General Mammalian Physiology – Paper I BZO5T09

Syllabus topics (RTMNU)

• Structure and functions of Digestive glands: Salivary, Gastric, Intestinal, Liver and Pancreas
• Digestion and Absorption of Food: Carbohydrates, Proteins and Lipids
• Regulation of Digestion: Neural regulation of digestion
• Hormonal regulation - Gastrointestinal hormones
• Gastrointestinal Disorder: Achalasia, Gastritis, Pancreatitis, Colitis, Irritable Bowel Syndrome (IBS), and peptic ulcers

Structure and Functions of Digestive Glands

Digestive glands are glands that pour digestive juices (enzymes, mucus, bile, HCl) into the alimentary canal to break food into simple absorbable forms.

1. Salivary glands: Three pairs in man – parotid (largest, in front of ear; serous), submandibular (mixed) and sublingual (mainly mucous). They are compound tubulo-alveolar glands with serous and mucous acini. They secrete about 1–1.5 litres of saliva daily (pH about 6.8). Saliva has salivary amylase (ptyalin), lingual lipase, mucin, lysozyme and water. Functions: starts starch digestion, moistens and lubricates food, helps speech and taste, kills bacteria.
2. Gastric glands: Tubular glands in the stomach mucosa. Cells: chief (peptic) cells secrete pepsinogen and gastric lipase; parietal (oxyntic) cells secrete HCl and intrinsic factor (needed for vitamin B₁₂ absorption); mucous neck cells secrete mucus; G cells secrete gastrin. Gastric juice is strongly acidic (pH 1.5–2).
3. Intestinal glands: Crypts of Lieberkühn (all along small intestine) and Brunner's glands (in duodenum submucosa; alkaline mucus to protect against acid). Succus entericus contains maltase, sucrase, lactase, peptidases, nucleotidases and enterokinase.
4. Liver: Largest gland of the body. Made of hexagonal hepatic lobules with central vein, hepatic cords and sinusoids; Kupffer cells are phagocytic. It secretes bile (bile salts, bile pigments – bilirubin and biliverdin, cholesterol), stored in the gall bladder. Other functions: glycogen storage, deamination and urea formation, detoxification, synthesis of plasma proteins (albumin, fibrinogen, prothrombin), storage of vitamins A, D, B₁₂ and iron.
5. Pancreas: Mixed (heterocrine) gland. Exocrine acini secrete pancreatic juice (trypsinogen, chymotrypsinogen, carboxypeptidase, pancreatic amylase, lipase, nucleases) rich in bicarbonate. Endocrine part – islets of Langerhans (α cells: glucagon, β cells: insulin, δ cells: somatostatin).

Digestion and Absorption of Carbohydrates, Proteins and Lipids

Digestion is the process of converting complex, non-absorbable food into simple, absorbable molecules by enzymes. Absorption is the passage of these products through the intestinal wall into blood or lymph.

Enterokinase activates trypsinogen into trypsin; trypsin then activates chymotrypsinogen and more trypsinogen. Water is absorbed mainly in the small intestine and partly in the colon.

Regulation of Digestion: Neural and Hormonal

Neural regulation: The enteric nervous system (myenteric plexus of Auerbach controls movements; submucosal plexus of Meissner controls secretion) works locally. The parasympathetic system (vagus nerve) increases secretion and motility; the sympathetic system decreases them. Gastric secretion occurs in three phases:

1. Cephalic phase: sight, smell, thought of food → vagus → gastric juice.
2. Gastric phase: food stretches stomach and peptides stimulate gastrin.
3. Intestinal phase: acid chyme in duodenum releases hormones that slow gastric activity.

Hormonal regulation – Gastrointestinal hormones:

Gastrointestinal Disorders

• Achalasia: The lower oesophageal sphincter fails to relax due to loss of nerve cells; food is not passed into stomach. Symptoms: difficulty in swallowing (dysphagia), regurgitation, chest pain.
• Gastritis: Inflammation of stomach lining; causes – Helicobacter pylori, alcohol, painkillers (NSAIDs), stress. Symptoms: burning pain, nausea, vomiting.
• Pancreatitis: Inflammation of the pancreas when enzymes become active inside it and digest the gland itself. Causes: gallstones, alcohol. Severe upper abdominal pain; raised serum amylase and lipase.
• Colitis: Inflammation of the colon (infection, ulcerative colitis); diarrhoea with blood or mucus, cramps.
• Irritable Bowel Syndrome (IBS): A functional disorder with abdominal pain, bloating, and alternating diarrhoea and constipation, without visible damage; linked to stress and gut sensitivity.
• Peptic ulcer: An open sore in the stomach (gastric ulcer) or duodenum (duodenal ulcer) caused by acid-pepsin attack when mucus protection fails; main causes H. pylori and NSAIDs.

Likely exam questions

1. (Long, 8 marks) Describe the structure and functions of the liver and pancreas as digestive glands.
2. (Long, 8 marks) Explain the digestion and absorption of carbohydrates, proteins and lipids in mammals.
3. (Short, 4 marks) Write a note on gastrointestinal hormones.
4. (Short, 4 marks) What is a peptic ulcer? Give its causes.
5. (Short, 4 marks) Explain the neural regulation of gastric secretion.

Syllabus topics (RTMNU)

• Respiratory Organs in Mammals: Structure of lungs, Bronchial tree, Alveoli and respiratory membrane
• Mechanism of Breathing: Inspiration and expiration, Role of diaphragm and intercostal muscles, Lung volumes and capacities
• Transport of Respiratory Gases: Transport of oxygen by haemoglobin, Oxygen dissociation curve, Transport of carbon dioxide, Regulation of blood pH
• Respiratory disorders: Acute disorder (Apnoea, Dyspnoea, Hypoxia, Hypercapnia) and Chronic disorder (Asthma, Chronic Obstructive Pulmonary Disease (COPD))

Respiratory Organs: Lungs, Bronchial Tree, Alveoli and Respiratory Membrane

Lungs are a pair of spongy, cone-shaped organs in the thoracic cavity, covered by a double membrane, the pleura (pleural fluid reduces friction). The right lung has three lobes and the left lung two lobes (with a cardiac notch).

Bronchial tree: trachea → two primary bronchi → secondary (lobar) bronchi → tertiary (segmental) bronchi → bronchioles → terminal bronchioles → respiratory bronchioles → alveolar ducts → alveolar sacs → alveoli. Trachea and bronchi are supported by C-shaped cartilage rings; bronchioles have no cartilage but smooth muscle. The conducting zone (nose to terminal bronchiole) warms, moistens and filters air; the respiratory zone exchanges gases.

Alveoli: About 300 million tiny air sacs in both lungs, giving a huge surface area (about 70–100 m²). Wall has Type I pneumocytes (thin, for gas exchange), Type II pneumocytes (secrete surfactant, which lowers surface tension and prevents collapse) and alveolar macrophages (dust cells).

Respiratory membrane: The thin barrier (about 0.5 µm) between alveolar air and blood. Layers: alveolar fluid with surfactant, alveolar epithelium, its basement membrane, interstitial space, capillary basement membrane and capillary endothelium. Gases cross it by simple diffusion.

Mechanism of Breathing

Breathing (pulmonary ventilation) is the movement of air into (inspiration) and out of (expiration) the lungs due to pressure differences created by changes in thoracic volume.

1. Inspiration (active): The diaphragm contracts and becomes flat; external intercostal muscles contract and lift ribs and sternum up and out. Thoracic volume increases → intrapulmonary pressure falls below atmospheric → air rushes in.
2. Expiration (normally passive): Diaphragm and external intercostals relax; elastic recoil of lungs reduces volume → pressure rises above atmospheric → air goes out. In forced expiration, internal intercostals and abdominal muscles contract.

Lung volumes and capacities (normal adult values, approximate):

The instrument used is the spirometer.

Transport of Oxygen and the Oxygen Dissociation Curve

About 97% of O₂ is carried by haemoglobin as oxyhaemoglobin; only about 3% is dissolved in plasma. Each Hb molecule has four haem groups and binds four O₂ molecules: Hb + 4O₂ ⇌ Hb(O₂)₄. 100 mL of blood carries about 20 mL O₂.

Oxygen dissociation curve (ODC): a graph of % saturation of Hb against partial pressure of oxygen (pO₂). It is sigmoid (S-shaped) because binding of one O₂ makes binding of the next easier (cooperative binding). At pO₂ 100 mm Hg (alveoli) Hb is about 97% saturated; at 40 mm Hg (tissues) about 75%.

• Shift to the right (O₂ released more easily): high pCO₂, high H⁺ (low pH), high temperature, high 2,3-BPG. The effect of CO₂/pH is the Bohr effect.
• Shift to the left: the opposite conditions; foetal Hb also has a left-shifted curve.

Transport of Carbon Dioxide and Regulation of Blood pH

1. Dissolved in plasma – about 7%.
2. As carbamino-haemoglobin (CO₂ bound to amino groups of Hb) – about 23%.
3. As bicarbonate ions – about 70%. In RBCs, carbonic anhydrase speeds: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻. HCO₃⁻ moves to plasma and Cl⁻ moves into the RBC – the chloride shift (Hamburger phenomenon). H⁺ is buffered by Hb.

Deoxygenated Hb carries more CO₂ – the Haldane effect.

Regulation of blood pH (normal 7.35–7.45): by buffers (bicarbonate–carbonic acid, phosphate, proteins including Hb), by the lungs (more breathing removes CO₂ and raises pH) and by the kidneys (excrete H⁺, reabsorb HCO₃⁻).

Respiratory Disorders

Acute disorders:

• Apnoea: temporary stopping of breathing (e.g., sleep apnoea).
• Dyspnoea: difficult or laboured breathing, shortness of breath.
• Hypoxia: shortage of oxygen at tissue level (e.g., at high altitude, anaemia, CO poisoning).
• Hypercapnia: excess CO₂ in blood, causing acidosis, headache, drowsiness.

Chronic disorders:

• Asthma: allergic inflammation and spasm of bronchioles with extra mucus; wheezing and breathlessness. Triggers: dust, pollen, smoke. Treated by bronchodilators and inhaled steroids.
• COPD: long-term, mostly irreversible blockage of airflow – includes chronic bronchitis and emphysema (alveolar walls destroyed). Main cause: smoking and smoke from chulhas or industry.

Likely exam questions

1. (Long, 8 marks) Describe the mechanism of breathing and explain lung volumes and capacities.
2. (Long, 8 marks) Explain the transport of oxygen and carbon dioxide in blood. Add a note on the oxygen dissociation curve.
3. (Short, 4 marks) Describe the structure of the respiratory membrane.
4. (Short, 4 marks) What is chloride shift?
5. (Short, 4 marks) Write a note on asthma and COPD.

Syllabus topics (RTMNU)

• Blood: Composition and functions of blood
• Mechanism of blood clotting – intrinsic and extrinsic factors
• Heart and Cardiac Cycle: Structure of mammalian heart, Cardiac cycle
• Electrocardiogram (ECG) and Blood Pressure: Electrocardiogram (ECG), Blood pressure and its regulation, Hypertension and hypotension
• Lymphatic System: Composition and functions of lymph, Lymphatic vessels and organs

Blood: Composition and Functions

Blood is a fluid connective tissue made of plasma and formed elements, circulating in a closed system of vessels. An adult has about 5–6 litres of blood (about 7–8% of body weight); pH 7.35–7.45.

1. Plasma (about 55%): 90–92% water; plasma proteins (albumin – osmotic pressure; globulins – immunity and transport; fibrinogen and prothrombin – clotting); glucose, amino acids, lipids, salts, hormones, urea, gases.
2. Formed elements (about 45%):
   • RBCs (erythrocytes): biconcave, non-nucleated in mammals, contain haemoglobin; about 5 million/mm³; life about 120 days; carry O₂ and CO₂.
   • WBCs (leucocytes): 6000–8000/mm³; granulocytes (neutrophils – phagocytosis, eosinophils – allergy, basophils – heparin and histamine) and agranulocytes (lymphocytes – antibodies, monocytes – phagocytosis).
   • Platelets (thrombocytes): cell fragments, 1.5–4 lakh/mm³; help clotting.

Functions: transport of gases, nutrients, hormones and wastes; defence (immunity); clotting; regulation of temperature, pH and water balance.

Mechanism of Blood Clotting – Intrinsic and Extrinsic Pathways

Blood clotting (coagulation) is the change of liquid blood into a jelly-like clot to stop bleeding. It needs 13 clotting factors (I to XIII; factor VI is not used), calcium ions (factor IV) and vitamin K (for making prothrombin and factors VII, IX, X in the liver).

1. Extrinsic pathway: starts when damaged tissue releases tissue factor (thromboplastin, factor III). It acts with factor VII and Ca²⁺ to activate factor X. It is fast (seconds).
2. Intrinsic pathway: starts inside blood when factor XII contacts exposed collagen or a rough surface. Cascade: XII → XI → IX (with VIII, Ca²⁺, platelet phospholipid) → activates X. It is slower (minutes).
3. Common pathway: Activated factor X with factor V, Ca²⁺ and phospholipid forms prothrombin activator → Prothrombin → Thrombin → Fibrinogen (soluble) → Fibrin (insoluble threads). Factor XIII stabilises fibrin. Fibrin threads trap blood cells to form the clot; the clot then retracts and squeezes out serum.

Structure of Mammalian Heart

The heart is a hollow, muscular, four-chambered pump in the mediastinum, enclosed in a double pericardium. Wall layers: epicardium, myocardium (cardiac muscle) and endocardium.

• Chambers: two thin-walled atria (receive blood) and two thick-walled ventricles (pump blood); left ventricle has the thickest wall.
• Valves: tricuspid (right AV), bicuspid/mitral (left AV), held by chordae tendineae and papillary muscles; semilunar valves at the bases of the pulmonary artery and aorta.
• Vessels: superior and inferior vena cava → right atrium; pulmonary veins → left atrium; pulmonary artery from right ventricle; aorta from left ventricle.
• Conducting system: SA node (pacemaker, in right atrium wall) → AV node → bundle of His → right and left bundle branches → Purkinje fibres. The mammalian heart is myogenic.

Cardiac Cycle

The cardiac cycle is the sequence of events in one heartbeat, from the start of one beat to the start of the next. At 72 beats/min it lasts about 0.8 s.

1. Atrial systole (0.1 s): atria contract and push the last 20–30% of blood into ventricles.
2. Ventricular systole (0.3 s): AV valves close (first heart sound "lubb"); isovolumetric contraction; then semilunar valves open and blood is ejected (ejection phase).
3. Ventricular diastole / joint diastole (0.4 s): semilunar valves close (second sound "dupp"); isovolumetric relaxation; AV valves open and ventricles fill.

Stroke volume is about 70 mL; cardiac output = stroke volume × heart rate ≈ 70 × 72 ≈ 5 litres/min.

Electrocardiogram (ECG)

An ECG is a graphic record of the electrical activity of the heart taken from the body surface by an electrocardiograph.

• P wave: atrial depolarisation.
• QRS complex: ventricular depolarisation (atrial repolarisation is hidden in it).
• T wave: ventricular repolarisation.
• P–R interval (0.12–0.2 s): time for impulse from SA node to ventricles; longer in heart block.

Uses: detecting heart attack (myocardial infarction), arrhythmias and heart blocks.

Blood Pressure, its Regulation, Hypertension and Hypotension

Blood pressure is the force exerted by blood on the walls of arteries. Normal adult value is about 120/80 mm Hg (systolic/diastolic), measured by a sphygmomanometer. Pulse pressure = systolic − diastolic = 40 mm Hg.

Regulation: (1) Nervous – baroreceptors in carotid sinus and aortic arch send impulses to the cardiovascular centre in the medulla; vagus slows the heart, sympathetic nerves raise heart rate and constrict vessels. (2) Hormonal – adrenaline, noradrenaline, renin–angiotensin–aldosterone system, ADH raise BP; ANP lowers it. (3) Renal – control of blood volume.

Hypertension: BP persistently at or above about 140/90 mm Hg; risk of stroke, heart and kidney damage. Hypotension: BP below about 90/60 mm Hg; dizziness, fainting (seen in shock, blood loss).

Lymphatic System

Lymph is a colourless fluid formed from tissue fluid, containing lymphocytes, proteins and fats, but no RBCs and few platelets. Functions: returns tissue fluid and proteins to blood, absorbs fats (chylomicrons through lacteals), defence through lymphocytes.

Lymphatic vessels: lymph capillaries → lymphatic vessels (with valves) → thoracic duct (opens into left subclavian vein) and right lymphatic duct (into right subclavian vein).

Lymphatic organs: primary – bone marrow and thymus (produce and mature lymphocytes); secondary – lymph nodes (filter lymph), spleen (filters blood, destroys old RBCs), tonsils and Peyer's patches.

Likely exam questions

1. (Long, 8 marks) Describe the mechanism of blood clotting with reference to intrinsic and extrinsic pathways.
2. (Long, 8 marks) Describe the structure of the mammalian heart and explain the cardiac cycle.
3. (Short, 4 marks) Write a note on ECG.
4. (Short, 4 marks) Explain the regulation of blood pressure.
5. (Short, 4 marks) Give the composition and functions of lymph.

Syllabus topics (RTMNU)

• Structure of Mammalian Kidney: External and internal structure, Nephron structure, Blood supply of kidney, Juxtaglomerular apparatus
• Formation of Urine: Glomerular filtration, Tubular reabsorption, Tubular secretion, Counter-current mechanism, Dialysis
• Regulation of Urine Formation: Role of ADH, Role of aldosterone, Role of Angiotensin
• Regulation of water and electrolyte balance, Acid–base balance
• Disorders of Excretory System: Uremia, Renal failure, Nephritis, Renal Calculi (Kidney stones), Ketonuria

Structure of Mammalian Kidney

Kidneys are a pair of bean-shaped, reddish-brown organs on either side of the vertebral column at the back of the abdominal cavity, each about 10–12 cm long.

External structure: outer concave border has a notch, the hilum, through which renal artery, renal vein, nerves and ureter pass. Covered by a fibrous renal capsule.

Internal structure (L.S.): outer cortex and inner medulla. Medulla has 8–18 conical renal pyramids; cortex extends between them as columns of Bertini. Pyramids open by papillae into minor calyces → major calyces → renal pelvis → ureter.

Nephron: the structural and functional unit of the kidney (about 1 million per kidney). Parts:

1. Renal corpuscle (Malpighian body): Bowman's capsule (double-walled cup; inner wall of podocytes) + glomerulus (tuft of capillaries).
2. Proximal convoluted tubule (PCT): cuboidal cells with brush border.
3. Loop of Henle: descending and ascending limbs dipping into medulla.
4. Distal convoluted tubule (DCT) → opens into collecting duct.

Cortical nephrons have short loops; juxtamedullary nephrons have long loops and help concentrate urine.

Blood supply: renal artery → segmental → interlobar → arcuate → interlobular arteries → afferent arteriole → glomerulus → efferent arteriole (narrower, keeps pressure high) → peritubular capillaries and vasa recta → renal vein.

Juxtaglomerular apparatus (JGA): formed where DCT touches the afferent arteriole. It has juxtaglomerular cells (in the afferent arteriole wall; secrete renin), macula densa (special DCT cells sensing Na⁺) and extraglomerular mesangial cells. It controls GFR and blood pressure.

Formation of Urine

1. Glomerular filtration: Blood is filtered under pressure from glomerulus into Bowman's capsule (ultrafiltration). Net filtration pressure ≈ glomerular hydrostatic pressure (about 55–60 mm Hg) − (colloidal osmotic pressure about 30 + capsular pressure about 15–20) ≈ 10 mm Hg. GFR is about 125 mL/min or 180 L/day. Filtrate has everything of plasma except proteins and cells.
2. Tubular reabsorption: About 99% of filtrate is reabsorbed. PCT reabsorbs all glucose and amino acids, about 65–70% of Na⁺ and water, HCO₃⁻. Descending limb – permeable to water; ascending limb – impermeable to water, pumps out Na⁺ and Cl⁻. DCT and collecting duct reabsorb water and Na⁺ under hormonal control.
3. Tubular secretion: Tubule cells add H⁺, K⁺, NH₃, creatinine and drugs (penicillin) from blood into the filtrate; helps pH and ionic balance.

Counter-current Mechanism and Dialysis

The counter-current mechanism lets mammals make concentrated (hypertonic) urine. Filtrate flows in opposite directions in the two limbs of the loop of Henle (counter-current multiplier), and blood flows in opposite directions in the vasa recta (counter-current exchanger). NaCl pumped out of the ascending limb and urea recycled from the collecting duct build an increasing osmotic gradient in the medulla, from about 300 mOsm/L in cortex to about 1200 mOsm/L in inner medulla. When ADH is present, water leaves the collecting duct into this hypertonic medulla and urine becomes concentrated.

Dialysis (haemodialysis): an artificial kidney method for patients with kidney failure. Blood from an artery is passed (with heparin) through a cellophane tube in dialysing fluid that has the same composition as plasma but no wastes. Urea and other wastes diffuse out; cleaned blood returns to a vein with anti-heparin. Peritoneal dialysis uses the peritoneum as the membrane.

Regulation of Urine Formation: ADH, Aldosterone and Angiotensin

• ADH (vasopressin): made in hypothalamus, released from posterior pituitary when blood becomes concentrated. It inserts water channels (aquaporins) in DCT and collecting duct → more water reabsorbed → less, concentrated urine. Lack of ADH causes diabetes insipidus.
• Renin–Angiotensin–Aldosterone system (RAAS): Fall in BP or Na⁺ → JG cells release renin → angiotensinogen (from liver) → angiotensin I → (ACE in lungs) → angiotensin II. Angiotensin II constricts vessels, raises BP, and stimulates adrenal cortex to release aldosterone, which increases Na⁺ reabsorption and K⁺ secretion in DCT; water follows sodium.
• ANP from the heart atria does the opposite: more Na⁺ and water loss.

Water and electrolyte balance is maintained by thirst, ADH and aldosterone. Acid–base balance: kidneys secrete H⁺ (buffered by phosphate and ammonia) and reabsorb or produce new HCO₃⁻, keeping blood pH 7.35–7.45.

Disorders of the Excretory System

• Uremia: accumulation of urea and other nitrogen wastes in blood due to kidney failure; nausea, fatigue, confusion; treated by dialysis.
• Renal failure: kidneys fail to filter blood. Acute – sudden (shock, dehydration, toxins), often reversible; chronic – slow, progressive (diabetes, hypertension); may need dialysis or kidney transplant.
• Nephritis (glomerulonephritis): inflammation of glomeruli, often after streptococcal infection; protein and blood in urine, swelling, high BP.
• Renal calculi (kidney stones): hard crystals of calcium oxalate, uric acid or phosphate in kidney or ureter; severe pain (renal colic), blood in urine. Prevention: plenty of water.
• Ketonuria: presence of ketone bodies (acetone, acetoacetic acid) in urine; seen in uncontrolled diabetes mellitus and starvation.

Likely exam questions

1. (Long, 8 marks) Describe the structure of a nephron and explain the mechanism of urine formation.
2. (Long, 8 marks) Explain the hormonal regulation of urine formation with reference to ADH, aldosterone and angiotensin.
3. (Short, 4 marks) Write a note on the counter-current mechanism.
4. (Short, 4 marks) What is the juxtaglomerular apparatus?
5. (Short, 4 marks) Write short notes on renal calculi and uremia.