Homeostasis UM1010 Past Paper PDF

Homeostasis UM1010 Kathryn Taylor slides adapted from Darrel Where opportunity creates success Brooks/ Allyson Clelland Learning Define and explain the concept of homeostasis Objectives...

Homeostasis UM1010 Kathryn Taylor slides adapted from Darrel Where opportunity creates success Brooks/ Allyson Clelland Learning Define and explain the concept of homeostasis Objectives Explain the processes of homeostasis Evaluate the effect of failure of homeostasis on health, with examples Physiology Physiology is the study of the function of the human body. Function can often be related to the structure (Anatomy). We can split the functions into 4 broad categories: 1. Protection, support and movement 2. Communication and control 3. Circulation and immunity 4. Energy supply and fluid balance We can break the body into systems for ease of study eg: urinary, reproductive, circulatory, but the systems will interact with each other to create a functional organism  Claude Bernard In the 19th Century, Claude Bernard originally proposed the concept of the ‘milieu intérieur ’ which stated that complex organisms can maintain their internal environment ‘fairly constant’ in the face of challenges from the external world In 1926, Walter Cannon extended the concept and coined the term “Homeostasis” Walter Cannon  Introduction The physiology of the body is often described as homeostatic mechanisms that control the cellular environment. Cell function relies on an adequate energy supply There is integration of activities of different cells through both electrical and chemical signalling molecules The cell membrane is important in these functions and forms a barrier between the intracellular and extra cellular environments across which molecules are transported. Cells, Function and Homeostasis The elemental constituents of the body are cells, whose survival and function are possible only within a narrow range of physical and chemical conditions, such as temperature, oxygen concentration, osmolarity, and pH. Therefore, the whole body can survive under diverse external conditions only by maintaining the conditions around its constituent cells within narrow limits. The body has an internal environment, which is kept constant to ensure survival and proper functioning of the body’s cellular constituents. The process whereby the body maintains constancy of this internal environment is referred to as homeostasis. The internal environment The purpose of homeostasis is to provide an optimal fluid environment for cellular function. The body fluids are divided into two major functional compartments: Intracellular fluid (ICF) is the fluid inside Extracellular fluid (ECF) is the fluid outside cells, which is subdivided into the interstitial cells. fluid and the blood plasma. The concept of an internal environment in the body correlates with the interstitial fluid bathing cells. Body Fluid Compartments Body fluid compartments. Intracellular fluid (ICF) is separated from extracellular fluid (ECF) by cell membranes. ECF is composed of the interstitial fluid bathing cells and the blood plasma within the vascular system. Interstitial fluid is separated from plasma by capillary endothelia. Transcellular fluid is part of the ECF and includes epithelial secretions such as the cerebrospinal and extraocular fluids. ECF has a high [Na+] and a low [K+], whereas the opposite is true of ICF. All Citation: Chapter 1 General Physiology, kibble JD. The Big Picture Physiology: Medical Course & Step 1 Review, 2e; 2020. Available at: https://accessmedicine.mhmedical.com/content.aspx? compartments have the same sectionid=245544050&bookid=2914 Accessed: January 11, 2021 What is homeostasis ? Internal environment – cell cytosol/interstitial fluid Definition ‘maintenance of a relatively constant internal environment despite changes in the external environment External environment Ambient conditions Presence or absence of food and drink Level of exercise (causing excesses and Which components of the internal environment are under homeostatic control (part of the internal environment)? NO YES Temperature Heart Rate Blood pressure Body Fat pH Gas levels (O2, CO2 ) Osmolality This does not mean that heart rate is not involved in homeostatic control: eg Electrolytes heart rate will rise as you exercise to Calcium help compensate for gas level changes Glucose Hormones Summary of Homeostasis Normal homeostatic state Change causes loss of homeostasis Attempts made to compensate for change Compensation Compensation inadequate adequate Health Health risk maintained What does this mean clinically? You can take a temperature to Arterial pH 7.35-7.45 see whether it is in the normal Bicarbonate 24-28 mEq/L range Sodium 135-145 mEq/L You can measure blood Calcium 2.1 – 2.6 mmol/L pressure Oxygen 17.2-22 ml/100ml Urea 12-35 mg/100 ml You can take blood and analyse Amino acids 3.3-5.1 mg/100ml the results for a variety of Protein 6.5-8 g/100ml parameters Total lipids 400-800 mg/100ml Glucose 75-110 mg/100ml carbonate Sodium Oxygen 17.2-22 ml/100ml Amino acids 3.3-5.1 mg/100ml Protein 6.5-8 g/100ml Some examples of physiological controlled variables The Set Point - Feedback Loops Control centre Receptor Effectors s Stimulus Effect s Effects negate stimulus Negative feedback (reflex) Internal environment compared to a ‘set Integrati point’ ng centre Receptors Effectors Change to external Effects environment The effects result in a change back towards the  Model of Homeostasis 1. Sensor – measures the value of the regulated variable 2. Mechanism for establishing ‘normal range’ of values for the regulated variable. i.e. The ‘set point’- which can change 3. An ‘error detector’ that compares the signal being transmitted by the sensor with the ( value of the regulated variable) with the set point. The result of this comparison is an error signal that is interpreted by the controller. 4. The controller interprets the error signal and determines the value of the outputs of the effectors. 5. The effectors determine the value of the regulated variable. Generic homeostatic regulatory system Fig. 1. Diagram of a generic homeostatic regulatory system. If the value of the regulated variable is disturbed, this system functions to restore it toward its set point value and, hence, is also referred to as a negative feedback DOI: (10.1152/advan.00107.2015) system. Homeostasis Homeostasis of an element can be controlled locally or systemically. There may be multiple mechanisms of control involving a number of organs or systems – Eg regulation of blood pressure can involve the heart, smooth muscle and the kidney Reflex/extrinsic: control system outside the tissue being controlled eg negative feedback Local (intrinsic): regulation within a tissue. Direct effect eg autoregulation Homeostasis PATTON, KEVIN T., PhD, Anatomy and Physiology, 2, 23-37 Intracellular: control of intracellular processes Levels of control. The many complex processes of the body are coordinated at multiple levels: intracellular (within cells), intrinsic eg enzymes (within tissues and organs), and extrinsic (organ to organ). Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. Fluid and electrolyte balance PATTON, KEVIN T., PhD, Anatomy and Physiology, 43, 999-1018 Homeostasis of the total volume of body water. A basic mechanism for adjusting intake to compensate for excess output of body fluid is diagrammed. Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. Types of Receptors Monitor pressure e.g. blood pressure in Baroreceptors carotid arteries Monitor level of chemical substances e.g. oxygen, carbon dioxide and pH in carotid arteries Chemoreceptors Monitor temperature e.g. in skin and Thermoreceptor internal organs s Osmoreceptors Monitor osmolarity (solute concentration) Glucoreceptors Monitor level of glucose e.g. beta-cells in pancreas Negative feedback Upper The value (e.g. pH) will increase threshold until it reaches a threshold above the set point Set point Reaching the threshold triggers messages to be sent to the Lower effectors to take action threshold The action of the effectors causes the value to start to fall Once the value falls below a threshold under the set point, it will trigger the effectors to take a different action The result is OSCILLATION either side of the set point Positive feedback Internal environment Integrati compared to a ‘set ng point’ centre Receptors Effectors Change to external Effects environment The effects result in a change FURTHER AWAY FROM the norm Positive feedback The value changes in some way (can be up or down) The change triggers a further change in the same direction An external influence is required to break the cycle This is rarely a Positive Feedback Homeostasis PATTON, KEVIN T., PhD, Anatomy and Physiology, 2, 23-37 Positive feedback loop. An example of positive feedback occurs during labour when stretch of the uterus and birth canal beyond the set point is detected and triggers the release of oxytocin (OT). OT stimulates stronger and more frequent uterine mu... Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. To make a change you need to know that there has been a change: have a system to detect and implement Temperature set point Not everyone’s set point, or “normal”, body temperature is the same. This Figure shows the difference in body temperatures observed in a group of healthy students. You can see that temperatures varied widely. This explains why some people are comfortable at a temperature that is too cold for others around them—their temperature set point must be naturally lower. Range of normal body temperatures. In a well-controlled experiment, a group of healthy students show a wide range of normal rectal temperatures. The average  Mean 36.8 SD 0.4 Median 36.8 Max 37.5 Min 35.8 Range 1.7 Temperature in 0.1 degree increments Homeostasis PATTON, KEVIN T., PhD, Anatomy and Physiology, 2, 23-37 Circadian cycles. The body’s internal clock mechanisms raise and lower set points for some variables in a daily high-low rhythm, as these examples show. Shaded areas represent typical sleep times. Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. Homeostasis of blood glucose Homeostasis of blood glucose. The range over which a given value, such as the blood glucose concentration, is maintained is accomplished through homeostasis. Note that the concentration of glucose fluctuates above and below a normal setpoint value 5 mmol/L (90 mg/100 mL) within a normal setpoint range 4.4 to 5.6 mmol/L (80 to 100 mg/100 mL). Copyright © 2019 © 2019, Elsevier Limited. All rights reserved. Homeostasis PATTON, KEVIN T., PhD, Anatomy and Physiology, 2, 23-37 Glucose Homeostasis  Why is homeostasis so important? Changes in the conditions within the cell (such as pH and temperature) can or irreversible damage to proteins Important proteins within cells include enzymes, receptors and transport proteins Changes to these proteins can threaten the life of the cell Temperature regulation Homeostasis PATTON, KEVIN T., PhD, Anatomy and Physiology, 2, 23-37  Homeostatic Mechanisms Regulatory mechanisms that compensate Local/intrinsic mechanisms for changes away from a stable condition. Regulation within a tissue involving no external systems Intracellular mechanisms May be direct effect or Action taken within the cells local nerve reflexes modification of enzymes within Reflex/extrinsic mechanisms cells, causing changes to their Control system outside function organ or tissue being controlled Involves nervous or endocrine systems and CNS  Anticipation Anticipation (Feed-Forward Control) – the effect can be triggered before any changes have occurred e.g. increase in heart rate before exercise i.e. before any changes in blood gases have occurred Effects on the negative feedback loop Anticipation: Response is triggered before the stimulus eg increased heart rate and sweating in exercise. The body knows that we will need increased blood transport to lungs and muscles and that there will be overheating so response starts before temperature increases or CO2 increases Sensitisation: Effect of more than one stimulus can cause the effect to be greater than the sum of individual stimuli. The loop is sensitised eg low O 2 and high CO2 both increase breathing (ventilation) rate Feed Forward: Similar to anticipation- but where the response is reduced before the threshold. eg. Thirst reflex. When you drink you will stop before the osmoreceptors detect a return to plasma osmolality because there are also osmoreceptors in the mouth. Feedforward example For example, when you eat a meal, the stomach stretches and this triggers stretch sensors in the stomach wall. As you would expect, the stretch sensors trigger a feedback response that causes the release of digestive juices and contraction of stomach muscles. This is normal negative feedback because secretion and muscle activity eventually get rid of the food and bring the stretch of the stomach back down to normal. It will continue as long as there is food to stretch the stomach. At the same time, the stretch stimulus is triggering the small intestine and related organs to increase secretion there as well— before the food has arrived. In other words, information from one feedback loop (in the stomach) has leaped ahead to the next logical feedback loop (in the intestines) to get the second loop ready ahead of time. Another example of feed-forward control occurs when you see or smell food and your salivary glands respond by secreting saliva and your stomach starts to contract rhythmically as it secretes its own juices in anticipation of food being eaten. Feed-forward causes a feedback loop to anticipate a stimulus before it actually happens. Introduction and homeostasis Naish, Jeannette, Medical Sciences, 1, 1-14 Control of body temperature by negative feedback. (A) Responses to an increase in body temperature; (B) responses to a decrease in body temperature. Copyright © 2019 © 2019, Elsevier Limited All rights reserved. Heat production is a byproduct of metabolism. Heat production is a byproduct of metabolism. The most important factors that determine heat production are (1) basal metabolic rate; (2) muscle activity (including shivering); (3) thyroxine; (4) epinephrine, norepinephrine, and sympathetic stimulation; (5) body temperature, with increasing cell metabolism as temperature increases; and (6) metabolism associated with food digestion, absorption, and storage (thermogenic effect of food). The rate of heat loss is determined by (1) the rate of heat conduction to the skin and (2) the rate of heat conduction from the skin to the surroundings. Negative Feedback During Exercise Body temperature may increase above the set point during exercise. The hypothalamus receives feedback from temperature sensors and responds to the high body temperature by triggering the activity of sweat glands (the effectors). As sweat evaporates from the skin, it carries heat away from the body and thus reduces the body’s temperature back toward the set point. During exercise relatively stable oxygen and carbon dioxide levels are maintaind in the blood. As our muscles work, they remove a large amount of oxygen from the blood, thus lowering the blood oxygen level below its set point. At the same time, blood carbon dioxide levels climb dramatically above its set point. Chemical sensors in blood vessels send feedback to the brainstem through sensory nerves. Integrators in the brain respond by increasing the rate and depth of breathing, which increases the rate of adding oxygen to and removing carbon dioxide from the bloodstream. All of which brings the “blood gases” back toward their set points—and brings the body back toward its normal conditions. Many other negative feedback mechanisms operate during exercise to maintain normal acid levels in the blood, maintain normal water content in body tissues, and more  Set-points can be modified: Thermoregulation : hypothalamus (integrator) Increase in set-point for core body temperature during fever one form of acclimatization to environmental oxygen level – some people who have spent a very long time at altitude have a lower set point for P aO2 The efficiency of the negative feedback loop can be altered Sensitivity - more than one stimulus can sensitise the loop e.g. low PaO2 and high PaCO2 both trigger increased ventilation, however the response when both occur together is greater than the sum of when they occur Fever During a fever, bacteria The above-normal cause bone-marrow temperatures are thought macrophages to secrete to help defend against substances called microbial invasion because endogenous pyrogens they stimulate the motion, The endogenous pyrogens activity, and multiplication are released into the blood of white blood cells and stream and cause the increase the production of hypothalamic set point to antibodies. At the same be increased time, elevated heat levels This results in initiation of may directly kill or inhibit feedback mechanisms that the growth of some increase body temperature bacteria and viruses that can tolerate only a narrow Body temperature rises temperature range above normal Fig. 16.6Modulation of Fever and Acute Phase Response Pain, Temperature Regulation, Sleep, and Sensory Function Allen, Jodi A., McCance & Huether’s Pathophysiology, 16, 474-508 Copyright © 2023 Copyright © 2023 by Elsevier Inc. Infection All rights reserved. and inflammation initiate the release of exogenous pyrogens from pathogens and endogenous pyrogens from macrophages and other immune cells. Endogenous pyrogens and PGE 2 act on the hypothalamus to elevate the temperature set point and initiate fever and the acute phase response. Fever is modulated by antipyretic mediators (cryogens) from both the CNS and periphery which suppress the febrile response and prevent damage from excessively high temperatures. BBB , Blood brain barrier; AVP , arginine vasopressin; CRP , C-reactive protein; IFN , interferon; IL , interleukin-1, interleukin-6; MCH , melanocortin; PGE 2 , prostaglandin E 2 ; TNF -α, tumor necrosis factor- alpha Benefits of Fever Moderate fever helps the body respond to infectious processes through several mechanisms. 1.Raising of body temperature kills many pathogens and adversely affects their growth and replication. 2.Higher body temperatures decrease serum levels of iron, zinc, and copper— minerals needed for bacterial replication. 3.Increased temperature causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells. 4.Heat increases lymphocytic transformation and motility of polymorphonuclear neutrophils, facilitating the immune response. 5.Phagocytosis is enhanced, and production of antiviral interferon is augmented. Suppression of fever with antipyrogenic medications can be effective but should be used with caution. Infection and fever responses in older adult persons and children may vary from those in normal adults. Importance of Homeostasis Optimal cell and system function requires tightly controlled conditions Uncontrolled variability in these conditions can cause damage, disease and death. Untreated Diabetes: – Blood vessel damage from high glucose levels resulting in : Atherosclerosis, retinopathy, kidney disease – Nerve damage: foot ulcers, sexual dysfunction, digestive issues (diahorrea / constipation) – Organ damage: Pancreas, kidney – Ketoacidosis, coma from hypo and hyperglycaemia can be fatal. Homeostasis in the young and old Preterm infants, newborns and older people have more problems maintaining homeostasis. Preterm: – Liver development: immature affects blood protein and can lead to hypoproteinemic oedema. Lack of protein decreases oncotic pressure and leads to loss of fluid from the blood vessels into surrounding tissues. – Acid-base and blood glucose homeostasis: eg blood limits can be very wide 20-100mg/dl and are more likely to be variable if feeding is irregular – Calcium fluctuates more widely, (normal limit? 9-11mg/100ml) which can result in hypo-calcaemic tetany Spontaneous twitch of hands and feet. Increased reflex Low levels of calcium cause an increase in permeability to Sodium and depolarisation Effects of Fever at the Extremes of Age Older Adult Persons McCance & Huether’s Subtle or atypical responses to infectious fever Pathophysiology, Ninth Edition are often accompanied by dehydration, and in Rogers, Julia L., DNP, APRN, CNS, FNP-BC, severe systemic infection there may be no FAANP fever. Symptoms can include feeling cold or warm, having strange body sensations, headache, vivid dreams, and hallucinations. Severe systemic infections may cause alternating hypothermia and high fever in a 24 h period. Infants and Children Infected babies may not develop infectious fever in the first few days of life. Young infants (less than 60–90 days of age) often present with fever and no other symptoms, making differential diagnosis difficult. Children develop higher temperatures than adults for relatively minor infections, and any skin vasoconstriction can lead to a rapid increase in body temperature. Febrile seizures before age 5 years are more common and can be related to an autosomal dominant polygenic inheritance. Severe systemic infections may cause alternating hypothermia and high fever in a 24 h period, the same as elderly adults. Adaptation responses What we would normally think of as a homeostatic response Accommodation: immediate physiological change in sensitivity of cells to changes in the external environment Acclimation; long term physiological adaptations Acquired in response to exposure to artificial or simulated respons changes in environment es Acclimatisation: long term physiological changes resulting from exposure to natural changes in environment Genetic adaptation: physiological or Inherited morphological changes that occur as a result of respons ‘survival of the fittest’, following long term exposure es