Spring 2019, prof. MUDr. Marie Nováková, Ph.D. REGULATION HOMEOSTASIS „homeo“ + „stasis“ Claude Bernard „complex organisms are able to maintain their internal environment [extracellular fluid (ECF)] fairly constant in the face of challenges from the external world“ „a free and independent existence is possible only because of the stability of the internal milieu” Walter Cannon „maintaining a steady state within an organism regardless of whether the mechanisms involved were passive (e.g., water movement between capillaries and the interstitium reflecting a balance between hydrostatic and osmotic forces) or active (e.g., storage and release of intracellular glucose)“ Arthur Guyton Introduced a concept of homeostasis as active regulatory mechanism aimed on minimizing of internal environment disturbances Homeostatic mechanisms – homeostatic regulations - Keeping of regulated variable of internal environment within the range - Reduction of „noise“ during information transport in physiological systems Reaching set point REGULATED variable („sensed“) - Sensor - Physiological range - Blood pressure (baroreceptors) - Body temperature (termoreceptors) NON-REGULATED variable („controlled“) - Variables which can be changed or modulated - Sensor in not located in the system - Keeping the variable constant - Heart rate – autonomous nervous system HOMEOSTATICALLY REGULATED VARIABLES REGULATION Control of living systems. Living systems – open systems; their existence depends on flow of energy, substrates and signaling molecules between organism and environment in both directions. Appears at all levels of system (cell – whole organism). Regulation nervous vs. Regulation humoral. BASIC TYPES OF FEEDBACK SERIAL PARALLEL NEGATIVE DIRECT NEGATIVE INDIRECT FEEDBACK NEGATIVE POSITIVE Deviation oscillates or continuously increases. POSITIVE FEEDBACK PHYSIOLOGICAL Ensuring of systems, activation PATHOLOGICAL Instability - death NEGATIVE FEEDBACK • plays a role in regulations • compensates the difference of regulated parameter • minimizes the difference between real values of regulated parameter and so-called desired value Regulated system Regulator Input value of regulator Regulatory deviation Regulated parameter Desired value POSITIVE FEEDBACK • No regulatory effect • It does not compensate the deviation, but amplifies it POSITIVE FEEDBACK - EXAMPLES Late follicular phase (approx. 2 days before ovulation) - High estradiol levels from preovulatory follicles = change of negative feedback into positive feedback - GnRH release - Sensitisation of adenohypophysis to GnRH - Increased LH secretion - Stimulation of further estradiol secretion and following stimulation of LH secretion - Permissive effect of progesterone POSITIVE FEEDBACK - EXAMPLES Estradiol upregulates - Oxytocin receptors - Prostaglandins receptors - Gap junctions Oxytocin - Prostaglandins E2 and F2a - Direct activation of PLC and Ca channels = release of Ca from intracellular stores - Bleeding after placenta expulsion - Nipples stimulation - milk ejection POSITIVE FEEDBACK - EXAMPLES Thrombin • Very low amount of thrombin insufficient for fibrinogen activation • Four important feedback mechanisms 1 2 3 4 POSITIVE FEEDBACK - EXAMPLES Aggregation of platelets POSITIVE FEEDBACK - EXAMPLES Spring 2019, prof. MUDr. Marie Nováková, Ph.D. PHYSIOLOGY OF ADAPTATION Adaptation or Environmental Physiology It studies the influence(s) of environment on living systems and their ability to adapt to changed conditions REACTION (sec, min) vs. ADAPTATION (min, hours, days) REACTION (REGULATION): direct, immediate response of organism on environmental changes ADAPTATION = a complex of biochemical, functional and structural changes in organism caused by long-lasting and repeated environmental changes ADAPTATION INDIVIDUAL GENETICALLY FIXED MECHANISMS OF ADAPTATION = processes which lead to new, functionally better parameters. Aim is to reach new, more advantageous qualities for surviving of the individual or species. DURATION OF ADAPTATION: Minutes - years MECHANISMS OF ADAPTATION 1. Changed plasticity of nervous system • changes at molecular level in CNS • gene expression changes • regulation of number of neurites • changes in neuronal nets (cortical fields) 2) Changes in organ size (adaptation to exercise) 3) Changes of autonomous tonus (athletes) 4) Temporary changes of skin colour (sunbathing) CLASSIFICATION OF ADAPTATIONS a) According to target parameter • To cold • To heat • To dietary changes • To high altitude • To changed air composition • To physical exercise ………. b) According to output •Adaptations at the level of five basic senses •Adaptation changes of behavior ADAPTATION TO COLD AND HEAT ADAPTATION TO COLD AND HEAT ADAPTATION TO COLD 1. PROTECTION FROM HEAT LOSS ( feather, vasoconstriction, increased amount of adipose tissue under the skin) 2. INCREASE OF HEAT PRODUCTION ( higher metabolic exchange) 3. DOWNWARDS SHIFT OF SET-POINT ( opposite to fever, behaviour as in hibernating animals ) 18th century: surviving of sailors in cold water 1887: V. Priesnitz, S. Kneipp People suffer from low temperatures less in winter than in summer. ADAPTATION INSULATIVE METABOLIC HYPOTHERMIC Acclimation. Human: as tropical animals Seal, fog, seagull: arctic animals (thermoneutral zone between 20 – 40°C, thermoregulating below 20°C) In humans always all three mechanisms activated at the same time. In adapted – O2 consumption decreases, HR not changed, BP increases (by 20 – 40mmHg), feeling of discomfort is lower (starts at lower temperature), downward shift of set-point (by 0.75°C) ADAPTATION PROCESS - Mainly new value of set-point - Changed diet (higher energy consumption, but NO increase of body mass, slowly increases body fat percentage) - Cold diuresis (excretion of Na+ and K+) – up to 60x, mediated by ANF, haemoconcentration, increased number of leucocytes and erythrocytes - Glycaemia changes: in non-adapted people decreases (stress), in adapted - increases (no stress) - Decrease of threshold for pain on skin ( total habituation – decreased sensitivity of receptors); stress analgesia in the course of adaptation - Decrease of threshold for muscle shivering ADAPTATION TO HEAT 1) SWEAT PRODUCTION may be doubled 2) THREASHOLD FOR SWEATING decreases to lower temperatures (both core and periphery) 3) DECREASED CONTENT OF ELECTROLYTES IN SWEAT 4) FEELING OF THIRST increases 5) HIDROMEIOSIS (decreased production of sweat in humid hot clima, after the period of profuse sweating; decreases idle dropping of sweat) 6) ADAPTATION OF TOLERANCE TO HEAT in inhabitants in the tropics, threshold for sweating is increased to higher body temperatures. ATTENTION must be paid to physical exercise !!! ADAPTATION TO HIGH ALTITUDE ADAPTATION TO HIGH ALTITUDE CARDIOVASCULAR RESPONSE: tachycardia and increased cardiac output at rest, more pronounced during exercise (BP increases during exercise only slightly) RESPIRATORY RESPONSE: increased minute ventilation, more pronounced during exercise ACID-BASE BALANCE: respiratory alkalosis (RQ> 1) O2 TRANSPORTATION: shift of dissociation curve to left FAST RESPONSE (reaction) (hours) HIGH ALTITUDE ACCLIMATISATION It takes at least several weeks, fully developed after months or years. CARDIOVASCULAR RESPONSE: HR and CO are normalized, pulmonary arterioles constrict – pulmonary hypertension RESPIRATORY RESPONSE: minute ventilation is stabilized (directly proportional to high altitude hypoxia), central chemoreceptors adapt INCREASED RELEASE OF ERYTHROPOETIN: polyglobulia, transport capacity of blood for O2 increases, viscosity of blood increases, density of mitochondria increases, myoglobin content increases ADAPTATION TO HIGH ALTITUDE ADAPTATION TO EXERCISE 1. Muscle hypertrophy 2. Athlete‘s heart Athlete‘s heart: •Hypertrophy dilatation •Increased volume reserve (1.5x) •Increased chronotropic reserve „Physiological“ hypertrophy •Prolongation of muscle fibres and increase of their thickness (NOT their number!!!) •Accompanied by normal or increased contractility (speed of ATP hydrolysis by myosin and maximal speed of muscle shortening are either normal or increased) •In muscles: increased number of mitochondria, increased activity of oxidative metabolism enzymes, proliferation of capillaries ADAPTATION TO EXERCISE ADAPTATION TO EXERCISE Transversal heart section: hypertonic heart with concentric hypertrophy (left) normal heart (middle) hypertonic heart with eccentric hypertrophy = hypertrophy + dilation (right) EXERCISE AND HEART – GOOD, BAD, HARMFULL ???