Lecture 2 - Introduction 2 PDF

HOMEOSTASIS = maintaining a constant internal environment. Claude Bernard Milieu interieur. (1813-1878) “The living body, though it has need of the surrounding environment, is nevertheless relatively independent...

HOMEOSTASIS = maintaining a constant internal environment. Claude Bernard Milieu interieur. (1813-1878) “The living body, though it has need of the surrounding environment, is nevertheless relatively independent of it.” “..a free and independent existence is possible only because of the stability of the internal milieu.” “The constancy of the internal environment is the condition for free and independent life: the mechanism that makes it possible is that which assured the maintenance, within the internal environment, of all the conditions necessary for Walter Cannon Features of (1871-1945) Homeostasis. 1. Homeostasis does not occur by chance, mechanisms in the body are present to maintain homeostasis. 2. A tendency to change must be met with factors that resist that change. 3. The homeostatic state consists of a number of cooperating mechanisms that occur at the same time, or in succession. 4. Considered both active and passive aspects of homeostasis. Homeostasis = maintenance of a constant internal environment. Critical variables Environmental factors that affect cells and can thus be maintained How cells communicate with one another to achieve homeostasis Homeostasis is within a range of values, not a single value. Disease / pathology Failure to maintain homeostasis Study of body functions in disease is called  “Internal Change” What is the Body’s Internal Environment? 1. Extracellular fluid (ECF) – the body’s internal environment that surrounds the cells 2. Intracellular fluid (ICF) – fluid within cells 3. ECF serves as buffer zone between outside world and ICF – kept relatively stable Internal and External environment  Homeostasis and Mass Balance Mass Balance – The amount of a substance in the body remains constant if any gain is offset by an equal loss – Gain Intake from outside + Metabolic production – Loss Excretion to outside + Metabolic usage Mass Flow – The rate of transport of a substance through the body or into or out of the body Example: Mass Balance of water Example: Mass Balance of water Water: A 70kg human has approx 42L water in body (3.5L in blood system) ~9L water pass through the digestive tract per day ~2L ingested (drink + food) ~2L excreted per day (urine/feces/sweat) ~7L are secreted into the lumen by the digestive tract to consume the nutrients you eat… This amount MUST BE reabsorbed. Water (fluid) balance is homeostatically controlled. Are passive (thermodynamically favorable) processes included in homeostasis? Are active (energy utilizing) processes included in homeostasis?  Homeostasis ≠ Equilibrium Generally homeostasis involves dynamic steady states Dynamic steady state – Materials are constantly moving between two compartments – Requires energy to sustain (ACTIVE) – No net movement between the compartments Equilibrium – Implies composition of compartments are identical – Usually thermodynamically favourable – tendency is to equalize without addition of energy (PASSIVE) Steady-state disequilibrium of Ions  “The constancy of the internal environment is the condition for free and independent life: the mechanism that makes it possible is that which assured the maintenance, within the internal environment, of all the conditions necessary for the life of the elements.” ENVIRONMENT: Homeostasis IS NOT an -water equilibrium with the -oxygen -chemicals environment, but the requiredproduction of an internal for lifeenvironment conducive to life itself. Steady-state disequilibrium of Ions S I VE P AS a nd e to T IVE i b u t A C n tr i on i c th c o C F a t e b o e n t v s I e o st il W movem ic ECF e hom one h e s. t h ion eosta tion, t antly rocess n homcentra edomi tive p o n p r a c c i s b y te d sta ntaine a i m  Control Systems Keep regulated variables within normal range. Homeostasis is stable because it can adjust variables dynamically. Setpoint = optimum range of values. Ignore the word “point”, it is not a single value. Control systems – Input signal – Integrating center – Output signal – Referred to in text as “reflex” systems… this essentially means negative feedback Negative feedback = resistance to a change in direction. Positive feedback = promotion toward a change in direction. Are both negative and positive feedback included in homeostasis? A simple control system  A simple negative feedback control system A simple positive/feed- forward control system Negative and positive feedback Positive feed-forward systems are rare. Example: Oxytocin positive feedback loop during birth…  Control Systems and Homeostasis Homeostasis requires negative feedback to continuously modulate the response Stimulus, sensor, input signal, integrating center, output signal, target, response NEGATIVE FEEDBACK modulates the homeostatic response loop – Negative feedback loops are homeostatic - stabilize variable that deviates from homeostasis – Positive feedback loops are not homeostatic – this would reinforce the variable’s deviation from homeostasis!! Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Negative feedback (reflex pathways) Oscillation around a setpoint A few last points Negative feedback. General mechanism underlying homeostasis. Does this mean all negative feedback is homeostatic? No! Not all negative feedback is homeostatic (glucocorticoid signaling). Positive feedback. Faster breathing in anticipation of exercise can help oxygen homeostasis but is not considered a homeostatic mechanism. Dare we compare: local control vs reflex control Reflex (or Long- Distance) control: Local cell or control: tissue that same cell or is affected tissue is is effected affected and by distant effected. cells. A MODEL OF HOMEOSTASIS  External Internal Disturbance Disturbance REGULATE alters D variabl e VARIABLE EFFECTO SENSOR R sends measures the signal to CONTROL variable effector affected CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance REGULATE alters D variabl e VARIABLE The Regulated Variable: EFFECTO SENSOR This is the component (chemical or physical) R that is detected by the body. It is kept within a limited range by sends measures homeostasis… if it deviates from this range, it the signal CONTROL to corrected to will be return to homeostasis. variable effector affected CONTROLLE CENTER ERROR It may not be the purpose of the homeostatic SET control. R DETECTOR POIN sendsThe body uses Examples: blood pressure. T blood pressure as a way error to homeostatically (variabl signal e) regulate water/fluid balance.  External Internal Disturbance Disturbance REGULATE alters D variabl e VARIABLE EFFECTO SENSOR R The Sensor: sends measures the This is what detects the regulated signal to CONTROL variable. variable effector affected CENTERERROR CONTROLLE SET Typically it is a cell that has receptors R DETECTOR for the variable. POIN sends T Example: baroreceptors on blood vessels error (variabl that detect signalblood pressure through e) membrane distortion.  The Control Center: External Internal Disturbance Disturbance REGULATE Receives signals that the variable has deviated. alters D Compares variabl the variable to the set point and sends VARIABLE eoutput signals to effect change in the body. This can be one cell or several cells that work EFFECTO SENSOR together to perform one function. R Example: medulla of the brain that controls blood pressure. sends measures the signal to CONTROL variable effector affected CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance REGULATE The Error Detector: alters D variabl e VARIABLE The error detector is a difficult concept. Part of this stems from a lack of knowledge on how it can variably respond to differences between the EFFECTO SENSOR variable and the set point. In some cases it is R understandable (baroreceptors on cells) The Error detector determines if the regulated sends measures the variable is at the set point or not. signal to CONTROL variable effector It lies within the control center. affected CONTROLLE CENTERERROR SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance REGULATE alters Thevariabl Set Point: D e VARIABLE This refers to a range of values that are acceptable for EFFECTO the regulated variable. SENSOR R It can change during different physiological states. Example: blood pressure has a set point during sends homeostasis, and a different one during normal measures the signal CONTROL to sleep, pregnancy. stress, variable effector affected CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance The Controller: REGULATE alters D variabl The component e VARIABLE of the control center that receives signals from the error detector. EFFECTO SENSOR The controllerR will fix the problem by increasing or decreasing the activity of the effectors. sends measures the Notesignal – in some cases both control center to functions are CONTROL done by the same variable effector affected cell! CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance REGULATE The D alters variabl Effector: e VARIABLE The effector receives the signal from the EFFECTO controller. It will alter the variable of the SENSOR homeostatic system. R Example: dilation or constriction of blood vessels will increase or decrease the sends volume of the circulatory system, measures the signal to CONTROL variable thereby affecting blood pressure. effector affected CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e)  External Internal Disturbance Disturbance REGULATE alters D variabl e VARIABLE EFFECTO SENSOR R sends measures the signal to CONTROL variable effector affected CENTERERROR CONTROLLE SET R DETECTOR POIN sends T error (variabl signal e) The cycle is complete. The deviation of the regulated variable has been detected, and homeostasis has been restored. Consider this schematic as a grouping of concepts for now. We will consider many different kinds of systems where the distinctions between these (i.e. sensor and controller) might not be present.