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Claude Bernard called the extracellular fluid the milieu interieur. Homeostasis is the maintenance of its variables (temperature, pH, glucose, ions, blood pressure) within narrow limits. A control system has a sensor, an integrating centre with a set point, and an effector. Negative feedback opposes a change and is the main mechanism. Gain measures how strongly the system corrects: gain = correction / remaining error. Positive feedback amplifies a change (childbirth, the upstroke of the action potential, blood clotting). Local control acts within a tissue (metabolic vasodilation) while reflex control involves nervous or hormonal pathways to distant effectors.

Structure: a preganglionic neuron (cell body in the CNS) synapses in an autonomic ganglion on a postganglionic neuron that reaches the effector. - Sympathetic: thoracolumbar outflow (T1-L2), short preganglionic and long postganglionic fibres, ganglia in the paravertebral chain and prevertebral ganglia. - Parasympathetic: craniosacral outflow (cranial nerves III, VII, IX, X and S2-S4), long preganglionic and short postganglionic fibres, ganglia near or in the target organ. Neurotransmitters: all preganglionic fibres and parasympathetic postganglionic fibres release acetylcholine (nicotinic receptors in ganglia, muscarinic at effectors). Most sympathetic postganglionic fibres release noradrenaline (alpha and beta receptors); sweat glands are sympathetic but cholinergic. The adrenal medulla is a modified ganglion releasing adrenaline. Afferent fibres and the central autonomic network (hypothalamus, brainstem nuclei such as the nucleus of the solitary tract) integrate reflexes. The divisions can antagonise (heart rate), cooperate (salivary glands, sexual function) or act alone (vascular tone, sweating is sympathetic only).

1. Define negative feedback and give an example. 2. What is the difference in ganglion location between the two divisions? 3. Which transmitter do preganglionic fibres release? 4. Give an organ innervated only by the sympathetic system.

1. A response that opposes the change that triggered it, for example baroreflex control of blood pressure. 2. Sympathetic ganglia are near the spinal cord; parasympathetic ganglia are near or within the target organ. 3. Acetylcholine. 4. Sweat glands, most blood vessels, or the adrenal medulla.

Conduction system: sinoatrial (SA) node (fastest pacemaker, about 70 beats per minute), internodal pathways, atrioventricular (AV) node (delay of about 0.1 s allowing ventricular filling), bundle of His, bundle branches, Purkinje fibres. Nodal action potential: no stable resting potential. The pacemaker (funny) current If through HCN4 channels slowly depolarises the cell, followed by T-type then L-type calcium channels for the upstroke, and potassium channels for repolarisation. Sympathetic stimulation increases If and heart rate; vagal acetylcholine decreases it. Ventricular action potential (about 250-300 ms) - Phase 0: rapid Na+ entry. - Phase 1: brief K+ efflux. - Phase 2 (plateau): Ca2+ entry through L-type channels balanced by K+ efflux. - Phase 3: repolarisation by K+ efflux. - Phase 4: resting potential about -90 mV. The long refractory period prevents tetanic contraction.

Cardiac myocytes contain sarcomeres (actin and myosin), T-tubules and a sarcoplasmic reticulum, and are joined by intercalated discs with gap junctions. Sequence: the action potential opens L-type calcium channels in T-tubules, a small calcium entry triggers calcium-induced calcium release through ryanodine receptors, cytosolic Ca2+ binds troponin C, tropomyosin moves and cross-bridges cycle. Relaxation: calcium is pumped back by SERCA (into the SR) and removed by the Na/Ca exchanger. Cardiac glycosides (digoxin) inhibit the Na/K pump, raising intracellular calcium and force.

Phases of the left ventricle 1. Atrial contraction (adds about 20 percent of filling). 2. Isovolumetric contraction: pressure rises with all valves closed; mitral valve closes (first heart sound S1). 3. Rapid ejection: aortic valve opens when ventricular pressure exceeds aortic pressure. 4. Reduced ejection, then aortic valve closure (second heart sound S2). 5. Isovolumetric relaxation. 6. Rapid filling after the mitral valve opens. End-diastolic volume is about 120 mL, end-systolic volume about 50 mL, so stroke volume is about 70 mL and ejection fraction about 60 percent. Heart sounds: S1 (AV valve closure) and S2 (semilunar valve closure). S3 in rapid filling can be normal in the young or indicate heart failure. Murmurs are turbulent flow across stenotic or leaking valves. The jugular venous pulse shows a, c and v waves.

Waves: P wave (atrial depolarisation), QRS complex (ventricular depolarisation), T wave (ventricular repolarisation). PR interval (0.12-0.20 s) reflects AV conduction delay; QT interval reflects ventricular action potential duration. Leads: the 12-lead ECG has three bipolar limb leads (I, II, III), three augmented limb leads (aVR, aVL, aVF) and six precordial leads (V1-V6), viewing the heart from different directions. A wave is positive when the depolarisation wave moves toward the positive electrode. Mean electrical axis: the mean vector of the QRS in the frontal plane, normally between -30 and +90 degrees. Clinical tip: ST elevation indicates myocardial infarction, absent P waves with irregular rhythm indicates atrial fibrillation, and a prolonged PR interval indicates AV block.

Cardiac output (CO) = heart rate x stroke volume, about 5 L/min at rest. Stroke volume determinants - Preload (end-diastolic volume): the Frank-Starling law says that greater filling gives a stronger contraction, until an optimum. - Afterload: the arterial pressure the ventricle must overcome. - Contractility (inotropic state): increased by sympathetic stimulation (beta1 receptors), decreased by heart failure. Heart rate: sympathetic (positive chronotropic) and vagal (negative). Resting tone is mainly vagal. Measurement: Fick principle (CO = oxygen consumption / arteriovenous oxygen difference), indicator dilution, thermodilution catheters, and echocardiography. Integration: cardiac output and venous return are equal in steady state, which is why filling and pumping are coupled.

1. What causes the pacemaker potential of the SA node? 2. Which phase of the ventricular action potential gives the plateau? 3. What events cause S1 and S2? 4. What does the QRS complex represent? 5. State the Frank-Starling law. 6. How is cardiac output measured with the Fick principle?

1. The funny current If through HCN channels, then calcium currents. 2. Phase 2, from L-type calcium entry. 3. S1: closure of AV valves. S2: closure of aortic and pulmonary valves. 4. Ventricular depolarisation. 5. Within limits, the greater the end-diastolic volume, the greater the stroke volume. 6. CO equals oxygen consumption divided by the arteriovenous oxygen content difference.

Composition: plasma (about 55 percent) and cells. Plasma is 90 percent water with electrolytes, nutrients, hormones and proteins: albumin (oncotic pressure, transport), globulins (transport, antibodies) and fibrinogen (clotting). Cells: red cells (haematocrit about 45 percent), white cells and platelets. Functions: transport of gases, nutrients and hormones; homeostasis (temperature, pH, osmolarity); defence; haemostasis.

Darcy's law: flow Q = (P1 - P2)/R. Poiseuille: resistance is proportional to viscosity times length and inversely proportional to the fourth power of the radius, so a small change in vessel radius has a large effect on flow. Velocity = flow / cross-sectional area. Total cross-sectional area is largest in the capillaries, so velocity is lowest there, allowing exchange. Flow patterns: laminar (quiet) and turbulent (noisy; Reynolds number above about 2000), for example murmurs and Korotkoff sounds. Bernoulli's principle relates pressure, velocity and height.

Arteries (compliance, pressure reservoir) -> arterioles (main site of resistance, adjustable) -> capillaries (exchange) -> venules and veins (capacitance vessels holding about 65 percent of blood volume). Arterial pressure: systolic about 120, diastolic about 80 mmHg; mean pressure = diastolic + one third of pulse pressure. Pulse pressure depends on stroke volume and arterial compliance. Capillary types: continuous, fenestrated, sinusoidal. Exchange by diffusion (main mechanism), transcytosis and filtration. Starling forces: filtration occurs where capillary hydrostatic pressure exceeds plasma oncotic pressure (arteriolar end), and reabsorption where oncotic pressure predominates (venular end). Excess fluid returns via lymphatics. Oedema results from raised hydrostatic pressure, low albumin, increased permeability or lymph blockage.

Local control: the myogenic response (vessels contract when stretched), metabolic vasodilation (adenosine, CO2, K+, H+, lactate, low O2), endothelial factors (nitric oxide dilates, endothelin constricts) and autoregulation of flow. Systemic control: sympathetic vasoconstrictor tone, circulating hormones (angiotensin II, vasopressin, adrenaline, natriuretic peptides). Baroreflex: baroreceptors in the carotid sinus and aortic arch detect stretch and signal via the glossopharyngeal and vagus nerves to the nucleus of the solitary tract. A fall in pressure reduces baroreceptor firing, which raises sympathetic activity and lowers vagal tone (increased heart rate, contractility and vasoconstriction). Long-term control is by the kidney (fluid balance) and the renin-angiotensin-aldosterone system. Blood pressure = cardiac output x total peripheral resistance.

- Coronary: flow occurs mainly in diastole (during systole the myocardium compresses the vessels), extraction of oxygen is already near maximal so more flow is needed with more work (metabolic control by adenosine). - Skeletal muscle: flow rises up to 20-fold in exercise through metabolic vasodilation; muscle pump helps venous return. - Cerebral: strong autoregulation, sensitive to CO2 (hypercapnia dilates), constant flow whatever the posture. - Cutaneous: main role is thermoregulation. Heat causes vasodilation and sweating; cold causes sympathetic vasoconstriction to conserve heat. Body temperature is regulated at about 37 degrees Celsius by the hypothalamus.

1. Why is arteriolar radius the major determinant of resistance? 2. Where is velocity of blood lowest and why? 3. Describe the Starling forces in a capillary. 4. What is the baroreflex response to a sudden fall in blood pressure? 5. When does the left ventricle receive most of its coronary flow?

1. Resistance varies with the inverse fourth power of the radius, and arterioles are muscular and adjustable. 2. In the capillaries, because their total cross-sectional area is the largest. 3. Filtration at the arteriolar end from hydrostatic pressure, reabsorption at the venular end from oncotic pressure. 4. Increased sympathetic activity and decreased vagal tone: higher heart rate, contractility and vasoconstriction. 5. In diastole.

Lung volumes: tidal volume (about 500 mL), inspiratory and expiratory reserve volumes, residual volume. Capacities: vital capacity, functional residual capacity (FRC, where lung recoil balances chest wall recoil), total lung capacity. Residual volume and FRC need a gas dilution or body plethysmography method. Mechanics: inspiration is active (diaphragm, external intercostals), quiet expiration is passive. Intrapleural pressure is negative (about -5 cmH2O at FRC). Compliance = change in volume / change in pressure. Reduced in fibrosis, increased in emphysema. Surfactant (made by type II pneumocytes) lowers surface tension, prevents alveolar collapse (Laplace law) and increases compliance. Its deficiency causes neonatal respiratory distress syndrome.

Flow = pressure difference / resistance. Flow is laminar in small airways and turbulent in the trachea and large bronchi. The main site of resistance is the medium bronchi, not the smallest airways, because their total cross-section is so large. Dynamic compression: during forced expiration, high pleural pressure compresses airways, which limits flow (effort independent). In obstructive disease (asthma, COPD) FEV1/FVC is reduced; in restrictive disease FEV1 and FVC fall proportionally with a normal or high ratio.

Minute ventilation = tidal volume x rate. Alveolar ventilation = (tidal volume minus dead space) x rate. Anatomical dead space is about 150 mL. Alveolar gas equation: PAO2 = PIO2 - PaCO2/R, with PIO2 about 150 mmHg at sea level. Alveolar PO2 is about 100 mmHg and PCO2 about 40 mmHg. Diffusion: proportional to area and the partial pressure gradient, inversely to barrier thickness. Oxygen equilibrates in about a third of the capillary transit time at rest, so it is normally perfusion limited. Carbon monoxide is diffusion limited and is used to measure diffusing capacity (DLCO). Diffusion is impaired in fibrosis and emphysema.

Oxygen: dissolved O2 is only 0.3 mL per 100 mL blood, while haemoglobin carries 1.34 mL per gram. Oxygen content = 1.34 x Hb x saturation + 0.003 x PO2. The oxygen-haemoglobin dissociation curve is sigmoid because of cooperativity. It shifts right (lower affinity, easier unloading) with increased CO2, H+ (Bohr effect), temperature and 2,3-BPG, and shifts left in the opposite conditions and with fetal haemoglobin. Carbon monoxide binds haemoglobin 240 times more tightly and shifts the curve left. Carbon dioxide: about 70 percent as bicarbonate (carbonic anhydrase in red cells, chloride shift), 20 percent as carbamino compounds, 10 percent dissolved. The Haldane effect: deoxygenated blood carries more CO2.

Pulmonary artery pressure is about 25/8 mmHg. Resistance falls with recruitment and distension of capillaries. Hypoxic pulmonary vasoconstriction diverts blood from poorly ventilated regions (the opposite of systemic vessels). Blood flow is greatest at the base because of gravity. Ventilation-perfusion ratio: ideal V/Q is about 0.8 overall. V/Q zero is shunt (perfusion without ventilation; not corrected by 100 percent oxygen), V/Q infinity is dead space. Causes of hypoxaemia: hypoventilation, diffusion limitation, V/Q mismatch, shunt.

Rhythm generation: pre-Botzinger complex in the medulla, with dorsal and ventral respiratory groups. The pontine respiratory group modulates the pattern. Chemoreceptors: central (medulla) respond to H+ from CO2 in cerebrospinal fluid, and are the main drive at rest. Peripheral (carotid and aortic bodies) respond to low PaO2 (below about 60 mmHg), high PaCO2 and low pH. Lung stretch receptors (Hering-Breuer reflex) and irritant receptors adjust breathing further. Clinical tip: in chronic CO2 retention (severe COPD) the hypoxic drive becomes important, so high-flow oxygen can cause hypoventilation.

1. Define FRC and explain why it is the resting lung volume. 2. What is the role of surfactant? 3. Why does carbon monoxide shift the oxygen dissociation curve to the left? 4. List the four causes of hypoxaemia. 5. Where is the peripheral chemoreceptor located and what does it detect?

1. Volume in the lungs at the end of quiet expiration, where inward lung recoil equals outward chest wall recoil. 2. It lowers surface tension, prevents collapse and increases compliance. 3. It binds haemoglobin with high affinity and increases affinity of the remaining sites. 4. Hypoventilation, diffusion limitation, V/Q mismatch, shunt. 5. Carotid and aortic bodies; they detect low PaO2, high PaCO2 and low pH.

The filtration barrier consists of fenestrated endothelium, the basement membrane and podocyte slit diaphragms. Size and negative charge determine what passes: albumin is largely excluded. GFR = Kf x (hydrostatic pressure in the capillary minus hydrostatic pressure in Bowman space minus oncotic pressure of plasma). Normal GFR is about 125 mL/min (180 L/day). Renal plasma flow is about 600 mL/min; filtration fraction is about 20 percent. Autoregulation keeps GFR stable for mean pressures of about 80-180 mmHg by the myogenic response and tubuloglomerular feedback (macula densa detects NaCl delivery and adjusts the afferent arteriole). Efferent constriction (angiotensin II) preserves GFR when pressure is low.

- Proximal tubule: reabsorbs about 65 percent of filtered sodium and water, nearly all glucose and amino acids (glucose by SGLT2, with a transport maximum), most bicarbonate. - Loop of Henle: the thin descending limb is water permeable, the thick ascending limb reabsorbs Na-K-2Cl (loop diuretic target) and is water impermeable, generating the medullary gradient. - Distal tubule: NaCl reabsorption (thiazide target) and calcium regulation by PTH. - Collecting duct: principal cells reabsorb sodium (aldosterone) and water (ADH through aquaporin-2) and secrete potassium; intercalated cells regulate acid-base. Clearance = urinary concentration x urine flow / plasma concentration. Inulin (and creatinine approximately) measures GFR; PAH clearance measures renal plasma flow.

Plasma osmolarity is held near 290 mOsm/kg. When osmolarity rises, osmoreceptors in the hypothalamus release ADH (vasopressin) and cause thirst. ADH inserts aquaporin-2 in collecting duct cells, so water is reabsorbed and urine is concentrated (up to about 1200 mOsm/kg). Countercurrent multiplier: the loop of Henle and urea recycling create a hyperosmotic medulla; vasa recta maintain it (countercurrent exchange). Without ADH (diabetes insipidus: central lack of ADH or nephrogenic resistance) large volumes of dilute urine are made.

Buffers: bicarbonate/CO2 (main extracellular), proteins including haemoglobin, phosphate. Henderson-Hasselbalch: pH = 6.1 + log([HCO3-]/(0.03 x PCO2)). Normal pH 7.4, PaCO2 40 mmHg, HCO3- 24 mmol/L. Disorders: respiratory acidosis (high CO2), respiratory alkalosis, metabolic acidosis (low HCO3-, use the anion gap), metabolic alkalosis. The lungs compensate within minutes, the kidneys within days by excreting H+ (as ammonium and titratable acid) and regenerating bicarbonate. Potassium: 98 percent is intracellular. Insulin, beta-agonists and alkalosis push K+ into cells. The kidney excretes the excess mainly in the collecting duct under aldosterone. Hyperkalaemia causes peaked T waves and arrhythmias; hypokalaemia causes weakness and arrhythmias.

1. What determines GFR? 2. Which part of the nephron reabsorbs most of the filtrate? 3. How does ADH concentrate the urine? 4. Interpret pH 7.25, PaCO2 30 mmHg, HCO3- 12 mmol/L. 5. Name two factors that shift potassium into cells.

1. Starling forces across the barrier and the filtration coefficient. 2. The proximal tubule. 3. It inserts aquaporin-2 water channels in the collecting duct. 4. Metabolic acidosis with respiratory compensation. 5. Insulin and beta-adrenergic stimulation (also alkalosis).

Hormone classes: peptides and proteins (water soluble, surface receptors, second messengers), steroids (lipid soluble, intracellular receptors, transported bound to proteins) and tyrosine derivatives (catecholamines act at the membrane, thyroid hormones inside the cell). Pituitary: neurohypophysis stores and releases oxytocin and ADH made in the hypothalamus. Adenohypophysis secretes TSH, ACTH, FSH, LH, GH and prolactin under hypothalamic releasing and inhibiting hormones via the hypophyseal portal system (TRH, CRH, GnRH, GHRH, somatostatin; dopamine inhibits prolactin). Axes: hypothalamus -> pituitary -> target gland -> hormone, with negative feedback (long loop) to the higher centres. Excess or deficiency can arise at any level.

Synthesis: iodide is trapped by the follicular cell (sodium-iodide symporter), oxidised by thyroid peroxidase and attached to tyrosines of thyroglobulin, forming T3 and T4. Colloid is stored and endocytosed on TSH stimulation. T4 is the main product; T3 is the active form (peripheral deiodination). Transport bound to thyroxine-binding globulin. Effects: increased metabolic rate, heat production, heart rate and contractility (more beta receptors), growth and brain development. Clinical tip: iodine deficiency causes goitre and hypothyroidism; Graves disease (TSH receptor antibodies) causes hyperthyroidism.

Medulla: adrenaline and noradrenaline, released by preganglionic sympathetic stimulation; effects: increased heart rate, glycogenolysis, lipolysis, bronchodilation. Cortex: zona glomerulosa (aldosterone; regulated by angiotensin II and potassium), zona fasciculata (cortisol; regulated by ACTH), zona reticularis (androgens). Cortisol: raises blood glucose (gluconeogenesis), catabolic on muscle, anti-inflammatory and immunosuppressive, permissive for catecholamines; secretion follows a circadian rhythm (peak in the morning) and rises with stress. Excess: Cushing syndrome. Deficiency: Addison disease.

Calcium is 99 percent in bone; free plasma Ca2+ is about 1.2 mmol/L. Low calcium raises neuromuscular excitability (tetany); high calcium reduces it. Parathyroid hormone (from chief cells, secreted when Ca2+ is low): increases bone resorption, kidney calcium reabsorption and phosphate excretion, and activates vitamin D (1-alpha hydroxylation). Vitamin D (calcitriol): made from cholesterol via skin (UVB), liver (25-hydroxylation) and kidney (1-alpha hydroxylation). Increases intestinal calcium and phosphate absorption. Calcitonin (thyroid C cells) lowers calcium modestly. Deficiency of vitamin D causes rickets in children and osteomalacia in adults.

Insulin (beta cells) is secreted when glucose and amino acids rise; it promotes glucose uptake (GLUT4) in muscle and fat, glycogen and triglyceride synthesis, protein synthesis, and inhibits lipolysis and gluconeogenesis. Glucagon (alpha cells) is released in fasting and rising with amino acids: it stimulates glycogenolysis, gluconeogenesis and ketogenesis in liver. Metabolic phases: the digestive (fed) phase, the postabsorptive phase (glycogenolysis), and the fasting phase (gluconeogenesis, lipolysis, ketone bodies). The brain uses glucose almost exclusively, and ketones in prolonged fasting.

GnRH pulses stimulate LH and FSH. LH acts on Leydig cells to make testosterone; FSH and testosterone act on Sertoli cells, which support spermatogenesis and secrete inhibin (negative feedback on FSH). Testosterone: male differentiation, spermatogenesis, secondary sex characteristics, anabolic effects on muscle and bone. Converted to dihydrotestosterone (5-alpha reductase) in prostate and skin, and to oestradiol by aromatase. Not covered in this chapter: female reproductive physiology and pregnancy, which are not in the slides.

1. Compare peptide and steroid hormone mechanisms. 2. What regulates aldosterone secretion? 3. What are the main actions of PTH? 4. How does the thyroid make T4? 5. Which hormones raise blood glucose? 6. Which cells make testosterone and which secrete inhibin?

1. Peptides bind surface receptors and use second messengers (fast); steroids enter the cell and change transcription (slow). 2. Angiotensin II and potassium. 3. It increases bone resorption and renal calcium reabsorption, reduces phosphate reabsorption and activates vitamin D. 4. Iodide trapping, oxidation, iodination of thyroglobulin tyrosines and coupling. 5. Glucagon, adrenaline, cortisol, growth hormone. 6. Leydig cells make testosterone; Sertoli cells secrete inhibin.

Functions: motility, secretion, digestion, absorption and defence. The wall has mucosa, submucosa, muscularis and serosa. Enteric nervous system: the myenteric plexus (motility) and the submucosal plexus (secretion and blood flow) can work independently, modulated by parasympathetic (increases activity) and sympathetic (decreases) input. GI hormones: gastrin (stomach acid), cholecystokinin (gallbladder contraction, pancreatic enzymes, slows gastric emptying), secretin (pancreatic bicarbonate), GIP and GLP-1 (incretins).

Saliva: made by parotid, submandibular and sublingual glands; contains water, amylase, lingual lipase, mucus and lysozyme; regulated by parasympathetic (abundant watery saliva) and sympathetic (scant thick saliva) input. Swallowing: voluntary oral phase, involuntary pharyngeal phase (closure of the airway) and oesophageal peristalsis; the lower oesophageal sphincter relaxes. Achalasia is failure of the sphincter to relax. Stomach: parietal cells secrete HCl (H+/K+ ATPase, the target of proton pump inhibitors) and intrinsic factor; chief cells secrete pepsinogen. Acid secretion is stimulated by gastrin, acetylcholine and histamine (H2 receptors) and inhibited by somatostatin. Three phases: cephalic, gastric, intestinal.

Motility: segmentation (mixing), peristalsis (propulsion), the migrating motor complex between meals, the ileocaecal valve controls entry into the colon. The colon has haustral contractions and mass movements; defecation is a reflex with voluntary control. Carbohydrates: amylase then brush border enzymes; glucose and galactose absorbed by SGLT1, fructose by GLUT5. Proteins: pepsin, pancreatic proteases, brush border peptidases; absorption of amino acids and di- and tripeptides (PepT1). Lipids: bile salts emulsify, lipase and colipase digest, micelles carry products to enterocytes, chylomicrons leave via lymph. Water and ions: most absorbed in the small intestine, the colon completes it.

Functions: metabolism of carbohydrates (glycogen storage, gluconeogenesis), lipids (lipoprotein synthesis, ketogenesis), and proteins (albumin, clotting factors, urea synthesis), detoxification and biotransformation of drugs, bile production and bilirubin excretion, storage (vitamins, iron), and immune function (Kupffer cells). Hepatic blood flow is about 1.5 L/min: portal vein (about 75 percent) and hepatic artery. Lipoproteins: VLDL exported by the liver, LDL carries cholesterol to tissues, HDL returns it.

Energy balance: intake (carbohydrate and protein about 4 kcal/g, fat 9 kcal/g, alcohol 7) versus expenditure (basal metabolic rate about 60 percent, physical activity, thermic effect of food about 10 percent). Positive balance gives weight gain. Basal metabolic rate is measured under standard conditions and depends on lean mass, age, sex and hormones (thyroid hormones). Respiratory quotient (CO2 produced / O2 consumed) is 1.0 for carbohydrate, 0.7 for fat and 0.8 for protein. Requirements: essential amino acids and fatty acids, vitamins and minerals, fibre and water. The body mass index (weight/height squared) classifies obesity.

1. Which two plexuses form the enteric nervous system? 2. What stimulates acid secretion by parietal cells? 3. How are glucose and fructose absorbed? 4. Describe fat digestion and absorption. 5. What is the respiratory quotient of fat?

1. Myenteric (Auerbach) and submucosal (Meissner). 2. Gastrin, acetylcholine and histamine. 3. Glucose by SGLT1 (with sodium) and fructose by facilitated diffusion (GLUT5). 4. Emulsification by bile salts, digestion by pancreatic lipase, micelles, re-esterification and chylomicrons into the lymph. 5. 0.7.

Neurons receive input on dendrites, integrate at the soma and axon hillock, and send output along the axon. Glia: astrocytes (support, potassium buffering, blood-brain barrier), oligodendrocytes and Schwann cells (myelin), microglia (immune cells). Sensory system: receptor (transduction), afferent pathway, thalamic relay, cortical processing. Coding: modality (labelled line), intensity (firing rate, number of receptors), location (receptive field) and duration (adaptation). Stevens power law relates perceived intensity to stimulus intensity.

Receptors: mechanoreceptors (Meissner, Merkel, Pacinian, Ruffini), thermoreceptors, nociceptors, and proprioceptors (muscle spindles, Golgi tendon organs). Cell bodies are in the dorsal root ganglia. Pathways: the dorsal column-medial lemniscus pathway (fine touch, proprioception, crosses in the medulla) and the anterolateral (spinothalamic) pathway (pain and temperature, crosses at the spinal level). Pain: nociceptors (A-delta fibres for fast pain, C fibres for slow pain) respond to noxious stimuli; peripheral sensitisation by inflammatory mediators, central sensitisation in the spinal cord, and descending modulation (periaqueductal grey, endogenous opioids). Types: nociceptive, neuropathic, referred.

Vision: light is refracted by the cornea and lens (accommodation) and focused on the retina; photoreceptors (rods for dim light, cones for colour and acuity) hyperpolarise in light via the phototransduction cascade; retinal ganglion cells project via the optic nerve to the lateral geniculate nucleus and visual cortex. Hearing: sound is collected by the outer ear, amplified by the middle ear ossicles (impedance matching) and transduced by hair cells of the organ of Corti in the cochlea; the basilar membrane is tonotopically organised (high frequencies at the base). Smell: olfactory receptor neurons express one of about 400 receptor types; axons go directly to the olfactory bulb. Taste: five primary tastes (sweet, sour, salty, bitter, umami) sensed by taste bud cells; carried by the facial, glossopharyngeal and vagus nerves.

Circadian rhythm: the suprachiasmatic nucleus of the hypothalamus is the master clock, entrained by light through the retina. Sleep: the EEG shows wakefulness (beta), relaxed wakefulness (alpha), non-REM stages 1-3 (theta to slow delta waves) and REM sleep (desynchronised, dreaming, muscle atonia). Cycles last about 90 minutes. Language: Broca area (production; damage causes non-fluent aphasia) and Wernicke area (comprehension; damage causes fluent aphasia), connected by the arcuate fasciculus; usually in the left hemisphere. Memory: short-term, working and long-term (declarative and procedural). The hippocampus is needed to form new declarative memories, as shown by patient H.M.; long-term potentiation is the cellular mechanism.

1. Compare the two main ascending sensory pathways. 2. Which fibres carry fast and slow pain? 3. How are sounds of different frequencies coded in the cochlea? 4. Which area is damaged in Broca aphasia? 5. Which structure was removed in patient H.M. and what was lost?

1. Dorsal column-medial lemniscus (fine touch and proprioception, crosses in the medulla) and spinothalamic (pain and temperature, crosses in the cord). 2. A-delta (fast) and C fibres (slow). 3. By place: high frequencies at the base and low frequencies at the apex of the basilar membrane. 4. The inferior frontal gyrus (Broca area). 5. The medial temporal lobes including the hippocampus; new declarative memories could not be formed.

A motor unit is an alpha motor neuron and the muscle fibres it supplies. Force increases by recruiting units (size principle: small, slow units first) and by increasing firing rate (summation). Reflexes - Myotatic (stretch) reflex: muscle spindle Ia afferents excite the homonymous motor neuron (knee jerk). - Golgi tendon reflex: Ib afferents inhibit the motor neuron when tension is high. - Flexion (withdrawal) reflex with crossed extension. Descending pathways (corticospinal, reticulospinal, vestibulospinal) modulate these circuits. Upper motor neuron lesions give spasticity and hyperreflexia; lower motor neuron lesions give flaccid paralysis and atrophy.

Vestibular labyrinth: otolith organs (utricle and saccule) detect linear acceleration and head tilt; semicircular canals detect rotation. Signals reach the vestibular nuclei, which drive the vestibulospinal tract (posture) and the vestibulo-ocular reflex (stabilises gaze). Locomotion: central pattern generators in the spinal cord produce rhythmic stepping; the mesencephalic locomotor region starts it, and somatosensory feedback adapts it.

Motor cortex: primary motor cortex (somatotopic map, corticospinal tract), premotor and supplementary motor areas (planning), and the posterior parietal cortex (sensory guidance). Basal ganglia (caudate, putamen, globus pallidus, subthalamic nucleus, substantia nigra): select and initiate movement through the direct pathway (facilitates) and indirect pathway (suppresses). Dopamine loss causes Parkinson disease (bradykinesia, rigidity, tremor); Huntington disease causes chorea. Cerebellum: compares intended and actual movement and corrects errors; involved in coordination, balance and motor learning. Damage causes ataxia and intention tremor on the same side as the lesion. Eye movements: saccades (fast shifts), smooth pursuit and vestibulo-ocular reflex, controlled by brainstem centres and the extraocular muscles.

1. Define a motor unit and the size principle. 2. What is the difference between the myotatic and Golgi tendon reflexes? 3. What does the vestibulo-ocular reflex do? 4. Which pathway do basal ganglia use to facilitate movement? 5. What are the signs of cerebellar damage?

1. An alpha motor neuron and the fibres it innervates; small units are recruited first. 2. The myotatic reflex contracts the stretched muscle; the Golgi tendon reflex relaxes a muscle under high tension. 3. It keeps the image stable on the retina during head movement. 4. The direct pathway. 5. Ataxia, intention tremor, dysmetria, on the side of the lesion.