General Mammalian Physiology II BZO6T13

Syllabus topics (RTMNU)

• Types of Muscles: Skeletal, smooth, and cardiac muscles
• Ultrastructure of muscle fiber
• Mechanism of Muscle Contraction: Sliding filament theory, Role of actin and myosin, Excitation–contraction coupling, Energy sources for contraction
• Properties of Muscles: Twitch, Tetanus, Summation, Tonus, All or none principle, Muscle fatigue and rigor mortis
• Neuromuscular Junction: Structure of neuromuscular junction, Role of acetylcholine, Transmission of impulse, Disorders of neuromuscular junction

Types of Muscles

Muscle tissue is a contractile tissue made of elongated cells (muscle fibres) that shorten to produce movement.

Ultrastructure of Skeletal Muscle Fibre

A muscle is made of bundles (fascicles) of muscle fibres. Each fibre is a long multinucleate cell covered by the sarcolemma, filled with sarcoplasm and many myofibrils.

• Sarcoplasmic reticulum (SR): network of smooth ER around myofibrils; stores Ca²⁺.
• T-tubules (transverse tubules): inward folds of sarcolemma; with two SR cisternae they form a triad.
• Sarcomere: the functional unit between two Z-lines (about 2.5 µm at rest). It has a dark A-band (thick myosin filaments, with overlapping actin) and light I-bands (thin actin only). The middle of the A-band has a lighter H-zone with an M-line.
• Thick filament: myosin – each molecule has a tail and two heads (with ATPase activity and actin-binding sites).
• Thin filament: two strands of F-actin twisted together, with tropomyosin lying in the groove and troponin complex (TnC binds Ca²⁺, TnI inhibits, TnT binds tropomyosin).

Mechanism of Muscle Contraction: Sliding Filament Theory

The sliding filament theory (H. E. Huxley and A. F. Huxley, 1954) states that muscle shortens because thin actin filaments slide over thick myosin filaments towards the centre of the sarcomere; the filaments themselves do not change length.

Excitation–contraction coupling (steps):

1. A nerve impulse reaches the neuromuscular junction; acetylcholine causes an action potential in the sarcolemma.
2. The action potential travels down T-tubules and causes the SR to release Ca²⁺.
3. Ca²⁺ binds troponin C; troponin–tropomyosin shift and expose myosin-binding sites on actin.
4. Cross-bridge cycle: energised myosin head (ADP + Pi) binds actin → releases Pi and ADP → power stroke pulls actin towards M-line → new ATP binds and detaches the head → ATP is hydrolysed and the head is "cocked" again.
5. Z-lines come closer; I-band and H-zone shorten; A-band stays the same.
6. Relaxation: Ca²⁺ is pumped back into SR (Ca²⁺-ATPase); tropomyosin covers binding sites again.

Energy sources: (1) stored ATP (a few seconds); (2) creatine phosphate + ADP → creatine + ATP; (3) anaerobic glycolysis (lactic acid formed); (4) aerobic respiration of glucose and fatty acids in mitochondria (main source in long exercise).

Properties of Muscles

• Simple twitch: one quick contraction in response to a single stimulus. It has a latent period (about 0.01 s), contraction period (0.04 s) and relaxation period (0.05 s).
• Summation: when two stimuli come close together, the second contraction adds to the first and is stronger (wave summation); recruiting more motor units is spatial summation.
• Tetanus: sustained, smooth maximum contraction when stimuli come so fast that the muscle cannot relax between them.
• Tonus (muscle tone): mild, continuous partial contraction of muscles even at rest; maintains posture.
• All-or-none principle: a single muscle fibre either contracts fully or not at all when the stimulus reaches threshold. (A whole muscle shows graded response.)
• Muscle fatigue: fall in contraction strength after long activity due to lactic acid, ATP shortage and ion changes.
• Rigor mortis: stiffness of muscles a few hours after death, because no ATP is available to detach myosin heads from actin. It passes off as proteins break down.

Neuromuscular Junction

The neuromuscular junction (motor end plate) is the synapse between a motor neuron's axon terminal and a skeletal muscle fibre.

Structure: axon terminal with synaptic vesicles containing acetylcholine (ACh) → synaptic cleft (about 50 nm) → folded sarcolemma (junctional folds) with nicotinic ACh receptors and the enzyme acetylcholinesterase.

Transmission: impulse reaches terminal → voltage-gated Ca²⁺ channels open → Ca²⁺ enters → vesicles release ACh by exocytosis → ACh binds receptors → Na⁺ enters → end-plate potential → muscle action potential. Acetylcholinesterase quickly breaks ACh into acetate and choline so the signal stops.

Disorders: Myasthenia gravis – autoimmune antibodies destroy ACh receptors → muscle weakness, drooping eyelids; treated by anticholinesterase drugs (neostigmine). Lambert–Eaton syndrome – antibodies against Ca²⁺ channels. Botulism – botulinum toxin blocks ACh release (paralysis). Curare blocks ACh receptors; organophosphate insecticides block acetylcholinesterase (spasms).

Likely exam questions

1. (Long, 8 marks) Describe the ultrastructure of skeletal muscle fibre and explain the sliding filament theory of muscle contraction.
2. (Long, 8 marks) Describe the structure of the neuromuscular junction and explain transmission of impulse across it.
3. (Short, 4 marks) Differentiate between skeletal, smooth and cardiac muscles.
4. (Short, 4 marks) Write a note on rigor mortis.
5. (Short, 4 marks) Explain tetanus and the all-or-none principle.

Syllabus topics (RTMNU)

• Structure of Neuron: Types of neurons, E.M. structure of neuron
• Nerve Impulse: Resting membrane potential, Action potential, Propagation of nerve impulse, Saltatory conduction
• Synapse: Structure of synapse, Chemical and electrical synapses, Synaptic transmission
• Neurotransmitters: Types of neurotransmitters, Synthesis and release, Mechanism of action, Disorders related to neurotransmitters

Structure of Neuron: Types and E.M. Structure

A neuron is the structural and functional unit of the nervous system, specialised to receive, conduct and transmit impulses.

Types: by structure – unipolar (one process; embryonic), pseudounipolar (sensory neurons of dorsal root ganglion), bipolar (retina, olfactory epithelium), multipolar (motor neurons, brain). By function – sensory (afferent), motor (efferent) and interneurons (association).

Electron-microscopic structure:

1. Cell body (cyton/soma): large nucleus with prominent nucleolus; Nissl granules (rough ER with ribosomes – protein synthesis); Golgi body, mitochondria; neurofibrils (neurofilaments and microtubules) for support and transport. No centriole – mature neurons do not divide.
2. Dendrites: short branched processes carrying impulses towards the cell body; have Nissl granules and dendritic spines.
3. Axon: single long process arising from the axon hillock (no Nissl granules); covered by axolemma; ends in branched terminals with synaptic knobs containing vesicles of neurotransmitter.
4. Myelin sheath: lipid layers formed by Schwann cells (PNS) or oligodendrocytes (CNS); gaps between are nodes of Ranvier. Outer layer of Schwann cell is the neurilemma.

Nerve Impulse: Resting Membrane Potential and Action Potential

A nerve impulse is a wave of electrical change (action potential) travelling along the neuron membrane.

Resting membrane potential (about −70 mV): the inside of a resting neuron is negative compared to outside (polarised). Causes:

• Na⁺–K⁺ pump sends out 3 Na⁺ and brings in 2 K⁺ using ATP.
• Membrane is more permeable to K⁺ (leak channels) than Na⁺; K⁺ leaks out.
• Large negative proteins and phosphates stay inside.

Action potential (steps):

1. Depolarisation: a stimulus reaching threshold (about −55 mV) opens voltage-gated Na⁺ channels; Na⁺ rushes in; inside becomes positive (about +30 to +40 mV).
2. Repolarisation: Na⁺ channels close and K⁺ channels open; K⁺ flows out; potential returns towards negative.
3. Hyperpolarisation: slight overshoot below −70 mV as K⁺ channels close slowly.
4. Na⁺–K⁺ pump restores ion distribution.

During the refractory period a new impulse cannot (absolute) or can only with a strong stimulus (relative) be produced. Action potential follows the all-or-none law.

Propagation of Nerve Impulse and Saltatory Conduction

In non-myelinated fibres, local currents from the active region depolarise the next region, so the impulse moves continuously and slowly (about 0.5–2 m/s).

In myelinated fibres, myelin insulates the axon and ion channels are concentrated at nodes of Ranvier, so the impulse jumps from node to node – saltatory conduction (Latin saltare = to jump). Advantages: much faster (up to about 100–120 m/s) and saves energy since fewer ions move.

Synapse: Structure, Chemical and Electrical Synapses, Transmission

A synapse is the junction between two neurons (or a neuron and an effector) where impulse passes from one to the next.

Structure of chemical synapse: presynaptic knob (vesicles, mitochondria) → synaptic cleft (20–40 nm) → postsynaptic membrane with receptors.

Synaptic transmission: impulse arrives → Ca²⁺ enters presynaptic knob → vesicles fuse and release neurotransmitter → it binds receptors → ion channels open → EPSP (Na⁺ in, depolarisation) or IPSP (Cl⁻ in or K⁺ out, hyperpolarisation) → transmitter removed by enzymes or reuptake.

Neurotransmitters

Neurotransmitters are chemicals released at synapses that carry signals from one neuron to the next cell.

Types: acetylcholine; biogenic amines – dopamine, noradrenaline, adrenaline, serotonin, histamine; amino acids – glutamate (main excitatory), GABA and glycine (inhibitory); neuropeptides – endorphins, substance P; gases – nitric oxide.

Synthesis and release: small transmitters are made in the axon terminal (e.g., ACh from acetyl-CoA + choline by choline acetyltransferase; dopamine from tyrosine) and stored in vesicles; peptides are made in the cell body and transported. Release is Ca²⁺-dependent exocytosis.

Mechanism of action: ionotropic receptors are ion channels that open directly (fast); metabotropic receptors act through G-proteins and second messengers (slow, long-lasting). Action ends by enzyme breakdown (acetylcholinesterase, MAO), reuptake or diffusion.

Disorders: Parkinson's disease – loss of dopamine neurons (tremors, rigidity); Alzheimer's disease – loss of cholinergic neurons (memory loss); depression – low serotonin/noradrenaline; schizophrenia – excess dopamine activity; epilepsy – imbalance of glutamate and GABA; myasthenia gravis – ACh receptor loss.

Likely exam questions

1. (Long, 8 marks) Explain the ionic basis of resting membrane potential and action potential.
2. (Long, 8 marks) Describe the structure of a chemical synapse and explain synaptic transmission.
3. (Short, 4 marks) Describe the E.M. structure of a neuron.
4. (Short, 4 marks) What is saltatory conduction?
5. (Short, 4 marks) Write a note on types of neurotransmitters.

Syllabus topics (RTMNU)

• Hypothalamus and Pituitary Gland: Hormones of hypothalamus, Anterior, Intermediate and Posterior pituitary hormones, Feedback regulation, Pituitary gland disorders
• Thyroid and Parathyroid Glands: Thyroid hormones and functions, Regulation of thyroid secretion, Parathyroid hormone and calcium balance, Disorders of thyroid and parathyroid gland
• Adrenal and Pancreatic Hormones: Hormones of adrenal cortex and medulla, Insulin and glucagon, Regulation of blood glucose, Disorders of adrenal gland and endocrine pancreas
• Mechanism of Hormone Action: Types of hormone receptors, Second messenger system, Signal transduction pathways

Hypothalamus and Pituitary Gland

The hypothalamus (floor of the diencephalon) links the nervous and endocrine systems. It controls the pituitary through releasing and inhibiting hormones carried by the hypothalamo-hypophyseal portal system (to the anterior lobe) and through nerve fibres (to the posterior lobe).

Hypothalamic hormones: TRH (thyrotropin-releasing), CRH (corticotropin-releasing), GnRH (gonadotropin-releasing), GHRH (growth hormone-releasing), somatostatin (GH-inhibiting), dopamine (prolactin-inhibiting).

The pituitary (hypophysis) is a pea-sized gland in the sella turcica of the sphenoid bone, called the "master gland".

Feedback regulation: mostly negative feedback – e.g., high thyroxine inhibits TRH and TSH release. A positive feedback example: oxytocin during childbirth.

Pituitary disorders: excess GH – gigantism (in children), acromegaly (in adults – large jaw, hands, feet); deficiency of GH – dwarfism (proportionate); ADH deficiency – diabetes insipidus; hypopituitarism (Simmonds' disease).

Thyroid and Parathyroid Glands

The thyroid is a butterfly-shaped gland in the neck with two lobes joined by an isthmus; made of follicles filled with colloid (thyroglobulin).

Hormones: thyroxine (T₄) and triiodothyronine (T₃) – made from tyrosine and iodine; calcitonin from parafollicular (C) cells lowers blood calcium.

Functions of T₃/T₄: increase basal metabolic rate and heat production (calorigenic), growth and brain development, metamorphosis in frogs, heart rate, and metabolism of carbohydrates, fats and proteins.

Regulation: hypothalamus (TRH) → anterior pituitary (TSH) → thyroid (T₃, T₄) → negative feedback to both.

Parathyroid glands: four small glands behind the thyroid; secrete parathormone (PTH), which raises blood Ca²⁺ by: releasing Ca²⁺ from bone (osteoclast activity), increasing Ca²⁺ reabsorption in kidney, and activating vitamin D for intestinal Ca²⁺ absorption. PTH and calcitonin work opposite to each other to maintain calcium balance.

Disorders:

• Hypothyroidism – cretinism (in children: stunted growth, mental retardation), myxoedema (in adults: puffy face, lethargy, weight gain); simple goitre due to iodine deficiency.
• Hyperthyroidism – Graves' disease (exophthalmic goitre: bulging eyes, high BMR, weight loss, nervousness).
• Hypoparathyroidism – low Ca²⁺ → tetany (muscle spasms). Hyperparathyroidism – high Ca²⁺, weak bones, kidney stones.

Adrenal and Pancreatic Hormones

The adrenal glands sit on top of the kidneys. Outer cortex has three zones:

• Zona glomerulosa: mineralocorticoids – aldosterone (Na⁺ retention, K⁺ loss, BP).
• Zona fasciculata: glucocorticoids – cortisol (raises blood glucose by gluconeogenesis, anti-inflammatory, stress).
• Zona reticularis: sex hormones (androgens).

Inner medulla secretes adrenaline (epinephrine) and noradrenaline – "fight or flight" hormones: raise heart rate, BP, blood glucose, dilate pupils and bronchioles.

Endocrine pancreas (islets of Langerhans): β cells – insulin (lowers blood glucose: glucose uptake by cells, glycogen formation in liver and muscle, fat synthesis); α cells – glucagon (raises blood glucose: glycogenolysis and gluconeogenesis in liver); δ cells – somatostatin.

Regulation of blood glucose: normal fasting level about 70–100 mg/dL. After a meal glucose rises → insulin released → glucose falls. In fasting glucose falls → glucagon (with adrenaline, cortisol, GH) → glucose rises.

Disorders: Addison's disease (cortex hyposecretion – weakness, low BP, bronze skin); Cushing's syndrome (excess cortisol – moon face, obesity of trunk, high sugar); Conn's syndrome (excess aldosterone – high BP); diabetes mellitus (Type 1 – no insulin, autoimmune; Type 2 – insulin resistance) with high blood sugar, glucose in urine, thirst; hypoglycaemia from excess insulin.

Mechanism of Hormone Action

Hormone receptors are specific proteins on or in target cells that bind a hormone and start a response.

1. Cell-membrane (surface) receptors: for water-soluble hormones – peptides, proteins, catecholamines (insulin, glucagon, adrenaline, FSH). Types: G-protein-coupled receptors, receptor tyrosine kinases (insulin), ion-channel receptors.
2. Intracellular receptors: for lipid-soluble hormones – steroids (cortisol, oestrogen, testosterone) and thyroid hormones. Hormone enters cell, binds receptor in cytoplasm or nucleus; hormone–receptor complex binds DNA (hormone response element) and switches genes on/off → new proteins. Slower but long-lasting.

Second messenger system (cAMP mechanism, E. W. Sutherland): hormone (first messenger) binds receptor → activates G-protein (Gs) → activates adenylate cyclase → ATP → cAMP (second messenger) → activates protein kinase A → phosphorylates enzymes → cell response (e.g., glycogen breakdown by adrenaline). Phosphodiesterase breaks cAMP to stop the signal.

Other signal transduction pathways: phospholipase C pathway – PIP₂ → IP₃ (releases Ca²⁺ from ER) + DAG (activates protein kinase C); Ca²⁺–calmodulin; cGMP pathway; receptor tyrosine kinase pathway (insulin) that leads to insertion of GLUT-4 glucose transporters.

Likely exam questions

1. (Long, 8 marks) Describe the hormones of the pituitary gland and their functions. Add a note on pituitary disorders.
2. (Long, 8 marks) Explain the mechanism of hormone action with reference to the second messenger (cAMP) system.
3. (Short, 4 marks) Write a note on the regulation of blood glucose.
4. (Short, 4 marks) Give the role of parathormone in calcium balance.
5. (Short, 4 marks) Write a note on Cushing's syndrome and Addison's disease.

Syllabus topics (RTMNU)

• Male Reproductive Physiology: Structure of male reproductive system, Spermatogenesis, Semen composition, Hormonal regulation, causes of male infertility and basic concepts of male contraceptive methods
• Female Reproductive Physiology: Structure of female reproductive system, Oogenesis, Menstrual cycle, Hormonal regulation, causes of female infertility, basic concepts of contraceptive methods, introduction to in vitro fertilization (IVF)
• Sensory Physiology: Physiology of vision, Physiology of hearing, Physiology of taste, Physiology of smell
• Homeostasis and Stress Physiology: Concept of homeostasis, Thermoregulation, Stress response
• Role of adrenal hormones in stress

Male Reproductive Physiology

Structure: a pair of testes in the scrotum (kept 2–3 °C below body temperature), each with seminiferous tubules (sperm formation; Sertoli cells nourish sperm) and interstitial Leydig cells (testosterone). Ducts: rete testis → vasa efferentia → epididymis (sperm maturation and storage) → vas deferens → ejaculatory duct → urethra in penis. Accessory glands: seminal vesicles, prostate, bulbourethral (Cowper's) glands.

Spermatogenesis: formation of sperms in seminiferous tubules: spermatogonia (2n) multiply by mitosis → primary spermatocytes (2n) → meiosis I → secondary spermatocytes (n) → meiosis II → spermatids (n) → spermiogenesis (change into sperm: acrosome, head, middle piece with mitochondria, tail). One primary spermatocyte gives four sperms. It takes about 64–74 days in man.

Semen composition: sperms plus seminal plasma – fructose (energy, from seminal vesicles), prostaglandins, citric acid and enzymes (prostate), mucus (Cowper's glands); slightly alkaline; normal count about 15 million/mL or more (WHO lower reference limit).

Hormonal regulation: GnRH (hypothalamus) → FSH and LH (pituitary). LH → Leydig cells → testosterone. FSH + testosterone → Sertoli cells → spermatogenesis. Sertoli cells secrete inhibin which inhibits FSH; testosterone inhibits GnRH and LH (negative feedback).

Causes of male infertility: low sperm count (oligospermia), no sperm (azoospermia), poor motility, blocked ducts, varicocele, hormonal imbalance, infections (mumps), smoking, alcohol, heat exposure.

Male contraceptive methods: condom (barrier, also protects from STIs), vasectomy (cutting and tying the vas deferens – permanent), withdrawal; hormonal male pills are still under research.

Female Reproductive Physiology

Structure: a pair of ovaries (follicles, oocytes; oestrogen and progesterone), fallopian tubes (infundibulum with fimbriae, ampulla – site of fertilisation, isthmus), uterus (perimetrium, myometrium, endometrium), cervix, vagina; external genitalia.

Oogenesis: oogonia multiply before birth → primary oocytes (arrested in prophase I) inside primordial follicles → at puberty, each month a follicle grows (primary → secondary → Graafian follicle) → meiosis I completes: secondary oocyte + first polar body → ovulation of secondary oocyte (arrested in metaphase II) → meiosis II completes only after sperm entry → ovum + second polar body. One oogonium gives one ovum.

Menstrual cycle (about 28 days):

1. Menstrual phase (days 1–5): endometrium breaks down and bleeds because progesterone falls.
2. Follicular/proliferative phase (days 6–13): FSH grows follicle; oestrogen rebuilds endometrium.
3. Ovulation (about day 14): LH surge releases the ovum.
4. Luteal/secretory phase (days 15–28): corpus luteum secretes progesterone; endometrium becomes thick and glandular. If no pregnancy, corpus luteum degenerates → menstruation.

Female infertility causes: failure of ovulation (PCOS, thyroid problems), blocked fallopian tubes (infection), endometriosis, uterine fibroids, age, hormonal imbalance.

Contraceptive methods: natural (rhythm/safe period), barrier (female condom, diaphragm), IUDs (Copper-T), oral pills (combined oestrogen + progestin; prevent ovulation), injectables, implants, surgical (tubectomy).

In vitro fertilisation (IVF): "test-tube baby" technique – ovaries stimulated with hormones → eggs collected → fertilised with sperm in the laboratory (or ICSI: sperm injected into egg) → embryo grown for 3–5 days → transferred into the uterus (embryo transfer).

Sensory Physiology: Vision and Hearing

Vision: light passes through cornea, aqueous humour, lens and vitreous humour and is focused on the retina. Photoreceptors: rods (dim light, contain rhodopsin = opsin + retinal from vitamin A) and cones (bright light and colour; three types – red, green, blue). Light changes 11-cis retinal to all-trans retinal → rhodopsin breaks down → hyperpolarisation of rod → signal to bipolar and ganglion cells → optic nerve → visual cortex (occipital lobe). Accommodation by ciliary muscles changing lens shape. Vitamin A deficiency causes night blindness.

Hearing: sound waves → external ear canal → tympanic membrane vibrates → ear ossicles (malleus, incus, stapes) amplify → oval window → fluid waves in cochlea → basilar membrane vibrates → hair cells of the organ of Corti bend against tectorial membrane → nerve impulses → auditory nerve → auditory cortex (temporal lobe). Different pitches stimulate different parts of the basilar membrane.

Sensory Physiology: Taste and Smell

Taste (gustation): chemoreceptors in taste buds on tongue papillae. Five basic tastes: sweet, sour, salty, bitter and umami. Dissolved chemicals bind receptors (sweet, bitter, umami by G-protein receptors; salty and sour through ion channels) → impulses through facial, glossopharyngeal and vagus nerves → gustatory cortex.

Smell (olfaction): olfactory epithelium in the roof of the nasal cavity has bipolar olfactory receptor neurons with cilia. Odour molecules dissolve in mucus, bind G-protein receptors → cAMP → depolarisation → olfactory nerve → olfactory bulb → olfactory cortex and limbic system (link with memory and emotion).

Homeostasis and Stress Physiology

Homeostasis (term by W. B. Cannon) is the maintenance of a constant internal environment (temperature, pH, glucose, water) despite changes outside. It works by feedback loops: receptor → control centre → effector; mostly negative feedback.

Thermoregulation: mammals are endotherms; body temperature about 37 °C is controlled by the hypothalamus (thermostat). In heat: sweating, vasodilation of skin vessels, less metabolism, panting. In cold: shivering, vasoconstriction, erection of hair, non-shivering heat from brown fat, more thyroxine and adrenaline.

Stress response (General Adaptation Syndrome, Hans Selye): alarm stage → resistance stage → exhaustion stage.

Role of adrenal hormones in stress: (1) quick response – sympathetic nerves → adrenal medulla → adrenaline and noradrenaline: faster heart, higher BP, more glucose, more blood to muscles ("fight or flight"); (2) longer response – hypothalamus (CRH) → pituitary (ACTH) → adrenal cortex → cortisol (raises glucose, reduces inflammation) and aldosterone (keeps BP by retaining Na⁺ and water). Long-term high cortisol can weaken immunity and raise BP.

Likely exam questions

1. (Long, 8 marks) Describe the menstrual cycle and its hormonal regulation.
2. (Long, 8 marks) Explain spermatogenesis and its hormonal control.
3. (Short, 4 marks) Write a note on IVF.
4. (Short, 4 marks) Explain the physiology of vision.
5. (Short, 4 marks) What is thermoregulation? How is it achieved in mammals?