from the duodenum to the colon.
That of Na+
, for example, is approximately 145 mmol/L in the duodenum, 125 mmol/L in the ileum
and only 40 mmol/L in the colon. Na+
is absorbed by various mechanisms, and the Na+
-K+
-ATPase on
the basolateral cell membrane is the primary driving mechanism for all of them.
 Symport of Na
+
and organic substances: Na
+
passively influxes into cells of the duodenum and
jejunum via symporter carriers, which actively cotransport glucose, amino acids, phosphates and other
compounds (secondary active transport). Since this is an electrogenic transport mechanism, a lumennegative
transepithelial potential (LNTP) forms that drives Cl– out of the lumen.
 Parallel transport of Na
+
and Cl
–
: Na+ ions in the lumen of the ileum are exchanged for H
+
ions while
Cl
–
is exchanged for HCO3
–
at the same time. The H
+
ions combine with HCO3
–
to yield H2O + CO2, which
diffuse out of the lumen. Most Na
+
, Cl
–
and, by subsequent osmosis, H2O is absorbed by this
electroneutral transport mechanism.
 Na
+
diffusion: Na
+
in the colon is mainly absorbed through luminal Na
+
channels.
This type of Na
+
transport is electrogenic and aldosterone-dependent. The related lumen-negative
transepithelial potential (LNTP) either leads to K
+
secretion or drives Cl
–
out of the lumen.
 The Cl
–
secretion mechanism of epithelial cells (mainly Lieberkühn’s crypts) is similar to that of the
acini of salivary glands. The efflux of Cl
–
into the lumen and the associated efflux of Na
+
and water are
stimulated by cAMP and regulated by neurons and hormones such as VIP (vasoactive intestinal
peptide) and prostaglandins. The physiological function of this form of H2O secretion could be to dilute
viscous chyme or to ensure the recirculation of water (from the crypts  lumen  villi  crypts) to
promote the absorption of poorly soluble substances.
 In addition to HCO3
–
from pancreatic juice, HCO3
–
is also secreted into the intestinal lumen by the
small and large intestine. K
+
is secreted (aldosterone-dependent) by crypt cells of the colon (luminal K
+
concentration 90 mmol/l!) and reabsorbed via the H
+
-K
+
pump of the surface epithelium. The
aldosterone-dependent K
+
secretion/absorption ratio determines the net amount of K
+
excreted.
Diarrhea results in losses of K
+
and HCO3
–
(hypokalemia and metabolic acidosis).
 Ca
2+
. The stool contains one-third of the dietary Ca
2+
intake. Ca
2+
is absorbed in the upper part of the
small intestine with the aid of intracellular calcium-binding protein (CaBP). Calcitriol increases CaBP
synthesis, thereby increasing Ca
2+
absorption. Deficiencies of vitamin D or substances that form waterinsoluble
compounds with Ca
2+
(phytin, oxalate, fatty acids) decrease Ca2+ absorption.
 Iron absorption occurs mainly in the duodenum. Fe supplied by the diet (hemoglobin, myoglobin
found chiefly in meat and fish) is absorbed relatively efficiently as a heme-Fe by HCP1 (heme carrier
protein 1). Within mucosal cells, Fe
3+
is released by heme oxygenase and reduced to Fe
2+
which is
transported across the cell by mobilferrin. It either enters the bloodstream or remains in the mucosa
as a ferritin-Fe(III) complex and returns to the gut lumen during cell turnover.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
73. Intermediary metabolism
74. Nitrogen balance
Nitrogen balance is the measure of nitrogen output subtracted from nitrogen input.
Blood urea nitrogen can be used in estimating nitrogen balance, as can the urea concentration in
urine.
 A positive value is often found during periods of growth, tissue repair or pregnancy. This
means that the intake of nitrogen into the body is greater than the loss of nitrogen from the
body, so there is an increase in the total body pool of protein.
 A negative value can be associated with burns, fevers, wasting diseases and other serious
injuries and during periods of fasting. This means that the amount of nitrogen excreted from
the body is greater than the amount of nitrogen ingested.
During growth and tissue repair (convalescence) the body is in positive N balance, i.e. intake is
greater than loss and there is an increase in the total body pool of protein. In fevers, fasting, and
wasting diseases the loss is greater than the intake and the individual is in negative balance; there is
a net loss of protein from the body
 It can be used in the evaluation of malnutrition.
Masaryk University Faculty of Medicine Physiology Exam
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75. Metabolism of cholesterol. Atherosclerosis.
Formation of Cholesterol
Besides the cholesterol absorbed each day from the gastrointestinal tract, which is called exogenous
cholesterol, an even greater quantity is formed in the cells of the body, called endogenous cholesterol.
Essentially all the endogenous cholesterol that circulates in the lipoproteins of the plasma is formed by the
liver, but all other cells of the body form at least some cholesterol.
The basic structure of cholesterol is a sterol nucleus. This is synthesized entirely from multiple molecules of
acetyl-CoA. In turn, the sterol nucleus can be modified by means of various side chains to form (1) cholesterol;
(2) cholic acid, which is the basis of the bile acids formed in the liver; and (3) many important steroid hormones
secreted by the adrenal cortex, the ovaries, and the testes.
Factors That Affect Plasma Cholesterol Concentration—Feedback Control of Body Cholesterol
Among the important factors that affect plasma cholesterol concentration are the following:
1. An increase in the amount of cholesterol ingested each day increases the plasma concentration
slightly. However, when cholesterol is ingested, the rising concentration of cholesterol inhibits the most
essential enzyme for endogenous synthesis of cholesterol, 3-hydroxy-3-methylglutaryl CoA reductase, thus
providing an intrinsic feedback control system to prevent an excessive increase in plasma cholesterol
concentration.
2. A highly saturated fat diet increases blood cholesterol concentration 15 to 25 per cent. This results from
increased fat deposition in the liver, which then provides increased quantities of acetyl-CoA in the liver cells for
the production of cholesterol.
3. Ingestion of fat containing highly unsaturated fatty acids usually depresses the blood cholesterol
concentration a slight to moderate amount.
4. Lack of insulin or thyroid hormone increases the blood cholesterol concentration, whereas excess thyroid
hormone decreases the concentration.
Specific Uses of Cholesterol in the Body
By far the most abundant nonmembranous use of cholesterol in the body is to form cholic acid in the liver. As
much as 80 per cent of cholesterol is converted into cholic acid. This is conjugated with other substances to
form bile salts, which promote digestion and absorption of fats.
A small quantity of cholesterol is used by (1) the adrenal glands to form adrenocortical hormones, (2) the
ovaries to form progesterone and estrogen, and (3) the testes to form testosterone.
Atherosclerosis
Atherosclerosis is a disease of the large and intermediate- sized arteries in which fatty lesions called
atheromatous plaques develop on the inside surfaces of the arterial walls.
One recent theory suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to
attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of
atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the
endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin.
Increased Low-Density Lipoproteins
An important factor in causing atherosclerosis is a high blood plasma concentration of cholesterol in the form
of low-density lipoproteins. The plasma concentration of these highcholesterol low-density lipoproteins is
increased by several factors, including eating highly saturated fat in the daily diet, obesity, and physical
inactivity.
Masaryk University Faculty of Medicine Physiology Exam
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76. Metabolism of iron
Iron Metabolism
The total quantity of iron in the body averages 4 to 5 grams, about 65 per cent of which is in the form
of hemoglobin. About 4 per cent is in the form of myoglobin, 1 per cent is in the form of the various
heme compounds that promote intracellular oxidation, 0.1 per cent is combined with the protein
transferrin in the blood plasma, and 15 to 30 per cent is stored for later use, mainly in the
reticuloendothelial system and liver parenchymal cells, principally in the form of ferritin.
Transport and Storage of Iron
When iron is absorbed from the small intestine, it immediately combines in the blood plasma with a beta
globulin, apotransferrin, to form transferrin, which is then transported in the plasma. The iron is loosely bound
in the transferrin and, consequently, can be released to any tissue cell at any point in the body. Excess iron in
the blood is deposited especially in the liver hepatocytes and less in the reticuloendothelial cells of the bone
marrow.
In the cell cytoplasm, iron combines mainly with a protein, apoferritin, to form ferritin. This iron stored as
ferritin is called storage iron.
Smaller quantities of the iron in the storage pool are in an extremely insoluble form called hemosiderin.
When the quantity of iron in the plasma falls low, some of the iron in the ferritin storage pool is removed easily
and transported in the form of transferrin in the plasma to the areas of the body where it is needed. A unique
characteristic of the transferrin molecule is that it binds strongly with receptors in the cell membranes
of erythroblasts in the bone marrow. Then, along with its bound iron, it is ingested into the erythroblasts by
endocytosis. There the transferrin delivers the iron directly to the mitochondria, where heme is synthesized.
When red blood cells have lived their life span and are destroyed, the hemoglobin released from the cells
is ingested by monocyte-macrophage cells. There, iron is liberated and is stored mainly in the ferritin pool to be
used as needed for the formation of new hemoglobin.
Absorption of Iron from the Intestinal Tract
Iron is absorbed from all parts of the small intestine, mostly by the following mechanism. The liver secretes
moderate amounts of apotransferrin into the bile, which flows through the bile duct into the duodenum. Here,
the apotransferrin binds with free iron and also with certain iron compounds, such as hemoglobin and
myoglobin from meat, two of the most important sources of iron in the diet. This combination is called
transferrin. It, in turn, is attracted to and binds with receptors in the membranes of the intestinal epithelial
cells. Then, by pinocytosis, the transferrin molecule, carrying its iron store, is absorbed into the epithelial cells
and later released into the blood capillaries beneath these cells in the form of plasma transferrin.
Iron absorption from the intestines is extremely slow, at a maximum rate of only a few milligrams per day.
This means that even when tremendous quantities of iron are present in the food, only small proportions can
be absorbed.
Regulation of Total Body Iron by Controlling Rate of Absorption
When the body has become saturated with iron so that essentially all apoferritin in the iron storage areas is
already combined with iron, the rate of additional iron absorption from the intestinal tract becomes greatly
decreased. Conversely, when the iron stores have become depleted, the rate of absorption can accelerate
probably five or more times normal. Thus, total body iron is regulated mainly by altering the rate of
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
77. Bone formation and resorption
The cells responsible for bone formation are osteoblasts and the cells responsible for bone
resorption are osteoclasts.
Later, ossification-specific factors begin to appear. One of the most interesting is the transcription
factor Cbfa1. Mice in which the gene for Cbfa1 is knocked out develop to term with their skeletons
made exclusively of cartilage; no ossification occurs.
Stromal cells in the bone marrow, osteoblasts, and T lymphocytes all express a molecule called
RANKL (RANK ligand) on their surface, and when they come in contact with appropriate monocytes
they bind to RANKL receptors (RANK) on the surfaces of the monocytes. They also secrete M-CSF,
and it binds to a receptor, c-fins, on the monocytes. This combination converts monocytes into
osteoclasts.
Osteoclasts erode and absorb previously formed bone. Throughout life, bone is being constantly
resorbed and new bone is being formed. First, osteoclasts resorb bone, and then osteoblasts lay
down new bone in the same general area.
Ossification (or osteogenesis) is the process of laying down new bone material by cells called
osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the
formation of normal, healthy bone tissue. Intramembranous ossification is the direct laying down of
bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves
cartilage as a precursor.
In fracture healing, endochondral osteogenesis is the most commonly occurring process, for example
in fractures of long bones treated by plaster of Paris, whereas fractures treated by open reduction
and stabilization by metal plate and screws may heal by intramembranous osteogenesis.
Masaryk University Faculty of Medicine Physiology Exam
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78. Hyperthermia and hypothermia
Hyperthermia
Is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the
body produces or absorbs more heat than it can dissipate. When the elevated body temperatures are
sufficiently high, hyperthermia is a medical emergency and requires immediate treatment to prevent
disability and death.
The most common causes are heat stroke and adverse reactions to drugs. Heat stroke is an acute
condition of hyperthermia that is caused by prolonged exposure to excessive heat and/or humidity.
The heat-regulating mechanisms of the body eventually become overwhelmed and unable to
effectively deal with the heat, causing the body temperature to climb uncontrollably. Hyperthermia
is a relatively rare side effect of many drugs, particularly those that affect the central nervous system.
In malignant hyperthermia, various mutations of the gene coding for the ryanodine receptor lead to
excess Ca2+
release during muscle contraction triggered by stress. This in turn leads to contractures of
the muscles, increased muscle metabolism, and a great increase in heat production in muscle. The
increased heat production causes a marked rise in body temperature that is fatal if not treated.
Hyperthermia can be created artificially by drugs or medical devices. Hyperthermia therapy may be
used to treat some kinds of cancer and other conditions, most commonly in conjunction with
radiotherapy.
Hyperthermia differs from fever in the mechanism that causes the elevated body temperatures: a
fever is caused by a change in the body's temperature set-point.
The opposite of hyperthermia is hypothermia, which occurs when an organism's temperature drops
below that required for normal metabolism.
Hyperthermia
In hibernating mammals, body temperature drops to low levels without causing any demonstrable ill
effects on subsequent arousal. When the skin or the blood is cooled enough to lower the body
temperature in nonhibernating animals and in humans, metabolic and physiological processes slow
down. Respiration and heart rate are very low, blood pressure is low, and consciousness is lost.
Humans tolerate body temperatures of 21-24 *C (70-75 *F) without permanent ill effects, and
induced hypothermia has been used in surgery. On the other hand, accidental hypothermia due to
prolonged exposure to cold air or cold water is a serious condition and requires careful monitoring
and immediate rewarming.
Masaryk University Faculty of Medicine Physiology Exam
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79. Functional morphology of nephron
The Nephron Is the Functional Unit of the Kidney
Each kidney in the human contains about 1 million nephrons,
each capable of forming urine.
Each nephron contains (1) a tuft of glomerular capillaries
called the glomerulus, through which large amounts of fluid
are filtered from the blood, and (2) a long tubule in which the
filtered fluid is converted into urine on its way to the pelvis of
the kidney.
The glomerulus contains a network of branching and
anastomosing glomerular capillaries that, compared with other
capillaries, have high hydrostatic pressure (about 60 mm Hg).
The glomerular capillaries are covered by epithelial cells, and
the total glomerulus is encased in Bowman’s capsule. Fluid
filtered from the glomerular capillaries flows into Bowman’s
capsule and then into the proximal tubule, which lies in the cortex of the kidney.
From the proximal tubule, fluid flows into the loop of Henle, which dips into the renal medulla. Each loop
consists of a descending and an ascending limb. The walls of the descending limb and the lower end of the
ascending limb are very thin and therefore are called the thin segment of the loop of Henle. After the ascending
limb of the loop has returned partway back to the cortex, its wall becomes much thicker, and it is referred to as
the thick segment of the ascending limb.
At the end of the thick ascending limb is a short segment, which is actually a plaque in its wall, known as the
macula densa. The macula densa plays an important role in controlling nephron function. Beyond the macula
densa, fluid enters the distal tubule, which, like the proximal tubule, lies in the renal cortex. This is followed by
the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct. The initial
parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the
medulla and becomes the medullary collecting duct. The collecting ducts merge to form progressively larger
ducts that eventually empty into the renal pelvis through the tips of the renal papillae. In each kidney, there
are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons.
Masaryk University Faculty of Medicine Physiology Exam
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80. Urine formation
Urine Formation Results from Glomerular Filtration,
Tubular Reabsorption, and Tubular Secretion
Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate
Urine formation begins when a large amount of fluid that is virtually free of protein is filtered from the
glomerular capillaries into Bowman’s capsule. Most substances in the plasma, except for proteins, are freely
filtered, so that their concentration in the glomerular filtrate in Bowman’s capsule is almost the same as in the
plasma. As filtered fluid leaves Bowman’s capsule and passes through the tubules, it is modified by
reabsorption of water and specific solutes back into the blood or by secretion of other substances from the
peritubular capillaries into the tubules.
For each substance in the plasma, a particular combination of filtration, reabsorption, and secretion occurs.
The rate at which the substance is excreted in the urine depends on the relative rates of these three basic renal
processes.
Filtration, Reabsorption, and Secretion of Different Substances
In general, tubular reabsorption is quantitatively more important than tubular secretion in the formation of
urine, but secretion plays an important role in determining the amounts of potassium and hydrogen ions and a
few other substances that are excreted in the urine. Most substances that must be cleared from the blood,
especially the end products of metabolism such as urea, creatinine, uric acid, and urates, are poorly reabsorbed
and are therefore excreted in large amounts in the urine. Certain foreign substances and drugs are also poorly
reabsorbed but, in addition, are secreted from the blood into the tubules, so that their excretion rates are high.
Conversely, electrolytes, such as sodium ions, chloride ions, and bicarbonate ions, are highly reabsorbed, so
that only small amounts appear in the urine. Certain nutritional substances, such as amino acids and glucose,
are completely reabsorbed from the tubules and do not appear in the urine even though large amounts are
filtered by the glomerular capillaries.
Each of the processes—glomerular filtration, tubular reabsorption, and tubular secretion—is regulated
according to the needs of the body. For example, when there is excess sodium in the body, the rate at which
sodium is filtered increases and a smaller fraction of the filtered sodium is reabsorbed, resulting in increased
urinary excretion of sodium.
The First Step in Urine Formation = Glomerular Filtration
Masaryk University Faculty of Medicine Physiology Exam
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81. Renal blood flow and its autoregulation
Renal blood flow
In a resting adult, the kidneys receive 1.2-1.3 L
of blood per minute, or just under 25% of the
cardiac output. Renal blood flow can be
measured with electromagnetic or other types
of flow meters, or it could be determined by
applying the Fick principle to the kidney – ie, by
measuring the amount of a given substance
taken up per unit of time and dividing this value
by the arteriovenous difference for the
substance across the kidney. Since the kidney
filters plasma, the renal plasma flow equals the amount of a substance excreted per unit of time
divided by the renal arteriovenous difference as long as the amount of red cells is unaltered during
the passage through the kidney.
. Renal blood flow can be measured by infusing p-aminohippuric acid (PAH) and determine its
urine and plasma concentrations. PAH is filtered by the glomeruli and secreted by the tubular cells,
so that its extraction ratio (arterial conc. minus the renal venous conc. divided by arterial conc.) is
higher. For example, when PAH is infused at low doses, 90 % of the PAH in arterial blood is removed
in a single circulation through the kidney. It has therefore become common to calculate the “renal
plasma flow” by dividing the amount of PAH in the urine by the plasma PAH level, ignoring the level
in renal venous blood. The value obtained should be called the effective renal plasma flow (ERPF) to
indicate that the level of renal venous plasma was not measured. In humans, ERPF averages about
625 mL/min.
Regulation of the Renal Blood flow
 Norepinephrine constricts the renal vessels.
 Dopamine causes renal vasodilatation and natriuresis.
 Angiotensin exerts a great effect on the efferent arterioles.
 Prostaglandins increase blood flow in the renal cortex and decrease flow in renal medulla
 Acetylcholine also produces renal vasodilatation.
 A high protein diet raises glomerular capillary pressure and increase renal blood flow
Autoregulation of Renal Blood Flow
When the kidney is perfused at moderate pressures, the renal vascular resistance varies with the
pressure so that renal blood flow is relatively constant. Renal autoregulation is present in denervated
and in isolated, perfused kidneys but is prevented by administration of drugs that paralyze vascular
smooth muscle. It is probably produced in part by a direct contractile response of the smooth muscle
of the afferent arteriole to stretch. NO may also be involved. Angiotensin II also appears to play a
role by constricting the efferent arterioles, thus maintaining the glomerular filtration rate.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
82. Glomerular filtration
Measuring GFR
The glomerular filtration rate (GFR) can be measured in
intact experimental animals and humans by measuring the
excretion and plasma level of a substance that is freely
filtered through the glomeruli and neither secreted nor
reabsorbed by the tubules. The amount of such a substance in
the urine per unit of time must have been provided by
filtering exactly the number of milliliters of plasma that
contained this amount. Therefore, if a substance is designed
by the letter X, the GFR is equal to the conc. of X in urine (Ux) times the urine flow per unit of time
(V) divided by the arterial plasma level of X (Px), or UxV/Px. This value is called the clearance of X (Cx).
Substances Used to Measure GFR
A suitable substance for measuring the GFR should be nontoxic and not metabolized by the body.
Inulin, a polymer of fructose, meets the criteria in humans and most animals and is extensively used
to measure GFR. In practice, a loading dose of inulin is administrated intravenously, followed by a
sustaining infusion to keep the arterial plasma level constant. After the inulin has equilibrated with
body fluids, an accurately timed urine specimen is collected and a plasma sample is obtained halfway
through the collection. Plasma and urinary inulin conc. are determined and the clearance calculated.
. In dogs, cats, rabbits, and a number of other mammalian species, clearance of creatinine (CCr)
can also be used to determine the GFR, but in primates, including humans, some creatinine is
secreted by the tubules and some may be reabsorbed. Plasma creatinine determinations are
inaccurate at low creatinine levels because the method for determining creatinine measures small
amounts of other plasma constitutes. In spite of this, the clearance of endogenous creatinine is
frequently measured in patients.
Normal GFR
The GFR in an average-sized man is approx. 125 mL/min. Values in women are 10% lower than those
in men. A rate of 125 mL/min is 7.5 L/h, or 180 L/d, whereas the normal urine volume is about 1 L/d.
Thus, 99% or more of the filtrate is normally reabsorbed.
Control of GFR
Factors include the size of the capillary bed, the permeability of the capillaries, and the hydrostatic
and osmotic pressure gradients across the capillary wall. For each nephron:
Kf, the glomerular ultrafiltraton coefficient, is the product of the glomerular capillary wall hydraulic
conductivity (i.e., its permeability) and the effective filtration surface area. PGC is the mean
hydrostatic pressure in the glomerular capillaries, PT the mean hydrostatic pressure in the tubule, πGC
the osmotic pressure of the plasma in the glomerular capillaries, and πT the osmotic pressure pf the
filtrate in the tubule.
>> The ratio of the GFR to the renal plasma flow (RPF), the filtration fraction, is normally 0.16-0.20.
Masaryk University Faculty of Medicine Physiology Exam
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83. Function of renal tubules
Mechanism of Tubular Reabsorption & Secretion
Small proteins and some peptide hormones are reabsorbed in the proximal tubules by endocytosis.
Other substances are secreted or reabsorbed in the tubules by passive diffusion between cells and
through cells by facilitated diffusion down chemical or electrical gradients or active transport against
such gradients. Movement is by way of ion channels, exchangers, cotransporters, and pumps.
. It is important to know that the pumps and other units in the luminal membrane are different
from those in the basolateral membrane. It is this different distribution that makes possible net
movement of solutes across epithelia.
. Like transport systems, elsewhere, renal active transport systems have a maximal rate, or
transport maximum (Tm), at which they can transport a particular solute. Thus, the amount of a
particular solute transport is proportionate to the amount present up to the Tm, for the solute, but at
higher conc., the transport mechanism is saturated and there is no appreciable increment in the
amount transported. However, the Tm for some systems are high, and it is difficult to saturate them.
. It should be noted that the tubular epithelium, like that of the small intestine and gallbladder, is a
leaky epithelium in that the tight junctions between the cells permit the passage of some water and
electrolytes. The degree to which the leakage by this paracellular pathway contributes to the net
flux of fluid and solute into and out of the tubules is controversial since it is difficult to measure, but
current evidence seems to suggest that it is a significant factor. One indication of this is that
paracellin-1, a protein localized to tight junctions, is related to Mg2+
reabsorption, and loss-offunction
mutation of its gene causes severe Mg2+
and Ca2+
loss in the urine.
84. Juxtaglomerular apparatus
The juxtaglomerular apparatus is a microscopic
structure in the kidney, which regulates the function
of each nephron. The juxtaglomerular apparatus is
named for its proximity to the glomerulus: it is
found between the vascular pole of the renal
corpuscle and the returning distal convoluted tubule
of the same nephron. This location is critical to its
function in regulating renal blood flow and
glomerular filtration rate. The three cellular
components of the apparatus are the macula densa,
extraglomerular mesangial cells, and
juxtaglomerular cells (also known as granular cells).
There are 3 different types of cells in the Juxtaglomerular Apparatus: Granular Cells, Mesangial Cells
and Macula Densa Cells.
Masaryk University Faculty of Medicine Physiology Exam
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Granular Cells
These are modified pericytes of glomerular arterioles. They are also known as Juxtaglomerular cells.
The granular cells secrete renin in response to:
 Beta1 adrenergic stimulation
 Decrease in renal perfusion pressure (detected directly by the granular cells)
 Decrease in NaCl absorption in the Macula Densa (often due to a decrease in glomerular
filtration rate, or GFR).
Macula Densa Cells
Macula densa cells are columnar epithelium thickening of the distal tubule. The macula densa senses
sodium chloride concentration in the distal tubule of the kidney and secretes a locally active
(paracrine) vasopressor which acts on the adjacent afferent arteriole to decrease glomerular
filtration rate (GFR), as part of the tubuloglomerular feedback loop. Specifically, excessive filtration at
the glomerulus or inadequate sodium uptake in the proximal tubule / thick ascending loop of Henle
brings fluid to the distal convoluted tubule that has an abnormally high concentration of sodium.
Na/Cl cotransporters move sodium into the cells of the macula densa. The macula densa cells do not
have enough basolateral Na/K ATPases to excrete this added sodium, so the cell's osmolarity
increases. Water flows into the cell to bring the osmolarity back down, causing the cell to swell.
When the cell swells, a stretch-activated non-selective anion channel is opened on the basolateral
surface. ATP escapes through this channel and is subsequently converted to adenosine. Adenosine
vasoconstricts the afferent arterioles via A1 receptors and vasodilates (to a lesser degree) efferent
arterioles via A2 receptors which decreases GFR. Also, when macula densa cells detect higher
concentrations of Na and Cl they inhibit Nitric Oxide Synthetase (decreasing renin release).
. The macula densa cells detect lower concentrations in Na and Cl and upregulate Nitric Oxide
Synthetase (NOS). NOS creates NO which catalyses the formation of prostaglandins. These
prostaglandins diffuse to the granular cells and activate a prostaglandin specific Gs receptor. This
receptor activates adenylate cyclase which increases levels of cAMP. cAMP augments renin release.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
85. Renal sodium transport
Na+ Reabsorption
The reabsorption of Na+
and Cl
plays
a major role
in body electrolyte and water metabolism. In
addition, Na+
transport is coupled to the
movement of H+
, other electrolyte, glucose, amino
acids, organic acids, phosphate, and other
substances across the tubule walls. In the proximal
tubules, the thick portion of the ascending limb of
Henle, the distal tubules, and the collecting ducts,
Na+
moves by cotransport or exchange from the
tubular lumen into the tubular epithelial cells
down its conc. and electrical gradients and is
actively pumped from these cells into the
interstitial space. Thus, Na
+
is actively transported
out of all parts of the renal tubule except the thin
portions of the loop of Henle. Na+
is pumped into
the interstitium by Na+
-K+
ATPase. It extrudes
three Na+
in exchange for two K+
that are pumped into the cell.
. The tubular cells are connected by tight junctions at their luminal edges, but there is space
between the cells along the rest of their lateral borders. Much of the Na+
is actively transported into
these extensions of the interstitial space, the lateral intercellular spaces.
. Normally about 60% of the filtered Na
+
is reabsorbed in the proximal tubule, primarily by the
Na+
–H
+
exchange. Another 30% is absorbed via the Na+
–2Cl
—
K+
cotransporter in the thick
ascending limb of the loop of Henle, and about 7% is absorbed by the Na
+
–Cl
cotransport
in the
distal convoluted tubule. The remainder of the filtered Na+
, about 3%, is absorbed via the ENaC
channels in the collecting ducts, and this is the portion that is regulated by aldosterone in the
production of homeostatic adjustments in Na+
balance.
Masaryk University Faculty of Medicine Physiology Exam
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87. Transport of glucose in kidneys
Glucose reabsorption in the kidneys is similar to glucose reabsorption in the intestine. Glucose and
Na+
bind to common carrier SGLT 2 in the luminal membrane, and glucose is carried into the cell as
Na+
moves down its electrical and chemical gradient. The Na+
is then pumped out of the cell into the
interstitium, and the glucose is transported by GLUT 2 into the interstitial fluid.
. The common carrier specifically binds the d isomer of glucose, and the rate of transport of
D-glucose is many times greater than that of L-glucose. Glucose transport in the kidneys is inhibited,
as it is in the intestine, by the plant glucoside phlorhizin, which competes with D-glucose for binding
to the carrier.
88. Urea formation
Most of the NH
4+
formed by deamination of amino acids in the liver is converted to urea, and the
urea is excreted in the urine. The NH
4+
forms carbamoyl phosphate, and in the mitochondria it is
transferred ornithine, forming citrulline. The enzyme involved is ornithine carbamoyltransferase.
Citrulline is converted to arginine, after which urea is split off and ornithine is regenerated.
.
Most of the urea is formed in the liver, and in severe liver disease the blood urea nitrogen (BUN)
falls and blood NH3 rises. Congenital deficiency of ornithine carbamoyltransferase can also lead to
NH3 intoxication, even in individuals who are heterozygous for this deficiency.
Masaryk University Faculty of Medicine Physiology Exam
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89. Hyper- and hypotonic urine. Counter-current system.
Hyper- and hypotonic urine
The osmolality of plasma and glomerular filtrate is about 290 mOsm/kgH2O (=Posm); that of the final
urine (Uosm) ranges from50 (hypotonic urine in extreme water diuresis) to about 1200mOsm/kg H2O
(hypertonic urine in maximally concentrated urine).
Countercurrent Systems
A simple exchange system A simple exchange system
(A1) can consist of two tubes in which parallel streams
of water flow, one cold (0 *C) and one hot (100 *C). Due
to the exchange of heat between them, the water leaving
the ends of both tubes will be about 50 *C, that is, the
initially steep temperature gradient of 100 *C will be
offset.
In countercurrent exchange of heat (A2), the fluid
within the tubes flows in opposite directions. Since a
temperature gradient is present in all parts of the tube,
heat is exchanged along the entire length. Molecules can
also be exchanged, provided the wall of the tube is
permeable to them and that a concentration gradient
exists for the substance.
If the countercurrent exchange of heat occurs in a hairpinshaped
loop, the bend of which is in contact with an
environment with a temperature different from that
inside the tube (ice, A3), the fluid exiting the loop will
be only slightly colder than that entering it, because heat
always passes from the warmer limb of the loop to the
colder limb.
!Countercurrent exchange of water in the vasa
recta of the renal medulla (A6 ) occurs
if the medulla becomes increasingly hypertonic
towards the papillae (see below) and if the vasa recta are
permeable towater. Part of the water diffuses by osmosis
from the descending vasa recta to the ascending ones,
thereby “bypassing” the inner medulla (A4).
Due to the extraction of water, the concentration of all
other blood components increases as the blood approaches the papilla. The plasma osmolality in the vasa
recta is therefore continuously adjusted to the osmolality of the surrounding interstitium, which rises towards
the papilla. The hematocrit in the vasa recta also rises. Conversely, substances entering the blood in the renal
medulla diffuse from the ascending
to the descending vasa recta, provided the walls of both vessels are permeable to them (e.g., urea; C). The
countercurrent exchange in the vasa recta permits the necessary supply of blood to the renal medulla without
significantly altering the high osmolality of the renal medulla and hence impairing the urine concentration
capacity of the kidney.
In a countercurrent multiplier such as the loop of Henle, a concentration gradient between the two limbs is
maintained by the expenditure of energy (_A5). The countercurrent flow amplifies the relatively small gradient
at all points between the limbs (local gradient of about 200 mOsm/kgH2O) to a relatively large gradient along
the limb of the loop (about 1000 mOsm/kgH2O). The longer the loop and the higher the one-step gradient, the
steeper the multiplied gradient. In addition, it is inversely proportional to (the square of) the flow rate in the
loop.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
90. Osmotic and water diuresis
Water diuresis
Is the excretion of urine after drinking water; results from reduced secretion of the antidiuretic
hormone of the neurohypophysis in response to the lowered osmotic pressure of the blood.
Osmotic diuresis
Osmotic diuresis is increased urination caused by the presence of certain substances in the small
tubes of the kidneys. The excretion occurs when substances such as glucose enter the kidney tubules.
The substances cause an increase in the osmotic pressure within the tubule, causing retention of
water within the lumen, and thus reduces the reabsorption of water, increasing urine output (ie.
diuresis). The same effect can be seen in therapeutics such as Mannitol.
. Substances in the circulation can also increase the amount of circulating fluid by increasing the
osmolarity of the blood. This has the effect of pulling water from the interstitial space, making more
water available in the blood and causing the kidney to compensate by removing it as urine. In
hypotension, often colloids are used intravenously to increase circulating volume in themselves, but
as they exert a certain amount of osmotic pressure, water is therefore also moved, further increasing
circulating volume. As blood pressure increases, the kidney removes the excess fluid as urine.
. Sodium, chloride, potassium are excreted in Osmotic diuresis, originating from Diabetes Mellitus
(DM). Osmotic diuresis results in dehydration from polyuria and the classic polydipsia (excessive
thirst) associated with DM.
Differences
It is important to recognize the difference between osmotic diuresis and water diuresis. In water
diuresis, the amount of water reabsorbed in the proximal portions of the nephron is normal, and the
maximal urine flow that can be produced is about 16mL/min. In osmotic diuresis, increased urine
flow is due to decreased water reabsorption in the proximal tubules and loops and very large urine
flows can be produced.
Masaryk University Faculty of Medicine Physiology Exam
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91. Micturition
Urination, also known as micturition, is the process of disposing of urine from the urinary bladder
through the urethra to the outside of the body. In healthy humans the process of urination is under
voluntary control. In infants, elderly individuals and those with neurological injury, urination may
occur as an involuntary reflex. In other animals, in addition to urination serving the purpose of
expulsion of waste material, the act can serve to mark territory or express submissiveness.
Physiologically, micturition involves coordination between the central, autonomic and somatic
nervous systems. Brain centers that regulate urination include the pontine micturition center,
periaqueductal gray, and the cerebral cortex.
In healthy individuals, the lower urinary tract has two discrete phases of activity: the storage (or
guarding) phase, when urine is stored in the bladder; and the voiding phase, when urine is released
through the urethra. The state of the reflex system is dependent on both a conscious signal from the
brain and the firing rate of sensory fibers from the bladder and urethra. At low bladder volumes,
afferent firing is low, resulting in excitation of the outlet (the sphincter and urethra), and relaxation
of the bladder.At high bladder volumes, afferent firing increases, causing a conscious sensation of
urinary urge. When the individual is ready to urinate, he or she consciously initiates voiding, causing
the bladder to contract and the outlet to relax. Voiding continues until the bladder empties
completely, at which point the bladder relaxes and the outlet contracts to re-initiate storage.
The muscles controlling micturition are controlled by the autonomic and somatic nervous systems.
During the storage phase the internal urethral sphincter remains tense and the detrusor muscle
relaxed by sympathetic stimulation. During micturition, parasympathetic stimulation causes the
detrusor muscle to contract and the internal urethral sphincter to relax. The external urethral
sphincter (sphincter urethrae) is under somatic control and is consciously relaxed during micturition.
Masaryk University Faculty of Medicine Physiology Exam
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92. Effects of thyroid hormones
Physiologic functions of thyroid hormones
Calorigenic effect
- the body’s metabolic rate in increased along with oxygen consumption and heat production
- ↑ metabolic rate and ↑ oxygen consumption are a criterion of thyroid gland activity  +/-
20% deviation indicates abnormal function of thyroid gland
- Thyroid gland is also stimulated when exposed to the cold to increase heat production
Metabolic effects
- rapid uptake of glucose by the cell
- enhanced glycolysis
- enhanced gluconeogenesis
- increased glucose absorption from GIT
- mobilization of fatty acids from adipose tissue is enhanced
- oxidation of fatty acids is enhanced
- it decreases cholesterol , phospholipids and TAG concentration in the plasma
- enhanced secretion of cholesterol into bile
- increases number of LDL receptors on the liver and therefore decreases LDL concentration in
the blood
Effects on growth and development
- is especially important for growth in childhood
- essential for normal bone growth
- it potentiates the effects of growth hormone
- hyperthyroidism causes rapid and enhanced growth of children
- hypothyroidism causes prolonged and reduced growth of children
Effects on CVS
- increased blood flow and CO
I. increased metabolism  grater quantities of metabolic end products 
vasodilation  increased blood flow  increased cardiac output
- increased heart rate
I. direct effect on excitability
II. indirect effect - TH increase the number and affinity of -adrenergic receptors in
the heart  consequently increase its sensitivity to inotropic and chronotropic
effects of catecholamines (tachycardia, increase of cardiac output)
- increased heart strength
Effects on CNS
- in hypothyroidism – brain development is retarded, mental retardation develops,
myleinisation of nerve fibers is defective (prolonged reflex time which is also of use in
diagnosis in clinical practice  Achilles tendon reflex)
- leading to cretinism with symptoms described above + failure of bone growth
- soft tissue growth is normal therefore giving the child an obese appearance
- in hyperthyroidism – extreme nervousness and psycho-neurotic tendencies
Effects on catecholamines
- Thyroid hormones potentiate effects of catecholamines on metabolic rate, nervous system
and cardiovascular system
-  level of TH =  efficiency of catecholamines
-  level of TH =  efficiency of catecholamines
Masaryk University Faculty of Medicine Physiology Exam
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93. Metabolism of iodine; Thyroid hormones synthesis
Biosynthesis of thyroid hormones
- all chemical reactions occur within the Thyroglobulin molecule
- iodide (I)
is taken up from the blood by iodide pumps and transferred into the
colloid
- Perchlorate decreases iodide uptake by competitive inhibition
- TSH stimulates the active transport of iodide
- Oxidation of iodide to iodine by peroxidases and H2O2
- Iodination of thyrosines within the thyroglobulin molecule
I. 1 iodine + thyrosine = MIT, 2 iodines + thyrosine = DIT
- Coupling of iodothyrosines:
- DIT + DIT = tetraiodothyronine (T4 - thyroxine)
- MIT + DIT = triiodothyronine (T3)
- every step of the biosynthesis is stimulated by TSH
- T3 and T4 are than taken up from the colloid by pinocytosis
- The vesicles fuse with lysosomes
I. T3 and T4 are converted into active form by proteases
- They are then released into the blood where they bind carrier proteins
1. TBG – thyroxine binding globulin highest affinity
2. TBPA – thyroxine binding prealbumin
3. albumin highest binding capacity
- thyroxine is largely a prohormone and only 25% as active as T3
- it is therefore converted to T3 via deiodination by deiodinase
- this involves the removal of an iodine from the outer ring
- if it occurs on the inner ring – inactive reverse T3 is formed
I. which can still bind the receptor and acts as a competitive inhibitor
II. the condition is called Reverse T3 Dominance
III. it may also be a physiological condition if T3 action needs to be low
IV. e.g. during stress situations adrenal gland releases excessive cortisol which
inhibits the conversion of T4 to T3
Masaryk University Faculty of Medicine Physiology Exam
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94. Hyper- and hypothyroidism
Hyperthyroidism
Causes of Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves’ Disease)
In most patients with hyperthyroidism, the thyroid gland is increased two to three times normal size.
The number of cells is increased greatly and each cell increases its rate of secretion severalfold.
Plasma TSH concentrations are less than normal in almost all patients and often are essentially zero.
Other substances that have actions similar to those of TSH are found in the blood in almost all these
patients. These substances are immunoglobulin antibodies that bind with the same membrane
receptors that bind TSH. They induce continual activation of the cAMP system of the cells, with
resultant development of hyperthyroidism. These antibodies are called thyroid-stimulating
immunoglobulin and are designed TSI. They have a prolonged stimulating effect on the thyroid
gkand, lasting for as long as 12 hours, in contrast to a little over 1 hour for TSH. The high level of
thyroid hormone secretion caused by TSI in turn suppresses the anterior pituitary formation of TSH.
The antibodies that cause hyperthyroidism almost certainly occur as the result of autoimmunity that
has developed against thyroid tissue.
Thyroid Adenoma. Hyperthyroidism occasionally results from a localized adenoma (a tumor) that
develops in the thyroid tissue and secretes large quantities of thyroid hormone. This is different from
the more usual type of hyperthyroidism, in that it usually is not associated with evidence of any
autoimmune disease. An interesting effect of the adenoma is that as long as it continues to secrete
large quantities of thyroid hormone, secretory function in the remainder of the thyroid is almost
totally inhibited because the thyroid hormone from the adenoma depresses the production of TSH by
the pituitary gland.
Symptoms of Hyperthyroidism
 a high state of excitability, intolerance to heat, increased sweating, mild to extreme weight loss,
varying degrees of diarrhea, muscle weakness, nervousness or other psychic disorders, extreme
fatigue but inability to sleep, and tremor of the hands.
Exophthalmos. Most people with hyperthyroidism develop some degree of
protrusion of the eyeballs. This condition is called exophthalmos. The cause of
the protruding of eyes is edematous swelling of the retro-orbital tissues and
degenerative changes in the extraocular muscles. In most patients,
immunoglobulins can be found in the blood that reacts with the eye muscles.
Masaryk University Faculty of Medicine Physiology Exam
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Treatment of Hyperthyroidism. The most direct treatment for hyperthyroidism is surgical removal of
the thyroid gland.
 Propylthiouracil (inhibits thyroid hormone synthesis by blocking peroxidase)
 Thyroidectomy
 β-blockers (adjunct therapy)
Other way is to inject radioactive iodine, which can destroy most of the secretory cells of the
thyroid gland. Usually 5 millicuries of radioactive iodine is given to the patient.
Hypothyroidism
Hypothyroidism, like hyperthyroidism, probably is initiated by autoimmunity against the thyroid
gland, but immunity that destroys the gland rather than stimulates it. The thyroid glands of most of
these patients first have autoimmune “thyroiditis”, which means thyroid inflammation. This cause
progressive deterioration and finally fibrosis of the gland, with resultant diminished or absent
secretion of thyroid hormone.
Endemic Colloid Goiter Caused by Dietary Iodide Deficiency. The term “goiter” means greatly
enlarged thyroid gland. The mechanism for development of large endemic goiters is the following:
Lack of iodine prevents production of both thyroxine and triiodothyronine. As a result, no hormone is
available to inhibit production of TSH by the anterior pituitary; this causes the pituitary to secrete
excessively large quantities of TSH. The TSH then stimulates the thyroid cells to secrete tremendous
amounts of thyroglobulin colloid into the follicles, and the gland grows larger and larger. But because
of lack of iodine, thyroxine and triiodothyronine production does not occur in the thyroglobulin
molecule and therefore does not cause normal suppression of TSH production by the anterior
pituitary. The follicles become tremendous in size, and the thyroid gland may increase 10 to 20 times
normal size.
Idiopathic Nontoxic Colloid Goiter. The exact cause of the enlarged thyroid gland in patients with
idiopathic colloid goiter is not known, but most of these patients show signs of mild thyroiditis;
therefore, it has been suggested that the thyroiditis causes slight hypothyroidism, which then leads
to increased TSH secretion and progressive growth of the noninflamed portions of the gland. This
could explain why these glands usually are nodular, with some portions of the gland growing while
other portions are being destroyed by the thyroiditis.
Among the abnormalities often encountered are the following:
1. Deficient iodide-trapping mechanism, in which iodine is not pumped adequately into the thyroid cells
2. Deficient peroxidase system, in which the iodides are not oxidized to the iodine state
3. Deficient coupling of iodinated tyrosine in the thyroglobulin molecule, so that the final thyroid
hormones cannot be formed
4. Deficiency of the deiodinase enzyme, which prevents recovery of iodine from the iodinated tyrosines
that are not coupled to form the thyroid hormones (this is about two thirds of the iodine), thus leading
to iodine deficiency
Finally, some foods contain goitrogenic substances that have a propylthiouracil-type of
antithyroid activity, thus also leading to TSH-stimulated enlargement of the thyroid gland. Such
goitrogenic substances are found especially in some varieties of turnips and cabbages.
Masaryk University Faculty of Medicine Physiology Exam
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Physiological Characteristics of Hypothyroidism. The physiological effects include fatigue and
extreme somnolence with sleeping up to 12 to 14 hours a day, extreme muscular sluggishness,
slowed heart rate, decreased cardiac output, decreased blood volume, sometimes increased
body weight, constipation, mental sluggishness, failure of many trophic functions in the body
evidenced by depressed growth of hair and scaliness of the skin, development of a froglike husky
voice, and , in severe cases, development of an edematous appearance throughout the body
called myxedema.
Myxedema. Myxedema, develops in the patient with almost total lack
of thyroid hormone function. In this condition, for reasons not
explained, greatly increased quantities of hyaluronic acid and
chondroitin sulfate bound with protein form excessive tissue gel in
the interstitial spaces, and this causes total quantity of interstitial
fluid to increase. Because of the gel nature of the excess fluid, it is
mainly immobile, and the edema is nonpitting type.
Atherosclerosis in Hypothyroidism. Lack of thyroid hormone increase the quantity of blood
cholesterol because of altered fat and cholesterol metabolism and diminished liver excretion of
cholesterol in the bile. The increase in blood cholesterol is usually associated with increased
atherosclerosis.
Diagnostic Tests in Hypothyroidism. The free thyroxine in the blood is low. The basal metabolic
rate in myxedema ranges between -30 and -50. And the secretion of TSH by the anterior pituitary
when a test dose of TRH (thyrotropin-releasing hormone) is administered is usually greatly
increased.
Treatment of Hypothyroidism. It is easy to maintain a steady level of thyroid hormone activity in the
body by daily oral ingestion of a tablet or more containing thyroxine.
Masaryk University Faculty of Medicine Physiology Exam
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95. Endocrine Pancreas
The pancreas is composed of two major types of tissues:
(1) the acini, which secrete digestive juice into the
duodenum, and (2) the islets of Langerhans, which secrete
insulin and glucagon directly into the blood.
1 to 2 million cellular islets of Langerhans are distributed
throughout the pancreas. They consist of endocrine cells
and are known as the islet organ.
The islets produce at least 2 antagonistic hormones:
Insulin promotes glycogen synthesis in the liver and
thereby lowers the blood sugar level. Glucagon leads to
glycogenolysis in the liver and so raises the blood sugar level.
Using immunohistochemistry and special staining techniques, three major types of cells can be
distinguished. A-cells about 20% of all cells, produce glucagon and a gastrin inhibitory polypeptide
(GIP). β-cells constituting about 60% of all cells, secrete insulin and amylin, a hormone that is often
secreted in parallel to insulin, although its function is unclear. D-cells are about 10% and secrete
somatostatin, which regulates insulin release (inhibitory). In addition D-cells contain β-endorphin.
In addition, at least one other type of cell, the PP-cell. is present in small numbers in the islets and
secretes a hormone of uncertain function, called pancreatic polypeptide.
The close interrelations among these cell types in the islets of Langerhans allow cell-to-cell
communication and direct control of secretion of some of the hormones by the other hormones.
For instance, insulin inhibits glucagon secretion, amylin inhibits insulin secretion and somatostatin
inhibits the secretion of both insulin and glucagon.
The islets are permeated by wide capillaries. A microcirculation exists between the individual islet
and the surrounding exocrine tissue through small insuloacinar portal vessels (influence, for example
of the D-cells on the activity of the exocrine pancreas).
Sympathetic fibers stimulate the secretion of glucagon and inhibit that of insulin, which is stimulated
by the vagus nerve. Serotininergic nerve fibers inhibit the release of insulin.
Masaryk University Faculty of Medicine Physiology Exam
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96. Insulin – mechanism of action
Insulin synthesis
- insulin is secreted by beta cells from islands of Langerhans
- it is synthesized as preproinsulin containing a leader sequence of aa. which is
removed once it enters the ER  GA  stored in vesicles
- proinsulin has 1/10 the activity of insulin, after removal of the C-peptide insulin is
formed (shortly before secretion)
- it consists of an A and B chain connected via disulfide bridges
- insulin circulates unbound in the blood and has a half time of 5 minutes
- 80% is degraded in the liver and kidneys by insulin protease
Insulin secretion
- as mentioned before insulin is stored in vesicles
- these are released in response to high glucose levels in the blood
- beta cells contain GLUT-2 transporter which facilitate the transport of glucose inside
the cells (at a rate that is proportional to the blood concentration in the physiologic
range) GLUT-2 does not depend on insulin
- inside the cell it is converted to glucose 6-P by glucokinase
- ATP which closes ATP-sensitive K+ channels
- that causes the cell membrane to depolarize and opens voltage-gated Ca2+ channels
- Ca2+ influx leads to fusion of insulin vesicles with the membrane
- Insulin is released via exocytosis
- Additional voltage-gated K+ channels open and K+ diffuses outside the cell which
restores the resting membrane potential
Non-metabolic effects
- mild antidiuretic effects  water retention (less glucose in urine)
- hypoglycemic dose of insulin can induce lung edema
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Metabolic effects of insulin
- increased permeability of glucose, amino acids, K+ within seconds
I. glucose via GLUT transporters
- glycogen synthesis in skeletal muscle and liver (via glycogen synthase)
- TAG synthesis in adipocytes and liver (in the liver formed VLDL transports TAGs to
adipocytes)
- Inhibition of liver phosphorylase – glycogen is not split to glucose
- Activation of glucokinase – phosphorylation of glucose – cannot diffuse back
- Stimulates Glycolysis – activates phosphofructokinase and pyruvate kinase
- Inhibition of gluconeogenesis and its enzymes
I. Pyruvate carboxylase
II. Fructose 1,6-bisphosphatase
III. Glucose 6-phosphatase
- Inhibition of HSL (hormone sensitive lipase – TAG of adipocytes to FFAs)
- Transport of glucose into adipocytes – converted to glycerol 3-P
- Stimulation of protein synthesis
- Inhibition of protein degradation (signals that aa. are not needed for gluconeogenesis)
Effects of insulin on fat metabolism
- insulin promotes fat synthesis and storage
I. first it increases the transport of glucose into the liver cell
II. where it is converted to glycogen
III. after a certain concentration of glycogen is reached (5 – 6 %)
IV. the glycogen inhibits its further synthesis
V. the excess glucose is glycolytically cleave to pyruvate
VI. enters the TCA cycle and is converted to Acetyl-CoA
VII. Acetyl-CoA is formed in excess and causes increase of citrate
VIII. Citrate is a major stimulant of fat synthesis and acetyl-CoA is a major component for
fatty acid synthesis
IX. Citrate stimulates acetyl-CoA carboxylase, which catalyzes the carboxylation of
acetyl-CoA to malonyl-CoA
X. Fatty acid synthesis proceeds and eventually TAGs will be formed
XI. These are released from the liver via lipoproteins
XII. Insulin further stimulates lipoprotein lipase which is present in the endothelium of
capillaries in adipose tissue
XIII. Lipoprotein lipase splits TAGs into FFAs and glycerol which diffuse into the
adipocytes and are converted back to TAGs
XIV. Insulin also inhibits hormone-sensitive lipase
XV. And promotes glucose transport through the membrane from which glycerol is
formed that accepts FFAs transported in the lipoproteins
Effect of insulin on protein metabolism and growth
- insulin has a direct effect on permeability of cells to amino acids
- increases uptake of amino acids by the cells and incorporation into proteins
- increases translation of mRNA  activates ribosomal maschinery
- stimulates especially formation of enzymes needed for storage of carbohydrates and fats
- inhibits the rate of protein breakdown and therefore release of amino acids
- in the liver it depresses gluconeogenesis since abundant glucose is present therefore
conserving the body’s proteins
- growth hormone and insulin act synergistically on body growth
I. in the absence of one of them the body fails to grow probably because of their
differences in specificity for amino acid uptake
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
97. Hyper- and hypoglycaemia. Diabetes mellitus.
Hyperglycemia
Or high blood sugar is a condition in which an excessive amount of glucose circulates in the blood
plasma. This is generally a blood glucose level higher than 10 mmol/l (180 mg/dl), but symptoms may
not start to become noticeable until even higher values such as 15-20 mmol/l (270-360 mg/dl).
However, chronic levels exceeding 7 mmol/l (125 mg/dl) can produce organ damage.
In diabetes mellitus, hyperglycemia is usually caused by low insulin levels (Diabetes mellitus type 1)
and/or by resistance to insulin at the cellular level (Diabetes mellitus type 2), depending on the type
and state of the disease. Low insulin levels and/or insulin resistance prevent the body from
converting glucose into glycogen (a starch-like source of energy stored mostly in the liver), which in
turn makes it difficult or impossible to remove excess glucose from the blood.
Hypoglycemia
Develops when the insulin concentration is too high. Glucose levels of <2 mmol/L (35 mg/dL) produce
glucose deficiencies in the brain, which can lead to coma and hypoglycemic shock.
The excessive intake of carbohydrates can overload glycogen stores. The liver therefore starts to
convert glucose into fatty acids, which are transported to and stored in fatty tissues in the form of
triacylglycerols.
Diabetes mellitus (DM)
One type of DM is insulin-dependent diabetes mellitus (IDDM), or type 1 DM, which is caused by an
insulin deficiency. Another type is non-insulin-dependent DM (NIDDM), or type 2 DM, which is
caused by the decreased efficacy of insulin and sometimes occurs even in conjunction with increased
insulin concentrations.
DM is characterized by an abnormally high plasma glucose concentration
(hyperglycemia), which leads to glucosuria.
Large quantities of fatty acids are liberated since lipolysis is no longer inhibited. The fatty acids can
be used to produce energy via acetylcoenzyme A (acetyl-CoA); however, this leads to the formation
of acetoacetic acid, acetone (ketosis), and β-oxybutyric acid (metabolic acidosis). Because hepatic fat
synthesis is insulin-independent and since so many fatty acids are available, the liver begins to store
triacylglycerols, resulting in the development of fatty liver.
Masaryk University Faculty of Medicine Physiology Exam
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98. Adrenal cortex. Functions, malfunctions.
The two adrenal glands lie at the superior poles of the two kidneys.
Each gland is composed of two distinct parts, the adrenal medulla and
the adrenal cortex.
The Adrenal Cortes Has Three Distinct Layers
1. The zona glomerulosa, a thin layer of cells that lie just
underneath the capsule, constitutes about 15 per cent of the
adrenal cortex. These cells are the only ones in the adrenal
gland capable of secreting significant amounts of aldosterone
because they contain the enzyme aldosterone synthase, which
is necessary for the synthesis of aldosterone. The secretion of
these cells is controlled mainly by the extracellular fluid
concentration of angiotensin II and potassium, both of which
stimulate aldosterone secretion.
2. The zona fasciculata, the middle and widest layer, constitutes about 75 per cent of the
adrenal cortex and secretes the glucocorticoids cortisol and corticosterone, as well as small
amounts of adrenal androgens and estrogens. The secretion of these cells is controlled in
large part by the hypothalamic-pituitary axis via adrenocorticotropic hormone (ACTH).
3. The zona reticularis, the deep layer of the cortex, secretes the adrenal androgens
dehydroepiandrosterone (DHEA) and androstenedione, as well as small amounts of
estrogens and some glucocorticoids. ACTH also regulates secretion of these cells, although
other factors such as cortical androgen-stimulating hormone, released from the pituitary,
may also be involved.
Adrenocortical Hormones Are Steroids Derived from Cholesterol
All human steroid hormones, including those produced by the adrenal cortex, are synthesized
from cholesterol. Approximately 80 per cent of the cholesterol used for steroid synthesis is
provided by low-density lipoproteins (LDL) in the circulating plasma. The LDLs, which have high
concentrations of cholesterol, diffuse from the plasma into the interstitial fluid and attach to
specific receptors contained in structures called coated pits on the adrenocortical cell
membranes. The coated pits are then internalized by endocytosis, forming vesicles that
eventually fuse with cell lysosomes and release cholesterol that can be used to synthesize
adrenal steroid hormones.
ACTH which stimulates adrenal steroid synthesis, increases the number of adrenocortical cell
receptors for LDL, as well as the activity of enzymes that liberate cholesterol from LDL.
Once the cholesterol enters the cell, it is delivered to the mitochondria, where it is cleaved by the
enzyme cholesterol desmolase to form pregnenolone; this is the rate-limiting step in the
eventual formation of adrenal steroids. Essentially all these steps occur in the mitochondria and
the endoplasmic reticulum.
Masaryk University Faculty of Medicine Physiology Exam
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Adrenocortical Hormones Are Bound to Plasma Proteins
Approximately 90 to 95 per cent of the cortisol in the plasma binds to plasma proteins, especially
a globulin called cortisol-binding globulin or transcortin and, to a lesser extent, to albumin. This
high degree of binding to plasma proteins slows the elimination of cortisol from the plasma;
therefore, cortisol have a relatively long half-life of 60 to 90 minutes. Only about 60 per cent of
the circulating aldosterone combines with the plasma proteins, so that about 40 per cent is in the
free form; as a result, aldosterone has a relatively short half-life of about 20 minutes.
Adrenocortical Hormones Are Metabolized in the Liver
The adrenal steroids are degraded mainly in the liver and conjugated especially to glucuronic acid
and, to a lesser extent, sulfates. About 25 per cent of these conjugates are excreted in the bile
and then in the feces. The remaining conjugates formed by the liver enter the circulation but are
not bound to plasma proteins, are highly soluble in the plasma, and therefore filtered readily by
the kidneys and excreted in the urine.
The normal conc. of aldosterone in blood is about 6 nanograms per 100ml, and the average
secretory rate is approx. 150 µg/day (0.15mg/day).
The conc. of cortisol in the blood averages 12 µg/100ml, and the secretory rate averages 15 to 20
mg/day.
Functions of the Mineralocorticoids – Aldosterone
 Mineralocorticoid deficiency causes severe renal sodium chloride wasting and
hyperkalemia
 Aldosterone increases renal tubular reabsorption of sodium and secretion of potassium
 Excess aldosterone increases extracellular fluid volume and arterial pressure but has only
a small effect on plasma sodium conc.
 Excess aldosterone causes hypokalemia and muscle weakness; Too little aldosterone
causes hyperkalemia and cardiac toxicity
 Excess Aldosterone increases tubular hydrogen ion secretion, and causes mild alkalosis
 Aldosterone stimulates sodium and potassium transport in sweat glands, salivary glands,
and intestinal epithelial cells; the effect on the sweat glands is important to conserve
body salt in hot environments, and the effect on the salivary glands is necessary to
conserve salt when excessive quantities of saliva are lost. Aldosterone also greatly
increases sodium absorption by the intestines, especially in the colon, which prevents
loss of sodium in the stools.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
Cellular Mechanism of Aldosterone Action
1st
, because of its lipid solubility in the cellular membranes, aldosterone diffuses readily to the
interior of the tubular epithelial cells.
2nd
, in the cytoplasm of the tubular cells, aldosterone combines with a highly specific cytoplasmic
receptor protein, a protein that has a stereomolecular configuration that allows only aldosterone or
very similar compounds to combine with it.
3rd
, the aldosterone-receptor complex or a product of this complex diffuses into the nucleus, where it
may undergo further alternations, finally inducing one or more specific portions of the DNA to form
one or more types of messenger RNA related to the process of sodium and potassium transport.
4th
, the messenger RNA diffuses back into the cytoplasm, where, operating in conjugation with the
ribosomes, it causes protein formation. The proteins formed are a mixture of (1) one or more
enzymes and (2) membrane transport proteins that, all acting together, are required for sodium,
potassium, and hydrogen transport through the cell membranes. One of the enzymes especially
increased is sodium-potassium adenosine triphosphatase, which serve as the principal part of the
pump for sodium and potassium exchange at the basolateral membrane of the renal tubular cells.
Thus, aldosterone does not have an immediate effect on sodium transport; rather, this effect await
the sequence of events that leads to the formation of the specific intracellular substances required
for sodium transport.
Regulation of Aldosterone Secretion
1. Increased potassium ion conc. in the extracellular fluid greatly increases aldosterone
secretion.
2. Increased activity of the rennin-angiotensin system (increased levels of angiotensin II) also
greatly increases aldosterone secretion.
3. Increased sodium ion conc. in the extracellular fluid very slightly decreases aldosterone
secretion.
4. ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little
effect in controlling the rate of secretion.
Malfunctions
Hypoadrenalism-Addison’s Disease, results from failure of the adrenal cortices to produce
adrenocortical hormones, and this in turn is most frequently caused by primary atrophy of the
adrenal cortices.(includes mineralocorticoid and glucocorticoid deficiency, and melanin
pigmentation).
Hyperadrenalism-Crushing’s syndrome, mostly ascribable to abnormal amounts of cortisol, but
excess secretion of androgens may also cause important effects.
Primary Aldosteronism (Conn’s syndrome), occasionally a small tumor of the zona glomerulosa cells
occurs and secretes large amounts of aldosterone; hypokalemia, slight increase in extracellular fluid
and blood volume, very slight increase in plasma sodium conc., and, almost always, hypertension.
Especially interesting are occasional periods of muscle paralysis caused by hypokalemia.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
99. Metabolic and anti-inflammatory affects of glucocorticoids
- Adrenocortical hormones are synthesized from the same precursor – cholesterol
(most steps are catalyzed by cytochrome P450 enzymes)
- 95% of secreted glucocorticoids are cortisol only a small amount constitutes
corticosterone and cortisone
- Secretory rates of glucocorticoids are high in the morning and low in the late evening
(circadian rhythm)
- More than 90% of glucocorticoids are bound to plasma proteins
I. 2 globulin (transcortin, CBG – corticosteroid-binding protein)
II. albumins
- bound steroids are physiologically inactive, but they have longer half-life (60 – 90
min)  protection against degradation
- they are degraded in the liver
I. reduction
II. conjugation with glucoronic acid
III. excretion mainly via urine (15% in the stool)
Effects on carbohydrate metabolism
- stimulation of gluconeogenesis in the liver mainly by using the aminoacids from
protein degradation
I. enhances transcription of enzymatic machinery in the liver
II. increases the release of amino acids from extrahepatic tissue such as muscle
into the plasma
- increase in glucose which is used to produce glycogen in the liver
I. glycogen can be converted to glucose in times of need stimulated by
epinephrine
- moderate decrease in glucose utilization  inhibiting oxidation of NADH/H+
I. NAD+ is needed in glycolysis as oxidizing agent
- Excess glucocorticoids decrease sensitivity of tissues such as skeletal muscle and
adipose tissue to insulin which causes a rise in blood glucose levels
- the hyperglycemia may be high enough to cause adrenal diabetes
Effects on protein metabolism
- protein synthesis mainly of enzymes needed for gluconeogenesis in the liver but also
plasma proteins
I. switch on mRNA transcription for enzymes
II. but also increase of plasma proteins
III. enhances transport of aa into hepatocytes
- protein degradation in extrahepatic tissues
I. but in skeletal muscle and myocardium
II. decreased formation of enzymes and proteins in general in extrahepatic
tissues
III. reduces transport of aa into extrahepatic cells
 cortisol mobilizes amino acids from extrahepatic tissues
Masaryk University Faculty of Medicine Physiology Exam
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Effects on fat metabolism
- mobilization of fatty acids and cholesterol  stimulates HSL  increase in FFAs
- enhances oxidation of FFAs (energy metabolism is shifted to the lipids)
I. reduces the uptake of glucose to form α-glycerophosphate (glycerol 3-P)
therefore oxidation may prevail
- Cushing syndrome: centripetal obesity due to excess cortisol
I. Fat deposition in the head and chest region (moon face)
II. Fat is probably more rapidly generated in these regions as compared to the
periphery which results in centripetal obesity
NOTE: the shift in energy metabolism takes several hours and is not as rapid as that caused by low
insulin
BONE - decrease of bone formation (major effect)
- increase of bone absorption
MUSCLE - protein catabolic effect  muscle atrophy and weakness
- positive inotropic effect
CT - inhibition of synthesis of collagen, GAGs and hyaluronic acid
- thinning of the skin  easily ruptured
CVS - enables response of vessels to vasoconstrictive stimuli (Epinephrine, Norepinephrine)
KIDNEY - increases perfusion of kidney  increase in glomerular filtration
- hypocorticalism  decreased GF  water retention  toxic amounts of water
CNS - can elevate the mood, interferes with sleep
- receptors in brain stem, reticular activating system, hippocampus
Anti-inflammatory effects
 administration of large amounts of cortisol blocks the inflammatory response
- either by prevention:
I. stabilizes lysosomal membranes  low conc. of proteolytic enzymes
II. decrease of capillary permeability
III. decrease of phagocytosis and migration of WBCs
IV. suppresses the immune system (production of lymphocytes)
V. attenuates fever via inhibition of IL-1 from WBCs
1. 2 – 5 due to decrease in prostaglandins and leukotrienes
- or by rapid resolution:
I. blocks factors promoting inflammation (histamine, bradykinin ,leukotrienes,
prostaglandins)
II. accelerates healing
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Regulation of cortisol secretion
Mental & physical stress  hypothalamus  CRF  ACTH  G protein  adenylyl cyclase  cAMP
 protein kinase A  CEH (cholesterol hydrolase)
CEH – catalyzes formation of pregnenolone from cholesterol
NOTE: corticotropin (ACTH) stimulates the formation of 20 -hydroxycholesterol the zona
glomerulosa is also stimulated by angiotensin II
Negative feedback is exerted by cortisol itself on the hypothalamus and the ACTH secreting cells in
the anterior pituitary gland
Stimuli of glucocorticoids secretion comprise
- infection
- trauma
- hypoglycaemia
- depression
- anxiety
Masaryk University Faculty of Medicine Physiology Exam
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100. Adrenal medulla. Synthesis of cathecholamines
The adrenal medulla is part of the adrenal gland. It is located at the
center of the gland, being surrounded by the adrenal cortex. It is
the inner most part of the adrenal gland, consisting of cells that
secrete epinephrine, norepinephrine, and a small amount of
dopamine in response to stimulation by sympathetic preganglionic
neurons.
The adrenal medulla consists of irregularly shaped cells grouped
around blood vessels. These cells are intimately connected with the sympathetic division of the
autonomic nervous system. In fact, these adrenal medullary cells are modified postganglionic
neurons, and preganglionic autonomic nerve fibers lead to them directly from the central nervous
system.
Synthesis of cathecholamines
Dopamine is the first catecholamine to be synthesized from steps shown.
Norepinephrine and epinephrine, in turn, are derived from further
modifications of dopamine. Synthesis of norepinephrine begins in the
axoplasm of the terminal nerve endings of adrenergic nerve fibers but is
completed inside the secretory vesicles. It is important to note that the
enzyme dopamine hydroxylase requires copper as a cofactor and DOPA
decarboxylase requires PLP . The rate limiting step in the biosynthesis is
hydroxylation of tyrosine.
Cortex
Medulla
Masaryk University Faculty of Medicine Physiology Exam
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101.Hypothalamo-pituitary system
- The hypophysis or pituitary gland is a small gland (1cm diameter) and it lies on the sella turcica
- Physiologically it is divided into the anterior part (adenohypophysis) and the posterior part
(neurohypophysis)
- The hypophysis and hypothalamus are joined by the infundibulum or the hypophyseal stalk
- Six important peptide hormones plus several less important ones are secreted by the anterior
pituitary, and two important peptide hormones are
secreted by the posterior pituitary
Anterior hypophysis
 Growth hormone (GH) promotes growth of the
entire body by affecting protein formation, cell
multiplication, and cell differentiation. (from
somatotropes)
 Adrenocorticotropin (corticotropin) controls the
secretion of some of the adrenocortical
hormones, which affect the metabolism of
glucose, proteins, and fats. (from corticotropes)
 Thyroid-stimulating hormone (TSH) controls the
rate of secretion of thyroxine and
triiodothyronine by the thyroid gland, and these
hormones control the rates of most intracellular
chemical reactions in the body. (from
thyrotropes)
 Prolactin promotes mammary gland development and milk production. (from
lactotropes/mamotropes)
 Two separate gonadotropic hormones, follicle-stimulating hormone and luteinizing hormone
(FSH/LH), control growth of the ovaries and testes, as well as their hormonal and
reproductive activities. (from gonadotropes)
Posterior hypophysis
- Antidiuretic hormone (also called vasopressin) controls the rate of water excretion into the
urine, thus helping to control the concentration of water in the body fluids.
- Oxytocin helps express milk from the glands of the breast to the nipples during suckling and
possibly helps in the delivery of the baby at the end of gestation
Masaryk University Faculty of Medicine Physiology Exam
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The connection
- secretion by the anterior pituitary is controlled by hormones called hypothalamic releasing and
hypothalamic inhibitory hormones secreted within the hypothalamus itself at the median
eminence by unconventional nerve endings into minute blood vessels called hypothalamichypophyseal
portal vessels adenohypophysis
- In the anterior pituitary, these releasing and inhibitory hormones act on the glandular cells to
control their secretion
- The posterior pituitary consists of many supporting structures called pituicytes. They support
nerve endings coming from the supra-optic and paraventricular nuclei of the thalamus.
- These nerves carry ADH and Oxytocin with protein carrier molecules called neurophysins.
- ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is formed primarily in the
paraventricular nuclei.
- When nerve impulses are transmitted downward along the fibers from the supraoptic or
paraventricular nuclei, the hormone is immediately released from the secretory granules in the
nerve endings by the usual secretory mechanism of exocytosis and is absorbed into adjacent
capillaries.
- Both the neurophysin and the hormone are secreted together, but because they are only loosely
bound to each other, the hormone separates almost immediately. The neurophysin has no
known function after leaving the nerve terminals.
Masaryk University Faculty of Medicine Physiology Exam
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102.Glandotropic hormones of anterior pituitary gland
Pituitary Gonadotropins & Prolactin
FSH and LH are each made up of an α and an β subunit. They are glycoproteins that contain the
hexoses mannose and galactose, the hexosamines N-acetylgalactosamine and N-acetylglycosamine,
and the methylpentose fucose. They also contain sialic acid. The carbohydrate in the gonadotropin
molecules increases their potency by markedly slowing their metabolism. The half-life of human FSH
is about 170 min; and the half-life of LH is about 60min. Loss-of-function mutations in the FSH
receptors cause hypogonadism. Gain-of-function mutations cause a spontaneous form of ovarian
hyperstimulation syndrome, a condition in which many follicles are stimulated and cytokines are
released from the ovary, causing increased vascular permeability and shock.
The half-life of prolactin is about 20min.
Receptors
The receptors of FSH and LH are serpentine receptors coupled to adenyl cyclase through Gs. In
addition, each has an extended, glycosylated extracellular domain. The human prolactin receptor
resembles the growth hormone receptor and is one of the superfamily of receptors that includes the
growth hormone receptor and receptor for many cytokines and hematopoietic growth factors. It
dimerizes and activates the JAK-STAT and other intracellular enzyme cascades.
Actions
The testes and ovaries become atrophic when the pituitary is removed or destroyed. FSH helps
maintain the spermatogenic epithelium by stimulating Sertoli cells in the male and is responsible for
the early growth of ovarian follicles in the female. LH is tropic to the Leydig cells and, in females, is
responsible for the final maturation of the ovarian follicles and estrogen secretion from them. It is
also responsible for ovulation, the initial formation of the corpus luteum, and secretion of
progesterone. Prolactin causes milk secretion from the breast after estrogen and progesterone
priming. Its effect on the breast involves increased action of mRNA and increased production casein
and lactalbumin. Prolactin also inhibits the effects of gonadotropins, possibly by an action at the level
of the ovary.
Masaryk University Faculty of Medicine Physiology Exam
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103. Growth hormone and growth factor (IGF)
Growth hormone, also called somatotropic hormone or somatotropin. It causes growth of almost all
tissues of the body which are capable of growing. It promotes increased sizes of the cells and
increased mitosis, with development of greater number of cells and specific differentiation of certain
types of cells such as bone growth cells and early muscle cells.
Metabolic effects
Including (1) increased rate of protein synthesis in most cells of the body; (2) increased mobilization
of fatty acids from adipose tissue, increased free fatty acids in the blood, and increased use of fatty
acids for energy; and (3) decreased rate of glucose utilization throughout the body.
Growth hormone promotes protein deposition in tissues by:
 Enhancement of amino acid transport through the cell membranes
 Enhancement of RNA translation to cause protein synthesis by the ribosomes
 Increased nuclear transcription of DNA to form RNA
 Decreased catabolism of proteins and amino acids
Growth hormone enhances fat utilization for energy
In tissues throughout the body, growth hormone enhances the conversion of fatty acids to acetyl
coenzyme A and its subsequent utilization for energy. Therefore, under the influence of growth
hormone, fat is used for energy in preference to the use of carbohydrates and proteins.
“Ketogenic” effect of growth hormone. Under the influence of excessive amounts of growth
hormone, fat mobilization from adipose tissue sometimes becomes so great that large quantities of
acetoacetic acid are formed by the liver and released into the body fluids, thus causing ketosis. This
excessive mobilization of fat from adipose tissue also frequently causes a fatty liver.
Growth hormone decreases carbohydrate utilization
Growth hormone causes multiple effects that influence carbohydrate metabolism, including (1)
decreased glucose uptake in tissues such as skeletal muscle and fat, (2) increased glucose production
by the liver, and (3) increased insulin secretion. Each of these changes results from growth hormoneinduced
“insulin resistance”, which attenuates insulin’s actions to stimulate the uptake and
utilization of glucose in skeletal muscle and fat and to inhibit gluconeogenesis (glucose production)
by the liver; this leads to increased blood glucose concentration and a compensatory increase in
insulin secretion.
Necessity of insulin and carbohydrate for the growth-promoting action of growth hormone.
Growth hormone fails to cause growth in animals that lacks a pancreas; it also fails to cause growth if
carbohydrates are excluded from the diet. Especially important is insulin’s ability to enhance the
transport of some amino acids into cells, in the same way that it stimulates glucose transport.
Growth Hormone Stimulates Cartilage and Bone Growth
This results from multiple effects of growth hormone on bone, including (1) increased deposition of
protein by the chondrocytic and osteogenic cells that cause bone growth, (2) increased rate of
reproduction of these cells, and (3) a specific effect of converting chondrocytes into osteogenic cells,
thus causing deposition of new bone.
Growth hormone strongly stimulates osteoblasts. Therefore, the bones can continue to become
thicker under the influence of growth hormone.
Growth Hormone Exerts Much of its Effect Through Intermediate Substances Called
“Somatomedins” (Also Called “Insulin-Like Growth Factors)
Masaryk University Faculty of Medicine Physiology Exam
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Acromegalic patient.
It has been found that growth hormone causes the liver to form several small proteins called
somatomedins that have the potent effect of increasing all aspects of bone growth. Many of the
somatomedin effects on growth are similar to the effects of insulin on growth. Therefore, the
somatomedins are also called insulin-like growth factors (IGFs). At least for somatomedins have been
isolated, but so far the most important of these is somatomedin C (also called IGF-I).
Short duration of action of growth hormone but prolonged action of somatomedin C.
Somatomedin C attaches strongly to a protein carrier in the blood that, like somatomedin C, is
produced in response to growth hormone. As a result, somatomedin C is released only slowly from
the blood to the tissues, with half-life of about 20 hours (20 min. for growth hormone). This greatly
prolongs the growth-promoting effects of the bursts of growth hormone secretion.
Regulation of Growth Hormone Secretion
Several factors to a person’s state of nutrition or stress are known to stimulate secretion:
1. starvation, especially with severe protein deficiency
2. hypoglycemia or low conc. of fatty acids in the blood
3. exercise
4. excitement
5. trauma
Role of the Hypothalamus, Growth Hormone-Releasing Hormone, and Somatostatin in the Control
of Growth Hormone Secretion. It is known that growth hormone secretion is controlled by two
factors secreted in the hypothalamus and then transported to the anterior pituitary gland through
the hypothalamic-hypophysial portal vessels. They are growth hormone-releasing hormone and
growth hormone inhibitory hormone (also called somatostatin).
The part of the hypothalamus that causes secretion of GHRH is the ventromedial nucleus.
GHRH stimulates growth hormone secretion by attaching to specific cell membrane receptors on the
outer surfaces of the growth hormone cells in the pituitary gland. The receptors activate adenylyl
cyclase system inside the cell membrane, increasing the intracellular level of cyclic adenosine
monophosphate (cAMP). This has both a short-term and a long-term effect. The short-term effect is
to increase calcium ion transport into the cell; within minutes, this causes fusion of the growth
hormone secretory vesicles with the cell membrane and release of the hormone into the blood. The
long-term effect is to increase transcription in the nucleus by the genes to stimulate the synthesis of
new growth hormone.
Abnormalities of Growth Hormone Secretion
 Panhypopituitarism – decrease in secretion may be
congenital, mostly result of a tumor.
 Dwarism –result from generalized deficiency of
anterior pituitary secretion during childhood.
 Gigantism – excessive production of growth hormone.
Body tissues grow rapidly, incl. bones.
 Acromegaly – if an acidophilic tumor occurs after adolescence – that is, after the epiphyses
of the long bones have fused with the shafts – the person cannot grow taller, but the bones
become thicker and the soft tissue can continue. Enlargement is especially marked in the
bones of the hands and feet and in the membranous bones (e.g. skull, vertebrae), because
their growth does not cease at adolescence.
Masaryk University Faculty of Medicine Physiology Exam
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104. Formation and secretion of posterior pituitary hormones
The posterior pituitary gland, also called the
neurohypophysis, is composed mainly of glial-like cells
called pituicytes. The pituicytes do not secrete hormones;
they act simply as a supporting structure for large numbers
of terminal nerve fibers and terminal nerve endings from
nerve tracts that originate in the supraoptic and
paraventricular nuclei of the hypothalamus. These tracts
pass to the neurohypophysis through the pituitary stalk
(hypophysial stalk). The nerve endings are bulbous knobs
that contain many secretory granules. These endings lie on
the surface of capillaries, where they secrete two posterior
pituitary hormones: (1) antidiuretic hormone (ADH), also
called vasopressin, and (2) oxytocin.
The hormones are initially synthesized in the cell bodies of the supraoptic and paraventricular nuclei
and are then transported in combination with “carrier” proteins called neurophysins down to the
nerve endings in the posterior pituitary gland.
ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is formed primarily in the
paraventricular nuclei. When nerve impulses are transmitted downward along the fibers from the
supraoptic or paraventricular nuclei, the hormone is immediately released from the secretory
granules in the nerve endings by the usual secretory mechanism exocytosis and is absorbed into
adjacent capillaries. Both the neurophysin and the hormone are secreted together, but because they
only are loosely bound to each other, the hormone separates almost immediately.
Both oxytocin and ADH (vasopressin) are polypeptides, each containing nine amino acids.
Physiological Functions of ADH
In the absence of ADH, the collecting tubules and ducts become almost impermeable to water, which
prevents significant reabsorption of water and therefore allows extreme loss of water into the urine,
also causing extreme dilution of the urine. In the luminal membranes of the tubular epithelial cells of
the collecting ducts, immediately inside the cell membranes are large number of special vesicles that
have highly water-permeable pores called aquaporins. When ADH acts on the cell, its first combines
with the membrane receptors that activate adenylyl cyclase and cause the formation of cAMP inside
the tubular cell cytoplasm. This causes phosphorylation of elements in the special vesicles, which
then causes the vesicles to insert into the apical cell membranes, thus providing many areas of high
water permeability.
Regulation of ADH
Osmotic regulation. There are modified neuron receptors called, osmoreceptors. The exact location
of the receptors is not known. When the extracellular fluid becomes to concentrated, fluid is pulled
by osmosis out of the osmoreceptors cell, decreasing its size and initiating appropriate nerve signals
in the hypothalamus to cause additional ADH secretion.
Concentrated body fluids stimulate the supraoptic nuclei, whereas dilute body fluids inhibit them.
Vasoconstrictor and Pressure Effects of ADH, and Increased ADH Secretion Caused by Low Blood
Volume. Higher conc. of ADH have a potent effect on constricting the arterioles throughout the body
and therefore increasing the arterial pressure. For this reason, ADH has another name, vasopressin.
One of the stimuli for causing intense ADH secretion is decreased blood volume.
Masaryk University Faculty of Medicine Physiology Exam
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The atria have stretch receptors that are excited by overfilling. When excited, they send signals to the
brain to inhibit ADH secretion. Decreased stretch of the baroreceptors of the carotid, aortic, and
pulmonary regions also stimulates ADH secretion.
Oxytocin Hormone
Oxytocin Causes Contraction of Pregnant Uterus. The hormone oxytocin, in accordance with its
name, powerfully stimulates contraction of the pregnant uterus, especially toward the end of
gestation.
Oxytocin Aids in Milk Ejection by the Breasts. Oxytocin plays an especially important role in
lactation. In lactation, oxytocin causes milk to be expressed from the alveoli into the ducts of the
breasts so that the baby can obtain it by suckling.
This mechanism works as follows:
 The suckling stimulus on the nipple of the breast causes signals to be transmitted through
sensory nerves to the oxytocin neurons in the paraventricular and supraoptic nuclei in the
hypothalamus, which causes release of oxytocin by the posterior pituitary gland.
 The oxytocin is then carried by the blood to the breasts, where it causes contraction of
myoepithelial cells that lie outside of and form a latticework surrounding the alveoli of the
mammary glands.
 In less than a minute after the beginning of suckling, milk begins to flow.
105. Hypothalamic releasing hormones (see q. 101)
106. Parathormone, vitamin D and calcitonin
Three hormones are primarily concerned with the regulation of calcium.
1,25-Dihydroxycholecalciferol is a steroid hormone formed from vitamin D by successive
hydroxylation in the liver and kidneys. Its primary action is to increase calcium absorption from the
intestine. Parathyroid hormone (PTH) is secreted by the parathyroid glands. Its main action is to
mobilize calcium from bone and increase urinary phosphate excretion. Calcitonin, a calcium-lowering
hormone that in mammals is secreted primarily by cells in the thyroid gland, inhibits bone
reabsorption.
Parathyroid hormone (PTH)
 Is the major hormone for the regulation of serum [Ca2+
].
 Is synthesized and secreted by the chief cells of the parathyroid glands.
1. Secretion of PTH
 is controlled by serum [Ca2+
] through negative feedback. Decreased serum [Ca2+
] increases
PTH secretion.
 Mild decreases in serum [Mg2+
] stimulate PTH secretion.
 Severe secretion in serum [Mg2+
] inhibit PTH secretion and produce symptoms
of hypoparathyroidism (e.g., hypocalcemia).
 The second messenger for PTH secretion by the parathyroid gland is cAMP.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
2. Actions of PTH
 Is coordinated to produce an increase in serum [Ca2+
] and a decrease in serum [phosphate].
 The second messenger for PTH actions on its target tissues is cAMP.
a. PTH increases bone resorption, which brings both Ca2+
and phosphate from the bone mineral
into the ECF. Alone, this effect on bone would not increase the serum ionized [Ca2+
] because
phosphate complexes Ca
2+
.
 Resorption of the organic matrix of bone is reflected in increased hydroxyproline
excretion.
b. PTH inhibits renal phosphate reabsorption in the proximal tubule and, therefore, increases
phosphate excretion (phosphaturic effect). As a result, the phosphate resorbed from bone is
excreted in the urine, allowing the serum ionized [Ca
2+
] to increase.
 cAMP generated as a result of the action of PTH on the proximal tubule is excreted in the
urine (urinary cAMP).
c. PTH increases renal Ca
2+
reabsorption in the distal tubule. Which also increases the serum
[Ca
2+
].
d. PTH increases intestinal Ca2+
absorption indirectly by stimulating the production of 1.25dihydrocholecalciferol
in the kidney.
Vitamin D
 Provides Ca
2+
and phosphate to ECF for bone mineralization
 In children, vitamin D deficiency causes rickets.
 In adults, vitamin D deficiency causes osteomalacia.
1. Vitamin D metabolism
 The active form of vitamin D is 1,25-dihydroxycholecalciferol.
 The production of 1,25-dihydroxycholecalciferol in the kidney is catalyzed by
the enzyme 1α-hydroxylase.
 1α-hydroxylase activity is increased by the following:
a. serum [Ca
2+
]
b. PTH levels
c. serum [phosphate]
2. Actions of 1,25-dihydroxycholecalciferol
 are coordinated to increase both [Ca
2+
] and [phosphate] in ECF to mineralize new bone.
a. Increases intestinal Ca
2+
absorption. Vitamin D-dependent Ca
2+
-binding
protein (calbindin D-28K) is induced by 1,25-dihydroxycholecalciferol.
> PTH increases intestinal Ca
2+
absorption indirectly by stimulating 1α-hydroxylase and
increasing production of the active form of vitamin D.
b. Increases intestinal phosphate absorption.
c. Increases renal reabsorption of Ca
2+
and phosphate
d. Increase bone resorption, which provides Ca
2+
and phosphate from “old” bone
to mineralize “new” bone.
Calcitonin
 is synthesized and secreted by the parafollicular cells of the thyroid.
 secretion is stimulated by an increase in serum [Ca
2+
]
 acts primarily to inhibit bone resorption.
 can be used to treat hypercalcemia.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
107. Vasopressin and natriuretic hormone
Physiological Functions of ADH (=antidiuretic hormone = vasopressin)
In the absence of ADH, the collecting tubules and ducts become almost impermeable to water, which
prevents significant reabsorption of water and therefore allows extreme loss of water into the urine,
also causing extreme dilution of the urine. In the luminal membranes of the tubular epithelial cells of
the collecting ducts, immediately inside the cell membranes are large number of special vesicles that
have highly water-permeable pores called aquaporins. When ADH acts on the cell, its first combines
with the membrane receptors that activate adenylyl cyclase and cause the formation of cAMP inside
the tubular cell cytoplasm. This causes phosphorylation of elements in the special vesicles, which
then causes the vesicles to insert into the apical cell membranes, thus providing many areas of high
water permeability.
Regulation of ADH
Osmotic regulation. There are modified neuron receptors called, osmoreceptors. The exact location
of the receptors is not known. When the extracellular fluid becomes to concentrated, fluid is pulled
by osmosis out of the osmoreceptors cell, decreasing its size and initiating appropriate nerve signals
in the hypothalamus to cause additional ADH secretion.
Concentrated body fluids stimulate the supraoptic nuclei, whereas dilute body fluids inhibit them.
Vasoconstrictor and Pressure Effects of ADH, and Increased ADH Secretion Caused by Low Blood
Volume. Higher conc. of ADH have a potent effect on constricting the arterioles throughout the body
and therefore increasing the arterial pressure. For this reason, ADH has another name, vasopressin.
One of the stimuli for causing intense ADH secretion is decreased blood volume.
The atria have stretch receptors that are excited by overfilling. When excited, they send signals to the
brain to inhibit ADH secretion. Decreased stretch of the baroreceptors of the carotid, aortic, and
pulmonary regions also stimulates ADH secretion.
Natriuretic hormone
Masaryk University Faculty of Medicine Physiology Exam
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Two of these are secreted by the heart. The muscle cells in the atria and, to a much lesser extent, in
the ventricles contain secretory granules. The granules increase in number when NaCl intake is
increased and extracellular fluid expanded, and extracts of arterial tissue cause natriuresis.
The first natriuretic hormone isolated from the heart was atrial natriuretic peptide (ANP), a
polypeptide with 17-amino-acid ring formed by a disulfide bond between two cysteines. The
circulating form of this polypeptide has 28 amino acid residues. ANP was subsequently isolated from
other tissues, including the brain, where it exists in two forms that are smaller than the circulating
ANP. A second natriuretic polypeptide was isolated from the porcine brain and named brain
natriuretic peptide (BNP; also known as B-type natriuretic peptide). It is also present in the brain in
humans, but more is present in the heart. A third member of this family has been named C-type
natriuretic peptide (CNP) because it was the third in the sequence to be isolated. CNP is present in
the brain, the pituitary, the kidneys, and vascular endothelial cells. However, very little is present in
the heart and the circulation, and it appears to be primarily a paracrine mediator.
Actions
ANP and BNP in the circulation act on the kidneys to increase Na+
excretion, and injected CNP has a
similar effect. They appear to produce this effect by dilating afferent arterioles ad relaxing mesangial
cells. Both of this actions increase the glomerular filtration. In addition, they act on the renal tubules
to inhibit Na+
reabsorption. Other actions include an increase in capillary permeability, leading to
extravasation of fluid and a decline in blood pressure. CNP has the greatest dilator effect on veins.
These peptides also inhibit rennin secretion and counteract the pressor effects of cathecholamines
and angiotensin II.
In the brain, ANP is present in neurons. In general, the effects of ANP in the brain are opposite to
those of angiotensin II, and ANP-containing neural circuits appear to be involved in lowering blood
pressure and promoting natriuresis.
Natriuretic Peptide Receptors
Three different natriuretic peptide receptors (NPR)
have been isolated and characterized.
The NPR-A and NPR-B receptors both span the cell
membrane and have cytoplasmic domains that are
guanylyl cyclases. ANP has greatest affinity for the
NPR-A receptor, and CNP has the greatest affinity for
the NPR-B receptor. The third receptor, NPR-C, binds
all three peptides but has a markedly shortened cytoplasmic domain. Some evidence suggests that it
acts via G-proteins to activate phospholipase C and inhibit adenylyl cyclase. However, it has also been
argued that this receptor does not trigger any intracellular change and instead a clearance receptor
that removes natriuretic peptides from the blood stream and then releases them later, helping to
maintain a steady blood level of the hormones.
Secretion & Metabolism
The conc. of ANP in plasma is about 5 fmol/mL in humans. ANP secretion is increased when the ECF
volume is increased by infusion of isotonic saline and when atria are stretched. BNP secretion is
increased when ventricles are stretched. ANP secretion is also increased by immersion in water up to
the neck, a procedure that counteracts the effect of gravity on the circulation and increases central
venous and consequently atrial pressure. Plasma levels of both hormones are elevated in congestive
heart failure.
Circulating ANP has a short half-life. It is metabolized by neutral endopeptidase (NEP), which is
inhibited by thiorphan. Therefore, administration of thiorphan increases circulating ANP.
Masaryk University Faculty of Medicine Physiology Exam
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108. Endorphins and enkephalins
Opioid Peptides
The brain and the gastrointestinal tract contain receptors that bind morphine. The search for
endogenous ligands for these receptors led to the discovery of two closely related pentapeptides,
called enkephalins, that bind to these opioid receptors. One contains methionine (met-enkephalin),
and one contains leucine (leu-enkephalin). These and other peptides that bind to opioid receptors
are called opioid peptides. The enkephalins are found in nerve endings in the gastrointestinal tract
and many different part of the brain, and they appear to function as synaptic transmitters. They have
analgesic activity when injected into the brain stem. They also decrease intestinal motility.
Opioid receptors
There are 3 opioid receptors: µ, κ, and δ. They differ
in physiological effects, distribution, and affinity for
various opioid peptides. All three are serpentine
receptors coupled to Gq, and all inhibit adenylyl
cyclase.
Endorphins
Endorphins are endogenous opioid polypeptide compounds. They are produced by the pituitary
gland and the hypothalamus in vertebrates during exercise, excitement, pain, consumption of spicy
food and orgasm, and they resemble the opiates in their abilities to produce analgesia and a feeling
of well-being. Endorphins work as "natural pain relievers".
When a nerve impulse reaches the spinal cord, endorphins are released which prevent nerve
cells from releasing more pain signals.
Mechanism of action
β-endorphin is released into blood from the pituitary gland and into the spinal cord and brain from
hypothalamic neurons. β-endorphin is a cleavage product of pro-opiomelanocortin (POMC) which is
also the precursor hormone for adrenocorticotropic hormone (ACTH). The behavioral effects of βendorphin
are exerted by its actions in the brain and spinal cord, and probably the hypothalamic
neurons are the major source of β-endorphin at these sites. In situations where the level of ACTH is
increased (e.g. Cushing‘s syndrome), the level of endorphins also increases slightly.
β-endorphin has the highest affinity for the μ1 opioid receptor, slightly lower affinity for the μ2 and δ
opioid receptors and low affinity for the κ1 opioid receptors. μ opioid receptors are the main receptor
through which morphine acts. Classically, μ opioid receptors are presynaptic, and inhibit
neurotransmitter release; through this mechanism, they inhibit the release of the inhibitory
neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be
released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and
lead to aberrant synaptic plasticity, which causes addiction. Opioid receptors have many other and
more important roles in the brain and periphery however, modulating pain, cardiac, gastric and
vascular functions as well as possibly panic and satiation, and receptors are often found at
postsynaptic locations as well as presynaptically.
Masaryk University Faculty of Medicine Physiology Exam
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109. Pineal gland. Circadian rhythm.
Anatomy of Pineal Gland
The pineal gland arises from the roof of the third ventricle and is connected by a stalk to the
posterior commissure and habenular commissure. The pineal stroma contains neuroglia and
parenchymal cells. Like other endocrine glands, the pineal has highly permeable fenestrated
capillaries. In young animals and infants, the pineal is large, and the cells tend to be arranged in
alveoli. It begins to involute before puberty, and, in humans, small concretions of calcium phosphate
and carbonate (pineal sand) appear in the tissue.
It produces melatonin, a hormone that affects the modulation of wake/sleep patterns and
photoperiodic (seasonal) functions.
Regulation of Secretion
Melatonin synthesis and secretion is increased during the dark period of the day and maintained at a
low level during daylight hours. This remarkable diurnal variation of secretion is brought about by
norepinephrine secreted by the postganglionic sympathetic nerves (nervi coranii) that innervate the
pineal. The norepinephrine acts via β-adrenergic receptors in the pineal to increase intracellular
cAMP, and the cAMP in turn produces a marked increase in N-acetyltransferase activity. This results
in increased melatonin synthesis and secretion.
This discharge of the sympathetic nerves to the pineal is entrained to the light-dark cycle in the
environment via the retinohypothalamic nerve fibers to the suprachiasmatic nuclei.
Function of the Pineal Gland
Injected melatonin has effects on the gonads, but at least in some species these effects are
sometimes stimulating and sometimes inhibitor, depending on the time of day the hormone is
injected. This observation led to the hypothesis that the diurnal change in melatonin secretion
functions as a timing signal that coordinates endocrine and other internal events with the light-dark
cycle environment. Evidence supporting this timing function of melatonin includes the observation
that in blind people with free-circadian rhythms, melatonin injections entrain the rhythms.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
110. Ovarian cycle and its control
It is defined as cyclic changes in the ovaries of sexual mature females. The cycle includes 3 phases:
. 1. preovulatory (estrogenic) – follicles gradually grow and produce estrogen, the phase is
. controlled by FSH produced by adenohypophysis.
. 2. Ovulatory or ovulation – a time of follicle rupture and expelling of the secondary oocyte.
. 3. postovulatory (progesteronic) – a phase of formation of the corpus luteum and production of
. progesterone. It is controlled by LH produced by the adenohypophysis.
Ovarian follicle growth (Ovarian cycle)
- follicular phase
o primordial follicles with a single layer of granulosa cells are present
o develop into primary oocytes which have several layers of granulosa cells after the
secretion of FSH and LH
o esp. FSH secretion promotes follicle maturation into secondary oocytes which obtain
theca cells (derived from the spindle-shaped fibroblasts)
 theca cells  secrete androgen precursor
 granulosa cells  convert the precursor into estradiol (an estrogen)
o which further mature into Graafian follicles developing an antrum due to the
accumulation of the follicular fluid (which contains the estrogens)
 the estrogens stimulate formation of FSH receptors
 increasing the sensitivity of granulosa cells to FSH
 FSH and estrogens also promotes formation of LH receptors
o One Graafian follicle outgrows the others which undergo atresia allowing only one
follicle to leave the ovaries
o Ovulation – occurs 14 days after onset of menstruation
o LH is necessary for final maturation of follicle and ovulation (LH surge)
o LH also stimulates conversion of granulosa and theca cells into progesteronesecreting
cells
o Ovulation occurs due to swelling of follicle and rupture of the stigma
- luteal phase
o after ovulation the remaining granulosa and theca cells become lutein cell forming
the corpus luteum
o this step is stimulated by LH
o secreting mainly progesterone but also estrogen
o LH stimulates secretion of female sex hormones by the corpus luteus
 If fertilization occurs and therefore development of fertilized ovum into
blastocyst it will secrete hCG (human chorionic gonadotropin)
 Corpus luteum is called – corpus luteum graviditatis
 If fertilization does not occur the corpus luteum involutes into the corpus
albicans (scar tissue) 12 days after ovulation
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
111. Uterine cycle
 the menstrual phase - from the 1rst to 4th days of the cycle, is characterized by menstrual
bleeding. The phase is induced by rapidly decrease of the levels of progesterone and
estrogens. The endometrium is reduced to only the basalis containing the basal portions of
the uterine glands.
 the proliferative phase - (follicular phase - because it coincides with the development of
ovarian follicles and the production of estrogen)- from 5th to 14th days. Is characterized by
proliferation of uterine gland cells as well as connective tissues cells and deposition of the
ground substance. The endometrium is 2-3 mm thick and contains straight and unbranched
uterine glands, coiled arteries grow into the regenerating stroma. The phase is controlled
with estrogens.
 the secretory phase (luteal phase )- starts after ovulation and ends at day 26, controlled with
progesterone secreted by the corpus luteum. The functionalis becomes thicker (5-6 mm at
the end of the s. p.) and edematous. Gland are coiled and branched and their cells begin to
accumulate glycogen below the nuclei. Functionalis can be divided into the pars compacta
(superficially) and pars spongiosa (contains dilated lumens of uterine glands).
 the ischemic phase - days 27 to 28. Is characterized by a spasm of coiled blood vessels
following with subsequent ischemia and necrosis of blood vessel walls and of the
functionalis. Immediately after blood constriction follows ruptures of vessels and menstrual
bleeding.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
!
112. Physiology of pregnancy
 is characterized by steadily increasing levels of estrogen and progesterone, which maintain
the endometrium for the fetus, suppress ovarian follicular function (by inhibiting FSH and LH
secretion), and stimulate development of the breasts.
 The rate at which the corticotropin-releasing hormone (CRH) concentration rises seems to
determine the duration of the pregnancy.
1. Fertilization
– If fertilization occurs, the corpus luteum is rescued from regression by human chorionic gonadotropin (hCG),
which is produced by the placenta.
2. First trimester
– The corpus luteum (stimulated by hCG) is responsible for the production of estradiol and progesterone.
– Peak levels of hCG occur at gestational week 9 and then decline.
3. Second and third trimester
– Progesterone is produced by the placenta.
– Estrogens are produced by interplay of the fetal adrenal gland and the placenta. The fetal adrenal gland
synthesized dehydroepiandrosterone-sulfate (DHEA-S), which is then hydroxylated in the fetal liver. These
intermediates are transferred to the placenta, where enzymes remove sulfate and aromatize to estrogens. The
major placental estrogen is estriol.
– Human placental lactogen (hPL 0= human chorionic somatomammotropin, hCS) is produced throughout
pregnancy. It stimulates mammary enlargement and lactogenesis.
4. Parturition
– Throughout pregnancy, progesterone increases the threshold of uterine contraction.
– Near term, the estrogen/progesterone ratio increases, which makes the uterus more sensitive to contractile
stimuli.
– Estrogens increases uterine contractility, partly by increasing the number of gap junctions between adjacent
uterine smooth muscle cells.
– From 7
th
month onward, estrogen secretin continues to increase while progesterone secretion remains
constant or perhaps even decreases slightly.
5. Lactation
– Estrogens and progesterone stimulate the growth and development of the breasts throughout pregnancy.
– Prolactin levels increase steadily during pregnancy because estrogen stimulates prolactin secretion from the
anterior pituitary.
– Lactation does not occur during pregnancy because estrogen and progesterone block the action of
prolactin on the breast.
– After parturition, estrogen and progesterone levels decrease abruptly and lactation occurs.
– Lactation is maintained by suckling, which stimulates both oxytocin and prolactin secretion.
– Ovulation is suppressed as long as lactation continues because prolactin has the following effects:
. a. Inhibits hypothalamic GnRH secretion.
. b. Inhibits the action of GnRH on the anterior pituitary, and consequently inhibits LH and FSH secretion.
. c. Antagonizes the actions of LH and FSH on the ovaries.
–> Oxytocin is released in the last 2-3 weeks approx. Increased levels of oxytocin results in increased
contraction and opposite (positive feedback).
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
113. Physiology of parturition and lactation
Parturition
- Parturition means birth of the baby. Toward end of pregnancy,
uterine develops such strong contractions that the baby is expelled.
- Hormonal factors that increase uterine contractility:
o Estrogens increase the number of gap junctions between adjacent
uterine smooth muscle cells.
o Oxytocin secreted by the neurohypophysis specifically causes
uterine contraction
o Fetal oxytocin, cortisol, prostaglandins
- Mechanical factors that increase uterine contractility:
o Fetal movements can also elicit smooth muscle contraction.
o Stretch or irritation of the cervix
- Onset of Labor – A positive feedback mechanism for its initiation:
o Labor - the weaker uterine contractions becomes stronger and causes the stretching of cervix
and later force the baby through the birth canal, thereby causing parturition.
o Positive feedback theory –suggests that stretching of the cervix by the fetus’s head finally
becomes great enough to elicit a strong reflex increase in contractility of the uterine body.
This pushes the baby forward, which stretches the cervix more and initiates more positive
feedback to the uterine body. Thus, the process repeats until the baby is expelled.
Lactation
- development of the breasts is stimulated by the monthly increase in estrogen and is even
more stimulated by the large amount secreted during pregnancy
o only during pregnancy the mammary glands fully develop
- 4 other hormones play important roles in the development of the glands
o Growth hormone
o Prolactin
o Parathyroid hormone
o Glucocorticoids
o insulin
- these hormones are necessary to provide Ca2+,
glucose, amino acids and fats for the breast
milk
- progesterone causes synergistically with all aforementioned hormones growth of the breast
lobules and their secretory characteristics (like that of endometrium)
- estrogen and progesterone inhibit lactation
- prolactin (from the hypophysis) and human chorionic somatomammotropin stimulate the
secretion of milk
- However the net effect is only a small amount of milk secretion per day
- After parturition progesterone and estrogen levels decline and prolactin prevails
- Ejection process of milk
o Milk is continuously secreted into the duct system but not ejected
o Baby suckles on the nipples – spinal cord – hypothalamus – oxytocin is released by
neurohypophysis and prolactin secretion by adenohypophysis
o Oxytocin causes contraction of myoepithelial cells which surround the alveoli which causes
milk ejection
o Prolactin stimulates secretion of milk and ensures future supply of breast milk
- Composition of breast milk: Lactose, Casein, Water, Linoleic acid, Electrolytes esp. Ca2+
,
Vitamins (A,B,C,D), IgA.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
114. Endocrine function of the testes
Testosterone
– is the major androgen synthesized and secreted by the Leydig cells.
– LH increases testosterone synthesis by stimulating cholesterol desmolase, the first step in the
. pathway.
– Accessory sex organs (e.g., prostate) contain 5α-reductase, which converts testosterone
. to its active form, dihydrotestosterone.
– 5α-reductase inhibitors (finasteride) may be used to treat benign prostatic hyperplasia because
. they block the activation of testosterone to dihydrotestosterone in the prostate.
Regulation of testes
1. Hypothalamic control – GnRH
. – Arcuate nuclei of the hypothalamus secrete GnRH into the hypothalamic-hypophysial portal blood.
. GnRH stimulates the anterior pituitary to secrete FSH and LH.
2. Anterior pituitary – FSH and LH
. – FSH acts on the Sertoli cells to maintain spermatogenesis. The Sertoli cells also secrete inhibin, which is
. involved in negative feedback of FSH secretion.
. – LH acts on the Leydig cells to promote testosterone synthesis. Testosterone acts via an intratesticular
. paracrine mechanism to reinforce the spermatogenic effects of FSH in the Sertoli cells.
3. Negative feedback control – testosterone and inhibin
– Testosterone inhibits the secretion of LH by inhibiting the release of GnRH from the hypothalamus and by
. directly inhibiting the relase of LH from the anterior pituitary.
– Inhibin (produced by the Sertoli cells) inhibits the secretion of FSH from the anterior pituitary.
Actions of Testosterone
– Differentiation of epididimys, vas deferens, and seminal vesicles
– Pubertal growth spurt
– Cessation of pubertal growth spurt (epiphyseal closure)
– Libido
– Spermatogenesis in Sertoli cells (paracrine effect)
– Deepening of voice
– Increased muscle mass
– Growth of penis and seminal vesicles
– Negative feedback on anterior pituitary
Actions of dihydrotestosterone
– Differentiation of penis, scrotum, and prostate
– Male hair pattern
– Male pattern baldness
– Sebaceous gland activity
– Growth of prostate
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
115. Sex reflexes
Coordinated sexual activity depends on a series of reflexes integrated at many neural levels an its
absent after cord transection. However, genital manipulation in male spinal animals and humans
produces erection and even ejaculation. In female spinal dogs, vaginal stimulation causes tail
deviation and movement of the pelvis into the copulatory position.
116.Regulation of body fluid volume
Fluid Intake and Output Are Balanced During Steady-State Conditions
The relative constancy of the body fluids is remarkable because there is continuous exchange of fluid and
solutes with the external environment as well as within the different compartments of the body.
Daily Intake of Water
Water is added to the body by two major sources: (1) it is ingested in the form of liquids or water in the food,
which together normally add about 2100 ml/day to the body fluids, and (2) it is synthesized in the body as a
result of oxidation of carbohydrates, adding about 200 ml/day. This provides a total water intake of about 2300
ml/day.
Daily Loss of Body Water
Insensible Water Loss. Some of the water losses cannot be precisely regulated. For example, there is a
continuous loss of water by evaporation from the respiratory tract and diffusion through the skin, which
together account for about 700 ml/day of water loss under normal conditions. This is termed insensible water
loss because we are not consciously aware of it, even though it occurs continually in all living humans.
The average water loss by diffusion through the skin is about 300 to 400 ml/day. This loss is minimized by
the cholesterol-filled cornified layer of the skin, which provides a barrier against excessive loss by diffusion.
Insensible water loss through the respiratory tract averages about 300 to 400 ml/day. As air enters the
respiratory tract, it becomes saturated with moisture, to a vapor pressure of about 47 mm Hg, before it is
expelled. Because the vapor pressure of the inspired air is usually less than 47 mm Hg, water is continuously
lost through the lungs with respiration. In cold weather, the atmospheric vapor pressure decreases to nearly 0,
causing an even greater loss of water from the lungs as the temperature decreases.
Fluid Loss in Sweat.
The volume of sweat normally is about 100 ml/day, but in very hot weather or during heavy exercise, water loss in sweat
occasionally increases to 1 to 2 L/hour.
Water Loss in Feces. Only a small amount of water (100 ml/day) normally is lost in the feces. This can increase to several
liters a day in people with severe diarrhea. For this reason, severe diarrhea can be life threatening if not corrected within a
few days.
Water Loss by the Kidneys. The remaining water loss from the body occurs in the urine excreted by the kidneys. There are
multiple mechanisms that control the rate of urine excretion. In fact, the most important means by which the body
maintains a balance between water intake and output, as well as a balance between intake and output of most electrolytes
in the body, is by controlling the rates at which the kidneys excrete these substances.
Regulation of Fluid Exchange and Osmotic Equilibrium Between Intracellular and Extracellular Fluid
The relative amounts of extracellular fluid distributed between the plasma and interstitial spaces are
determined mainly by the balance of hydrostatic and colloid osmotic forces across the capillary membranes.
The distribution of fluid between intracellular and extracellular compartments, in contrast, is determined
mainly by the osmotic effect of the smaller solutes— especially sodium, chloride, and other electrolytes—
acting across the cell membrane. The reason for this is that the cell membranes are highly permeable to water
but relatively impermeable to even small ions such as sodium and chloride. Therefore, water moves across the
cell membrane rapidly, so that the intracellular fluid remains isotonic with the extracellular fluid.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
117.Regulatio of constant osmotic pressure
Osmoregulation
The osmolality of most body fluids is about 290mOsm/kg H2O, so that the intracellular fluid (ICF) and
extracellular fluid (ECF) are generally in osmotic balance. Any increase in the osmolality of ECF due,
for example, to NaCl absorption or water loss, results in an outflow of water from the intracellular
space (cell shrinkage). A fall in extracellular osmolality due to drinking or infusion of large volumes of
water or to sodium loss (e.g. in aldosterone deficit) results in an inflow of water to the cells from the
ECF (cell expansion). Both volume fluctuations endanger the cell’s functioning, but the cell can
protect against them.
The osmolality of the ECF as a whole must be tightly regulated to protect cells from large volume
fluctuations. Osmoregulation is controlled by central osmosensors (or osmoreceptors) located in
circumventricular organs (SFO and OVLT, see below). H2O fluctuations in the gastrointestinal tract are
monitored by peripheral osmosensors in the portal vein region and communicated to the
hypothalamus by vagal afferent neurons.
Water deficit. Net water losses (hypovolemia) due, for example, to sweating make the ECF
hypertonic. Osmolality rises of only 1–2% are sufficient to increase the secretion of ADH (antidiuretic
hormone = vasopressin), from the posterior lobe of the pituitary. ADH decreases urinary H2O
excretion.
Fluid intake from outside the body is also required, however. The likewise hypertonic cerebrospinal
fluid (CSF), via osmosensors in the OVLT (organum vasculosum laminae terminalis) and SFO
(subfornical organ) stimulates the secretion of (central) angiotensin II (AT II) which trigger
hyperosmotic thirst.
Isotonic hypovolemia, for example following blood loss or secondarily following hyponatremia also
stimulates thirst (hypovolemic thirst). The sensors for hypovolemia are primarily the atrial volume
sensors. Via their afferent pathways and the nucleus tractus solitarii (NTS) secretion of central AT II is
triggered in the SFO and via the sympathetic nervous system and β1-adrenoceptors in the kidney the
peripheral renin-AT-II system (RAS) is activated. A drop in mean blood pressure below approx.
85mmHg triggers very high renin secretion directly in the kidney.
Thirst is a subjective perception and motivation to search for fluids and drink. The thirst that is a
homeostatic response to hyperosmolality or hypovolemia (_0.5% of body weight: thirst threshold)
triggers primary drinking. Drinking quenches the thirst before osmolality has completely normalized.
This pre-resorptive thirst quenching is astonishingly accurate as regards the estimate of volume, due
to afferent signals from volume sensors and osmosensors in the throat, gastrointestinal tract, and
liver.
Relaxin, a peptide hormone produced by the corpus luteum in pregnant
women, binds to receptors in the SFO and OVLT. It causes thirst and
stimulates ADH secretion. Despite the reduced plasma osmolality during
pregnancy, which would suppress thirst and ADH secretion, relaxin
evidently provides for normal or even increased fluid intake during
pregnancy.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
118. Regulation of calcium metabolism
Parathormone, vitamin D and calcitonin
Three hormones are primarily concerned with the regulation of calcium.
1,25-Dihydroxycholecalciferol is a steroid hormone formed from vitamin D by successive hydroxylation in the
liver and kidneys. Its primary action is to increase calcium absorption from the intestine. Parathyroid hormone
(PTH) is secreted by the parathyroid glands. Its main action is to mobilize calcium from bone and increase
urinary phosphate excretion. Calcitonin, a calcium-lowering hormone that in mammals is secreted primarily by
cells in the thyroid gland, inhibits bone reabsorption.
Parathyroid hormone (PTH)
 Is the major hormone for the regulation of serum [Ca
2+
].
 Is synthesized and secreted by the chief cells of the parathyroid glands.
1. Secretion of PTH
 is controlled by serum [Ca
2+
] through negative feedback. Decreased serum [Ca
2+
] increases PTH
secretion.
 Mild decreases in serum [Mg
2+
] stimulate PTH secretion.
 Severe secretion in serum [Mg
2+
] inhibit PTH secretion and produce symptoms
of hypoparathyroidism (e.g., hypocalcemia).
 The second messenger for PTH secretion by the parathyroid gland is cAMP.
2. Actions of PTH
 Is coordinated to produce an increase in serum [Ca
2+
] and a decrease in serum [phosphate].
 The second messenger for PTH actions on its target tissues is cAMP.
e. PTH increases bone resorption, which brings both Ca
2+
and phosphate from the bone mineral into the
ECF. Alone, this effect on bone would not increase the serum ionized [Ca
2+
] because phosphate
complexes Ca
2+
.
f. PTH inhibits renal phosphate reabsorption in the proximal tubule and, therefore, increases
phosphate excretion (phosphaturic effect). As a result, the phosphate resorbed from bone is excreted
in the urine, allowing the serum ionized [Ca
2+
] to increase.
g. PTH increases renal Ca
2+
reabsorption in the distal tubule. Which also increases the serum [Ca
2+
].
h. PTH increases intestinal Ca
2+
absorption indirectly by stimulating the production of 1.25dihydrocholecalciferol
in the kidney.
Vitamin D
 Provides Ca
2+
and phosphate to ECF for bone mineralization
 In children, vitamin D deficiency causes rickets.
 In adults, vitamin D deficiency causes osteomalacia.
Actions of 1,25-dihydroxycholecalciferol
 are coordinated to increase both [Ca
2+
] and [phosphate] in ECF to mineralize new bone.
b. Increases intestinal Ca
2+
absorption. Vitamin D-dependent Ca
2+
-binding
protein (calbindin D-28K) is induced by 1,25-dihydroxycholecalciferol.
> PTH increases intestinal Ca
2+
absorption indirectly by stimulating 1α-hydroxylase and increasing
production of the active form of vitamin D.
b. Increases intestinal phosphate absorption.
c. Increases renal reabsorption of Ca
2+
and phosphate
d. Increase bone resorption, which provides Ca
2+
and phosphate from “old” bone
to mineralize “new” bone.
Calcitonin
 is synthesized and secreted by the parafollicular cells of the thyroid.
 secretion is stimulated by an increase in serum [Ca
2+
]
 acts primarily to inhibit bone resorption.
 can be used to treat hypercalcemia.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
119. Regulation of glycaemia
Blood sugar regulation is the process by which the levels of blood sugar, primarily glucose, are maintained by
the body.
. Blood sugar levels are regulated by negative feedback in order to keep the body in homeostasis. The levels
of glucose in the blood are monitored by the cells in the pancreas's Islets of Langerhans. If the blood glucose
level falls to dangerous levels, the Alpha cells of the pancreas release glucagon, a hormone whose effects on
liver cells act to increase blood glucose levels. They convert glycogen into glucose (this process is called
glycogenolysis). The glucose is released into the bloodstream, increasing blood sugar levels.
When levels of blood sugar rise, whether as a result of glycogen conversion, or from digestion of a meal, a
different hormone is released from beta cells found in the Islets of Langerhans in the pancreas. This hormone,
insulin, causes the liver to convert more glucose into glycogen (this process is called glycogenesis), and to force
about 2/3 of body cells (primarily muscle and fat tissue cells) to take up glucose from the blood through the
GLUT4 transporter, thus decreasing blood sugar. When insulin binds to the receptors on the cell surface,
vesicles containing the GLUT4 transporters come to the plasma member and fuse together by the process of
exocytosis and thus enabling a facilitated diffusion of glucose into the cell. As soon as the glucose enters the
cell, it is phosphorylated into Glucose-6-Phosphate in order to preserve the concentration gradient so glucose
will continue to enter the cell. Insulin also provides signals to several other body systems, and is the chief
regulatory metabolic control in humans.
Hormones that influence blood glucose level
Hormone Tissue of Origin Metabolic Effect Effect on Blood Glucose
Insulin Pancreatic β Cells
1) Enhances entry of glucose into cells; 2) Enhances storage of
glucose as glycogen, or conversion to fatty acids; 3) Enhances
synthesis of fatty acids and proteins; 4) Suppresses breakdown of
proteins into amino acids, of adipose tissue into free fatty acids.
Lowers
Somatostatin Pancreatic D Cells
1) Suppresses glucagon release from α cells (acts locally); 2)
Suppresses release of Insulin, Pituitary tropic hormones, gastrin and
secretin.
Raises
Glucagon Pancreatic α cells
1) Enhances release of glucose from glycogen; 2) Enhances synthesis
of glucose from amino acids or fatty acids.
Raises
Epinephrine Adrenal medulla
1) Enhances release of glucose from glycogen; 2) Enhances release
of fatty acids from adipose tissue.
Raises
Cortisol Adrenal cortex 1) Enhances gluconeogenesis; 2) Antagonizes Insulin. Raises
ACTH Anterior pituitary
1) Enhances release of cortisol; 2) Enhances release of fatty acids
from adipose tissue.
Raises
Growth Hormone Anterior pituitary Antagonizes Insulin Raises
Thyroxine Thyroid
1) Enhances release of glucose from glycogen; 2) Enhances
absorption of sugars from intestine
Raises
Food and blood sugar regulation
Some edible mushrooms are noted for the ability to lower blood sugar levels.
Masaryk University Faculty of Medicine Physiology Exam
REBAND AHMED Spring Semester 2010
120. Regulation of adrenal cortex