Body water
Fluid and electrolyte balanceFluid and electrolyte balance
Biochemistry II
Lecture 8 2008 (J.S.)
1
Body water
about 60 % of the body weight (55 % taken usually for women)
2/3 intracellular fluid (ICF, 40 % b.w.)2/3 intracellular fluid (ICF, 40 % b.w.)
1/3 extracellular fluid (ECF, 20 % b.w.)
interstitial fluid and lymphECF ICF
blood plasma (5 % b.w.)
interstitial fluid and lymph
(ISF, 15 % b.w.)
ISFISF
plasma
The water content of the body changes
– with age: about 75 % in the newborn,
less than 50 % in the elders,less than 50 % in the elders,
– with the total fat content, there are
only 10 % water in adipose tissue.
2
only 10 % water in adipose tissue.
"Transcellular" fluids"Transcellular" fluids
include water that is present at the moment within the GIT, abdominal
and pleural cavities, as well as spinal fluid, urine, and bile. In adults, theand pleural cavities, as well as spinal fluid, urine, and bile. In adults, the
volume is about 2 litres (2 – 3 % b.w.) under normal conditions.
In most clinical considerations the volume of transcellular fluids is notIn most clinical considerations the volume of transcellular fluids is not
taken into account, but it must be considered, when ascites or other
large exsudates might be awaited.
3
The movement of ions and polar neutral molecules across cell membranes
is due to the existence of specific transport proteins (including ion pumps).
Diffusion of water molecules is possible, but it is slow and not efficient.
AquaporinsAquaporins are membrane proteins that form water channels and
account for the nearly free and rapid two-way moving of water molecules
across most cell membranes (about 3 × 109 molecules per second).across most cell membranes (about 3 × 109 molecules per second).
Aquaporin channel structure
Aquaporins consist of six membrane-spanning segmenst arranged in two hemi-pores,
which fold together to form the "hourglass-shaped" channel.
The highly conserved NPA motifs (Asn-Pro-Ala) may form a size-exclusion pore, giving the
channel its high specifity.
4
channel its high specifity.
In membranes, some of aquaporin types exist as homotetramers, or formIn membranes, some of aquaporin types exist as homotetramers, or form
regular square arrays.
Aquaporins are controlled by means of gene expression, externalization of silencedAquaporins are controlled by means of gene expression, externalization of silenced
channels in the cytoplasmic vesicles, and also by the changes in intracellular pH
values (e.g., increase in proton production inhibits water transport through AQP-2
and increases the permeability of AQP-6).and increases the permeability of AQP-6).
More than 12 isoforms of aquaporins were identified in humans, 7 of
which are located in the kidney.which are located in the kidney.
Examples:
AQP1 (aquaporin-1), opened permanently, is localized in red blood cells,AQP1 (aquaporin-1), opened permanently, is localized in red blood cells,
endothelial and epithelial cells, in the proximal renal tubules and the thin
descendent limb of the loop of Henry.
AQP2 is the main water channel in the renal collecting ducts. It increases tubuleAQP2 is the main water channel in the renal collecting ducts. It increases tubule
wall permeability to water under the control of ADH: If ADH binds onto the V2
receptors located in the basolateral membrane, AQP2 in the membranes of
cytoplasmic vesicles is phosphorylated and exposed in the apical plasmacytoplasmic vesicles is phosphorylated and exposed in the apical plasma
membrane. Reabsorbed water leaves cells through AQP3 and AQP4 in the
basolateral plasma membrane.
5
basolateral plasma membrane.
The movement of water across cell membranes
is controlled by osmolalityis controlled by osmolality
ECF ICFExamples of four simplified causes of water movements:
(Any other solute can substitute sodium salt in the examples.)(Any other solute can substitute sodium salt in the examples.)
Significant loss of solute-free waterSodium salt retention or overload
Hypernatraemia (hyperosmolality of ECF)
→ hyperosmolar expansion of ECF, decrease
in ICF volume (cellular dehydration).
Hypernatraemia (hyperosmolality of ECF) by
dehydration → cellular dehydration
Solute-free water excess "Pure" sodium salt loss
Hyponatraemia by dilution (a decrease in ECF Hyponatraemia (hypoosmolal ECF) → decrease
Expansion of ICF →increase in intracranial pressure, imminent danger of cerebral oedema.
Hyponatraemia by dilution (a decrease in ECF
osmolality) → expansion of ICF volume, oedema
Hyponatraemia (hypoosmolal ECF) → decrease
in ECF volume, expansion of the cell volume.
6
Expansion of ICF →increase in intracranial pressure, imminent danger of cerebral oedema.
Na+ concentration (as well as osmolality) depends on changes in
both ECF volume and amount of Na+ in ECF:
normal Na+
amount in ECF
both ECF volume and amount of Na+ in ECF:
180 –
–
[Na+] / mmol l–1
(proportional to
osmolality)
amount in ECF
Na+ retention
160 –
–
hypernatraemia
(hyperosmolal ECF)
Na+ retention
or overload
140 –
–
hyponatraemia
(hypoosmolal ECF)
(hyperosmolal ECF)
120 –
–
(hypoosmolal ECF)
Na+ losses
ECF lossexcess water, water retention
100 –
ECF loss
decrease in extracellular volume
excess water, water retention
expansion of the EC volume
normal body
weight
7
weight
The approximate calculation of Na+ ion deficit
in patients with hypovolaemic hyponatraemia:
Na+ deficit = (140 – [Na+] ) × 0.6 × kg b.w. (in millimoles)
The approximate calculation of water deficit in patients with hypernatraemia:The approximate calculation of water deficit in patients with hypernatraemia:
water deficit =
[Na+] – 140
× 0.6 × kg b.w. (in litres)water deficit =
[Na+]
× 0.6 × kg b.w. (in litres)
8
The daily water intake and loss in an adult personThe daily water intake and loss in an adult person
Water intake at least 2000 ml/d Water loss at least 2000 ml/dWater intake at least 2000 ml/d
drink > 1200 ml
food 500 ml
Water loss at least 2000 ml/d
urine > 1200 ml
expired air 300 mlfood 500 ml
metabolism 300 ml
1 g saccharide → 0.55 ml
1 g protein → 0.41 ml
expired air 300 ml
sweat and
perspiration 500 ml
(profuse sweating up to litres /d)1 g protein → 0.41 ml
1 g fat → 1.07 ml
Attention should be paid to the water intake
(profuse sweating up to litres /d)
faeces 100 ml
Attention should be paid to the water intake
in the childhood and namely in the elders
(the feeling of thirst is impaired or lacking)
9
Intestinal fluid Per day: FOOD / FLUIDS oral intake 2000 mlIntestinal fluid
balance
1000 mlsaliva
SECRETION
2000 ml
400 mlbile
gastric
400 ml
1000 ml
RESORPTION
pancreatic
bile
2000 ml
RESORPTION
5000 ml
jejunal
sum total 9000 ml
600 ml
2900 ml
ileal
sum total 9000 ml
1000 ml
10
FAECES 100 ml/d
Osmolality of blood plasma
men 290 ±±±± 10 mmol / kg H2O
women 285 ±±±± 10 mmol / kg H2Owomen 285 ±±±± 10 mmol / kg H2O
Osmolality of biological fluids is measured by means of osmometers
that are based mostly on the cryoscopic principle.
Osmolality of blood plasma depends predominantly on the concentrations
of Na+, K+, glucose, and urea.
that are based mostly on the cryoscopic principle.
of Na+, K+, glucose, and urea.
Even if the osmolality of a sample is known (it has been measured), it is
useful to compare the value with the approximate assessment:
osmolality (in mmol / kg H2O) ≈ 2 [Na+] + [glucose] + [urea] (in mmol l–1).
useful to compare the value with the approximate assessment:
An osmotic gap can be perceived in this way. The measured value
is higher than the calculated rough estimate, if there is a highis higher than the calculated rough estimate, if there is a high
concentration of an unionized compound in the sample (e.g. alcohol,
ethylene glycol, acetone).
11
One gram of ethanol per litre will increase the osmolality by about 22 mmol / kg H2O.
Osmometers – cryoscopic principle:
Depression of the temperature of solidifying is one of the colligativeDepression of the temperature of solidifying is one of the colligative
properties that depends only on the activity of solutes in solutions.
Thermistors able to measure temperature differences less than 0.01 °CThermistors able to measure temperature differences less than 0.01 °C
are required.
Cryoscopic constant
K´(water) = 1.85 K kg mol–1K´(water) = 1.85 K kg mol–1
- i.e. Increase in osmolality
+ 10 mmol / kg H2O will depress
the temperature of solidifyingthe temperature of solidifying
by – 0.0185 °C.
Osmolality in mol / kg H2O
equals ∆∆∆∆ϑϑϑϑ / K´(water).
12
Oncotic pressure – colloid osmotic pressure (COP)Oncotic pressure – colloid osmotic pressure (COP)
Within the extracellular fluid, the distribution of water between blood
The capillary wall, which separates plasma from the interstitial fluid, is
plasma and interstitial fluid depends on the plasma protein concentration.
Oncotic pressure is a small fraction of the osmotic pressure that is
The capillary wall, which separates plasma from the interstitial fluid, is
freely permeable to water and electrolytes, but restricts the flow of proteins.
Oncotic pressure is a small fraction of the osmotic pressure that is
induced by plasma proteins.
ρ (plasma proteins) = 62 – 82 g / l c ≈ 1 – 1.3 mmol / lρ (plasma proteins) = 62 – 82 g / l c ≈ 1 – 1.3 mmol / l
ρ (plasma albumin) = 35 – 50 g / l c = 0.52 – 0.75 mmol / l
(albumin – about 80 % of oncotic pressure)
Oncotic pressure of blood plasma equals approx. 3 kPa (2.7 – 3.3 KPa).
Values 2.7 – 1.4 kPa - sizable oedemas, imminent danger of pulmonary oedema;Values 2.7 – 1.4 kPa - sizable oedemas, imminent danger of pulmonary oedema;
< 1.4 kPa – unless albumin is given i.v., survival is hardly possible.
13
The movement of fluid between plasma and interstitial fluid
Oncotic pressure can be measured by means of colloid osmometers.
14
Ions in body fluids
VENOUS ISF INTRACELLULAR
15
VENOUS
PLASMA / SERUM
ISF
FLUID
Ions in blood plasma / serum
16
Effective "strong ion difference" (SIDeff)
SIDeff = [Na+] + [K+] + 3 – [Cl–] – [UA–]
Effective "strong ion difference" (SIDeff)
SIDeff = [Na+] + [K+] + 3 – [Cl–] – [UA–]
The value SIDeff determinates the concentration
of plasma buffer bases BBp
.
SIDeff
tration of plasma buffer bases BBp
.
Normal range = 42 ± 3 mmol / l)
UA–
SIDeff then can be calculated from measurable
concentrations of plasma buffer bases::
SIDeff = [HCO3
– ] + 0.28 Alb(g/l) + 1.8 [Pi]
Strong ion ratio [Na+]+[K+] / [Cl–] (normal value 1.35 – 1.43)Strong ion ratio [Na+]+[K+] / [Cl–] (normal value 1.35 – 1.43)
is occasionally used as another sign of strong ion imbalance
that is typical for hyperchloridaemic acidosis or
hypochloridaemic alkalosis).
17
hypochloridaemic alkalosis).
Unmeasured anions (UA–)Unmeasured anions (UA–)
SIDeff
[UA–] = [Na+] + [K+] + 3 – [Cl–] – SIDeff
UA–
Normal range 8 ± 2 mmol / l
Components: sulfateComponents: sulfate
lactate
acidic ketone bodies
the other carboxylic acids
Corrected value for water content:
the other carboxylic acids
[UA–]corr = [UA–] × 140 / [Na+]measured
Corrected value for water content:
18
Anion gap (AG) – a simple accessory parameterAnion gap (AG) – a simple accessory parameter
that may call an attention to the possible increase in UA–:
HCO3
–
AG = [Na+] + [K+] + 3 – [Cl–] – [HCO3
–]
Usual values 19 ± 2 mmol/l.
AG AG represents the "space" filled in by
unmeasured anions,
Usual values 19 ± 2 mmol/l.
unmeasured anions,
proteins, and
phosphates.
In hypoproteinaemia, AG value should be corrected:
AGcorr = AGobserved + 0.25 × (Albref – Albmeasured)
(decrease in albumin by 1 g/l enables an increase
In hypoproteinaemia, AG value should be corrected:
(decrease in albumin by 1 g/l enables an increase
in HCO3
– by 1 mmol/l)
19
Water and osmolality control
Antidiuretic hormone (ADH, Arg-vasopressin, AVP)Antidiuretic hormone (ADH, Arg-vasopressin, AVP)
released from the nerve terminals in posterior pituitary
AldosteroneAldosterone
secreted from the zona glomerulosa of adrenal cortex
after activation of the renin-angiotensin system (RAS)after activation of the renin-angiotensin system (RAS)
Natriuretic peptides ANP and BNP
secreted from some kinds of cardiomyocytes in heart atria andsecreted from some kinds of cardiomyocytes in heart atria and
chambers
20
Water and osmolality control
INTAKE OF Na+ WATER LOSS
Osmolality increase Decrease in ECF volume
Filling of heart Filling of arteries
OSMOSENSORS VOLUMOSENSORS
Filling of heart
upper chambers Filling of arteries
hypothalamus liver heart juxtaglomerular cells
Increase
Secretion of renin
Sensation
of thirst
Secretion of
ADH (vasopressin)
Increase
of HMV
Secretion of
aldosteroneof thirst
Renal
ADH (vasopressin)
Better filling
of arteries
aldosterone
WATER INTAKE
Renal
RETENTION OF WATER RETENTION OF Na+
21
Antagonistic action of
natriuretic peptides ANP and BNP
Antidiuretic hormone (ADH, Arg-vasopressin, AVP)
is a nine amino acid cyclic peptide:
Cys–Tyr–Phe–Gln–Asn–Cys–Phe–Arg–Gly
S S
Vasopressin receptors V2 are in the basolateral membranes of cells
renal of renal collecting ducts (see picture 5).renal of renal collecting ducts (see picture 5).
Vasopressin receptors V1 are responsible for the vasoconstriction.
22
The renin-angiotensin system (RAS)
Fluid volume decrease
Blood pressure decrease
Blood osmolality decrease
ANGIOTENSINOGEN
(blood plasma α2-globulin, >400 AA)
THE JUXTAGLOMERULAR CELLS
of the renal afferent arterioles
Blood osmolality decrease
Protein
renin
(a proteinase) of the renal afferent arterioles
release into the blood
ANGIOTENSIN I
(a decapeptide)
angiotensin-converting enzyme
(ACE, a glycoprotein in the lung,His-Leu (ACE, a glycoprotein in the lung,
endothelial cells, blood plasma)
ANGIOTENSIN II
His-Leu
Stimulation of ALDOSTERONE production
ANGIOTENSIN II
(an octapeptide)
in zona glomerulosa cells of adrenal cortex
Vasoconstriction of arterioles
ANGIOTENSIN III
Rapid inactivation
23
Rapid inactivation
by angiotensinases
Angiotensin II and III
α angiotensinogen:
NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leu–Leu–Val–Tyr
N-Terminal sequence of the plasma α2-globulin angiotensinogen:
renin
Decapeptide angiotensin I:
–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–LeuNH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leu
angiotensin converting enzyme (ACE)angiotensin converting enzyme (ACE)
Octapeptide angiotensin II:
–Asp–Arg–Val–Tyr–Ile–His-Pro–PheNH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe
aminopeptidase
Heptapeptide angiotensin III:
Arg–Val–Tyr–Ile–His-Pro–PheArg–Val–Tyr–Ile–His-Pro–Phe
inactivating angiotensinases
24
inactivating angiotensinases
Aldosterone
(hemiacetal form)
(11β,21-dihydroxy-3,20-dioxo-4-pregnen-18-al )(11β,21-dihydroxy-3,20-dioxo-4-pregnen-18-al )
25
Natriuretic peptides
Brain natriuretic peptide (BNP)
which, despite its name, is largely
of cardiac ventricular origin.
Atrial natriuretic peptide (ANP)
of cardiac ventricular origin.
Both peptides have a cyclic sequence (17 amino acyl residues) closed
by a disulfide bond; ANP consists of 28 residues, BNP of 32.by a disulfide bond; ANP consists of 28 residues, BNP of 32.
They originate from C-ends of their precursors (126 and 108 residues) by
hydrolytic splitting and have short biological half-lives. Released N-terminalhydrolytic splitting and have short biological half-lives. Released N-terminal
sequences are inactive, but because they are long-lived, they
determination is useful.
26
determination is useful.
Both ANP and BNP have been shownBoth ANP and BNP have been shown
– to have diuretic and natriuretic effects,
– to induce peripheral vasodilatation, and
– to inhibit the release of renin from the kidneys and– to inhibit the release of renin from the kidneys and
aldosterone from the adrenal cortex.
These peptides are viewed as protectors against volume overload andThese peptides are viewed as protectors against volume overload and
as inhibitors of vasoconstriction (e.g. during a high dietary sodium intake).
Membrane receptors for natriuretic peptides are of unique kind –
they exhibit intrinsic guanylate cyclase activity; binding of NPs onto
receptors increases intracellular concentration of cGMP.receptors increases intracellular concentration of cGMP.
27