Blood Physiology PDF

Blood 1  Blood Blood is a vital fluid circulate within Cardio Vascular System (CVS), and its volume is 5600ml. Blood Functions: 1- Transport function (glucose, O2, CO2). 2- Defensive function (WBCs, anti-bodies). 3- Hemostatic function (stop bleeding). 4- Ho...

Blood 1  Blood Blood is a vital fluid circulate within Cardio Vascular System (CVS), and its volume is 5600ml. Blood Functions: 1- Transport function (glucose, O2, CO2). 2- Defensive function (WBCs, anti-bodies). 3- Hemostatic function (stop bleeding). 4- Homeostatic function (keeps the composition of the tissue fluid constant). Blood Composition: 45% cells: 1- Red blood corpuscles (RBCs). 2- White blood cells (WBCs). 3- Platelets 55% plasma: 1- Water 90 %. 2- Inorganic substances (Na, Cl). 3- Organic substances (protein, lipid, glucose). 4- Gases (CO2, O2). PLASMA PROTEINS Concentration: 7.2 gm /dl. Composition: 1- Albumin : its concentration 3.5 – 5 g/dl. 2- Globulin : its concentration 2.5 g/dl. 3- Fibrinogen : its concentration 0.4 g/dl. 4- Prothrombin: its concentration 0.01 g/dl. Site of formation: All types of plasma protein are formed in liver except 50% of Globulin formed in plasma cells. 2 Albumin – Globulin ratio (A/G ratio) It is a ratio between albumin and globulin concentration. - Normally = 1.2 – 1.6. - It decreases in liver and kidney diseases. Functions: A- Specific functions: 1- Osmotic function it is function of albumin where water withdrawn from tissue to plasma by osmotic pressure of albumin (28 mmHg). 2- Defensive function it is function of gamma globulin while alpha and beta globulin have transport function. 3- Viscosity of the blood it is function of fibrinogen, the importance of this viscosity is to maintain arterial blood pressure. 4- Clotting of the blood it is function of fibrinogen and Prothrombin. B- Nonspecific functions: 1- Plasma proteins act as a carrier for important elements of the blood (vitamins, hormones). 2- Buffer function: plasma proteins adjust PH of blood at 7.4. Buffering function of plasma protein represent 15% of buffering power of blood. 3- Diet reserve: plasma proteins act as a source for rapid replacement of tissue protein. 4- Capillary permeability: plasma proteins control movement of substances across capillaries (in and out) through the pores. 3  Erythropoiesis It is process of formation of RBCs. Erythropoiesis takes place in: Fetus > liver and spleen. Children > bone marrow. Adult > end of long bone. Above 20 year > membranous bone. Factor affecting erythropoiesis: 1-Healthy bone marrow 2- Liver and Kidney 3- Oxygen supply to tissue 4- Hormones 5- Diet 1- Healthy bone marrow is essential for formation of normal RBCs as it is site of formation. Destruction of bone marrow leads to anemia known as aplastic anemia which is (normocytic normochromic anemia). Bone marrow may be destroyed by drugs, radiation, and tumors. 2- Liver and kidney are essential for formation of normal RBCs as both are considered to be site of formation of erythropoietin hormone (15% liver – 85% kidney ) also liver is considered to be site of storage of iron and B12. 3- O2 supply to tissue is one of the most important factors in formation of RBCs decrease O2 supply will lead to stimulation of formation of RBCs through increase Erythropoietin hormone. Decrease O2 supply occurs in heart and lung disease, high altitude and haemorrhage. 4- Hormones erythropoietin – androgen – cortisone and thyroid hormone are essential for formation of RBCs. 4 Erythropoietin hormone site of formation : Fetus > liver Adult > 15% liver and 85% kidney Erythropoietin stimulated by : 1- Hypoxia 2-Alkalosis 3- Androgen 4- Adenosine 5- Cobalt salt 6- Catecholamine Erythropoietin hormone accelerates all stages of erythropoiesis and that is why in renal failure patient develops anemia. 5 5- Diet Diet must contain vitamins as folic acid and B12, metals as iron, copper and cobalt and protein for formation of RBCs. Iron absorption 1- Iron absorbed in ferrous state while iron in diet is ferric. 2- Reduction of ferric to ferrous occurs by gastric Hcl and ascorbic acid (vitamin C). 3- Iron absorbed mainly in upper part of small intestine (duodenum). 4- Part of iron is delivered to mitochondria. 5- Remaining part is either combined with apoferritin (in intestine) or carried in plasma on transferrin. 6- Iron combined with apoferritin is changed to ferritin which is main storage of iron. 7- Iron transported in blood bound mainly to transferrin to all part of body and stored in liver as ferritin. 8- Deficiency in iron is due to decrease iron intake or decrease iron absorption or chronic blood loss lead to microcytic anemia. NB: apoferritin is present in intestine and liver. 6 B12 absorption 1- Intrinsic factor secreted by gastric gland (parietal cell). 2- Intrinsic factor combines with vitamin B12 for protection and transport of B12. 3- Vitamin B12 absorbed from lower part of small intestine (ileum). 4- Vitamin B12 enter mucosal cell with Intrinsic factor by pinocytosis. 5- Inside cell vitamin B12 set free in order to be absorbed to blood where it bound to transcobalamineII to every part in the body and stored in liver. 6- Deficiency in vitamin B12 may be due to decrease in vitamin B12 absorption lead to anemia known as macrocytic anemia. Iron B12 Function important for formation of - DNA formation hemoglobin and myoglobin - Cell division - Cell maturation - Formation of myelin sheath Storage in liver in liver Requirement 0.6 mg/day 5 g/day Site absorption upper part of small intestine lower part of small intestine Deficiency lead to microcytic anemia macrocytic anemia Need Hcl and vitamin C for reduction intrinsic factor for protection of ferric iron to ferrous from Hcl 7  Anemia Anemia is a decrease in number of RBCs, hemoglobin content or both. Anemia is considered when RBCs count → < 4.5 million in males & < 3.9 million in females & Hb content → < 13.5 gm % in males < 11.5 gm % in females. Blood indices: 1-Mean corpuscular Hb (MCH) = amount of Hb in single RBC = Hb content X 10 RBC count in million - Normally, it is 25-32 picogram. - Values less than 25 picogram are called hypochromic. 2-Mean corpuscular volume (MCV) = volume of single RBC = Hematocrit value X 10 RBC count in million - Normally, it is 80 -95 µ3 - Values less than 80 are called microcytes and values more than 95 are called macrocytes. Anemia is classified according to blood indices into: 1-Normocytic normochromic anemia : i.e normal blood indices 2-Microcytic hypochromic anemia : i.e lower blood indices 3-Macrocytic anemia : i.e. higher blood indices. 1-Normocytic normochromic anemia: Causes: a- Aplastic anemia: decrease RBC synthesis due to bone marrow inhibition by: antibiotic – malignant tumor – irradiation. b- Hemolytic anemia: excessive hemolysis of RBC due to : 8  i- Intrinsic disorders of RBCs: - Membrane disorders: e.g. spherocytosis where cells are spherical, small & fragile - Hemoglobin disorders: e.g. sickle cell anemia where RBCs contain abnormal Hb S which precipitate at low oxygen tension & hemolysis - Enzyme disorders: e.g. decrease glucose-6-phosphate dehydrogenase which reduces ferric to ferrous. Oxidants as aspirin cause hemolysis. NB : Favism : hemolysis on eating beans. ii- Extrinsic disorders: - Antibody causing hemolysis e.g. erythroblastosis foetalis - Bacterial toxins - Chemicals e.g. benzene derivatives. - Drugs e.g anti convulsant & anti malarial. c- Acute blood loss: (Acute haemorrhage). 2- Microcytic hypochromic anemia: Small RBC with low Hb content inside caused by iron deficiency Causes of iron deficiency anemia: a- Decrease dietary intake: → starvation as in children & pregnancy where there is increase in their needs. b- Decrease iron absorption as in: - Gastrectomy where HCl is absent - Small intestine diseases - Vitamin C deficiency - increase phosphate & phytate where they form insoluble salts with iron. c- Chronic blood loss: as in piles, peptic ulcer & ankylostoma. N.B. Tea decrease iron absorption because it contains tannic acid & theophylline 9  3- Macrocytic anemia: Due to decrease vit B12 or folic acid → decrease DNA → decrease proliferation of erythroblasts → megalocytes which are macorcytes. Causes of folic acid deficiency: - Decrease intake in diet - Increase demands as in pregnancy - Deficient absorption as in intestinal diseases - Antifolate drugs used in treatment of cancer Causes of vit B12 deficiency: - Deficient absorption as in intestinal diseases. - After gastrectomy due to absence of intrinsic factor. - Liver diseases. - Deficiency of vit B12 in diet which is rare. Pernicious anemia: - It is a familial disease of elderly & more common in women - It is an autoimmune disease- There is an immune reaction against gastric parietal cells leading to achlorhydia and absent intrinsic factor. - There is degeneration of posterior and lateral column of spinal cord leading to neurological manifestations. Treatment of anemia: 1- In each type, try to treat the cause: a- In iron deficiency : give ferrous salts by mouth, in severe cases give iron by injection. b- In pernicious anemia: give B12 by injection through the whole life. c- Macrocytic anemia due to folic acid deficiency is treated by folic acid. 2- In severe cases, blood transfusion is needed 10  Hemostasis It is prevention of blood loss after injury and is done by the following mechanisms: 1- Vascular spasm i.e. vasoconstriction. 2- Platelet reactions and temporary hemostatic plug formation. 3- Formation of blood clot. Clotting mechanisms - Clotting factors are present in plasma in an inactive form. - Clotting mechanisms concern with activation of an inactive clotting factor lead finally to formation of fibrin clot. Fibrin formation occur through 2 pathways: 1- Intrinsic pathway 2- Extrinsic pathway 11 Extrinsic pathway 1- Extrinsic path way start by release of thromboplastin from injured tissue. 2- Thromboplastin activates factor VII. 3- Factor VII active activate factor X. 4- Factor X active convert prothrombin to thrombin in presence of Ca, platelets and factor V. 5- Thrombin converts fibrinogen to fibrin monomer. 6- Fibrin monomer converted to fibrin clot by active factor XIII and Ca. 12 Intrinsic pathway 1- Collagen fiber activate factor XII this activation is helped by high molecular weight kininogen and plasma kallikrein. 2- Active factor XII activate factor XI. 3- Active factor XI activate factor IX. 4- Active XI, active VIII, Ca and platelets form complex activate factor X. 5- Factor X active convert prothrombin to thrombin in presence of Ca, platelet and factor V. 6- Thrombin converts fibrinogen to fibrin monomer. 7- Fibrin monomer converted to fibrin clot by active factor XIII and Ca. 13  Anti-clotting mechanisms Functions: 1- Limit tendency of blood to clot 2- Break down already formed blood clot Mechanism: 1- general 2- specific general specific a) Vascular endothelium is smooth and not a) Anti thrombin III inactivate active factor suitable for formation of plug or clot. IX-X-XI and XII. b) Liver remove and inactivate activated b) Prostacyclin inhibit platelet aggregation clotting factor. and limit platelet plug. c) Heparin. c) Fibrinolytic system. d) Protein C, Protein S. inactivate factors V & VIII Inactivate inhibitor of tissue plasminogen activator Increase plasmin formation Fibrinolysis: 14  Anti-coagulants Anti-coagulants are substance that prevent blood clotting In vitro In vivo 1 Oxalate slat Heparin 2 Citrate salt Dicumarol 3 Silicon 4 Heparin Dicumarol Heparin 1- Source Plant source Basophils, mast cells & liver 2-Intake Oral (by mouth) Injection intravenous i.v. & intramuscular i.m. 3- Onset & Slow onset & long duration Rapid onset & short duration duration 4- Chemistry Similar to vitamin K Sulphated mucopolysaccharide 5- Site of action Only in vivo In vivo & In vitro 6- Action Competes with vitamin K. So, -It increases antithrombin III inhibits its utilization by liver activity. (competitive inhibition). - It prevents activation of factor IX It decreases synthesis of - It has a clearing action→it factors II, VII, IX, X, prtn C & increases lipase enzyme which clears prtn S. blood from lipids after meals. 7- Antidote Vitamin K Protamine Sulphate 1% (basic protein) 15  Autonomic Nervous System 16  Autonomic Nervous System The functions of the body are coordinated by two control systems: a) Endocrine system which secretes hormones: affect distal organs – act slowly- has prolonged action b) Nervous System: responsible for rapid regulation of various systems. It is divided into: Central nervous System (CNS) and Peripheral nervous system. 17  Transverse section (TS)of spinal cord demonstrates that cord can be divided into H central zone (gray matter) surrounded by peripheral part (white matter). The gray matter is divided into three horns of cells on each side: 1. Dorsal horn concerned with sensation. 2. Ventral horn concerned with movement. 3. Lateral horn concerned with autonomic. The unit of structure of nervous system is nerve cell (neuron). It is formed of: cell body & processes which are two types: A-dendrites: short branching that carry impulses towards cell body. B-axon: long none branching that carry impulses from cell body. 18 Axon may be: - Myelinated covered by myelin sheath. - Non myelinated where myelin sheath is absent. From functional point of view, the nervous system can be divided into 2 systems: Autonomic Somatic Control Involuntary Voluntary Type 2 types One Efferent nerve 2 efferent One Muscle Smooth- cardiac Skeletal Perform all involuntary Perform all voluntary Function process processes Acetylcholine Chemical transmitter Acetylcholine Norepinephrine Autonomic ganglia Present Absent Rise from LHC AHC 19  Autonomic Nervous System It is the part of nervous system which controls involuntary actions i.e. glands, cardiac muscles and smooth muscles. It is divided into: sympathetic & parasympathetic nervous system. Sympathetic Nervous System Origin: lateral horn cells of all thoracic and upper 3 lumbar segments (thoracolumbar). 20 - Functions: (during fear, fight, flight and exercise) Functions: ▪ Head & Neck: ▪ Eye: 1. Pupil dilatation (mydriasis) due to contraction of dilator pupillae muscle 2. Elevation of upper eye lid & widening of palpebral fissure due to contraction of lid smooth muscles. 3. Relaxation of ciliary muscle---→decrease power of lens to see far objects. 4. Vasoconstriction of conjunctival vessels & decrease tear secretion of lacrimal glands. ▪ Skin: 1. Increase sweat gland secretion 2. Vasoconstriction of blood vessels 3. Hair erection by contraction of piloerector muscles. ▪ Salivary glands: 1. Stimulate trophic viscid secretion (decrease secretion). 2. Vasoconstriction of blood supply ❖ Horner Syndrome: A lesion in the cervical sympathetic chain resulting in the following: a) Meiosis: constriction of pupil b) Ptosis: dropping of upper eye lid. c) Anhydrosis: failure of sweating on that side of face---→dry skin. d) Warm& red skin: due to vasodilatation of blood vessels. All these manifestations occur on diseased side only 21 (2)Thorax: - Functions: ▪ Heart: 1. increase excitability & rate of conduction. 2. Increase force of contraction (+ve inotropic effect). 3. Increase heart rate (+ve chronotropic effect). 4. Vasodilatation of coronary vessels (indirect effect). ▪ Lung: 1. Bronchodilatation by relaxation of bronchial muscles. 2. Vasoconstriction of pulmonary vessels. (3)Abdomen: - Function: ▪ Liver: 1. Glycogenolysis---→hyperglycemia & increase metabolic rate. 2. Increase fibrinogen synthesis which limits bleeding. ▪ Spleen: Contraction of its capsule--→increase RBC into circulation & hematocrite value. ▪ Adrenal medulla: Secretion of 80% adrenaline & 20% noradrenaline. ▪ Gastrointestinal tract: Inhibition of plain muscle (wall) of stomach, small intestine & proximal part of large intestine but motor to the sphincters e.g. pyloric sphincter. ▪ Blood vessels: Mainly vasoconstriction of arterioles but there is also vasodilatation of some arterioles of abdominal viscera. 22 (4)Pelvis: - Functions: ▪ Rectum: retention of feces. 1. Inhibition of plain muscles of wall of rectum. 2. Contraction of internal anal sphincter. ▪ Urinary bladder: retention of urine. 1. Inhibition of plain muscles of wall of bladder. 2. Contraction of internal urethral sphincter. ▪ Male genitalia: 1. Contraction of vas deferens, seminal vesicles and prostatic plain muscles ----→ejaculation. 2. Vasoconstriction of blood vessels of external genital organs--- →shrinkage of penis. ▪ Female genitalia: Variable effect according to stage of menstrual cycle. ▪ Blood vessels: Mainly vasoconstriction of blood vessels of pelvic viscera. 23  Parasympathetic Nervous System ❑ Parasympathetic is the craniosacral outflow of autonomic nervous system. ❑ The cranial outflow includes: - Occulomotor, facial and glossopharyngeal nerves which supply head & neck. - Vagus nerve which supply thorax & abdomen. 24 ❑ The sacral outflow includes: pelvic branches of S2, S3, and S4 which supply pelvic viscera. ❑ Parasympathetic nerve supply is anabolic i.e. energy preserving. ❑ No parasympathetic to sweat glands, skin, spleen, suprarenal medulla and ventricles. ❑ Functions: (during rest) (1)Head & Neck: ▪ Occulomotor Nerve (3rd cranial nerve): ▪ Functions: 1. Pupil constriction (miosis)by contraction of constrictor pupillae muscle. 2. Contraction of ciliary muscle leading to increase power of lens necessary for near vision. ▪ Facial nerve (7th cranial nerve): ▪ Functions: 1. Secretomotor & vasodilator to the glands. 2. Vasodilatation of anterior 2/3 of tongue. ▪ Glossopharyngeal nerve (9th cranial nerve): ▪ Functions: 1. Secretomotor& vasodilator to parotid gland. 2. Vasodilatation of posterior 1/3 of tongue. (2)Thorax & (3) Abdomen :Vagus nerve (10th cranial nerve) ▪ Functions: ❖ Thorax: ▪ Heart: 1. Inhibition of all atrial properties (NO vagal supply to ventricles). 2. Decrease coronary flow & O2 consumption. ▪ Lungs: 25  1. Bronchial constriction. 2. Dilatation of pulmonary blood vessels ▪ Abdomen: 1. GIT: Motor to esophagus, stomach, small intestine, proximal part of large intestine but inhibitory to sphincters and secretory to glands of stomach, small intestine, liver and pancreas. 2. Gall bladder: motor to wall and inhibitory to sphincter of oddi i.e. evacuation of gall bladder. (4)Pelvis: sacral outflow ❑ Functions: ▪ Defecation: a. Contraction of wall of rectum. b. Inhibition of internal anal sphincter. ▪ Micturition: a. Contraction of wall of urinary bladder b. Inhibition of internal urethral sphincter. ▪ Male genitalia: a. Erection: vasodilatation of blood vessels of penis. b. Secretory to seminal vesicle & prostate. ▪ Female genitalia: Vasodilatation 26 Nerve 27  Nerve The function of nerves is to carry messages to & from central nervous system. The unit of structure of the nervous system is neuron which is specialized for rapid transfer & integration of information. ❖ Neuron: It is formed of cell body & cell processes ▪ The cell body (Soma): -It is surrounded with cell membrane. It contains cytoplasm & nucleus. -Cytoplasm contains mitochondria, Golgi apparatus, endoplasmic reticulum, pigment, fat, glycogen, neurofibrils & Nissil granules which are rich in ribose nucleic acid (RNA) and play an important role in metabolism of cell. ▪ The processes: The dendrites: short branches which receive the ingoing impulses. The axon or nerve fiber which is a long process of the cell & usually carries impulses from the nerve. It is surrounded with the plasma membrane which is a continuation of cell membrane. It ends in a number of synaptic knobs which contain vesicles rich in chemical transmitters. 28 Two types of nerve fibers are found: (a)Myelinated nerve fibers: ❑ The axon is surrounded by a myelin sheath, made by Schwann cells, (important for rapid conduction of nerve impulse) & outer neurolemmal sheath (important for regeneration of 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” which are uninsulated area. (b) Non-myelinated nerve fibers: The myelin sheath is absent. The axon is surrounded by Schwann cells. ❖ Excitability: -It is the ability of living tissues to respond to changes in environment. -The most excitable tissues in the body are nerves & muscles. ▪ Stimulus: It is the change in the environment. ▪ Types of stimuli: Electrical – mechanical – chemical – thermal Electrical stimulus is preferred because: 1/It is similar to natural stimuli inside the body. 2/It can be controlled. 3/It can be accurately measured. 4/It leaves the tissue undamaged. ▪ Method of nerve stimulation: For electrical stimulation of nerve: 2 stimulating electrodes are put on surface of nerve fiber: One connected to anode of stimulator & the other is connected to cathode of same stimulator. The important element is the cathode which induces flow of current 29 *Conductivity: Is the ability of nerve fiber to propagate impulse. Action potential It is rapid change in membrane potential due to stimulation of nerve fiber by adequate stimuli. I - Ionic change During rest: membrane potential = -70 mv. Application of stimuli: These stimuli must be threshold to stimulate the nerve. Stimulus artifact which is small oscillation indicates time of application of stimuli. Latent period: This is period between applications of stimuli and beginning of response. 1. Partial depolarization where membrane potential decrease to -55 mv due to opening of some voltage gated Na channels and entry of Na+. 2. Firing level at -55 mv all Na channels are opened. 30 3. Complete depolarization: where membrane potential decrease then lost then reversal of polarity occur to (+35 mv) due to opening of all voltages gated Na channels and entry of Na. 4. Repolarization phase where membrane potential return to resting due to inactivation of Na channels and opening of K channels. Repolarization process starts rapid then when 70% completed it slow down. (Repolarization is due to K exit). 5. After depolarization: membrane potential become below resting level caused by K exit and slow closure of K channels. 6. After hyper polarization: membrane potential return to resting level by Na – K pump. NB: step 5 & 6 collectively known as hyperpolarization. Voltage gated Na channels may be: - At rest → closed from outside (-90 mV). - Activated → opened from outside (-90 to +35 mV). - In activated → closed from inside (+35 to -90 mV). Voltage gated K channels may be: - At rest → closed from inside (-90 mV). - Activated → opened (+35 to -90 mV). 31 Muscle 32  Muscle Skeletal muscle form 40 % of body while smooth and cardiac muscle form 10%. Skeletal Muscle Functions: 1- Locomotion and breathing 2- Maintain posture and stabilize the joints. 3- Heat production. 4- Help venous drainage. Skeletal muscle to contract must be depolarized. Action potential in muscle results from nerve impulse arriving at neuromuscular junction. Neuromuscular transmission: ❑ Motor end plate: It is the junction between motor neuron & muscle fiber. Each skeletal muscle fiber receives one axon terminal. The axon terminal lies in a groove called synaptic gutter (invagination of skeletal muscle fiber). 33  The axon terminals (end feet) contain synaptic vesicles containing acetyl choline concentrated around dense bars. Synaptic cleft which is the space between nerve terminal & fiber membrane contain basal lamina to which acetyl choline esterase is bound. The post synaptic membranes contain junction folds on which acetyl choline receptors are found. Events of neuromuscular transmission: 1) Action potential is propagated into the nerve terminal. 2) Acetyl choline release: Ca++ enter nerve terminal through Ca++ channels according to electrochemical gradient--→leading to marked increase in exocytosis of acetyl choline containing vesicles. Later on, new vesicles are formed from invaginations of pre-synaptic membrane. 3) Acetyl choline binds to acetyl choline receptors on end plate membrane causing End plate potential (EPP). EPP: is graded – non propagated 4) EPP depolarize muscle membrane to firing level→leading to action potential. 5) Action potential is conducted in both directions along muscle fiber- →initiating muscle contraction. 6) Acetyl choline is degraded rapidly by acetyl choline esterase preventing multiple muscle contraction. 34 Miniature End plate potential: It is the minute depolarization at motor end plate due to spontaneous release of acetyl choline at rest. Properties of neuromuscular transmission: 1) It is unidirectional i.e. in one direction only from nerve to muscle 2) There is delay of 0.5 msec. It is time needed for: Acetyl choline release- inflow of Na+- depolarization to firing level. 3) Easily fatigued as a result of repeated stimulation & exhaustion of acetyl choline vesicles. 4) Effect of ions: -Ca++ increases neuromuscular transmission because it cause rupture of acetyl choline vesicles. -Mg++ decreases neuromuscular transmission because it block rupture of vesicles. 5) Effect of drugs: A) Drugs stimulating neuromuscular transmission: Drugs having acetyl choline like action e.g. metacholine- carbacole & - nicotine small dose (persisting minutes to hours). - Drugs having anticholine-esterase activity e.g. Neostigmine, physostigmine & DIF (di isopropyl fluoro phosphate) B) Drugs blocking neuromuscular transmission: Curariform drugs i.e. Curare. It competes with acetylcholine at receptors preventing its binding, thus preventing increase Na+ permeability and depolarization. 35 Myasthenia Gravis: ❑ It is a hereditary disease affecting female more than male. ❑ It is an autoimmune disease where patients have antibodies against their own acetyl choline activated receptors. ❑ It may be caused by presence in blood of curare like substance. - OR Secretion of small amount of acetyl choline. ❑ It is characterized by weakness of skeletal muscle. ❑ If disease is intense, patient may die of paralysis particularly of respiratory muscle. ❑ Treatment: -Anticholine esterase (e.g. neostigmine) increases acetyl choline affecting muscular activity. 36 Cardiovascular System 37  Circulation Introduction: The cardiovascular system is composed of the heart and a closed system of blood vessels. Heart: It beats automatically & regularly before birth till death. A-Systole: cardiac contraction to eject blood. B-Diastole: cardiac relaxation to be filled with blood. 38  The heart is formed of 2 separate pumps: 1. Right side, which pumps blood to lungs against low resistance and under low pressure i.e. volume pump 2. Left side, which pumps blood to the whole body against high resistance and under high pressure i.e. pressure pump. Each pump is formed of : 1. Atrium: thin wall- function mainly as reservoir of blood, 70% of blood goes from atria to ventricles by pressure gradient. Atrial systole (contraction) is to evacuate 30 % of venous return to ventricles. 2. Ventricle: thick wall- acting as a pump: Right ventricle acts as a volume pump, it propels blood through pulmonary vessels. Left ventricle acts as a pressure pump, it propels blood through peripheral circulation (Aorta). Valves: The function of a valve is to allow the passage of blood in one direction only and not the reverse. 39 1- A.V.V.: Atrioventricular valves are 2: a-Right AVV is the tricuspid valve (formed of 3 cusps) b-Left AVV is the mitral valve (formed of 2 cusps) 2- Semilunar Valves (their opening looks like a crescent) a- Aortic valve: between left ventricle & aorta b- Pulmonary valve: between right ventricle & pulmonary artery Circulation is divided into 2 circulations : 1. Greater, Systemic or General Circulation: from left ventricle, oxygenated blood is pumped to aorta→to all parts of body via arteries & arterioles and capillaries →venules→veins→SVC & IVC→to right atrium. 2. Lesser, Pulmonary circulation: from right ventricle, deoxygenated blood is pumped to pulmonary artery→pulmonary capillaries (where gas exchange occurs)→4 pulmonary veins →left atrium. Cardiac properties: Excitability: i.e. Action potential. Rhythmicity: i.e. initiation of regular impulses independent of nerves. Conductivity i.e. spread of cardiac excitation Excitation-Contraction Coupling: (contractility) i.e. depolarization of Action potential causes calcium release from sarcoplasmic reticulum to initiate contraction. Action Potential: Action Potential of ordinary cardiac muscle fibers: RMP = -90 mV(ionic bases: like skeletal muscle) AP is composed of the following phases: 40  Phase 0: Depolarization Sudden depolarization and reversal of polarity from -90 mV to +20 mV. Ionic bases: Na+ influx due to opening of fast Na+ channels. Repolarization: is triphasic. Phase 1: Small rapid repolarization to + 10 mV. Ionic bases: K efflux due to opening of fast K+ channels and inactivation of Na+ channels and Cl in. Phase 2: = Plateau: Repolarization slow down and membrane potential is around zero mV for about 200 msec. Ionic bases: Balance between Ca++ influx through long-lasting Ca++ Channels together with Na+ influx and outflow of K+ through K+channels. Phase 3: Rapid repolazation to RMP due to: o Closure of L-lasting Ca++ channels. o Inactivation of Na+ channels. o Activation of K+ channels leading to K+ efflux. 41  Rhythmicity It is the ability of heart to beat regularly and initiate its own regular impulse in dependent on any nerve supply Rhythmic cell Rhythmic cell characterized by SAN discharge at rate 90 /min Discharge spontaneously AVN discharge at rate 60 /min Membrane potential is unstable no R.M.P Purkinje discharge at rate 30 /min It has no plateau Membrane more permeable to Na and Ca Firing level = -40 mV Peak of AP= +10 mV Factors increase HR Factors decrease HR Sympathetic stimulation Parasympathetic catecholamine acetylcholine increase temperature hyperkalemia hypokalemia Ca-channel blocker thyroxin Contractility ▪ Definition: It is the ability of the cardiac muscle to contract to pump blood.Contraction start after excitation of cardiac wave 1- Inotropic state The ability of cardiac muscle to develop force (contract), i.e., Contractile state can be increased (positive inotropic) or decreased (negative inotropic). Positive inotropics factors: factors that increase contractility. 1- Sympathetic stimulation (β1-adrenergic). 2- Catecholamines. 3- Glucagon hormone. 42 4- Digitalis. 5- Xanthines, e.g. caffeine. All act through increasing Ca++ in sarcoplasm. Negative inotropics factors: factors that decrease contractility. 1- Parasympathetic stimulation. 2- Acetylcholine. 3- Hypoxia (due to ischemia) 4- Calcium channel blockers. 5- Anaesthetics. 6- Anti arrhythmic drugs. Cardiac Output (CO) ❑ Stroke volume SV: is the volume of blood pumped by each ventricle per beat = 70 ml SV = End diastolic volume – End systolic volume = EDV - ESV = 135 - 65 = 70 ml ❑ EDV is the volume of blood in the ventricle at end of diastole ❑ ESV is the volume of blood in the ventricle at end of systole ❑ Ejection fraction = It is the fraction of the EDV that is ejected with each beat. Ejection fraction is greater than 55%. Ejection fraction is used in clinical practice as a measure of contractility of the hear ❑ Cardiac output = Minute volume: is the volume of blood pumped by each ventricle per minute. CO = SV X HR = 70 X 70 = 5 L/min 43  ❑ Cardiac index: volume of blood pumped by each ventricle per minute per square meter body surface area = 3.2 L/min/m2 ❑ Cardiac output in various conditions: Unchanged in: sleep, moderate changes in external temperature Increased in: Excitement (50 – 100%) Exercise (700 %) Exposure to high temperature Eating (30 %) Epinephrine secretion End of pregnancy Inspiration Shifting from standing to recumbent position Decreased in: Sitting or standing from lying position Rapid arrhythmia Heart failure 44  Arterial Blood Pressure Definitions: ❑ Arterial blood pressure (ABP): it is the pressure of blood on arterial wall ❑ Systolic pressure (SP): it is the maximum pressure reached during systole 120 mmHg (90 –160) ❑ Diastolic pressure (DP): it is the minimum pressure reached during diastole 70 mmHg (60 – 90) ❑ Pulse pressure: = Systolic pressure – diastolic pressure = 50 mmHg ❑ Mean systemic arterial pressure: MAP: it is the average pressure in arteries throughout the cardiac cycle = DP + 1/3 Pulse pressure = 70 + 1/3 x 50 = 90 mmHg. Measurement: 2 methods 1-Direct: by cardiac catheter 2-Indirect: by sphygmomanometer. Physiological Variations in ABP: 1-Age: ABP increases with age due to loss of elasticity New born = 80/40 4 years = 100/65 20 years = 120/70 60 years = 150/90 2-Sex: Below 45 y female have less ABP than male Above 45 y the pressure increases in female due to hormonal changes. 3-Race: Europeans + Americans > Orientals due to: stress & high cholesterol in diet. 4-Emotions:-→sympathetic ---→Increase ABP especially SP 5-Exercise: -→increase SP + decrease DP 6-Gravity: each 1 cm below heart increases ABP by 0.77 mmHg Each 1 cm above the heart decreases ABP by 0.77 mmHG 45 Endocrine 46  Endocrine The endocrine system is composed of many organs (glands) which secrete hormones * Functions of hormones: (1) Regulation of biochemical reactions (2) Regulation of body processes e.g. growth, maturation, regeneration, reproduction and pigmentation. * Endocrine glands: * They are glands that secrete hormones directly into blood: 47 Pituitary- Thyroid - Parathyroid - Suprarenal (cortex & medulla) - Islets of Langerhans (endocrine pancreas) - Pineal glands (secrete melatonin), gonads (testis and ovaries). * Other glands with endocrine functions: (1)Heart: secretes ANP (atrial naturetic peptide). (2)Kidney: secretes erythropoietin, renin & 1-25 dihydroxycholecalciferol. (3)Liver : secretes somatomedins & 25 dihydroxycholecalciferol. (4)Skin: secretes calciferol (vit D3). (5)Gastrointestinal tract: gastrin, secretin, CCK, VIP (local action). * Nervous & Endocrine inter-relation: (1)Hypothalamic hypophyseal portal circulation: that transports releasing or inhibiting factors that secreted from hypothalamus to reach anterior pituitary (Vascular connection). (2)Hypothalamic-hypophyseal tract: that transports ADH & oxytocin. - These hormones are synthesized in supraoptic (ADH) & paraventricular (oxytocin) nuclei in hypothalamus. - Then transported down the axons of these neurons to their endings in posterior lobe of pituitary where they are stored. - They are secreted (when needed) in response to electrical activity in the endings (Nervous connection). Pituitary Gland Hormones of Anterior Pituitary Gland: 1. Growth hormone GH 2. Prolactin hormone 3. Follicle stimulating hormones FSH 48 4. Luteinizing hormone LH 5. Thyroid stimulating hormone TSH 6. Adrenocorticotrophic hormone ACTH Hormones of Posterior pituitary gland: antidiuretic hormone (ADH) & oxytocin Growth Hormone It is polypeptide hormone Functions: A) Stimulates growth of bone and soft tissues: On viscera, it stimulates hypertrophy (increase size of cells) & hyperplasia (increase number of cells) On skeleton, it stimulates chondrogenesis leading to growth of the epiphyseal cartilage & elongation of bone. B) It is diabetogenic hormone i.e. induces hyperglycemia C) It has a lipolytic activity D) It is anabolic hormone i.e. stimulates protein synthesis. Control: 1. Growth hormone is under hypothalamic control i.e. it is stimulated by growth hormone releasing hormone (GHRH) & inhibited by growth hormone inhibiting hormone (GHIH) (secreted from hypothalamus). Both GHRH and GH inhibit their own release by feedback on the hypothalamus and anterior pituitary, respectively. 2. Growth hormone secretion is increased by sleep, stress, fasting, exercise & hypoglycemia Growth hormone deficiency: During infancy & childhood l, GH deficiency leads to failure of growth with short stature which is known as pituitary dwarfism 49  Growth hormone excess: 3. Before puberty leads to Gigantism (tall person with enlarged organs). 4. After puberty leads to Acromegaly ( increase growth of hands , feet with protrusion of mandible). Antidiuretic hormone (ADH) o Functions: 1. Reabsorption of water from renal collecting ducts. 2. Vasoconstriction of blood vessels. o Control: Increase plasma osmolarity or decrease plasma volume stimulates ADH secretion (through arterial baroreceptors or volume atrial receptors). The thyroid gland It secretes T3 & T4 (thyroxine) Functions of thyroid hormones: A) Stimulates growth especially in early life B) It is diabetogenic hormone i.e. induces hyperglycemia C) It has lipolytic activity D) It is anabolic in normal physiological and catabolic in supraphysiological doses (i.e. excess dose) E) It has calorigenic action: stimulate metabolic rate & increase heat production F) On CNS: it is important for myelination of nerves in infants and synaptic transmission G) On CVS: it increase heart rate & myocardial contractility 50  Control of thyroid hormone secretion: Pituitary control which secretes TSH & Hypothalamic control which secretes thyroid releasing hormone (TRH) o Hyperthyroidism due to excessive production of thyroid hormones leads to nervousness, weight loss with increase appetite, tremor, sweating, and tachycardia with intolerance to heat. The most common cause is Gravis disease which is autoimmune disease. o Deficiency of thyroid hormones during infancy leads to cretinism. Cretinism is characterized by retardation of physical, mental & sexual development. o Deficiency of thyroid hormones in adults leads to myxoedema with slow mentation, decrease heart rate, weight gain, decrease appetite, dry skin and hair with intolerance to cold. Parathyroid gland It secretes parathormone hormone which is Ca raising hormone The other hormones which regulates Calcium level are: vitamin D & calcitonin Functions of parathormone: Ca raising hormone a. On bone: stimulates osteoclasts which resorb bone calcium & inhibits osteoblasts (bone building cells). b. On kidney: stimulates Calcium reabsorption from renal tubules & increase phosphate excretion. c. On intestine: stimulates calcium reabsorption through activation of vitamin D Control of parathormone: low calcium & high phosphate stimulate PTH secretion. It is not under control of pituitary 51 Functions of vitamin D (1,25 dihydroxycholecalciferol) A) On intestine: stimulates calcium reabsorption B) On bone: depends on prevailing plasma calcium o If low calcium---→ stimulates osteoclasts o If high calcium--→ stimulates osteoblasts. C) On kidney: stimulates calcium reabsorption o Functions of calcitonin: Ca lowering hormone A) On bone: activate osteoblasts (increase calcium precipitation in bone) & inhibits osteoclasts B) On kidney: inhibits renal calcium reabsorption o Tetany: is defined as an increased neuromuscular excitability caused by low ionized calcium. Normal level of Calcium in plasma: 9 – 11 mg % Causes of tetany: -Decrease secretion of parathormone -Alkalosis leading to decrease ionized calcium Tetany will be presented by carpo-pedal spasm and may be presented by laryngeal spasm o Carpal spasm: Flexion of wrist, extended inerphalangeal joints with adduction of thumbs o Pedal spasm: flexion of toes Suprarenal gland It consists of suprarenal cortex & adrenal medulla Suprarenal cortex secretes: glucocorticoids & mineralocorticoids Suprarenal medulla secretes: adrenaline & noradrenalin. 52  Function of glucocorticoids (cortisol): A) Diabetogenic hormone: it induces hyperglycemia B) Lipolytic hormone C) Anabolic intrahepatic (inside liver) & catabolic extrahepatic (outside liver) D) Anti – inflammatory E) Anti-allergic F) Suppression of immune system Control of Glucocorticoid secretion: pituitary control which secretes ACTH & hypothalamic control which secretes CRH (corticotrophin releasing hormone) Functions of mineralocorticoid (aldosterone): A) Increase Sodium reabsorption from kidney, intestine, salivary & sweat glands B) Increase potassium secretion from kidney, intestine, salivary & sweat glands. C) Increase water reabsorption. Control of mineralocorticoids: 1. Renin angiotensin system: Renin is secreted from juxtaglomerular apparatus of kidney in response to decrease arterial blood pressure and extracellular fluid volume. Renin ACE Angiotensinogen Angiotensin I Angiotensin II Angiotensin II stimulates aldosterone secretion 2. High K+ level 3. Low Na+ Hypersecretion of glucocorticoids leads to Cushing syndrome which is characterized by hyperglycemia, protein catabolism, delay healing of wounds, muscle wasting, and osteoporosis. 53 It is characterized by moon face & buffalo body (accumulation of adipose tissue on face, neck, trunk & girdle). Hypofunction of suprarenal cortex leads to Addison's disease which is characterized by hypoglycemia, hypotension & hyperpigmentation Pancreas Functions of Pancreas: It has endocrine & exocrine functions *Exocrine functions: secretion of digestive enzymes & aqueous bicarbonate *Endocrine functions: secretion of insulin & glucagon. Functions of insulin: 1. Lowers blood glucose by increasing uptake of glucose by tissues – stimulating glycogen formation from glucose- decrease gluconeogenesis. 2. Simulates lipogenesis 3. It is anabolic hormone Functions of glucagon: 4. Increase blood glucose 5. Stimulates lipolysis 6. It is catabolic hormone 7. Calorigenic action: secondary to hyperglycemia 8. Large dose: Positive inotropic & chronotropic effect. Deficiency of insulin leads to diabetes mellitus which characterized by: High blood glucose concentration- Polyuria (excess urine volume) - Polyphagia (excess food intake) - Polydipsia (excess drinking) - Acidosis and ketosis (ketone body formation). 54 Reproductive system 55  Male reproductive system Male reproductive system consists of : (1) Primary sex organ (testis) (2) Secondary sex organs (duct i.e. vas deferens & epididymis…and accessory sex glands i.e. seminal vesicles- prostate-bulbourethral gland-external genitalia). (3) External organs: Penis Testis consist of : (1) Seminefrous tubules: its function is spermatogenesis i.e. formation and release of spermatozoa (2) Interstitial cells of Leydig which secrete testosterone and small amount of estrogen. Blood supply of testis: spermatic arteries & spermatic veins parallel and opposite to each other to permit countercurrent exchange of heat and testosterone between them 56 Seminefrous tubules contain: 1- precursor germ cells which form spermatozoa 2- Sertoli cells: which extend from base to lumen Spermatogenesis Formation of spermatozoa in seminefrous tubules (4 phases). The time for complete cycle of spermatogenesis is 64 days (look to embryology) Factors affecting spermatogenesis: 4 hormonal 4 non hormonal (1) LH: a-Stimulates interstitial cells to secrete testosterone b- Important for early stage of spermatogenesis (2) FSH: a- growth & maturation of testis b- growth & development of sertoli c- important for late stage of spermatogenesis. d- stimulates androgen binding protein (ABP) 57 (3) Androgen (testosterone) a-essential for development of germinal epithelium & miosis b-essential for maturation of sperm. -Testosterone is kept in high concentration locally because: a- local secretion of testosterone by Leydig cells b- secretion of androgen binding protein (ABP) (sertoli cells) c- counter current mechanism by testicular vein & testicular artery: high amount of testosterone in venous blood diffuse back into arterial blood reaching the testis. *Exogenous testosterone through feedback inhibit LH & spermatogenesis. (4) Other hormones: 1-Inhibin (polypeptide secreted by sertoli cells) inhibits FSH. 2-Activin stimulates FSH 3-Estrogen: small amount is needed for spermatogenesis 4-Leptin: has a role in onset of puberty and start of spermatogenesis. 5-Growth hormone and prolactin: stimulates early division. 6-Thyroxin: myxoedema inhibits spermatogenesis. (5)Temperature: 32 – 350C Maintained by: a- thin skin b-NO subcutaneous fat c-Presence of sweat gland. d-Presence of Dartos & cremasteric muscle: e-Counter current heat exchange between spermatic arteries & veins. 58 (6) Diet: a- A balanced diet is essential for development, maturation, and normal function of tubules. It includes vitamin A, B, C, E (important for spermatogenesis). -Vitamin A deficiency leads to keratinization of tubular epithelium -Vitamin E deficiency leads to irreversible tubular damage. (7)Atomic radiation: Large dose of X rays leads to irreversible damage of germinal epithelium but Leydig cells continue to secrete testosterone. (8)Other factors: O2 lack & toxins inhibit spermatogenesis. 59  Female Reproductive System It includes primary sex organs (2 ovaries: secrete hormones & Oogenesis) & secondary sex organs (2 fallopian tubes-uterus-vagina-Bartholin gland-external genitalia-2 mammary glands) 60  Oogenesis Formation & release of ova & oocytes- It occurs entirely in embryonic life (look to embryology) Ovarian cycle -It is the period between successive ovulations. It includes 3 stages: follicular maturation-Ovulation-Corpus luteum formation 1)Follicular maturation: At puberty, anterior pituitary begins secretion of FSH to promote maturation of follicles. In each cycle, 10-15 follicles start to grow under influence of FSH. One follicle (which contain high estrogen receptor) grow faster & secrete large amount of estrogen. Estrogen inhibit 61 FSH by negative feedback, thus the single follicle completes its development into a mature graafian follicle and the other follicles regress. 2)Ovulation: at 14th day ,the rising level of estrogen (300%) for 72 hours exert a positive feedback on LH (LH surge) & FSH. LH cause swelling of follicle and its rupture releasing the ovum. 3)Corpus Luteum formation: under influence of LH. It is temporary endocrine structure occurring in emptied structure of the follicle. It secrete estrogen & progesterone. If no pregnancy, it degenerates because high level of estrogen, progesterone exert negative feedback on FSH, LH. This leads to withdrawal of estrogen & menstrual bleeding. If pregnancy occurs, it continues to grow & secrete its hormones in first half of pregnancy under effect of LH from anterior pituitary & chorionic gonadotrophin till placenta develops & takes hormonal function of corpus luteum Menstrual Cycle (endometrial cycle) ▪ Endometrium is divided into: -Superficial functional layer (outer 2/3): prepares for implantation of blastocyst. -Deep basal layer (inner 1/3): provides the regenerative endometrium. Proliferative (Estrogenic ) phase: Duration: from 5th day of menses up to 14th day (ovulation) Control: Estrogen secreted from growing ovarian follicle (during follicular phase) Changes: 1-Regeneration of endometrium due to rapid proliferation of endometrial stroma & epithelium. 2-Growth of endometrial glands but minimal secretion. 62 3-Development of endometrial blood vessels. Blood is rich in leucocytes & immunoglobulins. -Endometrium is 3 –4 mm thick (by time of ovulation). Secretory (progestational )phase: Duration: 14th day till onset of menstruation. Control: progesterone (mainly) and estrogen from corpus luteum. Changes: -Endometrial glands become tortuous (cork screw) and secretory (secretes clear fluid). -Spiral arteries become more tortuous. -Stromal cells are oedematous with lipid and glycogen deposits. -Endometrium is 5-6 mm thick. Degenerative phase (Menstruation): Duration: 3- 7 days. Control & changes: degeneration of corpus luteum leads to -→sudden drop in estrogen and progesterone level in blood leading to : -constriction of spiral arteries (by local prostaglandin)--→ischemia and necrosis of superficial functional layer of endometrium. -dilatation of spiral arteries follows due to release of vasodilator substances (PG) leading to --→gush of blood which removes necrotic endometrium + unfertilized ovum. -vessels then constrict and shutt off blood flow 63 Respiration 64  Respiration Introduction: RESPIRATION: is divided into external respiration & internal respiration I-External respiration: 1. Pulmonary ventilation. 2. Exchange of oxygen and carbon dioxide. 3. Transport of oxygen & carbon dioxide between the lungs and body tissues by the blood. 4. Exchange of oxygen and carbon dioxide between blood and tissues by diffusion. II-Internal respiration: Use of oxygen within mitochondria to generate ATP by oxidative phosphorylation & production of CO2 as a waste product. Non respiratory functions of the lungs: 1. Regulation of acid base balance. 65 2. Defense against pathogens. 3. Water & heat loss. 4. Increase venous return 5. Enhancing vocalization Air passes from pharynx to trachea to two main bronchi The bronchi repeatedly subdivide within the lungs, becoming smaller and changing in structure, until after 20 generation, the alveoli are reached. The total area of alveoli in contact of capillaries = 100 m2. The airways contain cartilage which gives their shape &support. They are surrounded by smooth muscle to allow change in diameter. Stimulation of vagus & histamine leads to bronchoconstriction. Stimulation of sympathetic leads to bronchodilatation through β2 receptors 66 o The alveoli contain the following cells: a) Type I cells overlying the basement membrane b) Type II cells which secretes surfactant. c) Alveolar macrophages which remove foreign particles inhaled in the lungs Pulmonary Ventilation - Air flows into or out of the lungs because of pressure gradients between the alveoli and the outside air (atmosphere). - The resting respiratory rate is 12-16 cycles/min - Tidal volume is the volume of air inspired or expired each cycle during rest equal 500 cc - Pulmonary ventilation = respiratory rate X tidal volume = 12 X 500 = 6000 c Mechanics of respiration 67 Each respiratory cycle is composed of: a- Inspiration b- Expiration ❖ Inspiration: 1. Inspiration is an active process 2. There is an increase in volume of thorax (increase all dimensions) 3. There is an increase in lung volume as it follows the thoracic wall. 4. There is decrease in intra-thoracic pressure (intrapleural) from -4 to -6 mmHg 5. There is decrease in intra-alveolar pressure to become – 1mmHg. 6. Air rushes in. The inspiratory muscles are: a. The diaphragm: It is the most important inspiratory muscle. It is supplied by phrenic nerve (3rd to 5th cervical segment). When it descends, it increases the vertical diameter. It is responsible for 75% of the change in chest volume 68  b. The external intercostal muscles: they run obliquely downward and forward from rib to rib. Contraction of external intercostal muscles increases: i. The lateral diameter by elevation of ribs. ii. Anteroposterior diameter by eversion of ribs. c. The accessory inspiratory muscles: contract only with deep (forced) inspiration. They are: i. Sternomastoid which lift the sternum. ii. Anterior serretai which lift many ribs. iii. Scaleni muscles which lift the first two ribs. ❖ Expiration: 1.Normally, expiration is a passive process. 2.It is due to elastic recoil of lungs & chest wall at end of inspiration 3.There is decrease in volume of thorax (decrease all dimensions due to relaxation of muscles) 4. There is decrease in lung volume. 5. Intra-thoracic pressure increases to -4 mmHg 6. Intra-alveolar pressureincreases to +1 mmH 7. Air forced out 8. Expiration becomes active: i. During forced expiration ii. In conditions of bronchial obstruction e.g bronchial asthma In such conditions, the expiratory muscles contract. Expiratory muscles are: a. Internal intercostal muscles which run obliquely downward and backward from rib to rib so, they pull ribs downward. 69  b. Abdominal muscles which when contract it increase intra- abdominal pressure and push diaphragm up. INSPIRATION EXPIRATTION Inspiration : active process Expiration : passive Thorax volume increase Thorax volume decrease Lung volume increase Lung volume decrease Intra pleural pressure decrease Intra pleural pressure increase Intra alveolar pressure decrease Intra alveolar pressure increase Inspiratory muscle Expiratory muscle - diaphragm only during forced expiration -external intercostal muscle internal intercostal muscle - accessory inspiratory abdominal muscle muscles > steromastoid > serratus anterior. > scaleni muscles. Pulmonary Ventilation Static Lung Volumes & Capacities: (1) Tidal volumes (5) Inspiratory capacity (2) Inspiratory reserve volume (6) Functional residual capacity (3)Expiratory reserve volume (7) Vital Capacity (4)Residual volume (8) Total Lung Capacity (A)Lung Volumes: 1. Tidal volume (TV): it is the volume of air inspired or expired each respiratory cycle during rest = 500 cc. 70 2. Inspiratory reserve volume (IRV): it is the maximum volume of air which can be inspired by deep inspiration after a normal inspiration. It equals 3000 cc. 3. Expiratory reserve volume (ERV): it is the maximum volume of air which can be expired by forced expiration after a normal expiration. It equals 1100 cc. 4.Residual volume (RV): it is the volume of air that remains in the lungs after forced maximal expiration. It equals 1200 cc. i.e. it cannot be expired. It can be expelled after opening the chest to allow the lung to collapse completely. (B) Lung capacities: more than one volume 71 1. Inspiratory capacity (IC): it is the maximal volume of air that can be inspired by deep inspiration after normal expiration It equals TV + IRV = 3500 cc 2. Functional residual capacity (FRC): it is the volume of air remaining in the lung after normal expiration (i.e. at the resting expiratory level). It equals ERV + RV = 2300 cc 3. Vital capacity (VC): it is the maximal volume of air that can be expired by a maximal expiration following a maximal inspiration It equals IRV + ERV + TC = 4600 cc 1. Total lung capacity (TLC): it is the maximal volume of air present in the lung after a maximal inspiration. It equals IRV + TV+ ERV + RV= 5800cc All pulmonary volumes and capacities: - 10 % less in females than in males - Greater in athletes. - Less in recumbent than in standing position - Can be measured by 2 ways: o By the spirometer: it can measure tidal volume, inspiratory reserve volume, expiratory reserve volume, inspiratory capacity and vital capacity. o By Dilution method: it can measure the residual volume, functional residual capacity and total lung capacity. 72 Digestive System 73  Digestive System Introduction The alimentary tract provides the body with water, electrolytes and nutrients. This is achieved by: movement of food in gastrointestinal tract (GIT), secretion of digestive juices, absorption of digestive products, and circulation of food through GIT & control of these functions by nerves & hormones. 74 Hormones of GIT Gastrin CCK Secretin GIP Site Antrum of Upper small Upper small Upper small stomach & upper intestine intestine intestine small intestine -Distension Polypeptide, Decline in pH < -Decline in pH Stimuli of secretion -Soup extract amino acids, 4.5 < 4.5 -Rise in pH fat, bile salts -CHO & fat -Vagus - stimulate Hcl -evacuation of -inhibits Hcl Actions -inhibits Hcl - trophic to gall bladder -stimulates GIT mucosa -stimulates -stimulates insulin. - contraction pancreatic pancreatic of LES enzymatic juice aqueous juice -potentiates - potentiates secretin CCK -inhibits gastric -inhibits gastric emptying emptying VIP Motilin Somatostatin Site Upper small intestine Upper small intestine Upper small intestine Stimulus Digestive products Digestive products Presence of Hcl -VD -contraction of LES Actions -stimulates intestinal -stimulates antral & -inhibits gastrin & secretion of H2O & duodenal motility secretion. electrolytes -inhibits pancreatic -inhibits Hcl secretion 75 Gastric secretion ❑ Volume: 2.5 –3 liters/day ❑ pH: highly acidic ❑ Constituents: -Water - Ions: H+, Cl-, And Na+ & K+: varies with rate of secretion. At low rate: Na+ is high & H+ is low, vice versa. - Enzymes: pepsinogen, gelatinase & lipase. - Mucus -Intrinsic factor for absorption of vitamin B12 ▪ Functions of Hcl: 1) Activation of pepsinogen to pepsin. 2) Provide optimum pH for action of pepsin. 3) Aids protein digestion. 4) Dissolves food particles changing them into chyme 5) Cause precipitation of milk in stomach, so milk is exposed for long time to pepsin. 6)Maintains relative sterility of the stomach (i.e kills the bacteria). 7)Helps in absorption of iron & calcium. ▪ Mechanism of acid secretion: 1) H-K+ ATPase in luminal or apical border of parietal cells pump H+ in exchange of K+. It occurs against concentration gradient & needs ATP. 2) CO2 + H2O carbonic anhydrase H2CO3 H+ pumped into Lumen HCO3 76 3) HCO3 is secreted into blood in exchange with Cl- (antiports) which are actively pumped to the lumen (HCO3 ATPase). This is called Cl- shift phenomenon. 4) H+ unites with Cl- in lumen to form Hcl. 5) H+ & Cl- in lumen draws H2O passively leading to iso-osmotic Hcl. *Alkaline tide: it is temporary increase in pH of blood and urine during Hcl secretion. This is because, for each molecule Hcl formed in the lumen, a molecule of NaHCO3 is formed in blood. ▪ Stimulation of acid secretion: (1)Nervous: Vagus & intrinsic plexus: -50% of nerve signals to stomach are through vagus, the other 50% are through local reflexes (enteric nervous system). (2)Gastrin: Look before. Gastrin stimulates Hcl secretion. It is stimulated by signals from vagus & local enteric reflexes.. (3)Histamine: comes from cells in mucosa that resembles mast cells. Small amount of histamine is a necessary cofactor for exciting significant acid secretion by acetyl choline or gastrin. 77  The histamine receptors are H2 & its mechanism of action is cAMP & can be blocked by cimetidine. (4)Prostaglandin (PGE2): inhibit acid secretion.. 78 Kidney 79  Kidney *Kidney Functions : The Kidney are largely responsible for maintenance of constant internal environment through: *Excretion of waste products: Urea, uric acid. *Control of volume, osmotic pressure and electrolyte content of the extracellular fluid. *Endocrine functions : a) Renin – Angiotensin mechanism which regulates ABP b) Erythropoieitin hormone which stimulates Erythropoeisis (so, there is anemia in Kidney diseases). c) Formation of 1-25 dihydrocholecalciferol which control Ca++ and PO4 Plasma levels *Regulation of arterial blood pressure: A) Short term: through renin angiotensin system. b) Long term: excretion of Na+ & H2O. 80 *Regulation of acid base balance: A) Elimination of acids e.g. sulphuric & phosphoric acids. b) Regulation of buffer stores. *Gluconeogenesis: during prolonged fasting. *Secretion of prostaglandins (PGE, PGI2) & bradykinin: they are paracrine hormones that regulate renal blood flow. Physiological Anatomy of the Kidney : - Nephron is the functional unit of kidney. There are 1.3 million nephrons in each human kidney 81 The Nephron consists of: (1)Renal corpuscle (2) Renal tubule: It is formed of: It is divided into: Glomerulus & Bowman capsule Proximal convoluted tub. Loop of Henle –distal convoluted tub. Formation of Urine Urine is a result of three processes: 1-glomerular filtration 2-tubular reabsorption. 3-tubular secretion 82 Glomerular Filtration Rate: GFR *Glomerular Filtrate: is the fluid that filters through glomeruli into Bowman's capsule. *Glomerular Filtration Rate: is the amount of glomerular filtrate formed each minute in all nephrons of both kidneys. It equals : 125 ml/min - 180 lit/day (kidney filters in one day a volume of fluid that equals 60 times that of plasma volume)- In women: it is 10% less. *Glomerular filtrate is an ultrafiltrate of plasma through the glomerular capillary membrane i.e material of colloidal size (plasma protein) or more are not filtered, only substances of small MW are present in filtrate in the same concentration as plasma. *Glomerular Capillary Membrane : is formed of 3 layers: 83 1) Capillary endothelium : which have wide pores called fenestra 70-90 nm in diameter (not barrier for plasma protein) 2) Basement membrane: which has no pores, it is negatively charged forming anionic sites that repel anions of plasma (e.g. plasma proteins). 3) Bowman’s capsule epithelium: formed of podocytes with slit pores (25nm) *Forces causing glomerular filtration: [I] Forces acting on glomerular membrane: (1)Hydrostatic pressure of glomerular capillary (HPGC)(60 mmHg) - It helps filtration. (2)Colloidal Osmotic Pressure of Bowman’s capsule (COBC) (zero) as no protein in Bowman’s capsule (protein is not filtered). It helps filtration. (3)Colloidal Osmotic Pressure of Glomerular capillary (COGC) average=32 mmHg This force opposes filtration due to the osmotic power of plasma proteins. (4)Hydrostatic pressure of Bowman’s capsule (HPBC)(18 mmHg): It opposes filtration... The Net filtering forces or the filtration pressure (NFF) NFF= CHP + COPB – (COPG + HPB) = 60 + 0 - (32 + 18) = 60 - 50 = 10 mmHg 84 Practical 85  Hemoglobin determination ( by Sahli's hemoglobin meter ) Clinical significance: 1. To diagnose anemia and it's types 2. To diagnose polycythemia Material: (1 ) Measuring tube with two scales (2)Sahli's pipette ( 3 )Housing containing comparator block: 1. Central compartment for sahli's tube. 2. 2 lateral compartments containing the standard colour (4) Distilled water (5) 0.1 HCl 86 Principle of the test: Hemoglobin is converted to acid hematin compound (brownish in color) by the action of hydrochloric acid. The higher the hemoglobin concentration, the more intense the hematin color will be. Procedure: 1) Place 0.1 HCl in the graduated sahli's tube to around 10% mark on the scale. 2) Sterilize your finger with alcohol and leave it to dry. 3) Puncture your finger with lancet. 4) Place the tip of sahli's pipette in the blood drop and gently suck a column of blood up to 20mm mark ( 0.02 ml ) 5) Clean the outside of the pipette from any blood. 6) Insert the tip of pipette beneath the surface of the HCl in the sahli's tube and gently blow out the blood. 7) Mix the blood and HCl. 8) Let the tube to stand for 10 minutes.( why ) To be sure that all RBCs are hemolysed by HCL To be sure that all Hb got out from RBCs and bind to HCL forming acid hematin 9) Hold the tube up to a light and add distilled water drop by drop to the acid hematin solution until its colour matches the colour of standard colour on the comparator. 10) Read the scale on the sahli's tube to obtain: a. Percentage of Hb. b. Grams of Hb per 100 ml blood. 87 Calculation: Mean corpuscular hemoglobin (MCH) = × 10 Mean corpuscular volume (MCV) = MCV = Questions: 1) What is the role of HCl in determination of HB content? a. Hemolysis of RBCs b. Reaction with hemoglobin forming acid hematin (dark brown in colour) 2) What is the normal hemoglobin content? a. Adult male 13-17 gm / dl b. Adult female 12-16 gm / dl c. Newly bon infant 18-20 gm / dl d. In children 12 gm / dl 88  Determination of packed cell volumes Hematocrite value ( PCV ) PCV: volume of packed RBCs in 100 ml blood Materials: Microhematoci t centrifuge Heparinized capillary tube Sterile lancet Alcohol Procedure: 1. Sterile the finger with alcohol and leave it to dry. 2. Puncture the finger using sterile lancet. 3. Touch the red- circled end of a heparinized capillary tube to blood drop 4. Hold the tube in a horizontal position and allow the blood to enter. 5. Seal one end of the tube by wax. 6. Place the capillary tube in centrifuge for 15 min 7. Read the tube by using hematocrite scale by : a. The tube is put vertically on the chart b. Move the tube on the chart horizontally with the lower end of the packed RBCs at { O } line and the upper end of the plasma at the oblique line { 100 } position c. Read upper level of RBCs. 89  Upper level of RBCs Upper level of plasma Lower level of RBCs (Hematocrite chart) Normal values Male 40 – 50 % Female 35 – 45 % Plasma Buff coloured layer on the top of RBCs (white blood cells and platelets) RBCs Conditions that increase PCV Conditions that decrease PCV Polycythemia Anemia Dehydration (burn – polyuria – Over hydration (as in chronic excessive sweating ) renal failure) 90  ESR ( Erythrocyte sedimentation rate ) Definition: It is the rate of sedimentation of RBCs in mm/Hr. when anti coagulated blood is allowed to stand. It is a nonspecific test for inflammation and tissue damage. Prognostic test not diagnostic test. Principle of the test: When freshly drawn blood is mixed with an anticoagulant so that it will remain fluid, the erythrocytes will gradually settle to the bottom of the tube. Specific gravity of RBCs (1090) is greater than that of plasma (1030). The sedimentation process takes place in three stages : o Aggregation of erythrocytes into rouleaux. o Rapid fall o Packing of the rouleaux at the bottom of the tube Factors promoting rouleaux formation: 1. Fibrinogen 2. Immunoglobulin ( gamma globulin ) Fibrinogen and immunoglobulin lead to change of the repellent electrostatic negative surface charge of RBCs → increased rouleaux formation → causing the cells to fall rapidly Methods of determination: ❖ Westergreen method : (Blood + Na citrate) Normal values First hour Second hour Male 5mm 8mm Female 10mm 16mm 91  The height of plasma column over sedimenting cells reflect ESR RBCs Causes of high ESR Causes of low ESR Physiological : Pathological : Menstruation Hypofibrinogenemia Pregnancy Polycythemia Lactation Pathological : Any inflammatory conditions Malignancy 92  Bleeding time Definition: it is the time needed for stoppage of bleeding from a small superficial wound without formation of blood clot. Affected by: Integrity of vascular wall Platelet count Platelet function Materials: 1. Lancets 2. Filter paper 3. Alcohol ( 70% ) 4. Stop – watch 5. Cotton pieces Procedure: 1. Clean the tip of your finger with 70% alcohol , then dry it with a piece of cotton 2. Puncture the finger with lancet and record the time by the stopwatch 3. Wipe the blood drop by a piece of filter paper every 15 seconds intervals 4. Do not touch your finger when wiping the blood away 5. Continue this procedure until no more blood stains appear on the filter paper which indicates the stoppage of bleeding. 6. Stop the watch Normal bleeding time: 1 - 3 minutes Conditions in which bleeding time is prolonged: Vascular defect Thrombocytopenia ( decrease number of platelet count = purpura ) Thromboasthenia ( platelet dysfunction) 93  Coagulation time Definition: it is the time needed for stoppage of bleeding from small superficial wound by formation of blood clot Affected by: Clotting factors Materials: 1. Non – heparinized capillary tubes 2. Lancets 3. Cotton 4. Alcohol 70 % Procedure: 1. Clean the finger with 70 % alcohol, and then dry it with a piece of cotton. 2. Prick the finger with a lancet and record the time 3. Rapidly draw the blood into a non – heparinized capillary tube by holding the tube in the drop of blood in a horizontal position 4. At 30 seconds intervals, break off a small piece of the tube and see if clotting has occurred. Normal coagulation time: 3 – 5 minutes Conditions in which coagulation time is prolonged : Liver diseases Vitamin K deficiency Hemophilia o Hemophilia A : deficiency of factor VIII o Hemophilia B : deficiency of factor IX o Hemophilia C : deficiency of factor XI Anticoagulant therapy ( heparin - Dicumarol ) 94  Determination of blood group ( blood typing ) The cell membrane of RBCs contains antigens called agglutinogen. The most important are agglutinogen of ABO system and Rh group. ABO system Blood type Agglutinogen (antigen ) Agglutinin (antibody) A A Anti B B B Anti A AB A,B None O None Anti A , Anti B Blood group O is universal donor. Blood group AB is universal recipient. Law of blood transfusion: During blood transfusion we consider only the RBCs of donor and plasma of the recipient.in order to prevent agglutination. Agglutination: Meeting of the antigen with its antibody this may lead to break of RBCs. Materials: 1. Lancet 2. Microscopic glass slides 3. Anti A , Anti B and Anti D Procedure: 1. Sterile your finger to obtain blood. 2. Place 1 drops on each end of the slide. 3. Add 1 drop of anti A to one drop of blood and 1 drop of anti B to the other blood drop. 4. Mix the blood and antiserum for 1 -2 min. 5. Observe the slide for any agglutination of red cells (agglutination looks like red pepper grains. 95 Results: 1. if agglutination occurs on side A only : ( you have blood type A ) 2. if it occurs on side B only : ( you have type B ) 3. if it occurs on both sides : ( you have type AB ) 4. if no reaction occurs on both sides : ( you have type O ) Rh system: 1. Mix 2 drops of your blood with one drop of Anti D on slide. 2. Observe the slide for any agglutination. +ve -ve Importance of blood group determination: 1. Safe blood transfusion 2. Medico - legal importance.( can confirm that a certain man is not the father of definite child. it is negative test ) 3. Rh incompatibility : (erythroblastosis fetalis ) Complication of incompatible blood transfusion: 1. Shock ( due to release of histamine and other vasodilators ) 2. Hyperkalemia resulting in cardiac arrhythmia 3. Hemolytic jaundice 4. Blockage of renal tubules resulting in renal failure. 96  References 1- Guyton and Hall Textbook of Medical Physiology, 13th Edition. 2- Ganong's Review of Medical Physiology, 25th Edition. 3- Essentials of Medical Physiology Book by K. Sembulingam and Prema Sembulingam. 4- Physiology Textbook by Linda S Costanzo. 5- Berne & Levy Physiology Book by Bruce A Stanton, Bruce M Koeppen, Matthew N. Levy, and Robert M. Berne. 6- Medical Physiology E-Book Textbook by Emile Boulpaep and Walter Boron. 97