Human Physiology II - Homeostasis - PDF

HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Homeostasis Tutors Dr Kasimu Ibrahim Dr Ata Ali  Week 1, Lecture 1 At the end of this lecture, year 2 DDS students should be able to; define the term “internal environment” define the concept of “homeostasis” u...

HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Homeostasis Tutors Dr Kasimu Ibrahim Dr Ata Ali  Week 1, Lecture 1 At the end of this lecture, year 2 DDS students should be able to; define the term “internal environment” define the concept of “homeostasis” understand how the different body systems contribute towards achieving homeostasis 7/14/2024 2  Homeostasis Homeostasis was coined by Walter Cannon (1871-1945) in 1929 The maintenance of a stable “milieu interieur” or internal environment Claude Bernard (1813 - 1878) 7/14/2024 3  Homeostasis The fluid collectively contained within all body cells is called the intracellular fluid (ICF). The fluid outside the cells is called the extracellular fluid (ECF). The ECF is the internal environment of the body. The ECF consists of the plasma and the interstitial fluids 7/14/2024 4  Homeostasis ECF is transported in two stages - D -  Movement of blood through the body in the blood & vessels &  Movement of fluid between the capillaries & the - - intercellular spaces - 7/14/2024 5  Homeostasis The circulatory system distributes nutrients and oxygen around the body. Materials are thoroughly mixed between the plasma and the interstitial fluid across the capillaries Thus, nutrients and oxygen from the external environment are delivered to the interstitial fluid from where the cells - can pick them up! Wastes are deposited into the Interstitial fluid for eventual - removal 7/14/2024 6  Homeostasis All organs & tissues perform functions that help maintain homeostasis S 7/14/2024 7  Homeostasis Circulatory system: transports nutrients, oxygen, CO2, wastes, hormones from one part to another Digestive system: breaks down food, transfers water and electrolytes from the external to the internal environment, eliminates undigested food 7/14/2024 8  Homeostasis Respiratory system: imports oxygen and exports CO2 from the external environment, maintaining the PH of the body. 9) on 98 5 from plasma. - Urinary system: removes excess water, salt, acid, and other electrolytes from the plasma and eliminates them in the urine, along with waste products ⑳other than CO2. 7/14/2024 9  Homeostasis % % Endocrine system: regulates activities that require duration - rather than speed e.g. growth. Controls the concentration of nutrients and the volume and electrolyte composition of the ECF! cellular fluid ↳ External - Nervous system: controls bodily functions requiring swift actions, detects and corrects changes in the external environment, also responsible for higher functions (speech, memory, sleep). 7/14/2024 10  Homeostasis Skeletal system: support and protection for soft tissues and organs, stores large amounts of calcium, bone marrow produces all blood cells. Muscular system: moves bones, moves away from danger, moves towards food, temperature regulation, voluntary fine and complex movements. 7/14/2024 11  Homeostasis Sl : hair skin nails Soil , li , ; ↳ Integumentary system: protection against invaders, - temperature regulation & - & ↳ ↳ Immune system: defence against foreign invaders, tissue repair Reproductive system: important for the perpetuation of species 7/14/2024 12  Homeostatically regulated factors Concentration of nutrients: cells need a constant supply of nutrients to generate energy for cellular activities. Concentrations of O2 & CO2: cells need O2 for energy-yielding reactions and must remove CO2 to prevent acidosis Concentration of waste products: to prevent toxic effects on the cells. 7/14/2024 13  Homeostatically regulated factors pH: changes affect nerve cells and enzyme systems. Concentration of water, salt & other electrolytes: to maintain optimal volumes of the cells. Volume & pressure: to ensure body-wide distribution of plasma. Temperature: not too cold (slowed functions), too hot (destruction of proteins). 7/14/2024 14  Assessment What is homeostasis? Maintenance of nearly constant conditions in the internal environment Which of the following is referred to as the internal environment? a. Intracellular fluid b. Extracellular fluid c. Blood only d. Cerebrospinal fluid 7/14/2024 15  Assessment How does the cardiovascular system contribute to the maintenance of homeostasis? a) Maintaining PH of the body b) Removing excess water and salts from the body c) Defense against foreign invaders d) Transport of nutrients, gases, hormones and waste products List five homeostatically controlled factors in the body  Concentration of nutrients  Concentration of respiratory gases  Temperature  PH  Volume and pressure 7/14/2024 16  HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Control systems & feedback mechanisms Tutors Dr Kasimu Ibrahim Dr Ata Ali  Week 1, Lecture 2 At the end of this lecture, year 2 DDS students should be able to; know the characteristics of the control systems in the body. describe the feedback mechanisms of the control systems i.e. negative, positive and feed-forward control examine some control systems in the human body. 7/14/2024 2  Control systems of the body Thousands of control systems in the body ① o Genetic system oE Within the organs to control ② the functions of the individual parts (intrinsic) e.g. O2 in exercising skeletal muscle = o- Throughout the body to③control the interrelations between organs (extrinsic)- systemic, mediated by the endocrine and nervous systems 7/14/2024 Tre Tod 3  Homeostatic control systems ↳ g “Functionally interconnected network of - body components that operate to maintain a given factor in theWinternal environment relatively constant around an optimal level.” 7/14/2024 4  Components of control systems center) Sensor (receptor) Central & Integrating centre Effectors - - Feedback: responses made after a change has been detected 7/14/2024 5  Characteristics of control systems E detect deviations from normal in the internal environmental factor that needs to be held within narrow limits integrate this information with any other relevant information, and make appropriate adjustments to the activity of the body parts responsible for restoring this factor to its desired value. 7/14/2024 6  Feedback and Feed-Forward Control Negative feedback: promotes stability Positive feedback: promotes a change in one direction, instability, disease Feed-forward: anticipates change 7/14/2024 7  Negative Feedback Control of Arterial Pressure Promotes Stability Art. Pressure Sympathetic Activity Heart Rate Vasoconstriction 7/14/2024 8  Baroreceptor Reflex: Negative Feedback System - Promotes Stability 7/14/2024 9  Control of body temperature: Negative Feedback System - Promotes Stability 7/14/2024 10  Hemorrhagic Shock: Positive Feedback Severe Hemorrhage Venous Return + Cardiac Output Blood Pressure Coronary Blood Flow Cardiac Contractility 7/14/2024 11  Positive Feedback of Hemorrhagic Shock 7/14/2024 12  Examples of beneficial positive feedback Blood clotting: a cut in a blood vessel initiates events that activate clotting factors which activate more clotting factors enzymatically till the defect is closed and bleeding stops. Child birth: uterine contraction makes the head of the fetus stretch the cervix which sends signals through the uterine muscle to the body of the uterus causing more contractions till the baby is delivered 7/14/2024 13  Feed forward control Employed by the body to respond to an anticipatory change in a regulated variable E.g.=  Increase in Insulin secretion in response to the presence of food in the GIT to help prevent a rise in nutrient concentration after absorption.  Feed forward signals from the brain to the muscles to take care of potential sudden movements. 7/14/2024 14  Useful links https://www.youtube.com/watch?v=5G3aKGGI8hw https://www.youtube.com/watch?v=mn-2ob0F5e8 https://www.youtube.com/watch?v=zFuMxmAvz4s 7/14/2024 15 HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Transport across the cell membrane Tutors Dr Kasimu Ibrahim Dr Ata Ali  Week 1, Lecture 2 At the end of this lecture, year 2 DDS students should be able to; understand the structure of the cell membrane and its role in controlling how different substances enter or leave the cell. understand the different mechanisms by which substances cross the cell membrane differentiate between simple diffusion, facilitated diffusion and active transport. 7/14/2024 2  Cell Membrane: Bilayer of Phospholipids with Proteins Also called the plasma membrane Envelops the cell and is a thin, pliable, elastic structure. 7.5 to 10 nanometers thick. Composed almost entirely of proteins and lipids. The approximate composition is proteins, 55 percent; phospholipids, 25 percent; cholesterol, 13 percent; other lipids, 4% and carbohydrates, 3 percent. Cell Membrane: Bilayer of Phospholipids with Proteins 3 main types of lipids Phospholipids Sphingolipids & Cholesterol Lipid Bilayer The lipid bilayer is a barrier to water and water-soluble substances CO2 O2 H2O ions glucose N2 halothane urea  Cell Membrane … but, other molecules can still move through the membrane! urea CO2 ions H 2O O2 N2 isoflurane Membrane Proteins Provide specificity and function to a membrane. ion channels carrier proteins K+  Transport across the cell membrane Diffusion Active transport Occurs down a concentration Occurs against a concentration gradient gradient Through lipid bilayer or involves Involves a protein “carrier” a protein “channel” or “carrier” No additional energy required Requires ENERGY (ATP)  Simple Diffusion (a) Lipid-soluble molecules move readily across cell membranes (rate of diffusion depends on lipid solubility) (b) Water-soluble molecules cross cell membrane via channels or other transport proteins (a) (b)  Ion Channels Characteristics: Ungated channels Transport is determined by the size, shape, and charge of the channel and ion Gated channels Voltage (e.g., voltage-gated Na+ channels) Chemical (e.g., nicotinic acetylcholine receptor channels) Intracellular Na+ and other Na+ ions  Ion Channels Potassium channels are specific to potassium: they have a selectivity filter that draws water away from potassium and allow it to enter the channel. Sodium channels are specific to the transport of sodium: they are lined by negatively charged amino acids that literally draw sodium into the channel.  Difference between Carrier proteins and channels Only ions fit through the narrow channels, whereas small polar molecules such as glucose and amino acids are transported across the membrane by carriers. Channels can be open or closed, but carriers are always “open for business” Movement through channels is considerably faster than carrier-mediated transport is. When open for traffic, channels are open at both sides of the membrane at the same time, permitting continuous, rapid movement of ions between the ECF and ICF through these nonstop passageways. By contrast, carriers are never open to both the ECF and ICF simultaneously. They must change shape to alternately pick up passenger molecules on one side of the membrane and then drop them off on the other side, a time-consuming process. Difference between Carrier proteins and channels Carrier proteins Ion channels Small polar molecules like glucose Transport of ions and amino acids Always open for business Can be opened or closed The are never opened to both Movement is faster because both sides simultaneously. They need ends are opened when they are to undergo conformational open for traffic permitting rapid changes to transport passengers movement of ions between the across ECF and ICF Characteristics of carrier-mediated transport Specificity: Each carrier protein is specialized to transport a specific substance or, at most, a few closely related chemical compounds. Saturation: A limited number of carrier binding sites are available within a particular plasma membrane for a specific substance. Therefore, there is a limit to the amount of a substance a carrier can transport across the membrane in a given time. Competition. Several closely related compounds may compete for a ride across the membrane on the same carrier. If a given binding site can be occupied by more than one type of molecule, the rate of transport of each substance is less when both molecules are present than when either is present by itself.  Simple vs. Facilitated Diffusion simple diffusion Rate of diffusion Vmax facilitated diffusion Concentration gradient (Co-Ci) What limits the maximum rate of facilitated diffusion?  Facilitated Diffusion (also called carrier-mediated diffusion) The rate of diffusion is limited by the Vmax of carrier protein What is Net Diffusion? A B Magnitude of diffusion from side A to B Magnitude of diffusion from side B to A Magnitude of net diffusion (green arrow – red arrow)  Factors that affect the net rate of diffusion Increased concentration of a substance………………….. Increased surface area of the membrane…...................... Increased lipid solubility…………………………………….. Increased molecular weight of a substance………………… Increased thickness of the membrane………………………  Active Transport Primary Active Transport Molecules are “pumped” against an electrochemical gradient at the expense of energy (ATP) – direct use of energy Secondary Active Transport Transport is driven by the energy stored in the electrochemical gradient of another molecule (usually Na+) – indirect use of energy  Primary Active Transport 1. Na+-K+ ATPase Antiporter enzyme located on the plasma membrane of all animal cells Pumps sodium ions out of cells and pumps potassium ions into cells against electrochemical gradients Plays a critical role in regulating osmotic balance by maintaining Na+ and K+ balance  Primary Active Transport  subunit 100,000 MW binds ATP, 3 Na+, and 2 K+  subunit 55,000 MW function is not clear Transport is electrogenic but contributes less than 10% of the membrane potential  Primary Active Transport 2. Ca2+ ATPase Present on the cell membrane and the sarcoplasmic reticulum in muscle fibers Maintains a low cytosolic Ca2+ concentration 3. H+ ATPase Found in parietal cells of gastric glands (HCl secretion) and intercalated cells of renal tubules (controls blood pH) Concentrates H+ ions up to 1 million-fold  Secondary Active Transport - Involves the use of an electrochemical gradient (usually for sodium) - Protein cotransporters are classified as symporters or antiporters 1. Symporters: transport substance in same direction as a “driver” ion like Na+. Examples: Na+ AA Na+ gluc Na+ 2 HCO3-  Secondary Active Transport 2. Antiporters: transport substances in the opposite direction of a “driver” ion like Na+ Examples: Na+ Na+ Na+/HCO3- Ca2+ H+ Cl-/H+  Useful links https://www.youtube.com/watch?v=I1MZG6508IM https://www.youtube.com/watch?v=ol4nWorgiHI https://www.youtube.com/watch?v=Ypg_wUOcmBQ HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Control of Respiration Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/18  Week 2, Lecture 1 At the end of this lecture, year 2 DDS students should be able to; describe the neural mechanisms that control respiration describe the chemical control of respiration describe the control of respiration by other factors 2024/07/18 2  Control of respiration Respiration is principally under neural control However, it is also additionally controlled by:  Chemical control systems and  Other factors such as the proprioceptors and irritant receptors 2024/07/18 3  Neural control of respiration Components of neural control  Factors that generate the alternating inspiration- expiration rhythm  Factors that regulate the magnitude of ventilation to match body needs  Factors that modify respiratory activity to serve other purposes e.g. speech, sneezing 2024/07/18 4  Neural control of respiration There are two types (components) of neural control of respiration:  Voluntary: cerebral cortex, impulses sent to the respiratory motor neurons through the cortico-spinal tract  Spontaneous: medullary and pontine centers 2024/07/18 5  Neural control of respiration The respiratory centres are composed of several groups of neurons which control the rate, rhythm and force of respiration These centres are located bilaterally in the medulla oblongata and Pons of the brain stem 2024/07/18 6  Neural control of respiration The medullary neurons The medullar contains the respiratory control pattern generator The dorsal respiratory group of neurons  Contains inspiratory neurons whose descending fibres terminate on the respiratory motor neurons  Inspiration occurs when they fire  Important connection with the ventral respiratory group of neurons 2024/07/18 7  Neural control of respiration The dorsal respiratory group of neurons  They extend most of the length of the medulla  Most of the neurons are located diffusely in the nucleus of tractus solitarius (NTS)  Additional neurons in the adjacent reticular substance of the medulla also play a role in the control of respiration  These neurons discharge rhythmically to the contra-lateral phrenic motor neurons to bring about inspiration 2024/07/18 8  Neural control of respiration The ventral respiratory group of neurons  These neurons are found in the nucleus ambiguous rostrally and nucleus para-ambiguous caudally  They have both inspiratory and expiratory neurons which project to and drive motor neurons to the accessory muscles of respiration  Destruction of the DRG and VRG reduces the amplitude of respiration but does not abolish it, suggesting that they may not be obligatory parts of the respiratory control pattern generator 2024/07/18 9  Neural control of respiration The Pre-Botzinger Complex  This complex contains a group of pacemaker neurons which discharge rhythmically into the phrenic motor neurons  They may contain generator neurons for the respiratory rhythm The inspiratory neurons discharge rhythmically. The discharge is characterized by a burst of activity followed by a period of quiescence. This occurs about 12-15 times per minute. The expiratory neurons do not discharge spontaneously but can be excited by afferent stimuli from other sources 2024/07/18 10  Neural control of respiration The Pneumotaxic centre  It is situated in the reticular formation in the upper pons  It is formed by the neurons of the nucleus para-brachialis and kolliker-fuse nucleus  The centre controls the ‘switch off’ point of the inspiratory ramp, thus controlling the duration of the filling phase of the lung cycle 2024/07/18 11  Neural control of respiration The Pneumotaxic centre  Inhibits the DRG to stop inspiration and expiration starts  Increases the respiratory rate by reducing the duration of inspiration  Destruction of the pneumotaxic centre results in slower and deeper breathing/respiration 2024/07/18 12  Neural control of respiration The Apneustic centre  Located in the reticular formations of the lower pons  Prevents switching off of inspiratory neurons  Extra boost to the inspiratory drive 2024/07/18 13 2024/07/18 14  Neural control of respiration Vagal afferents  There are stretch receptors located in the walls of the bronchi and bronchioles  The receptors transmit signals through the vagus nerve into the DRG when the lungs are overstretched  This switches off the inspiratory ramp  HERING-BREUER REFLEX  VAGOTOMY produces an increase in the depth of inspiration because of the removal of the effect of vagal afferents 2024/07/18 15  Chemical control of respiration The respiratory centre is affected by chemical stimuli in the blood such as:  PCO2, PO2 and PH The chemo-receptors mediate the effects of these chemicals on the respiratory centre Chemo-receptors are of two types:  Central chemo-receptors  Peripheral chemo-receptors 2024/07/18 16  Chemical control of respiration Central chemo-receptors  They are located on the ventral surface of the medulla near the respiratory centre  The stimuli is increased PCO2 , while the mechanism of stimulation is CSF [H+] concentration  CO2 crosses the blood-brain barrier into the CSF, and gets hydrated: CO2+HO2 c H2CO3 c H++HCO3-  The H+ then stimulates the central chemo-receptors which in turn stimulate the respiratory centre which then causes hyperventilation 2024/07/18 17  Chemical control of respiration Peripheral chemo-receptors Consist of carotid and aortic bodies  The carotid bodies are located in the bifurcation of the common carotid arteries while the aortic bodies are located in the aortic arch region  Afferent nerve fibres from the carotid body ascend to the medulla through the carotid sinus and glossopharyngeal nerve (CNIX) while those from the aortic bodies ascend in the vagus nerve 2024/07/18 18  Chemical control of respiration Peripheral chemo-receptors The stimuli are:  Fall in PO2  Fall in PH  Increased PCO2 of arterial blood The blood flow to the carotid body is the highest in the body. It is about 2 litres/100g/min. This high blood flow ensures that slight changes in PO2, PCO2 and PH are sensed by the carotid bodies 2024/07/18 19  Control of respiration by other factors Higher Centres  Afferents from the limbic system reach the respiration centre  Increased respiration during emotional excitement is due to the effect of these afferents on the respiratory centre 2024/07/18 20  Control of respiration by other factors Cerebral Cortex  Control is through the cortico-spinal tract  Different from control by the respiratory centre in the medulla  The cortico-spinal tract that extends from the cerebral cortex to the motor neurons of the respiratory muscles bypass the respiratory centre 2024/07/18 21  Control of respiration by other factors Cerebral Cortex  Compression of the medulla or in diseases such as bulbar poliomyelitis results in cessation of involuntary respiration while leaving voluntary control intact  In such conditions, the person has to stay alive by breathing voluntarily  This is called ONDIES CURSE 2024/07/18 22  Control of respiration by other factors Proprioceptors  They are mechanoreceptors in muscles, tendons and joints  Afferents stimulate the RC during movement to bring about an increase in ventilation  Proprioceptors are very important in increasing ventilation before and during exercise Chemoreceptors Stretch receptors in the lungs 2024/07/18 23  Control of respiration by other factors Irritant receptors  Receptors in the mucosa of the trachea and bronchi that respond to irritants  They initiate the cough or sneeze reflex which involve a deep inspiration followed by a forceful expiration that expels the irritants 2024/07/18 24 2024/07/18 25  Useful links https://www.youtube.com/watch?v=_KNAKKNbq20 https://www.youtube.com/watch?v=9j6BpanhpKY 2024/07/18 26 HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Respiratory adjustments to exercise Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/18 1  Week 2, Lecture 2 At the end of this lecture, year 2 DDS students should be able to; describe the mechanisms for increasing the supply of oxygen to the muscles during exercise explain how excess carbon dioxide is removed from the body during exercise explain how heat loss is increased in the body during exercise 2024/07/18 2 Respiratory adjustments during exercise During exercise there is a need to:-  Increase oxygen supply to the exercising muscle  Remove excess carbon dioxide  Remove excess heat from the body 2024/07/18 3 Respiratory adjustments during exercise Increase oxygen supply to the exercising muscle is achieved by:  Increasing PO2 gradient between the alveoli and pulmonary venous blood  Increasing pulmonary blood flow: from 5L/min to about 30L/min oFactors 1 and 2 above combine to increase O2 supply to the tissue from 25ml/min to 400ml/min. oO2 consumption is still greater than O2 supply, oxygen debt incurred 2024/07/18 4 Respiratory adjustments during exercise Increasing O2 extraction from the blood, achieved by:  Increasing the PO2 gradient between the blood and the muscle  Reduction in the saturation of Hb and therefore more O2 is delivered to the muscles  The PCO2, temperature and 2, 3 – DPG concentration all increase in the tissue of the contracting muscle 2024/07/18 5 Respiratory adjustments during exercise Removal of excess carbon dioxide  Increases from 200ml/min to about 800ml/min  This ensures the removal of the excess CO2 produced by the exercising muscles 2024/07/18 6 Respiratory adjustments during exercise Increased heat loss Increasing vaporization of water from the mucous membrane of the mouth and respiratory passages 2024/07/18 7 Respiratory adjustments during exercise Overall ventilatory changes during exercise  Tidal volume, respiratory rate, respiratory minute volume and alveolar ventilation increase  There are four (4) phases that occur in the overall ventilatory changes during exercise 2024/07/18 8 Respiratory adjustments during exercise Overall ventilatory changes during exercise 2024/07/18 9 Respiratory adjustments during exercise Overall ventilatory changes during exercise Phase I Sudden increase in ventilation at the onset of exercise Due to stimulation of the respiratory centres by the higher centres and proprioceptors 2024/07/18 10 Respiratory adjustments during exercise Phase II  This is the increase in ventilation that occurs during exercise  The cause of this increase is unknown, it might be due to: oIncreased temperature oIncreased plasma potassium concentration (PCR) oIncreased sensitivity of the respiratory centre to CO2 2024/07/18 11 Respiratory adjustments during exercise Phase III  Corresponds to the abrupt fall in ventilation at the end of the exercise 2024/07/18 12  Respiratory adjustments during exercise Phase IV  Extra ventilation post-exercise  Extra amount of O2 consumed used to pay back the O2 debt incurred o It is used for the following: a. To oxidise part for the lactic acid to form CO2, water and energy b. To replenish ATP and creatine phosphate stores used up during exercise c. To replace O2 delivered to muscles by myoglobin 2024/07/18 13  Useful links https://www.youtube.com/watch?app=desktop&v=6B3TUj2cLgo 2024/07/18 14 HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Respiratory adjustments to high altitude Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/18 1  Week 2, Lecture 3 At the end of this lecture, year 2 DDS students should be able to; define and explain the symptoms of mountain sickness explain the concept of acclimatisation at high altitudes describe natural acclimatisation by natives at high altitudes 2024/07/18 2  Respiratory adjustments to high altitude Any altitude above 6000 meters from mean sea level is called a high altitude People can ascend to this level without any adverse effect At high altitudes the barometric pressure is low However, the amount of oxygen available in the atmosphere is the same as that at sea level 2024/07/18 3 2024/07/18 4  Respiratory adjustments to high altitude Partial pressure of gases, particularly O2 proportionally decreases leading to hypoxia. The CO2 at high altitudes is very much negligible and it doesn’t create any problem The barometric pressure decreases at different altitudes, and accordingly the partial pressure of oxygen also decreases leading to various effects on the body 2024/07/18 5 2024/07/18 6  Respiratory adjustments to high altitude Very rapid ascent to heights above 16,000 meters in an unpressured plane instantly leads to loss of consciousness and death 2024/07/18 7  Respiratory adjustments to high altitude At altitude below 16000 meters, the hypoxia may not lead to death but will produce symptoms of MOUNTAIN SICKNESS Mountain sickness is the condition characterized by adverse effects of hypoxia at high altitude. It is commonly developed in persons going to high altitude for the first time. It occurs within a day in these persons before they get acclimatized to the altitude. 2024/07/18 8  Respiratory adjustments to high altitude Symptoms of mountain sickness In mountain sickness, the symptoms occur mostly in the digestive system, cardiovascular system, respiratory system and nervous system.  Digestive system: loss of appetite, nausea and vomiting occur because of the expansion of gases in the gastrointestinal tract.  Cardiovascular system: heart rate increases 2024/07/18 9  Respiratory adjustments to high altitude Symptoms of mountain sickness  Respiratory system: pulmonary blood pressure increases due to increased blood flow resulting from vasodilatation induced by hypoxia. oIncreased pulmonary blood pressure results in pulmonary edema which causes breathlessness.  Nervous system: headache, depression, disorientation, irritability, lack of sleep, weakness and fatigue 2024/07/18 10  Respiratory adjustments to high altitude Acclimatization: compensatory mechanisms operating over some time to increase altitude tolerance While staying at high altitudes for several days to several weeks, a person slowly adapts or adjusts to the low oxygen tension, so that hypoxic effects are reduced It enables the person to ascend further 2024/07/18 11  Respiratory adjustments to high altitude Changes During Acclimatization  The various changes during acclimatization help the body to cope with the adverse effects of hypoxia at high altitudes. These compensatory mechanisms include:  Changes in the blood: oThe RBC count increases and packed cell volume rises from the normal value of 45% to about 59%. oThe haemoglobin content in the blood rises from 15 to 20 g%. So, the oxygen-carrying capacity of the blood is increased. oThus, more oxygen can be carried to tissues despite hypoxia. 2024/07/18 12  Respiratory adjustments to high altitude Changes During Acclimatization  Changes in the blood:  Increase in RBC count, packed cell volume and haemoglobin content is due to erythropoietin that is released from the juxtaglomerular apparatus of the kidney.  Changes in the cardiovascular system: oIncrease in the rate and force of contraction of the heart oIncrease in cardiac output and blood pressure oHypoxia-induced vasodilation increases blood supply to the vital organs 2024/07/18 13 2024/07/18 14  Respiratory adjustments to high altitude Changes During Acclimatization  Changes in the respiratory system oPulmonary ventilation increases up to 65% due to the stimulation of chemoreceptors. This helps the person to ascend several thousand feet oPulmonary hypertension develops due to increased cardiac output and pulmonary blood flow oDiffusing capacity of gases increases in the alveoli due to the increase in pulmonary blood flow and pulmonary ventilation. oIt enables more diffusion of oxygen in the blood. 2024/07/18 15  Respiratory adjustments to high altitude Acclimatization Compensatory changes in the tissue:  Increased tissue vascularity  Increased numbers of mitochondria for energy supply  Increased myoglobin concentration which facilitates O2 transport to the tissue  Increased concentration of cytochrome oxidase to ensure that internal respiration is efficient 2024/07/18 16  Respiratory adjustments to high altitude Natural acclimatisation by natives living at high altitudes Natives begin to acclimatise right from infancy The acclimatisation mechanisms include:  High ventilation capacity- body mass ratio  Hypertrophy of the right heart  Polycythaemia 2024/07/18 17 2024/07/18 18 2024/07/18 19  Useful links https://www.youtube.com/watch?app=desktop&v=P_4w k33cTVo 2024/07/18 20 HUMAN PHYSIOLOGY II COURSE CODE: 1601106 3 credit Units Respiratory adjustments to deep sea diving Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/18 1  Week 2, Lecture 4 At the end of this lecture, year 2 DDS students should be able to; describe the physiological changes in deep-sea diving explain nitrogen narcosis, its symptoms and treatment discuss oxygen toxicity, decompression sickness and their treatment. 2024/07/18 2  Respiratory adjustments to deep sea diving Barometric pressure increases with depth The increased pressure creates two major problems:  Compression effect on the body and internal organs  Decrease in volume of gases At sea level, the barometric pressure is 760mmHg = 1 atm It increases by 1 atm for every 33 feet (10 meters) depth This is due to the air above water and the weight of the water itself 2024/07/18 3  Respiratory adjustments to deep sea diving Nitrogen narcosis (rapture of the deep) Narcosis refers to unconsciousness or stupor produced by drugs Stupor means lethargy and suppression of feelings and sensations Nitrogen narcosis means the narcotic effect produced by nitrogen at high-pressure 2024/07/18 4  Respiratory adjustments to deep sea diving Nitrogen narcosis (rapture of the deep) Nitrogen is fat soluble. During compression by high barometric pressure N2 escapes from the blood vessels and dissolves in fat present in various parts of the body, especially the neuronal membranes. The dissolved N2 acts as an anaesthetic agent suppressing the neuronal excitability 2024/07/18 5  Respiratory adjustments to deep sea diving Nitrogen narcosis (rapture of the deep) Symptoms Similar to those of alcohol intoxication Euphoria, drowsiness, impaired work function and loss of consciousness 2024/07/18 6  Respiratory adjustments to deep sea diving Nitrogen narcosis (rapture of the deep) Prevention  Use of Helium as a substitute for Nitrogen to dilute oxygen during deep-water diving  Limiting the depth of dives  Safe diving procedures 2024/07/18 7  Respiratory adjustments to deep sea diving Nitrogen narcosis (rapture of the deep) Treatment  Symptoms completely disappear when the diver returns to a depth of 60ft.  No need for further treatment since Nitrogen has no hangover effects 2024/07/18 8  Respiratory adjustments to deep sea diving Oxygen toxicity  Breathing O2 at great pressure leads to O2 toxicity due to the production of oxygen-derived free radicals such as superoxide (O2-) anions and H2O2  Damages the lungs and produces CNS symptoms such as CONVULSION and COMA.  Prevented by replacing 100% O2 with a gas mixture containing 20% O2. 2024/07/18 9  Respiratory adjustments to deep sea diving Decompression sickness  Disorder that occurs when a person ascends rapidly to normal surroundings (atmospheric pressure) from an area of high atmospheric pressure like deep sea  Known as DYSBARISM, COMPRESSED AIR SICKNESS, CAISSON’s DISEASE, BENDS OR DIVER’S PALSY 2024/07/18 10  Respiratory adjustments to deep sea diving Decompression sickness  Dissolved N2 in the tissues and blood now diffuses into the lungs  If the diver ascends gradually, no problems occur  If the ascent is rapid, nitrogen is released too quickly and bubbles are formed in the tissue and blood- producing symptoms of decompression sickness which include: 2024/07/18 11  Respiratory adjustments to deep sea diving Decompression sickness  Pain in the tissues due to the presence of bubbles in the myelin sheaths of sensory nerve fibres  Paralysis as a result of bubbles in the myelin sheath of motor nerve fibres and occlusion of arteries of the brain.  Coronary ischemia when the bubbles occlude the coronary arteries  Chokes or dyspnoea due to blockage of the pulmonary capillaries by the bubbles 2024/07/18 12  Respiratory adjustments to deep sea diving Decompression sickness Treatment Recompressing the diver in a recompression chamber and Gradually decompressing him so that the nitrogen diffuses out without forming any bubbles 2024/07/18 13  Respiratory adjustments to deep sea diving Decompression sickness Prevention  Ascent should be slow while returning to mean sea level  Stay at regular intervals 2024/07/18 14  Respiratory adjustments to deep sea diving Air embolism  If a diver ascends rapidly and holds his breath at the same time air in the lungs expands and ruptures the pulmonary veins  Air enters the veins and obstructs the circulation causing air embolism  Air embolism could result in sudden death 2024/07/18 15  Respiratory adjustments to deep sea diving Scuba  Self-contained underwater breathing apparatus is used by deep sea divers and underwater tunnel workers  To prevent the ill effects of increased barometric pressure 2024/07/18 16  Useful links https://www.youtube.com/watch?v=AhcTGIPEyPU https://www.youtube.com/watch?v=9IZGNzj9S0w 2024/07/18 17  HUMAN PHYSIOLOGY II COURSE CODE: 1601106 4 credit Units The thyroid gland I Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/27  Week 3, lecture 1 At the end of this lecture, year one DDS students should be able to: describe the functional histology and hormones of the thyroid gland describe the synthesis, storage, and release of the thyroid hormones 2024/07/27 2  Thyroid gland An endocrine gland situated at the root of the neck on either side of the trachea Has two lobes connected in the middle by an isthmus Weighs about 20 to 40 g in adults Larger in females than in males Its function increases slightly during pregnancy and lactation and decreases during menopause 2024/07/27 3  Functional histology Composed of a large number of closed follicles Follicles are lined with cuboidal epithelial cells called follicular cells The follicular cavity is filled with a colloidal substance (thyroglobulin) secreted by the follicular cells (FCs). FCs secrete tetraiodothyronine (T4 or thyroxine) and triiodothyronine (T3). In between the follicles, the parafollicular cells which secrete calcitonin are present 2024/07/27 4  Hormones of the thyroid gland The thyroid gland secretes three hormones:  Tetraiodothyronine – T4 (thyroxine)  Triiodothyronine – T3  Calcitonin (to be discussed with the parathyroid gland) T4 is otherwise known as thyroxine and it forms about 90% of the total secretion T3 is only 9 to 10% but its potency is four times more than that of T4. 2024/07/27 5  Synthesis of thyroid hormones Synthesis of thyroid hormones takes place in thyroglobulin present in the follicular cavity. Iodine and tyrosine are essential for the formation of thyroid hormones. Iodine is consumed through diet and is converted into iodide and absorbed from the GI tract. Tyrosine is also consumed through diet and is absorbed from the GI. 2024/07/27 6  Synthesis of thyroid hormones For the synthesis of normal quantities of thyroid hormones, approximately 1 mg of iodine is required per week or about 50 mg per year. To prevent iodine deficiency, common table salt is iodized with one part of sodium iodide for every 100,000 parts of sodium chloride. Various stages involved in the synthesis of thyroid hormones are:  Thyroglobulin synthesis  Iodide trapping or iodide pump  Oxidation of iodide  Iodination of tyrosine  Coupling reactions 2024/07/27 7  Synthesis of thyroid hormones Thyroglobulin synthesis  The endoplasmic reticulum and Golgi apparatus in the follicular cells of the thyroid gland synthesize and secrete thyroglobulin continuously.  Each thyroglobulin molecule contains 140 tyrosine molecules.  After synthesis, the thyroglobulin is stored in the follicle. 2024/07/27 9  Synthesis of thyroid hormones Iodide trapping or iodide pump  Iodide is transported actively from the blood into the follicular cell against the electrochemical gradient by a process called iodide trapping.  Iodide is pumped with sodium into the follicular cell by a sodium- iodide symport pump.  From here, iodide is transported into the follicular cavity by an iodide-chloride pump. 2024/07/27 10  Synthesis of thyroid hormones Oxidation of Iodide  Iodide must be oxidized to elementary iodine because only iodine is capable of combining with tyrosine to form thyroid hormones.  The oxidation of iodide into iodine occurs inside the follicular cells in the presence of thyroid peroxidase 2024/07/27 11  Synthesis of thyroid hormones Iodination of tyrosine  The combination of iodine with tyrosine is known as iodination.  It takes place in the follicle within thyroglobulin.  First, iodine is released from follicular cells into the follicular cavity where it binds with thyroglobulin.  This process is called the organification of thyroglobulin.  In the thyroglobulin, iodine combines with tyrosine which is already present there.  Binding of iodine (I) with tyrosine is accelerated by the enzyme iodinase which is secreted by the follicular cells. Iodination of tyrosine occurs in several stages.  Tyrosine is iodized first into monoiodotyrosine (MIT) and later into diiodotyrosine (DIT). MIT and DIT are called the iodotyrosine residues. 2024/07/27 12  Synthesis of thyroid hormones Coupling reactions  The iodotyrosine residues get coupled with one another through coupling reactions.  The coupling occurs in different configurations to give rise to different thyroid hormones: o One molecule of DIT and one molecule of MIT combine to form triiodothyronine (T3) o Sometimes one molecule of MIT and one molecule of DIT combine to produce another form of T3 called reverse T3 or rT3. o Reverse T3 is only 1% of thyroid output. 2024/07/27 13  Synthesis of thyroid hormones Coupling reactions o Two molecules of DIT combine to form tetraiodothyronine (T4) which is thyroxine  Tyrosine + I = Monoiodotyrosine (MIT)  MIT + I = Diiodotyrosine (DIT)  DIT + MIT = Triiodothyronine (T3)  MIT + DIT = Reverse T3  DIT + DIT = Tetraiodothyronine or Thyroxine (T4) 2024/07/27 14  Synthesis of thyroid hormones 2024/07/27 15  Storage of thyroid hormones After synthesis, the thyroid hormones remain in the form of vesicles within thyroglobulin. In combination with thyroglobulin, the thyroid hormones can be stored for several months. The thyroid gland is unique in this, as it is the only endocrine gland that can store its hormones for a long period of about 4 months. So, when the synthesis of thyroid hormone stops, the signs and symptoms of deficiency do not appear for about 4 months. 2024/07/27 16  Release of thyroid hormones Thyroglobulin itself is not released into the bloodstream (only T3 & T4) In the peripheral tissues, T4 is converted into T3 The MIT and DIT are not released into the blood They (MIT and DIT) are de-iodinated by an enzyme called iodotyrosine deiodinase resulting in the release of iodine. The iodine is reutilized by the follicular cells for the synthesis of thyroid hormones 2024/07/27 17  Transport of thyroid hormones The normal plasma level of total T3 is 0.12 μg/dL and that of total T4 is 8 μg/dL. The thyroid hormones are transported in the blood in combination with three types of plasma proteins:  Thyroxine-binding globulin (TBG)  Thyroxine-binding prealbumin (TBPA)  Albumin 2024/07/27 19  Useful links https://www.youtube.com/watch?v=5aq_rxTbtws https://www.youtube.com/watch?v=epWJ2v5qy5E https://www.youtube.com/watch?v=hLNXJWLsjAE 2024/07/27 20  HUMAN PHYSIOLOGY COURSE CODE: 1601106 3 credit Units The thyroid gland II Tutors Dr Kasimu Ibrahim Dr Ata Ali 2024/07/27  Week 3, lecture 2 At the end of this lecture, year one DDS students should be able to: outline the physiological functions of the thyroid hormones in the human body describe the mechanism of action of the thyroid hormones discuss the regulation of the secretion of thyroid hormones discuss the applied physiology of some disorders of the thyroid gland. 2024/07/27 2 Physiological actions of the thyroid hormones Thyroid hormones have two major effects on the body:  To increase the overall metabolic rate in the body.  To stimulate growth in children. The actions of thyroid hormones are:  On the basal metabolic rate (BMR): o Thyroxine increases the metabolic activities of almost all tissues of the body except the brain, retina, spleen, testes and lungs. o It increases the basal metabolic rate (BMR) by increasing the oxygen consumption of the tissues. The action that increases the BMR is called calorigenic action. o 2024/07/27 3 Physiological actions of the thyroid hormones On protein metabolism:  Thyroid hormones increase the synthesis of proteins.  Thyroxine accelerates protein synthesis by increasing: o Translation of RNA in the cells o Transcription of DNA to RNA o Activity of mitochondria o Activity of cellular enzymes.  Though thyroxine increases protein synthesis, it also causes catabolism of proteins 2024/07/27 4 Physiological actions of the thyroid hormones On carbohydrate metabolism  Thyroxine stimulates almost all processes involved in the metabolism of carbohydrates  It increases: o Absorption of glucose from the GI tract o Glucose uptake by the cells, by accelerating the transport of glucose through the cell membrane o Breakdown of glycogen into glucose o Gluconeogenesis. 2024/07/27 5 Physiological actions of the thyroid hormones On fat metabolism  Thyroxine decreases fat storage by mobilizing it from adipose tissues and fat depots.  The mobilized fat is converted into free fatty acid and transported by blood.  Thus, thyroxine increases the free fatty acid level in the blood. 2024/07/27 6 Physiological actions of the thyroid hormones On plasma and liver fats  Thyroxine specifically decreases the plasma's cholesterol, phospholipids and triglyceride levels.  Hyposecretion of thyroxine increases the cholesterol level in plasma resulting in atherosclerosis.  Thyroxine also increases the deposition of fats in the liver leading to fatty liver. 2024/07/27 7  Physiological actions of the thyroid hormones On growth  Lack of thyroxine arrests growth while an increase in thyroxine secretion accelerates it especially in growing children.  Thyroxine is important in promoting the growth and development of the brain during fetal life and the first few years of postnatal life.  Lack of thyroid hormones at this period leads to mental retardation. On body weight  Increased thyroxine secretion decreases body weight and fat deposition and vice versa. 2024/07/27 8 Physiological actions of the thyroid hormones Other effects  Thyroxine increases the production of RBCs.  Increases heart rate and force of contraction of the heart  Causes vasodilation due to increased metabolic activity  Increases systolic blood pressure due to increased heart rate, force of contraction and blood volume  Decreases diastolic blood pressure due to vasodilation  Increases rate and force of respiration due to increased tissue demand for oxygen and the need for CO2 elimination  Increases appetite and food intake  Increases secretions and movements of the GIT 2024/07/27 9 2024/07/27 10  Regulation of secretion of thyroid hormones The secretion of thyroid hormones is controlled by the anterior pituitary and hypothalamus through a feedback mechanism 2024/07/27 11  Regulation of secretion of thyroid hormones Role of hypothalamus  The hypothalamus regulates thyroid secretion by controlling TSH secretion through thyrotropin-releasing hormone (TRH) from the hypothalamus.  From the hypothalamus, it is transported through the hypothalamo- hypophyseal portal vessels to the anterior pituitary.  After reaching the pituitary gland, the TRH causes the release of TSH. 2024/07/27 12 Regulation of secretion of thyroid hormones Role of pituitary gland Thyroid-stimulating Hormone  Thyroid-stimulating hormone (TSH) secreted by the anterior pituitary is the major factor regulating the synthesis and release of thyroid hormones.  TSH is a peptide hormone with one α-chain and one β-chain.  The normal plasma level of TSH is approximately 2 U/mL. 2024/07/27 13  Regulation of secretion of thyroid hormones Actions of TSH: It increases:  The number of thyroid cells, which are cuboidal in nature, and then converts them into columnar cells and causes the development of thyroid follicles  The size and secretory activity of the cells  The iodide pump and iodide trapping in the cells  The thyroglobulin secretion into the follicles.  Iodination of tyrosine and coupling to form the hormones  Proteolysis of the thyroglobulin, by which, the release of hormone is enhanced and the colloidal substance is decreased 2024/07/27 14 Regulation of secretion of thyroid hormones Feedback control  Thyroid hormones regulate their secretion through negative feedback control by inhibiting the release of TRH from the hypothalamus and TSH from the anterior pituitary Role of iodide  When the dietary level of iodine is moderate, the blood level of thyroid hormones is normal.  However, when iodine intake is high, the enzymes necessary for the synthesis of thyroid hormones are inhibited by iodide itself resulting in the suppression of hormone synthesis. 2024/07/27 15  Disorders of the thyroid gland Hyperthyroidism Causes of Hyperthyroidism  Graves’ disease o It is an autoimmune disease o Normally, TSH combines with surface receptors of thyroid cells and causes the synthesis of thyroid hormones o In Graves’ disease, the B lymphocytes produce autoimmune antibodies called thyroid-stimulating autoantibodies. o These antibodies act like TSH by binding with membrane receptors of TSH and activating the cAMP system of the thyroid follicular cells resulting in hypersecretion of thyroid hormones. 2024/07/27 16  Disorders of the thyroid gland Hyperthyroidism Causes of Hyperthyroidism  Thyroid adenoma o Sometimes, a localized tumour develops in the thyroid tissue. o It is known as thyroid adenoma and it secretes large quantities of thyroid hormones. 2024/07/27 17  Disorders of the thyroid gland Signs and symptoms of hyperthyroidism  Intolerance to heat because of the production of more heat during increased basal metabolic rate caused by hyperthyroidism  Increased sweating due to vasodilatation  Decreased body weight due to fat mobilization  Diarrhea due to increased motility of the GI tract  Muscular weakness due to excess protein catabolism  Neuronal disturbances such as nervousness, extreme fatigue, inability to sleep, mild tremors in hands  Toxic goitre  Oligomenorrhea or amenorrhea  Exophthalmos  Polycythemia  Tachycardia and atrial fibrillation. 2024/07/27 18  Disorders of the thyroid gland Hypothyroidism  Decreased secretion of thyroid hormones is called hypothyroidism.  Hypothyroidism leads to myxoedema in adults and cretinism in children.  Myxoedema is hypothyroidism in adults characterized by a generalized edematous appearance.  Causes of myxoedema o Myxedema occurs due to diseases of the thyroid gland, genetic disorders or iodine deficiency. o In addition, it is also caused by a deficiency of thyroid-stimulating hormone or thyrotropin-releasing hormone. 2024/07/27 19  Disorders of the thyroid gland  Signs and symptoms of myxedema o A typical feature of this disorder is an edematous appearance throughout the body. It is associated with the following symptoms:  Swelling of the face  Bagginess under the eyes  Non-pitting type of oedema, i.e. when pressed, it does not make pits and the oedema is hard  Atherosclerosis: the hardening of the walls of arteries because of the accumulation of fat  In myxedema, it occurs because of an increased plasma level of cholesterol which leads to the deposition of cholesterol on the walls of the arteries 2024/07/27 20  Disorders of the thyroid gland Hypothyroidism  Other general signs and symptoms of myxedema adults are:  Anemia, fatigue and muscular sluggishness, extreme somnolence with sleeping up to 14 to 16 hours per day.  Menorrhagia and polymenorrhea  Decreased cardiovascular functions such as reduction in rate and force of contraction of the heart, cardiac output and blood volume.  Increase in body weight, constipation, and mental sluggishness  Depressed hair growth, scaliness of the skin and frog-like husky voice  Cold intolerance. 2024/07/27 21  Disorders of the thyroid gland Hypothyroidism  Cretinism o Cretinism is the hypothyroidism in children characterized by stunted growth. Causes of cretinism  Cretinism occurs due to congenital absence of the thyroid gland, genetic disorder or lack of iodine in the diet. 2024/07/27 22  Disorders of the thyroid gland  Features of cretinism o A newborn baby may appear normal at the time of birth because thyroxine might have been supplied by the mother o A few weeks after birth, the baby starts developing signs like sluggish movements and croaking sounds while crying o Stunted growth with a bloated body o The tongue becomes so big, that it hangs down with the dripping of saliva. o The tongue obstructs swallowing and breathing and produces characteristic guttural breathing that may sometimes choke the baby 2024/07/27 23  Disorders of the thyroid gland Goitre  Goitre means enlargement of the thyroid gland  It occurs both in hypothyroidism and hyperthyroidism. 2024/07/27 24  Disorders of the thyroid gland Goitre  Goitre means enlargement of the thyroid gland.  It occurs both in hypothyroidism and hyperthyroidism. o Goiter in Hyperthyroidism – Toxic Goiter  Toxic goitre is the enlargement of the thyroid gland with increased secretion of thyroid hormones caused by a thyroid tumour. o Goiter in Hypothyroidism – Non-toxic Goiter  Non-toxic goitre is the enlargement of the thyroid gland without an increase in hormone secretion.  It is also called hypothyroid goiter 2024/07/27 25  Useful links https://www.youtube.com/watch?v=5aq_rxTbtws https://www.youtube.com/watch?v=epWJ2v5qy5E https://www.youtube.com/watch?v=hLNXJWLsjAE 2024/07/27 26