Channels: (a) Ligand gated Na+ channels, (b) Voltage gated Na+ channels: fast depoarisation above threshold AP (-50mV), have 3 states: resting (closed), open (active), inactive (unavailable= absolute refractory period), blocked by Tetrodoxin & local anaesthetics ;(c) K+ channels = delayed opening, re-polarise, relative refractory period. Blocked by TEA.
Nerve functions: (a) conduct electrical AP, (b) transport & secrete neurotransmitters (focal release to a few cells), & hormones (to all body).
Myelinated nerves = fast saltatory conduction between Nodes of Ranvier, smaller diameter axons & less energy. Soma = nerve cell body, Dendrite = input branches, Axon = output (branches near target). Synaptic transmission: AP runs along axon-> over varicosity -> opens voltage gated Ca channels -> Ca influx -> release neurotransmitter -> act on post-synaptic receptors, may open Na and K channels-> if enough synapses activated to depolarise to threshold (-50mV) then EPSP (Excitatory Post-synaptic potential) occurs.Facilitation: ^transmitter release, as repeated stimulation of same synapses.Inhibitory post-synaptic (IPSP) or Renshaw cell prevents multiple firing of motor neuron, as –ive feedback using glycine. CNS transmitters: Glutamic acid, Noradrenaline, Dopamine, 5-HT, ACh, Glycine, GABA, & 100 other peptides.
Nerve system has 3 functional blocks:
1. Detectors: (a) Sensory endings in skin, viscera, bone, with their cell bodies in dorsal root ganglion, eg. Simple stretch receptors in artery & vein walls, Pacinian corpusles (detect pressure, in dermis), Meisseners corpuscles (detect touch, in dermal ridges), Muscle spindle (detect muscle extension), Golgi tendon organ (detect tendon tension). (b) Special senses, sight, hearing, sensory receptor is part of neuron. Transduction = Conversion of stimulus into electrical changes, as sensor membrane depolarises. Generator potential: If electrical potential at sensor > threshold => AP to CNS. ^ stimulus => ^ AP frequency, but in adapting sensors (most sensors) =>rate of AP decreases even though stimulus unchanged. Receptive fields: Sensory axons branch into many nerve endings, stimulation within area appears to come from one point. Adjacent fields overlap to ^ accuracy.
2. Conduction: Spinal cord, White matter = mylinated axons, Grey matter = neurons & synapses. SENSORY PATHWAYS: (a)Touch receptor -> spinal cord -> dorsal columns - > synapse in medulla -> cross midline -> synapse in contralateral thalamus -> relay to somato-sensory cortex. (b) Pain -> synapse in ispilateral (ie. same side) neurons in spinal cord -> cross midline to opposite lateral spino-thalmic tract. (c) Poorly localised touch -> ventral contralateral tract. Ascending reticular activating system: sensory fibres also branch to upper reticular formation then to cerebral cortex to activate brain in general way. MOTOR PATHWAYS: (a) Premotor cortex (higher functions, planning movement & speech) -> Motor cortex (frontal lobe) has body map -> cortico-spinal tract through brain stem -> crosses midline in medulla or spinal cord-> synapses on spinal motor neurons. (b) Pyramidal system = via motor neurons in anterior horn of spinal cord. (c) Extrapyramidal system= activation & inactivation of A-alpha and A-gamma motorneurons. **Look at diagrams of tracts & pathways in Week 2 handout entitled "Sensory & motor functions & pathways of central nervous system" ***
3. Processing (CNS): Nucleus: aggregation of neurons, dendrites & synapses. Medulla: lowest part of brain,in line with spinal cord. Reticular formation: midline structure.Brainstem: medulla + midbrain. Cerebral cortex: conscious sensations, eg.somato-sensory cortex. Thalami: subcortical structures, contain relay nuclei for vision, pain, temperature. Brain stem nuclei & basalganglia: posture & locomotion control. Cerebellum: compares intended movement (from motor cortex & basal ganglia) with actual (sensory info. from muscles, joints, vision & vestibular apparatus)
To focus near object (visual acuity): (a) Cilary muscle (spincter muscle around lens) constricts to relax ligaments => thicker lens => nearer focus, (b) Bring visual axis closer together (as binocular vision), (c) Narrow pupil.
Deafness: (a) Obstructive deafness (eg. wax in canal) => loss of air conduction, but not bone conduction, (b) Sensory deafness (eg. Presbyausis and barotrauma) => loss of high frequency.**Look at hearing loss graphs in Week 3's lecture on hearing ***
Movement needs: (a) Planning: Ramp (slow build up), Ballistic (fast); (b) Stability; (c) Cerebralcortex - cerebellum - cerebral cortex loop to correct errors. *** Look at diagram at back of Week 4 handout on "Important spinal cord reflexes"and hand drawn figure showing Red nucleus ***
(a) Motor cortex = body map, controls opposite side, polysynaptic connections, controls movements not muscles. Pyrimidal tract - Upper motor neuron lesion: Lose of fine movement, ^ muscle tone => spasticity (clasp-knife rigidity) - no muscle wasting, ^ tendonreflex, Clonus = contraction-relaxation oscillation, Babinski = extensor-planter (big toe moves up) response.
(b) Basal ganglia, via extra-pyramidal tract, activate movement & background change in posture & muscle tone. Parkinson'ssyndrome: Tremor at rest, rigidity (flexor & extensor), ^tone (lead-pipe rigidity), Tremors + Rigidity = "Cogwheel", poverty of movement, esp. face, normal tendon reflexes.
(c) Cerebellum: compares intended with actual, feeds back to opposite side cerebral cortex, controls SAME side of body, balance, eye movement, synchronises muscle groups, learns (plasticity), no direct muscle pathways. Cerebellar damage: Intension tremor, poor coordination (can't tap bench lightly or play piano), no rapid movements, poor balance, nystagmus.
(d) Speech defects: Dysphonia (phonation), Dysarthria (articulation), Dysphasia (language). (i) Speaking heard word: Primary auditory area -> Wernicke's area (decodes & forms grammar) -> Broca's area -> Motor cortex (moves mouth, tongue, lungs, vocal cords). (ii) Speaking written word: Primary visual -> angular gyrus -> Wernicke's-> Broca's -> Motor cortex.
(e) Frontal pole damage => blunted effect, no social rules.
Brain is supplied by Anterior & Middle cerebralarteries = branches of Internal Carotid, and 4 branches of Basilar. Blockage => much damage. Posetron-Emission tomograph: shows increased blood flow to active regions. Magnetic-Resonance Angeography: blood flow through arteries for clot/tumor.
II. Optic: (a) Horner's syndrome (no symp to eye, no sweating, small pupil, ptosis); (b) Marcus-Gun or Afferentpupil defect (no direct pupil constriction, but normal constriction of bad eye when light in good eye); (c) Visual field defects (left optic nerve damage; pituitary tumor=>bitemporal hemi-inopea; Hapliodema=enlarged optic disk; MS=>Optic atrophy)
III. Occulomotor: 3rd nerve palsey (eg.anurism of internal carotid pressing on 3rd nerve): dilated pupil, eye closed, eye down & out (unopposed LR and SO).
IV. Trochlear: controls Superior Oblique eye muscle.
V. Trigeminal: (eg. pituitary tumor) test corneal reflex, facial sensation, mastation muscles, jaw jerk.
VI. Abducens: controls Lateral Rectus. 6th nerve palsey: squint, eye won't abduct, double vision looking to bad side.
VII. Facial: taste loss, Stapedius-Hyperacusis, facial expression.
VIII. Auditory-Vestibular: Weber's (fork on forehead like a "W", with ears at sides) & Renne's tests, wisper at 2 feet, Nystagmus.
IX. Glossopharyngeal, X. Vagus, and XI.Spinal accessory: Gag reflex, soft palet, cough, speech, sternomastoid, trapezius.
XII. Hypoglossal: tongue protrusion, speech. **Please Email any good anagrams for these nerves **
Signs of raised ICP: v pulse, ^BP,Cheyne-Stokes breathing, Hutchinson's pupils, limb movements. ICP Viciouscircle:v respiration => ^CO2 => ^arterial BP=> ^ICP => venous & arterial compression => ischaemia & odemia & obstruction of CSF => ^ICP => medulla-oblongata compresses => respiration stops.
Determine: History, Awareness, Pulse, BP, respiration, eye movements, corneal reflexes, movement (command, pain), tendon reflexes, plantar reflex. Glasgow coma scale: Eyes, motor & verbal scoredon 1=Absent to 5 or 6 = Spontaneous. Treatment: Ensure oxyenation, breathing, circulation, glucose, reduce ICP.
Anterior pituitary:
| Hypothalmus | Anterior pit. | Organ | Action |
| CRH (Corticotrophin RH) | ACTH (Adenocorticotrophin) MSH (Melanocyte stimulating hormone) | Adrenal cortex Melanin producing cells. | releases glucocorticoids |
| TRH (Thyrotrophin RH) | TSH (Thyroid SH) | Thyroid gland | Thyroid secretion |
| GnRH (Gonadotrophin RH) | FSH (Follicle SH)/LH (Luteinizing Hormone) | Gonads | Sperm & egg production. |
| PRH/PIH (Prolactin RH/IH) | Prolactin | Lactating breast | Milk production |
| GHRH/GHIH (Somatotrophin/Somatostatin) | hGH (human growth hormone) | Most tissues | Indirectly ^cell division, growth, protein, glycogen & glucose increase, fat breakdown. |
Note: RH = Releasing Hormone, IH = Inhibiting Hormone, SH = Stimulating Hormone.
Posterior pituitary: (a) Oxytocin from para-ventricular nucleus of hypothalamus => uterine contraction in labour & milk ejection.(b) ADH (Antidiuretic hormone) from supraoptic nucleus of hypothalamus=> ^water permeability in renal collecting ducts, but Na still excreted (low vol, high conc. urine).
Deficient of hypothalmus hormones:Panhypopituitarism or single hormone deficiency: vcorticosteroid, vthyroxine, vsexual function, dwarfism, diabetis insipidus.
Excess: ^corticosteroid, impaired reproduction(^prolactin blocks GnRH), giantism, diabetis mellitus, fluid retension, low osmolity.
Actions: (a) Intracellular: T4 -> T3 binds to receptors on nucleus => ^DNA transcription => ^protein synthesis =>^enzymes,^BMR, ^growth. (b) Whole body: ^BMR, ^O2 use, ^heat, ^carbohydrate metabolism, ^glucose absorption (in GIT & cells), ^fatty acid breakdown, ^protein turnover (synthesis & breakdown).(c )Systemic:^CNS activity, ^Heart rate/vPeripheral resistance, ^GIT secretion/motility. (d) Developmental: Early brain development (first 2 years), long bone growth (before epiphyseals fuse).
Deficiency due to: (a) Primary hypothyrodism, caused by thyroid itself (eg. iodine deficiency, enzyme defect, inflammation)=> v T3 & T4 => ^TSH => goitre. (b) Secondary hypothyrodism, as low TSH from anterior pituitary => thyroid atrophy. Deficiency consequences: (a) Metabolic: vBMR => cold intolerance, ^weight (on same calorie intake), vblood sugar, ^blood lipids.(b) Systemic: low resting heart rate, v gut motility =>constipation, slowed thinking (always happens me in exams! :-) ); (c) Developmental: Cretinism (irreversible, so newborns screened)
Excess due to: Hyperthyrodism as antibodies bind to TSH receptor (=> ^secretion => goitre), or adenoma of thyroid (=>^T4=>v TSH). Excess consequences: (a) Metabolic:^BMR=> heat intolerance, vasodilation, sweating, v weight, ^appeptite, (b) Systemic: ^Heart rate, arrhythmias, bounding pulse, ^gut motility=>diahorrea,mental overactivity & insomnia, brisk muscle reflex, weak muscles, ^symp=>anxiety & tremor. (c) Developmental: early closure ofepiphyseals => v adult height.
Regulation: (a) Circadian rythm: low 1-3am, peak7-9am (waking up); (b) Stress response: (rapid upto 20 fold rise,due to trauma, burns, infection, anxiety, exercise, hypoglycaemia).
Actions: (a) Intracellular: Binds to intracellularreceptor -> enters nucleus => ^transcription => ^enzymes & functional proteins. (b) Permissive catabolic: Proteins -> glycogen, Lipids->Energy, ^Appeptite. (c) Stress response: rapid rise of glucose, permissive symp vasoconstriction (^BP in exercise, anxiety, blood loss). (d) Anti-inflammatory (eg. v airway swelling in asthma,v pain in arthritis); (e) Immunosuppresant (v B & T lymphocyte response, v transplant rejection)
Deficiency: v appetite, v weight,v exercise tolerance, muscle weakness, hypoglycaemia when fasting,v trauma & infection tolerance => physical collapse, cardiovascular crisis, Patients on glucocorticoid theraphy need ^ dose when ill or before surgery to mimic normal rise.
Excess: Cushing's syndrome (due to excess ACTH, adrenal tumor, or longterm treatment in transplant patient) - hyperglycaemia (not v by insulin), protein breakdown => muscle wasting, osteoporosis,striae on skin, v growth in children, ^appeptite, ^weight, abnormalfat deposits (buffulo hump, moon face), ^BP (as a little mineralocorticoidaction of cortisol), hirsutism & acne (as a little androgenic action).
Regulation: (a) High plasma [K+]=> direct ^ aldosterone secretion; (b) Low arterial BP/Low extracellular fluid volume/Low plasma [Na+]=>Renin-Angiotensin system => ^aldosterone secretion, (c) Sufficient background ACTH is needed for (a) and (b) to work.
Actions: (a) ^active reabsorption of Na+ from distal convoluted tubule => osmotic reabsorption of H2O (so plasma [Na+] unchanged) => ^blood volume, (b) ^excretion of K+ => v plasma [K+] as H2Odoes not follow K+, (c) ^excretion of H+ => more alkaline plasma.
Deficiency: (a) Na/H2O loss => dehydration, plasma depletion, v BP => fatal in a few days if untreated, (b) K+ retension=> hyperkalaemia => ^ cardiac excitability => ventricular fibrillation (fatal), (c) H+ retension=> metabolic acidosis.
Excess: Primary hyperaldosteronism (eg. aldersterone secreting tumor): (a) Na+/H2Oretension => ^blood volume => ^BP => low renin & angiotensin, (b) K+ loss => hypokalaemia => possible muscle weakness, (c) H+ loss => metabolic alkanosis.
Hypoadrenalism or Addison's disease = Deficiency of both Glucocorticoid and Mineralo corticoid. (a) Primary = failure of adrenal cortex itself, eg. destruction by antibodies, tumor,or surgery. v feedback inhibition of ACTH => ^ MSH => pigmentation of buccal mucosa. Test dose of ACTH has no effect on steroid levels in blood or urine. (b) Secondary = v ACTH (eg. anterior pituitary damage). Test dose of ACTH => rapid adrenal response.
Excess: Adrenogenital syndrome: (a) rapid growth (but early epiphyseal fusion) & early puberty in boys, (b) masculinization of females (male build & hair distribution)
Oogenesis: (a) Primary oocytes (dipolid) all madebefore birth from oogonia, (b) Secondary oocyte (haploid) + 1st polar body, just before ovulation, (c) Mature ovum + 2nd polar body, after fertilization.
Ovarian cycle (28 days): Primordial follicle -> Graffian follicle -> Ovulation (day 14) -> Corpus Luteum -> Degenerates (day 24) Regulation: (a) GnRH (from hypothalamus) => FSH & LH (from anterior pituitay) (b) FSH => Follicle development, Oestrogen (from Granulosa cells) (c) LH => Ovulation, Progestrone & oestrogen (both from corpus luteum) & androgen (from theca cells), (d) Oestrogen & progesterone => -ive feedback on GnRH, FSH & LH, but when oestrogen very high it has +ive feedback on LH => ovulation.
Uterine cycle: Menstrual flow (day 0-4) -> Proliferative phase (days 4-14) -> Secretory phase (days 14-28); Regulation: (a) ^Oestrogen => Proliferative phase, hyperplasia of endometrium, many tube-like glands form (b) ^Progesterne => Secretory phase, glands become convoluted, glycogen rich secretions (c) v Progesterone => Ischaemia & infartion of endometrium (day 28) ** See graphs of hormone cycles in Week 9 handout "Female reproductive function" **
Spermatogenesis (occurs between sertoli cells) (a)Spermatatogonium -> Primary spermatocytes (diploid) -> Secondary spermatocytes (haploid) -> Spermatids, (b) Mature to spermatozoa in epididymus, then entervas deferens for storage. Regulation: (a) GnRH (from hypothalamus)=> FSH & LH (from anterior pituitary) (b) FSH => Spermatogenesis (Sertoli cells) & Inhibin release (=> inhibits FSH release), (c) LH => Testesterone (from Leydig cells), (d) Testesterone => maintains male reproduction system, spermatogenesis, secondary sex characteristics, bone & muscle growth, ^BMR, ^libido & aggression.
Intercourse: (a) Erection: erotic stimuli + mechano-receptors=> spinal reflex => para-symp vasodilation of penile arterioles, (b) Ejagulation: Emission (symp contracts smooth muscle in epididymis, vas deferens & glands) + Expulsion (rhythmical contraction of skeletcal muscle compresses urethra). Seminal vessels: make fructose & prostaglandins. Prostate: releases alkali, clotting factors, fibrinolysin. Bulbo-urethral glands: release mucus.
Blastocyst has outer trophoblast (formsfetal part of placenta), blastocoele (forms yoke sac), and innercell mass (forms embryo). Placenta has fetal (chorionic)and maternal (decidual) components. It performs nutrient & gasexchange, removes waste, protects from toxins & infections, and endocrine(oestrogen, progesterone, HCG & somatomammotropin, which must be thelongest word I know, and I don't know it too well!) production.
Regulation: (a) HCG (human chorionic gonadotrophin)=> prevents regression of cropus luteum, (b) oestrogen & progesterone (initially from corpus luteum, later from placenta) => maintain pregnancy preventing menstruation.
Effect on mother: (a) morning sickness (mostly 1st trimester), (b) 40% ^ cardiac output, (c) ^ O2 use & CO2 production => 20% ^respiratory minute volume, (c) ^reabsorption of Na & H2O=> 20% ^blood volume, (d) ^GFR (golumerular filtration rate) => micturation frequency, (e) 10% ^ weight, (f) need ^ vitamins,Ca, Fe.
Suckling => (a) v PIH (from hypothalamus) => ^Prolactin production, (b) ^oxytocin (from ant pit.) => contractionof myoepithelial cells => eject milk into ducts. (c) Prolactin inhibits GnRH => prevents ovulation. (d) Colostrum (first 5 days) has moreprotein, antibacterials, IgA antibodies, but less fat & lactose.
Why can't women be as simple as men - it would save me a lot of typing !! :-)
After birth: (a) Placenta gone => ^ peripheralresistence => ^ left atrial pressure, (b) Lungs expand =>v pulmonaryresistance => v right atrial pressure, (c) the now high left & low right atrial pressures => close foreman ovale. (d) Oxygenated blood causes Ductus arteriosis & Ductus venuosis to close. If left to right shunt remains => ^ ventricular work => possible cardiac failure.
Changes with aging: (a) v blood production (low Hb, RBC, heamocrit), (b) less elastic arteries => ^ systolic BP, (c) arthersclerosis => ischaemic damage (d)v lung compliance, ^AWR (airway resistance), v alveolar surface area=> v gas transfer, (e) v liver & kidney function=> v conjugation & GFR => v drug metabolism, (f) v muscle, bone & join flexibility, (g) v neuron count => difficulty remembering & adapting to new siuations (h) presbycuis (hearing loss) & presbyopia (loss of near vision), (i) skin wrinkling, prostate enlargement, menopause.
!!! Happy revising !!!