Introduction to Medical Physiology PDF

INTRODUCTION OF Medical Physiology PHY 104 For First Year Medical Students By Prof. Dr. Maged Haroun Professor of Physiology Head of Physiology Department Faculty of Medicine – MTI University 1 ...

INTRODUCTION OF Medical Physiology PHY 104 For First Year Medical Students By Prof. Dr. Maged Haroun Professor of Physiology Head of Physiology Department Faculty of Medicine – MTI University 1  CONTENTS Page Introduction 3 Organization of human body systems The cell membrane, control of internal environment (homeostasis) Transport across cell membrane: simple diffusion and osmosis Donnan effect & facilitated diffusion Active transport & vesicular transport Intercellular communication Nerve 16 Properties of the nerve: excitability and strength duration curve Resting membrane potential (RMP) Contribution of ion fluxes and Na2+ - K+ pump to RMP Action potential: phases and shape Ionic basis of action potential Electronic potentials and local response Excitability changes in nerve, factors affecting excitability Conduction and Propagation of the nerve impulse Metabolism 30 Basal metabolic rate and factors affecting it. Regulation of body temperature Control of food intake Biophysics 49 Blood flow, Poiseuille-Hagen Formula and Law of Laplace 2  INTRODUCTION OF MEDICAL PHYSIOLOGY ILOs: After this end of this chapter, students should be able to : Understand the basic components of the human body. Recognize the integration between body systems Define the internal environment. Define homeostasis. Understand the functions of cell membrane Determine the distribution of water and electrolytes in the different body compartments. Apply Fick`s principle to determine the volume of different body compartments. Understand the methods of transport of substances through the cell membrane. Identify simple diffusion and osmosis Recognize the transport of substances through the cell membrane by facilitated diffusion. Understand the concept of Donnan effect Describe the transport of substances through the cell membrane by active transport and vesicular transport Understand the mechanism and importance of homeostasis. Describe different ways of intercellular communications 3  INTRODUCTION Physiology is the study of the function of organs and systems of body. The Cell: The cell is the basic unit of the body. It varies in size, shape and structure. Different cells → different tissues → different organs → different systems → different functions. The body systems are: Regulatory systems: nervous and endocrine. Locomotor system: musculoskeletal. Reproductive system: sex organs and sex glands Cardiovascular system: heart and circulatory vessels. Respiratory system: ventilatory, gas exchange and transport. Digestive system: ingestion, digestion, and absorption. Urinary system: excretion of water-soluble substances and urination. Intra and extracellular fluids. Inside the 100 trillion variable cells of the body, there is a fluid, known as the intracellular fluid. It contains large amount of potassium, magnesium, and phosphate ions in addition to the cell nutrients as glucose, amino acids and fatty acids as well as the respiratory gases O2 and CO2. Outside the cells, there is a fluid known as the extracellular fluid which differs from the intracellular fluid. It contains large amounts of Na+, CI- and HCO3. The cell membrane is able by certain mechanisms to maintain these differences. 4 Regulation of body functions: The regulatory (organizer) systems in the body are: 1. Nervous system: Fast regulation, short duration (organizer): this system constitutes: Sensory component-, that translates and sends information about either the internal environment or the external environment Central component: integrative: that integrates the sensations and forms orders to be sent into the various organs and systems. Motor component: is the means by which orders are sent to organs and systems. 2. Endocrine system: hormonal system slower regulation and long duration. It secretes chemical substances (hormones) which are carried in blood to regulate the function of the body tissues and organs. (-)(-) A -----→ ++B Feedback mechanism: the majority of the control systems work by a negative feedback mechanism, e.g. the glucose control system if it feels that" the blood glucose is increasing, it decreases the rate of glucose production so that glucose does not increase, and the reverse is also true It is simply: ↓ Blood glucose → glucose control system → ↑ blood glucose. ↑ Blood glucose → glucose control system → ↓ blood glucose. Positive feedback: The stimulus progressively increases the response: Blood clotting & Uterine contractions during labor 5  THE CELL The cell is basically composed of: cell membrane, cytoplasm, cell organelles and nucleus. CELL MEMBRANE (Plasma Membrane): It is the structure that: a. Surrounds the internal structure of the cell b. Supports the internal structure of the cells. c. Selects the entry and exit of substances into and out of the cell. It is a very thin elastic structure, 4-10 nm thick, almost composed of bound lipids and proteins. a. LIPIDS are mostly: PHOSPHOLIPIDS composed of 2 opposing layers: Each layer is formed of: * Heads have polar groups, i.e. they are hydrophilic. * Tails have nonpolar groups, i.e. they are hydrophobic. The lipids is bilipid layer formed from phospholipid. The molecule of phospholipid is like match head, hydrophilic phosphate) = polar, and tail (non-polar; = hydrophobic (FA). 6  The phospholipid layer is arranged so that the heads arc in contact with external environment and cytoplasm. The fatty acid (tail) are contagious to each other inside cell membrane. The lipid layer is interrupted by proteins. Types of proteins: 1. Peripheral protein: Present either on inner surface or outer surface of cell membrane. 2. Integral protein: cross the whole thickness of cell membrane from inner surface to outer surface. It is considered, as H2O filled channels. The function of cell membrane proteins: 1- Act as receptor: (peripheral outer protein) receive orders from the endocrine system (hormones) or from nervous system (chemical transmitters). 2- Act as enzymes (peripheral inner protein) for the cell function. 3- Act as identity (Peripheral outer protein) recognition of self from non- self. 4- Acts as water filled channels. 2 types: a. Simple Channels (non gated) b. Gated Channels. 7 I- Simple Channels: Allow passage of small molecules which are water soluble as ions Na+ K+ Ca++ They pass by 1- Selective permeability (leak channels allow K+ 100 times than Na+ because hydrated Na+ 5'A > hydrated K+ 4'A. 2- Electrochemical gradient: The more the difference in cone, and charges, the more the passage of ions. II- Gated channels: They have gates. They control passage of substances in and out of cell. There are two types: 1- Voltage gated channels open when membrane potential is changed. 2- Ligand gated channels: open when the chemical substances (ligands) attach to gates either from outside Like: hormones, chemical transmitters (external ligands) or from inside as C-AMP (internal ligand). NB Some channels can be opened by stretch of membrane. Other Functions of Cell Membrane Proteins: 5- They act as carriers: They allow passage of large H2O soluble substances 1- Passively (no energy is required) with electrochemical gradient from high conc. to low conc. 2- Actively (energy is required) against electrochemical gradient. From low conc. to high conc. NB 1. Lipid soluble substances pass from bilipid layer. 2. Small H2O soluble pass-through channels. 3. Large H2O soluble pass-through carriers. 8 6- Act as intercellular connections: Surface proteins of near cells form a connection (Gap junctions or channel) Connexon through which ions can pass. Transport of Materials Through Cell Membrane (Permeation) The cell membrane is composed of proteins and lipids. This heterogenicity allows passage of some substances while others cannot pass. Mechanism of transport of substances across cell membrane: (1) Carrier independent transport: Does not need carrier. It occurs by: a. Simple diffusion: transport substances. b. Osmosis transport of H2O. c. Donnan effect: one substance affects movement of other substances. (2) Carrier dependent transport: a. Facilitated diffusion. b. Active transport. c. Vesicular transport. I. Carrier independent: a. Simple diffusion: transport of substances across cell membrane according to concentration gradient (electrochemical gradient) from high to low concentration. 9  It does not need carrier. It does not need energy. This simple diffusion for: o Water soluble, small substances → channels. o Lipid soluble substances -» bilipid layers. Simple diffusion may be: Influx: moving inside from outside. Efflux: moving outside from inside. Any particle in nature dissolved in H2O shows kinetic movement: It depends on temperature of that particles. It stops at absolute zero degree = -273°C. Above -273°C → starting movement. The more the temperature → the more the movement. Example Na+, K+, Ca++, CO2, O2 b. Osmosis: The transport of water across cell membrane according to concentration gradient → from high to low concentration of H2O or low to high concentration of salt 10  Osmosis is of clinical importance Solution given intravenously (IV.) must be iso-osmotic to plasma "isotonic". Solution contains more salt than plasma. o hypertonic. o hyperosmotic Solution contains less than plasma: o Hypotonic o hypo-osmotic Osmolality: molecular weight of any substance in gram dissolved in one liter of H2O = one osmol. e.g , Na+ Cl = 23 + 35-5 = 58.5 MW 58.5 gm NaCI / liter = 1 osmol. Amount of osmol of any fluid depends on amount of salt dissolved in H2O, i.e., number of osmols. c. Donnan effect: It is a mechanism by which one substance affects movement of other substances through membrane as intracellular proteins attract Na+ to cell and repel CL to outside cell. Anion: any ion like anode → (-ve) eg: Cl\ HCO3", proteins. Cation: any ion like cathode → (+ve). e.g.: Na +, K +, Ca+ +. Proteins (anions) present in any cell antagonize (prevent) efflux (diffusion outside) of cations as K+ and facilitate (help) the efflux of anions (Cl). End result of Donnan effect is unequal distribution of anion and cations across membrane. Donnan effect can be overcome by any pump as Na+ pump, or Ca++ pump, or Na+, K+ pump. 11 II. Carrier dependent transport: It occurs for too big substances which are H2O soluble and also for important substances needed by cells. Three mechanisms of carrier dependent transport. 1- Facilitated diffusion: 2- Active transport. 3- Vesicular transport. 1- Facilitated diffusion: Transport of substances according to concentration gradient from high to low. This substance is too big and H2O soluble, e.g.: glucose. It is done by carriers without energy. Factors affecting facilitated diffusion: 1. The concentration gradient of substances (the more-the more). 2. The number of carriers (the more-the more). 3. Affinity (combination) between the carrier and substance. 4. The rapidity of change of shape of carrier -* the more the more. 2- Active Transport: Transport of substance across cell membrane against concentration gradient (from low conc, to high conc). Energy is used from the A.T.P. (adenosine triphosphate) (energy store in cell) (either directly or indirectly). The substances must combine with carrier in cell membrane. 12 Types of active transport: (a) Primary active transport: Energy is derived directly from A.T.P. for ions: Na+, K+, Ca++ a. Ca++ pump: Ca++ is pumped from intracellular to extracellular against the concentration gradient (Ca+ + extracellular 10.000 times as intracellular). Energy is derived from A.T.P. ATP (adenosine triphosphate) → ADP (adenosine diphosphate) + P + Energy b. Na+ - K+ pump: The main extracellular cation is Na+. The main intracellular cation is K+ Any Na+ enters into the cell is pumped out. Any K+ outflow outside the cell is pumped in. Na+ and K+ combine with carrier which has 3Na+ binding sites and 2K+ binding sites. (b) Secondary active transport: Energy is derived from ATP indirectly for glucose transport o In the renal tubule (kidney). o Na+ is actively transported outside cell (Na+-K+ pump) basal border (primary active transport). o Na+ inflow through luminal border energizes 2ry active transport of glucose inside cell 13 Types of carriers: 1. Uniport: transport one substance in one direction as Ca + +. 2. Simport: transport two substances in one direction. Na+, glucose. 3. Antiport: transport two substances in two directions: Na + ,K+ (c) Vesicular transport: It is transport of very big substances into or out of cell by invagination to form vesicle containing this substance, it may be in form: A. Endocytosis: entry of substance inside cell. B. Exocytosis: Exit of substance outside cell. (A) Endocytosis: 1- Phagocytosis: cell eating = engulfing of very big substances as white blood cells eating micro- organisms without extracellular fluid. 2- Pinocytosis: Cell drinking substance with extracellular fluid. (B) Exocytosis: Exit substance outside cell in glandular tissue secretion of hormones, enzymes and in nerve cells → chemical transmitters. 14  Intercellular communications Cells communicate with each other via chemical messengers through several types of communication: 1- Intercellular Gap Junctions: a chemical substance passes directly from cell to cell. 2- Neural: neurotransmitters are released from one neuron across synaptic clefts which exist between contiguous nerve cells. (rapid mechanism). 3- Endocrine communication: certain cells secrete chemical hormone. The hormone reaches the cells over long distance via the blood stream. (Slow mechanism). 4- Neuroendocrine hormones are secreted by neurons into the circulating blood and influence the function of cells at another location in the body (intermediate mechanism). 5- paracrine communication The chemical substance may reach the nearby cells through diffusion in interstitial fluid. 6- autocrine communication. The chemical substance may act directly on the cell that produces it 7- Cytokines are peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones. Among the cytokines are interleukins & lymphokines that are secreted by helper cells and act on other cells of the immune system. Cytokine hormones as leptin which is produced by adipocytes are called adipokines. References: - Ganong’s Review of Medical Physiology, 26 Edition, 2019 - Guyton and Hall Textbook of Medical Physiology,14 Edition, 2020. 15  PHYSIOLOGY OF THE NERVE ILOs: At the end of this chapter the students should be able to: Name the parts of the neuron and the function of each. Define excitation and strength duration curve Study the RMP. Understand how Na+ & K+ movements determine the RMP Describe the changes in membrane permeability and ionic movements that underlie each of these phenomena. Describe the different phases of action potential. Learn about ion channels. Describe the changes in membrane permeability and ionic movements that underlie action potential Distinguish between myelinated and unmyelinated neurons and the significance of each. Define electrotonic potentials & local response and ionic movements that underlie each of these phenomena. Understand excitability changes in nerve and different factors affecting excitability. Describe how the action potential is conducted in different types of nerve fibers. 16  NERVE The unit of structure of the nervous system is the neurone (anatomical unit). Neuron: It is formed of cell body and cell processes. The cell body controls the metabolism of the whole neurone. It is surrounded with the cell membrane which extends over the cell processes. It contains the nucleus with nucleolus, mitochondria, endoplasmic reticulum, and Golgi apparatus. The cytoplasm contains neurofibrils and Nissil granules which are rich in ribonucleic acid (R.N.A.) and may play an important role in the protein synthesis for the cell. There is no centrioles, so they cannot divide. The Cell Processes: a) The dendrites which receive the ongoing impulses. b) The axon or nerve fibre which is a long process of the cell and usually carries impulses from the nerve. A nerve is formed of a large number of nerve fibres. Nerve Fibre (Axon): The axon is surrounded with the plasma membrane which is a continuation of the cell membrane. Two types of nerve fibres are found: a) Medullated nerve fibres = Myelinated: The axon is surrounded with myelin sheath and outer neurilemmal sheath of Schwan's cells. b) Non-medullated nerve fibre = Non myelinated: The medullary sheath is absent, and the neurilemmal sheath is the only covering for the axon. The myelin sheath is highly insulator to electric currents. It does not form a continuous layer, but is interrupted at intervals of 1 mm, called "Nodes of Ranvier". 17  PROPERTIES OF NERVES (I) Excitability, (II) Conductivity. I- Excitability: It is the ability of living tissue to respond to changes in the environment. Such changes are called stimuli. The stimulus may be electrical, chemical, mechanical, or thermal. The most excitable tissues in the body are the nerves and muscles. In order to study the functions of the nerve and muscle, these excitable tissues are stimulated by electrical stimuli because: a) They are similar to the natural stimuli inside the body. b) They do not injure the tissues (within limits). c) Their amplitude and duration can be accurately regulated. The physicochemical changes produced by the stimulus in the nerve is known as the nerve impulse. Once a nerve impulse is produced, it is conducted along the nerve fibre to its termination. Conduction of the nerve impulse along the nerve fibre is an active self-propagating process which requires energy. Electrical stimuli are of two types: a) Galvanic currents: 18  They are long in duration and low in intensity, e.g., currents obtained from a battery. b) Faradic currents: They are high in intensity and short in duration, e.g., induction currents. We use faradic currents to stimulate the nerve. · Nature of Excitability: Excitability is an electrical phenomenon. The electrical changes which accompany the process of excitation are very small being measured in millivolt (mV) and are very rapid, their duration being measured in milliseconds (msec). In order to record such changes, we need: micro-electrodes, CRO (cathode ray oscilloscope), and amplifier. Excitability is due to resting membrane potential. · The Effectiveness of Electrical Stimulus Depends On: 1-Intensity of stimulus: threshold is minimal intensity to cause nerve impulse, while subthreshold produces only local changes known as local response. 2-Rate of rise of intensity of stimulus: If intensity of subthreshold stimulus is increased slowly → no response (accommodation), but if increased rapidly → nerve impulse. 3-Duration of stimulus: Length of time must be applied to give a response, shown in strength-duration curve. · Strength-Duration Curve: 1-Within limits, the stronger the current the shorter its duration. 2-Stimuli of very short duration will not excite the nerve whatever its intensity (basis of electrical cautery). 3-Rheobase is threshold intensity of current of very long duration which can excite. The time needed by rheobase to excite is known as utilization time. 19  4-Chronaxie is a time factor. It is the time needed by the current which is double rheobase to excite. It is a measure of excitability (if the excitability is reduced, the chronaxie is prolonged). chronaxie The strength-duration curve Resting Membrane Potential: (R.M.P.) When 2 microelectrodes are placed on the outer surface of a resting nerve fibre, no potential difference is observed. However, when one of them is inserted into the interior of the nerve fibre, a constant potential difference is observed, with the inside negative relative to the outside. This resting membrane potential (R.M.P.) is found in almost all cells, but more marked in nerve cells and muscle cells. In large nerve fibres and in large skeletal muscle fibres, R.M.P. is about -90 mV, but in medium-sized neurones it is usually about -70 mV. In non-excitable cells (e.g., red blood cells, epithelial cells), the resting potential is approximately -20 to -40 mV. · Ionic Basis of the Resting Membrane Potential: The resting potential is produced by the movement of ions across the cell membrane. In nerve and muscle, it is determined mainly by the selective permeability of membrane and by the Na+-K+ pump. 20 1. Selective permeability of the membrane: K+ diffuses out of the cell down its concentration gradient through Na+-K+ "leak" channels, and Na+ diffuses back in, but since the (permeability of the membrane to K+ is much greater than it is to Na+ (at rest, being normally about 100 times as permeable), the passive K+ efflux is much greater than the passive Na+ influx. Since the membrane is impermeable to intracellular proteins and other organic anions which represent most of the intracellular anions, the K+ efflux is not accompanied by an equal eflux of anions and the membrane is maintained in a polarized state, with the outside positive relative to the inside. N.B. The Conc. of K+ intracellularly is 35 times as extracellular, while Conc. of Na+ extracellularly is 10 times the intracellular and Conc. of Cl- is 30 times extracellular to intracellular. So K+ diffuses out while Na+ and Cl- diffuse into the cell. N.B. K+ outflow is 100 times as Na+ inflow because hydrated K+ ion is 4 A while hydrated Na+ ion is 5 A (pass through leak channels during rest). The potassium ion mobility cannot continue forever but reaches a state of equilibrium. The positive charges created on the outside surface of the membrane repel the K+ and prevent their further diffusion from inside to outside the nerve fibre according to concentration (or osmotic) gradient. Equilibrium is reached when the electrical positive forces that repel K+ ions are equal to the osmotic forces. The inflow of K+ inside the fibre by electrical forces is equal to the outflow of K+ by osmotic forces. 2. Sodium-Potassium pump mechanism: In nerves, as in other tissues, Na+ is actively transported out of the cell and K+ is actively transported into the cell. More positive charges are pumped to the outside than to the inside (three Na+ ions to the outside and two K+ ions to the inside), leaving a net deficit of positive ions on the inside. 21  CONTRIBUTION OF DIFFERENT IONS TO RESTING MEMBRANE POTENTIAL a) Contribution of the Potassium Diffusion Potential: If we assume that the only movement of ions through the membrane is the diffusion of potassium ions, the membrane potential at the equilibrium stage will be the equilibrium potential for potassium (EK) and can be calculated from Nernst equation: EK = -61mv X log [K]in / [K]out Where: EK = the equilibrium potential (mV) for K+, and [K]in and [K]out = the intracellular and extracellular concentration of K+. EK + = - 61 mV. X log 35 = - 61mV. X 1.54 = - 94 mV. Nernst equation: for any univalent ion, the potential difference caused by movement of this ion across the membrane = (+) for anion, (-) for cation. concentrat ion inside E (millivolt ) =  61 x log concentrat ion outside 22  This means that if potassium ions were the only ion causing the resting potential, this resting potential would be equal to -94 mV. b) Contribution of the sodium diffusion potential: The equilibrium potential for Na+ as calculated from Nernst equation: ENa = -61mv X log [Na]in / [Na]out = - 61 mV. x Log 1 10 = - 61 x - 1 = + 61 mV. c) Goldman Equation: If we calculate membrane potential by diffusion of Na+, Cl- and K+ together, the calculated R.M.P. is -86 mV. d) Contribution of the Na+-K+ Pump: The continuous loss of positive charges from inside the membrane, creates an additional degree of negativity (about -4 mV additional) on the inside. Therefore, the net membrane potential with all these factors operative at the same time is -90 mV. Almost all of this potential is caused by K+ diffusion due to high permeability of the membrane to it. ·Changes in nerve accompanying nerve impulse and stimulation of nerve: (1) Electrical changes, i.e., action potential. (2) Excitability changes. Action Potential It is the rapid changes in the membrane potential following stimulation of the nerve fibre by adequate stimulus. Action potential is recorded by two microelectrodes (connected to amplifier and CRO) placed at a variable distance from the stimulator. (CRO: Cathode ray oscilloscope). 23 N.B. Excitability of the nerve is: Increased by decreased Ca++ and increased K+ extracellular. Decreased by high Ca++ and low K+ extracellular and local anesthesia. (1) Action potential: A nerve fibre is stimulated and the electrical changes which accompany excitation are recorded by two microelectrodes placed at a variable distance from the stimulator. The recording electrodes are so arranged that one electrode is placed on the outside of the membrane and the other inside the membrane of the nerve fibre. The recording electrodes are connected to cathode ray oscilloscope (CRO). 1.The application of the stimulus to the nerve fibre is indicated by stimulus artifact. This is followed by an interval where no change in membrane potential occurs until the nerve impulse reaches the recording electrodes. This interval is called the latent period. 2.When the impulse reaches the recording electrode on the outside of the nerve, the membrane potential decreases and becomes less than -90 mV. This is known as depolarization. 3.After an initial 25 mV depolarization (local response), i.e., the membrane potential drops from -90 to -65 mV, the rate of depolarization increases. The point at which this change in the rate of depolarization occurs is called the firing level. 4.The membrane is rapidly completely depolarized and the potential difference between the outer and inner surface of the membrane is zero, i.e., Isopotential. 5.The membrane potential is reversed so that the outer surface becomes negative in relation to the inner surface which is positive, and the potential differences is +35 mV. This is known as reversal of polarity or overshoot. Therefore, the magnitude of the action potential is 125 mV (-90 mV + 35 mV). 6.Repolarization sets in, the membrane potential returns rapidly to the resting level. 7.When repolarization is 70% completed, the rate of repolarization decreases, and the resting membrane potential level is reached slowly. This is known as after depolarization or negative after potential. 8.After reaching the resting level, the membrane becomes slightly hyperpolarized, i.e., the outer surface becomes more positive 24  than normal in relation to the inner surface. This state of slight hyperpolarization is relatively prolonged and is known as "hyperpolarization or positive after potential". Thereafter, the membrane potential is gradually reached. The sharp rise and rapid fall of the tracing on the cathode ray oscilloscope is called the "spike" and it lasts about 2 msec. The after depolarization lasts about 4 msec., while the hyperpolarization lasts 35-40 msec. Ionic Basis of Action Potential: 1-During the local response, the Na+ ions permeability is slightly increased due to opening of some Na+ channels. 2-When firing level is reached -65 mV, all voltage- gated Na+ channels will be opened (activated) leading to increased membrane permeability to Na+ and rapid depolarization and reversal of polarity due to Na+ inflow (ascending limb of spike). 3-Repolarization is due to inactivation of Na+ channels (closed), and opening of voltage gated K+ channels (activated) leading to increased membrane permeability to K+ ions which flow from inside to outside (descending limb of spike). When repolarization is 70% completed, the rate of repolarization is decreased because +ve charges created on outer surface decrease outflow of K+ (-ve after potential). 25 Gradually Na+ channels return to resting state. However, K+ channels close slowly leading to hyperpolarization before returning to resting state. N.B. There are 3 types of channels in the membrane: 1-Leak channel for Na+ and K+: opened during rest. 2-Voltage gated Na+ channel: opened during ascending limb of spike. 3-Voltage gated K+ channel: opened during descending limb of spike. N.B. There are 3 states of voltage gated Na+ channels: (has 2 gates): 1-Resting excitable state: closed from outside only but ready to open when membrane potential decreases. 2-Activated state: opened, allow Na+ inflow (ascending limb of spike). 3-Inactivated state: closed from inside when membrane potential reaches +ve 35 (tip of spike). N.B. K channels have only one gate inside, closed during rest and + opens during descending limb of spike. Electronic Potentials and Local Response: Although subthreshold stimuli do not produce an action potential, they produce electronic potentials, i.e., changes in membrane potential that do not propagate. · Catelectrotonus: This is a state of depolarization produced at the region of cathode. The depolarization is less than 7 mV. The membrane potential is reduced passively by the addition of negative charges to the outer surface of the membrane by the cathode. · Anelectrotonus: This is a state of hyperpolarization produced at the region of anode. It is produced by addition of positive charges to the outer surface of the membrane by the anode. The degree of hyperpolarization is proportional to the intensity of the current applied. High intensity current produces anodal block. 26 ·Local Response (Local Excitatory State): "Depolarization between 7- 25 mV": With stronger cathodal stimuli, a slight active change occurs and some Na+ activation gates will open and contribute to the depolarizing process, but the stimulus does not open enough gates to produce action potential. Thus, repolarization follows rapidly and the membrane potential returns to the resting level. (2) Excitability Changes during an Action Potential: 1.Local excitatory state: During the local response up to the firing level, the excitability is increased. 2.Absolute refractory period: During the ascending limb of the spike and the first third of descending limb (repolarization), the nerve fibre loses completely its excitability. No stimulus, however strong it may be, can excite the nerve fibre. It is due to opening of all Na+ channel plus inactivation of Na+ channel in 1/3 descending. 3.Relative refractory period: During the rest of the descending limb of the spike till the after depolarization, the excitability of the nerve fibre is decreased and a stimulus stronger than the 27  threshold is required to excite the nerve fibre. Some Na+ channels are resting, and others inactivated. 4.Supernormal phase: During the after depolarization, the excitability of the nerve fibre is increased. All Na+ channels are resting and near to firing level. 5.Subnormal phase: During the hyperpolarization, the excitability of the nerve fibre is decreased (away from firing level). (II) Conduction of the Nerve Impulse: It is the propagation of the action potential along the nerve fibre. (1) Conduction in unmyelinated nerve fibre: Positive charges from the membrane ahead the activated segment flow into the area of negativity = (area of current sink) produced by the action potential. The flow of positive charges decreases the membrane potential of the segment of the nerve fibre ahead of the activated segment. This is known as electrotonic depolarization. Such electrotonic depolarization initiates a local response and when the firing level is reached, an action potential is produced. 28 (2) Conduction in myelinated nerve fibre: Depends upon a similar process to that in unmyelinated nerves. However, the myelin sheath is an insulator and the current that flows through it is negligible. The positive charges jump from the resting node of Ranvier to the activated neighboring. This jumping of positive charges is called saltatory conduction. It is a rapid process and myelinated nerve fibres conduct up to 50 times faster than the fastest unmyelinated fibre. References: - Ganong’s Review of Medical Physiology, 26 Edition, 2019 - Guyton and Hall Textbook of Medical Physiology,14 Edition, 2020. 29  Metabolism ILOs: After this chapter, student should be able to: Define and understand the metabolic rate, its measurement and regulation Define BMR and determine its basal conditions and regulation Understand the regulation of body temperature and its abnormalities Describe the caloric value of food Understand the control of food intake and its abnormalities Define the respiratory quotient and know its importance Identify BMI & different categories of obesity 30  METABOLISM AND TEMPERATURE REGULATION Role of Adenosine Triphosphate (ATP) in Metabolism: ATP is the main source of energy in the body. It contains 2 high energy phosphate bonds. Each molecule of ATP will produce 12000 calories at physiological conditions, while during standard conditions (outside the body) it will produce 7300 calories. Functions of ATP: 1-Synthesis of many intracellular components and growth "protein synthesis". 2-Energy for muscle contraction (skeletal, cardiac, smooth muscles). 3-Active transport: a. For intestinal absorption. b. For renal reabsorption. c. Keeps concentration of ionic composition (extracellular, intracellular ions) constant. d. Many secretions of glands, e.g. (for GIT secretions). 4-Creation of ATP buffer compound or store house energy (creatine phosphate). Most of the energy produced is liberated as heat. ex: The heart is the best machine, 25% work energy in the heart, 12% in the skeletal muscle. By measuring the heat production of the body, we can estimate energy production and measure metabolic rate. 31  METABOLIC RATE Metabolic rate is the amount of heat produced by the body / hour/. It is a measure of energy used by the body / hour. It is measured in calories. MR: 70 calories / hour ± 10% N.B.: ·Calorie "c" amount of heat required to raise the temperature of 1gm of water → 1C. ·Kilocalorie: amount of heat required to raise the temperature of 1 kg of water → 1C. C = 1000 c. Measurement of metabolic rate: 1. Direct calorimetry: We put the patient (completely naked) in a calorimeter (small, insulated chamber), through which water is circulating. Amount of heat produced by the body / hour = amount of heat gained by water / hour. 2. Indirect calorimetry: The more the O2 consumption / hour, the more the heat produced / hour. Metabolic rate = O2 consumption (measured by metabolator) / hour multiplied by constant (energy equivalent of O2) = 4.825. 32 Energy equivalent of O2: It is the amount of heat produced when one liter of oxygen is used to oxidize different food materials for CHO=5, Fat=4.7 and protein = 4.5. For mixed food = 4.825 calories/liter O2. Method used to determine metabolic rate indirectly by measuring O2 consumption / hour using "metabolator": Metabolator: Drum filled with oxygen floating on a container filled with water which provides double wall water jacket to prevent escape of oxygen. Connected to this drum, 2 tubes: a) Inspiratory tube: through which air is directed through valves. b) An expiratory tube: This is conducted to a container filled with soda lime to absorb carbon dioxide. The level of the drum is decreased by the amount of oxygen consumption. This drum is counter balanced by weight. Connected to this weight, a lever which draws on a rotating drum. FACTORS AFFECTING THE METABOLIC RATE 1. Exercise: Normally: adult male 70 kg lying still in bed. His body consumes 1650 calories / day. Eating 200 calories / day Total: 1850 calories / day. 1-Sleep: 65 calories / h. 2-Lying still in bed: 77 calories / h → 1850 / 24. 3-Sitting in bed: 100 calories / h. 4-Standing relaxed: 105 calories / h. 5-Walking (slow): 200 calories / h. 33 6-Running: 500 calories / h. 7-Swimming: 600 calories / h. 8-Walking (very fast) "jogging", 650 calories / h. 9-Walking upstairs: 1100 calories / h. (17 times the normal resting metabolic rate). 2. Sympathetic stimulation: Epinephrine, norepinephrine stimulate glycogenolysis, oxidation of glucose, so there is increase in metabolic rate of an adult → 100%. 3. Hormones: Thyroxine: Hyperthyroidism "Grave's disease", 60-100% increase while in myxedema drops 50-60% decline. 4. Diet: SDA (specific dynamic action of food): Increase metabolic rate: 10-25% due to metabolic process in liver. SDA starts after one hour, reaches max 4-5 hours and ends by 12 hours. For protein = 25% while it is 10% for CHO and fat. Basal Metabolic Rate (BMR): Metabolic rate under basal conditions: 1-Post absorptive state: 12 hours fasting. 2-Restful sleep of the night before determination. 3-30 minutes completely reclining before determination, physical rest. 4-Mental rest away from any exciting stimuli. 5-Comfortable temperature: 20C-27C. BMR: 40 calories / hour/m2 ± 10% (under these basal conditions). 34  REGULATION OF BODY TEMPERATURE Body temperature: Body temperature is always kept constant at 37C, average (36.6-37.2C). It is measured through core temperature. Types of body temperatures: 1. Core temperature = Brain, blood temperature. It is measured orally but if measured rectally (+0.6C). 2. Skin temperature (shell): a) Hands, feet (28c). b) Head, chest, abdomen (34C). Core temperature is always constant except during illness but the skin temperature can be changed in different conditions. Body temperature is always kept constant, so long heat production equals heat loss. Heat balance = Balance, between heat loss and heat production. When heat production = heat loss. This is called "heat balance". Ways of heat loss: 1.Radiation. 60% 2.Conduction. 3% 3.Convection. 15% 4.Evaporation: 22% a) Sensible: Sweating. b) Insensible: Lung, skin. 35 Heat Loss: 1. Radiation: It represents 60% of the heat loss through the non evaporative loss either electromagnetic waves or infrared waves. It is the transfer of heat between two objects which are not in contact. The more the temperature difference, the more the heat loss by radiation. 2. Conduction: ·Not more than 3% heat loss. ·It is the transfer of heat between 2 objects which are in contact. The more the temperature difference, the more the heat loss by conduction. 3. Convection: It represents 15% of heat loss. It is the transfer of heat between 2 localities having different temperature by movement of air (convection currents). 4. Evaporation of H2O: Under basal conditions, it is about 22% of heat loss, each gram of water → heat loss 0.58 calories. Normally 600 ml of H2O / day is lost by insensible evaporation. This corresponds to 340 cal / day → 12-16 Cal/hour. This amount cannot share in the regulation of body temperature. It is fixed for any individual, whatever it is cold, or warm weather. Cooling effect of evaporation: 1 gm of H2O → 0.58 cal heat loss. SWEATING Sweating: "Sensible evaporation" or "Refrigeration mechanism". Rate of sweat: 0-2 liter / hour. ·Cold air: 0 liter / hour. ·Hot air unacclimatized person: 0.7 liter / hour (more solutes). ·Hot air acclimatized person: 2 liter / hour (less solutes). Composition of sweat: Hypotonic solution containing Na+, K+, Cl-, HCO3-, H2O and very little amount of urea. 36  SWEATING AND ITS REGULATION BY THE AUTONOMIC NS Mechanism of sweat secretion: 1. Primary = precursor sweat secretion secreted by the deep coiled acini. Composition is nearly the same as plasma ·Na+ = 145 mEq/L. ·Cl- = 110 mEq/L. 2. Modification in duct by: Reabsorption of Na+, Cl- (under effect of aldosterone). If the rate of secretion is very low: ·Na+ = 5 mEq/L. ·Cl- = 5 mEq/L. At high rate: ·Na+ = 60 mEq/L. ·Cl- = 60 mEq/L. Nervous regulation: Sympathetic cholinergic fibers arising from the preoptic area in the anterior hypothalamus which stimulates the thoraco-lumbar region. 37  REGULATION OF BODY TEMPERATURE Thermoregulatory System: System responsible for regulation of the body temperature. It is a feedback control system composed of: 1.Temperature receptors (thermoreceptors). 2.Temperature regulating center (hypothalamus) or "hypothalamic thermostat". 3.Effectors: a. Skin → Sweat → Erector pilae muscle. b. Muscle: c. Endocrine glands (hormonal): → Thyroid → Adrenaline and noradrenaline · Temperature receptors: a. Central thermoreceptors: Present in the preoptic area of the anterior hypothalamus for "core temperature". b. In spinal cord, viscera (abdomen) for "core temperature". c. Skin thermoreceptors "cold warm receptors" for "shell temperature". Cold receptors are 4-10 times more than the warm receptors. · Hypothalamic thermostat: (present in the posterior hypothalamus) It is a temperature regulating center causing integration between cold and warm impulses coming from the thermoreceptors. 38 I- Reaction of body during exposure to cold (Body is cooled): 1. Skin: a) Abolition of sweating ( temperature 37C). b) Pilo-erection: Contraction of the pilo erector muscles by sympathetic stimulation → erection of hairs and trapping of warm air by insulating layer → decrease heat loss. c)Cutaneous vasoconstriction (decrease skin temperature) by decreasing temperature gradient with the external environment → decrease heat loss. 2. Muscles: "non-chemical thermogenesis" Dorso-medial part of hypothalamus "primary motor area for shivering". a) Increase muscle tone all over the body of both antagonistic muscles (flexor and extensor). b) Shivering affects both antagonistic muscles (flexor, extensor, supinator, and pronator). c) Behavior response in the form of voluntary muscle contraction (clapping hands, stamping foot, putting on heavy clothes). This will lead to increase heat production 5 times more than normal. 3. Hormonal effect: "Chemical thermogenesis". a. Epinephrine and norepinephrine (secreted from the suprarenal medulla by sympathetic stimulation, causing glycogenolysis and increase glucose oxidation, so increase heat production → increase BMR by 100%. b. Increase secretion of thyroid hormone will increase metabolism all over the body so will increase heat production (after several days) → 20% - 40% increase in the weight of thyroid gland after several weeks. Mechanism: Increase thyrotropin releasing hormone (hypothalamus) → anterior pituitary TSH→ increase T3-T4. 39 II- Reaction of body to heat: Body is overheated: a) Sweating: Acclimatization to hot weather in the form of: 1. Increase secretion of sweat (non-acclimatized 0.7 L / h, acclimatized 2 L/h). 2. Decrease electrolytes content in sweat (decrease NaCl) due to depletion of salt content of the body thus increasing aldosterone. b) Cutaneous vasodilatation (increase skin temperature → increase heat loss). c) No muscle activity and no chemical thermogenesis. ABNORMALITIES OF TEMPERATURE REGULATION I- Fever: Febrile condition in which there is increase in the body temperature above normal range. Cause: 1-Brain lesions, damage, cerebral hemorrhage, tumors. 2-Bacterial toxins and tissue destruction. Mechanism of fever: Bacterial toxins lipopolysaccharides, protein degenerative products called "pyrogens" (pyrexia-increase temperature) cause resetting of the hypothalamic set point at higher level through stimulation of prostaglandins synthesis (increase prostaglandins at the hypothalamic thermostat). Rapid raising the body temperature (anti-drop measures) occurs by chills. II- Chills: 1-Vasoconstriction of the skin blood vessels. 2-No sweating. 3-Pilo-erection. 4-Shivering, increase muscle tone (shaking his body). 5-Putting on heavy clothes (behavior response). 6-Increase epinephrine, norepinephrine secretion. By this mechanism, within few minutes the body temperature will reach new set point. 40 III- Crises = flush: By resetting of the set point of the hypothalamic thermostat to a lower level. a) Sudden withdrawal of bacterial toxins, by antibiotics. b) Use of antipyretics. Mechanism: 1-Cutaneous vasodilatation. 2-Excessive sweating. Antipyretics: Drugs used to lower the body temperature as aspirin, aminopyrine, paracetamol. They inhibit prostaglandins synthesis. However, aspirin does not decrease the normal body temperature while antipyrines decrease even the normal body temperature. IV- Heat stroke and exhaustion: If body is exposed to excessive heat, this will either produce = heat stroke or heat exhaustion, depending upon whether air is dry or humid. a) Dry hot atmosphere = head exhaustion: due to excessive sweating as a result of excessive hypothalamic control → circulatory collapse (shock). There is excessive sweating leading to diminished salts and H2O in body → hypotension and bradycardia → circulatory collapse. Treatment: H2O and salts. b) Humid hot atmosphere = heat stroke (humidity is 100%) → failure of evaporation of sweat → marked rise of the body temperature and if reached 41-42.5, there is break down of the hypothalamus control → rise of temperature → denaturation of the enzymes and destruction of the tissue parenchyma: Local hemorrhage → dizziness, delirium, coma, and death. Treatment: Ice cold water bath for a limited period to prevent shivering, ice cold tanks, sponging and ice cold foments. 41  DIETARY BALANCE, FOOD INTAKE AND OBESITY Food intake must be at least always balanced in order to supply the metabolic need of the body. Average composition of the normal diet: ·Carbohydrate: 45% of the total energy produced by the diet. ·Fat 40% of the total energy produced by the diet. ·Proteins: 15% of the total energy produced by the diet. a) Complete proteins: Contain all essential amino acids as animal proteins or mixed plant proteins. b) Partial proteins: do not contain all essential amino acids, i.e. deficient of one of the essential amino acids. Kwashiorkor disease: It is a syndrome affecting newly born babies, who are fed high carbohydrates and low protein diet (partial proteins). There is a decrease intake of essential amino acid proteins. It is characterized by: 1-Decrease mentality and lethargy. 2-Low protein oedema. 3-Decrease rate of growth. 4-Obesity. Treatment: High complete protein in diet. Caloric value of balanced diet It is amount of heat when one gram of a substance is completely oxidized outside body. · Carbohydrate: 4.1 Cal/gm · Fat: 9.3 Cal/gm · Proteins: Urea + 4.35 Cal/gm ---→ 5.6 cal/gm. Calorie requirements: 1850 calories. ·200 gm CHO / 900 calories. 45% ·80-100 gm fat / 650-700 calories. 40% ·50-60 gm proteins / 250-280 calories. 15% 42 Physiological Calorie Value: The energy liberated from metabolism of substance inside the body. Inside the body, protein is not completely oxidized. It produces 4.35 Cal/gm + urea, this is called "physiological caloric value of food" while outside the body the "physical caloric value of food" is 5.6 Cal/gm. Physical and physiological calorie values of fat are the same and also the physical and physiological calorie value of carbohydrate are the same. Respiratory quotient = Respiratory exchange ratio: CO2 production Ratio between -------------------- at the same time O2 consumption ·Normally = 4/5 = 0.8. Importance of the respiratory quotient (R.Q): 1- To know the type of food oxidized. If carbohydrate is the only source of energy R.Q = 1. If fat is the only source of energy R.Q = 0.71. (Normally O2 consumption = 80 and CO2 production = 57 for fat) If protein is the only source of energy R.Q = 0.82. (Normally O2 consumption = 6 and CO2 production = 5 for protein). N.B.: 1-Diabetes mellitus R.Q is 0.71 (fat is the source of energy). 2-Diabetes mellitus if given insulin R.Q is 1. 3-R.Q of the brain is 1 (glucose is the only fuel of energy for the nervous system). Fasting: No food intake for less than 18 hours. Starvation: No food intake for more than 18 hours. 43  REGULATION AND CONTROL OF FOOD INTAKE Regulation of the food intake: Hunger: Graving for food accompanied by organic sensation associated with hunger pains (contraction of the stomach). Appetite: Graving for a specific type of food. Satiety: Sense of fulfillment for quest of food. Neuronal control of food intake: It is a controlled by the appestat which is composed of: 1-Feeding (hunger) center (lateral nucleus) of hypothalamus. 2-Satiety center: (ventromedial nucleus) of hypothalamus. Factors which control the hypothalamic appestat: or (Factors which regulate the food intake): 1.Higher centers: Limbic lobe: Infraorbital area, Hippocampus + amygdala (amygdaloid nucleus), Cingulate gyrus. This limbic lobe can stimulate or inhibit the feeding centers. 44 2.Short term (alimentary regulation): a. Stretch receptors in mouth and pharynx (oral receptors), stimulation of the oral receptors (mouth, pharynx) will inhibit the feeding center. b. Receptors in the stomach, intestine and anterior abdominal wall: Distension of the gastrointestinal tract (stomach, duodenum, anterior abdominal muscles) will decrease the feeding center. c. GIT hormones: Cholecystokinin (fat), insulin (carbohydrates) inhibit feeding center, and stimulate satiety center. 3.Long term (nutritional) regulation: Increase blood glucose, fatty acids, amino acids will stimulate the satiety center and inhibit feeding center. N.B.: Reciprocal relation between satiety and feeding center. a) Glucostatic theory: Decrease blood glucose will stimulate the feeding center. Increase blood glucose will inhibit the feeding center and will stimulate the satiety center. Proof: 1-Increase blood glucose level will cause an increase in the electrical activity of the satiety center. 2-Chemical study of the satiety center (ventromedial nucleus) only site which can concentrate glucose. b) Lipostatic theory: Increase fatty acids will inhibit the feeding center and stimulate the satiety center. c) Amino acids theory: Increase amino acids in the plasma will inhibit the feeding center and stimulate the satiety center. 4.Leptin hormone: Leptin (Greek word "Leptos" meaning thin): 45 Leptin is a protein hormone 167 AA which is produced by adipocytes and is thought to act on satiety center. The level of leptin is directly proportional to total fat in body. It is first discovered in ob/ob mice in which ob gene for leptin production is mutated and no leptin is produced. These obese mice are hyperphagic. However, when leptin is given, they stop eating and lose weight. Leptin acts on receptors in hypothalamus where it: a) Inhibits food intake. b) Counteracts the effects of neuropeptide Y (a potent feeding stimulant secreted by gut and hypothalamus). c) Stimulation of energy expenditure and reversal of obesity. d) Amelioration of insulin resistance. e) Stimulation of GnRH secretion and ovulation. The absence of functional hormone, or its receptors (decrease sensitivity to its action) leads to uncontrolled food intake and resulting obesity. OBESITY Definition: Obesity is excessive storage of fat, and increased body mass index. Cause: Energy input is more than energy output. For each 9.3 calories entering body, one gram of fat will be stored. N.B.: Normally, energy input = energy output. Caloric value of food = Work energy + heat energy ± stored chemical energy [A] [B] [C] · Work energy: 1-Mechanical work which represents 1/3 of total energy output (muscle contraction, cardiac contraction). 2-Active transport, reabsorption, action potential, and resting membrane potential. · Heat energy: Maintaining body temperature and excess will be lost to outside. · Stored chemical energy: Formation of macromolecules (fat, proteins, and carbohydrates). 46 · Energy balance: occurs when A=B, so, C=O. · Positive Energy balance: Occurs when A>B and C is +ve: if C is +ve in adult → Obesity. if C is +ve in children→ Growth and with excessive food intake will cause growth and obesity. · Negative energy balance: Occurs when A < B. So, C is negative (loss of weight). Etiology of Obesity: I. Decrease energy output: Sedentary life and lack of exercise. II. Increase energy input: a) Psychogenic and stressful conditions: Idea that healthy eating is 3 times a day and each one must be filling. Also, eating is a mean of release of tension (genetically determined). b) Hypothalamic disorder: Hypothalamic disease (genetically). c) Abnormality in hormone sensitive lipase in form of reduction. d) Overfeeding in early childhood: Increase food intake in early childhood will increase the number of fat cells which stabilizes during adult life. Number of fat cells can increase up to 3 times the normal. In adulthood, excessive food intake will cause hypertrophy of fat cells and not increase in number. e) Deficiency of leptin or its receptors (genetically). f) Medical treatment as corticosteroids, antidepressants,... etc. Treatment of Obesity: 1.Increase energy output: Exercise, walking, jogging. 2.Decrease energy input by: Restriction of fat, decrease intake of carbohydrate and plenty of vitamins and proteins (Diet pyramid). 3.Psychological treatment. 4.Anorexigenic drugs (centrally acting drugs): Amphetamine derivatives stimulate satiety center as ponderax, mirapront, isomeride, fenfluramine, etc. (very dangerous) 47 5.Drugs which stimulate metabolic rate as thyroxine. 6.Non centrally acting drugs as GI lipase inhibitors: Orlistat (Xenical) inhibits digestion of fat in intestine, so fat will be excreted in stools (30%). 7.Bulk forming diet as cellulose, bran... etc. 8.Acupuncture. Measurement of Obesity: 1-Body mass index (BMI): Obesity is usually measured by body mass index (BMI) which is body weight in kilograms divided by square of height in meters: Kg /Height m2 normal range 18.5 - 24.9. If more than 25, person is regarded to be overweight. 2-Waist circumference, obese man > 102 cm, obese women > 88 cm. 3-Skin fold thickness. 4-Bioelectric impedance method. 5-Body fat distribution by CT or MRI scan. 48  BIOPHYSICS ILOs: After this chapter, student should be able to: Learn about biophysics and the application in physiology Recognize Poiseuille Hagen Formula and factors affecting blood flow Understand Law of Laplace and its application in cardiovascular system 49  Biophysics The Blood Flow Flow means volume of fluid that crosses a point per unit time. The overall blood flow in the total circulation is defined as the amount of blood that is pumped into the aorta each minute, known as ‘the cardiac output’. Relationship between flow (F), pressure (P), and resistance (R) in blood vessels: - Flow is directly proportional to the effective perfusion pressure or “pressure gradient (∆P)” (P1 – P2). - Flow is inversely proportional to resistance of the vessel to blood flow (R). - Therefore, F=∆P÷R Resistance to blood flow is determined by: 1- Radius of the vessel (r): R  1/r4 2- Length of the vessel (L): R  L 3- Viscosity of blood (ƞ): Rƞ Poiseuille-Hagen Formula: Describes the relation between the flow in a long narrow tube (F), the viscosity of the fluid (ƞ), length of the tube (L) and the radius of the tu b e ( r ) : F = π ∆ P r4 / 8 ƞ L 50  Relationship between pressure, resistance, and flow Effect of radius on resistance: Resistance, and consequently blood flow, is markedly affected by radius of the vessel since, as shown in the formula, radius is raised to the fourth power (r4). Effect of viscosity on resistance: - The viscosity of the blood depends mainly on the hematocrit value. For example, in polycythemia, high hematocrit value can greatly increase resistance to blood flow. - Increased concentration of plasma proteins such as immunoglobulins can affect viscosity & blood flow, but their effect is minor. Effect of pressure on vascular resistance: Due to the elasticity of blood vessels, pressure tends to distend the vessel, increase its radius, and decrease its resistance to flow. This means that the same pressure gradient can produce higher flow in an elastic vessel than in a rigid one. Calculation of total peripheral resistance (TPR) of the systemic circulation: Total blood flow in cardiovascular system is the cardiac output (CO). This flow occurs under the effect of a pressure gradient between aortic pressure (mean arterial pressure MAP) and right atrial pressure (or central venous pressure CVP). CO = (MAP – CVP) / TPR TPR = (MAP – CVP) / CO = (90 – 0) / 5 = 18 Therefore, TPR equals about 18 mmHg/L/min. 51 Calculation of the resistance of the pulmonary circulation (Pul R): Total blood flow in pulmonary circulation is the cardiac output (CO). This flow occurs under the effect of a pressure gradient between pulmonary pressure (mean pulmonary pressure MPP) and left atrial pressure (LAP). Pul R = (MPP – LAP) / COP = (15 – 8) / 5 = 1.4 Therefore, pulmonary vascular resistance is only about 1.4 mmHg/L/min. Law of Laplace: This law describes the relationship between wall tension (T), distending pressure (P) and radius (r) of a hollow viscus: - In a cylinder as blood vessel: P = T/r - In simple words, this law calculates the tension generated in the vessel wall in order to balance the distending effect of pressure. Similarly, the law calculates the pressure that is generated inside the ventricle due to increased wall tension when the ventricle contract. Relationship between pressure, radius, and tension in hollow organ (law of Laplace). 52 Examples of applications of Laplace law in cardiovascular system: - Laplace law explains how thin- walled structures such as capillaries can withstand high pressure? In capillaries the developed wall tension will be small (T=Pr) because the radius is small. - Laplace law also explains why a dilated ventricle of the heart (this occurs in some heart diseases) has to generate more tension during contraction to elevate intraventricular pressure sufficiently to open semilunar valve. The law states that P = T/r. So, if radius is increased (dilated heart) then tension should proportionately increase in order to generate the same pressure normally needed to open semilunar valve. 53 References: - Ganong’s Review of Medical Physiology, 26 Edition, 2019 - Guyton and Hall Textbook of Medical Physiology,14 Edition, 2020. - The Central Nervous System | Anatomy and Physiology https://courses.lumenlearning.com/nemcc-ap/chapter/the-central- nervous-system/ - Central nervous system - TeachMePhysiology https://teachmephysiology.com/nervous-system/components/central- nervous-system/ - Basic structure and function of the nervous system https://openstax.org/books/anatomy-and-physiology/pages/12-1- basic-structure-and-function-of-the-nervous-system 54