Homeostasis Slides PDF

Homeostasis Slides for Lectures 1.1, 1.2, 2.1, 2.2 Dr Alison Jack Homeostasis 1.1 Dr Alison Jack [email protected]  Learning Outcomes Define the term homeostasis Explain the importance of maintaining constancy of the internal environment.  HOMEOSTASIS Homeostasi...

Homeostasis Slides for Lectures 1.1, 1.2, 2.1, 2.2 Dr Alison Jack Homeostasis 1.1 Dr Alison Jack [email protected]  Learning Outcomes Define the term homeostasis Explain the importance of maintaining constancy of the internal environment.  HOMEOSTASIS Homeostasis = “similar condition” (not identical condition!) Our bodies are constantly monitoring their internal state and responding to any threat that might disturb the “similar internal conditions” of the body. This monitoring goes on constantly in an effort to prevent disturbance and maintain optimum “similar conditions” or, in other words, a relatively constant internal environment in which all processes work optimally. This is Physiology! Our bodies are not very tolerant of substantial changes in our internal environment (e.g temperature, pH of bodily fluids, concentration of hormones etc) and respond in ways to minimise these changes. Failure to adequately correct imbalances results in illness and disease, or pathology [pathos – meaning suffering]. e.g. Diabetes Mellitus occurs when the body can no longer maintain Homeostasis requires integration of organ systems e.g. increased energy demand requires: Nervous, endocrine and Musculoskeletal system to seek, supply and access nutrients, Respiratory system to supply O2 , Alimentary system to break down food into useable forms and absorb across gut wall into bloodstream, Cardiovascular system to transport O2 and nutrients via the bloodstream to the cells and transport CO2 and waste from the cells to the Respiratory, Alimentary and Renal systems for disposal. Nervous and Endocrine systems co-ordinate and control all these systems. All these systems must integrate effectively in order to maintain an optimum internal environment within the body for all cells to function and ultimately produce energy. Homeostasis requires integration of organ systems e.g. increased energy demand requires: Nervous, endocrine and Musculoskeletal system to seek, supply and access nutrients, Respiratory system to supply O2 , Alimentary system to break down food into useable forms and absorb across gut wall into bloodstream, Cardiovascular system to transport O2 and nutrients via the bloodstream to the cells and transport CO2 and waste from the cells to the Respiratory, Alimentary and Renal systems for disposal. Nervous and Endocrine systems co-ordinate and control all these systems. All these systems must integrate effectively in order to maintain an optimum internal environment within the body for all cells to function and ultimately produce Requires energy =regulation Homeostasis!at cell, tissue and system level.  Basic concept of homeostasis Body usually has a range within which it can tolerate change Figure 1-4 Common everyday challenges to our internal environment: 1. External temperature 2. Access to nutrients 3. Exercise These factors impact on body fluid composition, energy stores and body temperature, and physiological mechanisms must act to counteract these potential threats to homeostasis. For example: eat a sugary donut, glucose absorbed across intestinal tract, blood glucose rockets skywards and all sorts of problems ensue…..only they don’t, because the hormone insulin comes along and effectively removes glucose from the blood almost as fast as it enters Or/ In Abu Dhabi the temperature can reach 40oC…but our bodies don’t. Heat loss is triggered by sweating and vasodilation and core body temperature remains close to the optimal 37oC. Experiments have shown naked humans can maintain core body temperature pretty close to 37oC in external temperatures ranging  no homeostatic regulation Internal Variable e.g body fluid concentration With homeostatic regulation or blood PLATEAU glucose levels External variable e.g. drinking water or eating a donut At extremes homeostasis does become less effective.  Homeostasis: A) Is fundamental for life B) Maintains monitored variables within a set range C) Allows us to live in hot countries and eat donuts D) All of the above Now pause and consider this question. You may think the answer is obvious but I want you to not only identify the correct answer but also be able to explain why the other answers are right or wrong.  Homeostasis: A) Is fundamental for life B) Maintains monitored variables within a set range C) Allows us to live in hot countries and eat donuts D)All of the above You should have said D – All of the above. Without homeostasis we would die. At a very simple level, being unable to maintain body temperature (a monitored variable) within a narrow range around 37oC disrupts all the biochemical reactions taking place inside our cells, leaving us unable to generate energy to power cellular function. Similarly, without homeostasis, eating a sugary donut would cause a dramatic rise in blood glucose which over time leads to irreversible eye, kidney and nerve Homeostasis 1.2 Dr Alison Jack [email protected]  Learning Outcomes Describe the principles behind negative feedback control systems. Explain what is meant by feed forward control. Illustrate the concept of homeostasis by outlining daily water balance in man.  Mechanisms to maintain Homeostasis 1.Negative feedback 2.Feedforward 3.Positive feedback  Mechanisms to maintain Homeostasis 1.Negative feedback (by far the most important) 2.Feedforward 3.Positive feedback  1. Negative Feedback mechanisms Negative feedback is the key mechanism by which homeostasis is maintained. When a condition that is homeostatically regulated (e.g. body temperature), is sensed to have shifted from the normal range, a signal (usually nervous or endocrine), is generated that produces a response (e.g. shivering or sweating), that corrects the original disturbance and brings the regulated condition back within the normal range. “Negative” feedback because the condition that triggered the homeostatic response becomes switched off/removed by that response. The size of the response is proportional to the size of the  Example of homeostasis using negative feedback - ve feedback A self-limiting response. Negative feedback removes the trigger that started the Characteristics of Negative Feedback systems 1. There is oscillation around the set point. 2. Restores the regulated condition after its initial disturbance, but cannot prevent it happening. Feed forward systems are more sophisticated and can, to some extent, predict and prevent change…. 2. Feed Forward Systems In Feed-forward control, (more sophisticated form of negative feedback), additional receptors permit system to anticipate change and therefore activate response earlier. In the previous example, while e.g. negative feedback prompts the thirst response, at the same time the kidney detects the increased body fluid concentration and pre-empts a state of dehydration. It responds by producing smaller volumes of urine, and a more concentrated form of urine, thus conserving water. 3. Positive feedback mechanisms Unsurprisingly, positive feedback has the opposite effect of negative feedback. Where negative feedback aims to restore disturbed conditions to optimum, positive feedback sets off a train of events that lead to an even greater disturbance. Such cycles usually lead to instability, and are common in pathophysiology, rare in normal physiology. However, they do occur, e.g. in the nerve action potential, in ovulation and sexual behaviour.  POSITIVE FEEDBACK e.g. in the ACTION POTENTIAL (message in the nervous system) Initial triggers allows positively charged Na+ ions charge inside cell to enter a nerve cell becomes more positive (depolarization) Na+ influx to nerve cell Na+ permeability + + = SELF AMPLIFICATION More about action potentials in Dr Cunningham's lectures. While positive feedback is associated with some elements of normal function it is more commonly associated with pathology. Consider the example of diabetes:  HOMEOSTATIC CONTROL OF BLOOD GLUCOSE Insulin MEAL [BG] Glucose uptake released by cells Negative feedback maintains homeostasis of [BG] Blood Glucose [BG] DIABETES BREAKDOWN OF HOMEOSTATIC REGULATION LACK OF INSULIN EFFECT MEAL [BG] Glucose uptake by cells Positive feedback Liver production Lack of glucose can lead to deregulation of of glucose uptake by cells homeostasis = leads body to Aim of diabetes treatment is to restore homeostatic control of [BG]. As a generalisation, Medicine is aimed at restoring homeostatic control when this is disturbed by illness or disease. There now follows two Single Best Answer (SBA) questions on the mechanisms we have looked at here. Please attempt them and then review the answers in the slides at the end. As before, I would like you to not only identify the correct answer but also be able to explain why the other answers are wrong. 1. Negative feedback regulation: A) Is the least common type of feedback B) Causes return to a set point C) Amplifies the response D) Disrupts homeostasis 2. Positive feedback regulation: A) Is the most common type of feedback B) Causes return to a set point C) Amplifies the response D) Predicts and prevents disruption of set point before it happens 1. Negative feedback regulation: A) Is the least common type of feedback B)Causes return to a set point C) Amplifies the response D) Disrupts homeostasis You should have said B – Causes a return to a set point Negative feedback is the most common type of homeostatic feedback. It aims to reduce the disturbance of a monitored variable – think about the example of getting dehydrated when working outside on a hot day. The threat to water balance in the body is countered by an increased thirst, driving the individual to seek water. Negative feedback is a key aspect of maintaining homeostasis 2. Positive feedback regulation: A) Is the most common type of feedback B) Causes return to a set point C)Amplifies the response D) Predicts and prevents disruption of You set shouldpoint have saidbefore itthehappens C - Amplifies response Positive feedback is uncommon in normal homeostasis although it does occur and is vitally important when it does. Remember the example of the sodium based action potential in nerves. Review this if necessary to understand how it amplifies the response (of sodium entry to the nerve cell). Without this positive feedback nerves would cease to function. Positive feedback cannot predict and prevent disruption before it Homeostasis 2.1 Where is the Water? Dr Alison Jack [email protected] Homeostasis: Summary of what we know so far. Homeostasis describes the processes by which the internal environment of the body is kept reasonably constant in such a way that it optimises all physiological and biochemical processes that support life. Maintenance of this state requires overall regulation of numerous cells, tissues and organs, Homeostatic often processes arelocated some controlled bydistance apart. subconscious neural or hormonal feedback or feed forward mechanisms that may be simple or very complex. They maintain body temperature, blood glucose levels, O2 and CO2 levels, water and ion balance, blood pressure and blood volume to name but a few examples.  Learning Outcomes Identify the different body fluid compartments. Explain the importance of the nature of the barriers which separate the body compartments. Water balance is a process that is homeostatically controlled. This is critical for life, but is also critical for what we will cover in my next set of lectures – Forces Acting Across Membranes! Water Balance Water makes up  60% body weight. Homeostatic maintenance of water is crucial because water affects the concentration of everything else in the body. Average daily water balance in adult male in a thermoneutral environment: Gains Drinking 1200mls Eating 1000 Metabolic 350 Total mls/24 hours 2550 Losses Insensible loss 900mls from skin and lungs Sweat 50 (up to 3L/hr) Faeces 100 Urine 1500 (0.5L 20L/day) Total mls/24 hours 2550  Basic concept of homeostasis What we gain, we must lose What we lose, we must replace Normal body water range Which processes are regulated in order to maintain water balance? Input is regulated by the thirst mechanism Output by regulation of kidney function (urinary losses) Other processes that alter water balance are also regulated, but their control is not aimed at maintaining water balance e.g. sweating is controlled as part of temperature regulation, so possible conflict between water and temperature regulation. Where is this water?  Where is the water in our body? Split between 3 compartments; 1.Intracellular fluid Extracellu 2.Interstitial fluid (fluid between cells) 3.Plasma (fluid component of blood) lar fluid Water can move freely between these compartments although movement is subject to forces such as osmosis. The body can survive only as long as the composition of the ECF is maintained in a state compatible with the survival of its individual cells i.e. composition of the ECF is very, VERY important. Figure 3-2 Average 70Kg, 21yo man water is distributed thus: Plasma 3L Blood Vessel Capillary Wall - permeable to everything but plasma Extracellular protein and blood cells Interstitial Fluid Fluid (ECF) (ISF) 14L 11L Cell membrane – selective permeability Important facts: Intracellular Capillary wall is permeable to Fluid (ICF) everything but plasma protein and 28L blood cells Cell membrane has selective permeability Water accounts for 60% of body weight Total body water ~42L We have twice as much ICF as ECF Approx 80% of ECF is ISF Approx 20% of ECF is plasma  You drink 1L of water. How is that water distributed in the body? A) Contained in the ECF B) Contained in the ICF C) 1/3 in ECF, 2/3 in ICF D) 2/3 in ECF, 1/3 in ICF Give this some consideration before moving on to the next slide where the answer is explained. E) ½ in ECF and ½ in ICF You should have said C to the previous question: 1/3 ECF, 2/3 ICF Plasma 3L When you drink 1/3 Blood Vessel Capillary Wall total water, or Interstitial Fluid body administer a water (ISF) is ECF drug that freely 11L crosses cell Cell membrane membranes, it will be Intracellular 2/3 distributed Fluid (ICF) total 28L body 1/3 ECF: 2/3 ICF. water is ICF Important! This is not the case with all fluids as Homeostasis 2.2 Where is the Water? Dr Alison Jack [email protected]  Learning Outcomes Define the dilution principle. Describe the use of the dilution principle in the measurement of body fluid compartments. Some Common Medical Termiology (Often describes the state when homeostasis Hyper = greater than normal has failed) Hypo = less than normal Aemia/emia = means in the blood Uria = means in the urine Glyc = related to glucose Glycosuria = glucose in the urine Hypoglycaemia = low blood glucose levels  Plasma Plasma is the fluid component of blood. It continuously moves through blood vessels, by the pumping action of the heart = dynamic component of the ECF. Plasma freely exchanges nutrients (e.g. O2, glucose, ions) and waste (e.g. CO2 and urea) with the ISF. Exchanges occur as blood passes through the capillaries of the body. Large vessels like arteries have walls too thick for exchange to take place. The composition of plasma and ISF are virtually identical except for plasma proteins, which are too large and  restricted to the plasma. ECF is  effectively homogeneous, with the one exception of ISF being devoid of plasma protein. Measurement of body fluid volumes based on the DILUTION PRINCIPLE, (3 things to remember ) 1. c = m/v,  v = m/c = Dilution Principle 2. ONLY plasma can be sampled, only compartments of which plasma is a component can be measured directly (plasma, ECF, TBW). 3. The NATURE of BARRIERS which separate compartments is crucial in determining the test substance. 10mg M= ? gluco se C = 1mg/ml glucose V = m/c = 10/1mg/ml = 10 mls Compartments that can be measured directly using the Dilution Principle: 1. Plasma Volume (PV): Since plasma proteins cannot cross the capillary walls, can use dyes or radioactive labels that attach to plasma proteins, e.g. Evans blue or I125albumin. 2. Extracellular Volume (ECF): Need something that freely crosses capillary walls, but cannot cross cell membranes, e.g. inulin, sucrose, mannitol, which are all too large to cross cell membrane or 24Na+ , 36Cl-, which are actively extruded from cells. 3. Total Body Water (TBW): There is no barrier to water in the body, so can use a loading dose of heavy water/ deuterated water (D2O). Other compartments (where plasma is not a component) cannot be directly sampled, calculate volume indirectly; Method of practice of dilution principle: 1. Inject a substance that will stay in one compartment only (plasma, ECF, TBW) 2. Then calculate the volume of distribution: = amount injected (minus any removed by excretion or metabolism), divided by the concentration in the sampled fluid. Example using sucrose which is restricted to ECF: 150mg of sucrose injected into plasma of 70kg man, [sucrose] blood sample after distribution = 0.01mg/ml 10mg were excreted or metabolised. What here Pause is theand volume of ECF? consider the above problem. Attempt the calculation before proceeding with the slide show. The answer is on the next slide. What is the volume of ECF? Sucrose is restricted to ECF: 150mg of sucrose injected into plasma of 70kg man, [sucrose] blood sample after distribution = 0.01mg/ml 10mg were excreted or metabolised. What is the volume of ECF? 150-10mg=140mg distributed in ECF. volume of distribution = 140mg/0.01mg/ml = 14000mls ECF volume = 14,000ml or 14L ECF bathing cells MUST be maintained at a constant composition, however the composition of the ICF differs markedly from the ECF, particularly for ions because cell membrane is a selective barrier: ICF mmol ECF mmol Note large Na+ 12 142 concentration gradient between K+ 150 4.2 ICF and ECF. Fundamental for Cl- 4 104 nerve and muscle function HCO3- 12 24 phosphates/ 125 10 sulphates protein 160 20 mg/ml (plasma) So why is it so important to maintain ECF constant??? What happens if homeostasis does not operate effectively? Consider an example where extracellular potassium concentration ([K+]ECF ) was allowed to increase beyond the normal range: Loss of concentration gradient between ECF and ICF This disrupts nerve and muscle function, including cardiac muscle ventricular fibrillation and death. ESSENTIAL to regulate ECF K+ (Kidney normally sorts it all out). Disease states and illness are associated with perturbation, and even breakdown, of homeostatic control mechanisms. Eg. in diabetes, breakdown of the normal regulation of blood glucose Hyperglycaemia (i.e. excess glucose in the “Normal” values are for a 70kg, 21 year old, healthy, male. All normal values refer to this standard. Proportions of body H2O will vary with age and gender. Females are “less wet”, because they have a higher proportion of body fat, which has less water content than muscle. Muscle contains ~70% water by weight, fat only 10% water. For the same reason, older people have lower water content. Can be important to know e.g. if treating with lipid Summary of homeostasis and its consequences Changes within the normal range are sorted out by physiological mechanisms which act to counteract change. Out with normal range, pathophysiological disturbances require clinical intervention to restore variables to normal range. If extreme disturbance may fall off the homeostatic plateau DEATH. A healthy 20 year old female with [K+]ECF of 4.2mmol/l doubles her normal K+ intake. After a week, which of these is most likely to be her [K+]plasma? A) 2.1mmol/l B) 4.2mmol/l C) 8.4mmol/l D) 12.6mmol/l Give this some consideration before moving on to the next slide. A healthy 20 year old female with [K+]ECF of 4.2mmol/l doubles her normal K+ intake. After a week, which of these is most likely to be her [K+]plasma? A) 2.1mmol/l B)4.2mmol/l C) 8.4mmol/l D) 12.6mmol/l You should have said B – 4.2mmol/l As we are discussing a healthy individual the kidney will sort out the excess K+ and excrete the excess in the urine – thus illustrating it’s valuable contribution to the homeostatic control of plasma ion concentrations.