[10/07, 9:41 am] Kashif Bhai Nmc: Cerebellum Basal ganglia Pain Corticospinal tracts Upper and lower motor lesions Hypothalamus Sleep Speech pathway and disoreders [10/07, 9:41 am] Kashif Bhai Nmc: Visual pathway Taste pathway Olfactory Colour vision Rods and cons Hearing loss [10/07, 9:41 am] Kashif Bhai Nmc: Thyroid Gluco corticoids Insulin Hypo and hyper thyroidism Mechanism of hormone action Parathyroid hormone Pitutary hormones (mainly posterior pitutary) Aldosterone answer these

Reading File

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Reading File

Here is a complete, exam-focused revision covering every topic on the list. Sources: Costanzo Physiology 7e, Kandel Principles of Neural Science 6e, Neuroscience: Exploring the Brain 5e, Sabiston Textbook of Surgery, and Medical Physiology (Boron & Boulpaep).

NEUROSCIENCE SECTION

1. CEREBELLUM

Structure: Foliated structure attached to the brainstem, dorsal to pons and medulla. Divided into three functional lobes: flocculonodular (vestibulocerebellum), anterior (spinocerebellum), posterior (cerebrocerebellum/neocerebellum).

Functions:

Coordination of movement (rate, range, force, direction)
Planning and execution of movement
Maintenance of posture and balance
Coordination of head and eye movements

Inputs: Sensory position info from spinal cord + motor info from cerebral cortex + vestibular info from inner ear.

Output pathway: Cerebellar cortex → deep cerebellar nuclei (dentate, interposed, fastigial) → thalamus → motor cortex.

Cerebellar lesions - Signs of Ataxia:

Delayed onset of movement
Overshoot/undershoot of target (dysmetria)
Dysdiadochokinesia - inability to perform rapid alternating movements
Intention tremor - tremor that increases as limb approaches target (perpendicular to direction of movement)
Rebound phenomenon - inability to stop a movement
Wide-based, staggering gait

Key distinction: Cerebellar = INTENTION tremor (worsens on movement). Parkinson's = RESTING tremor.

(Costanzo Physiology 7e)

2. BASAL GANGLIA

Components:

Striatum = Caudate nucleus + Putamen (main input station)
Globus pallidus (internal = GPi, external = GPe)
Subthalamic nucleus (STN)
Substantia nigra (pars compacta = SNc, pars reticulata = SNr)
Associated thalamic nuclei: Ventral anterior (VA) + Ventral lateral (VL)

Main Function: Aid in planning and execution of smooth, purposeful voluntary movements (via modulation of motor cortex). Also contribute to cognitive and affective functions.

Direct Pathway (excitatory net output → facilitates movement): Cortex → Striatum (↓ GPi/SNr) → ↓ Inhibition on Thalamus → ↑ Thalamus → ↑ Motor cortex

Net effect: MORE movement
Neurotransmitters: GABA (striatum to GPi), Glutamate (thalamus to cortex)
Dopamine D1 receptors on striatum EXCITE direct pathway

Indirect Pathway (inhibitory net output → suppresses unwanted movements): Cortex → Striatum (↓ GPe) → ↓ Inhibition of STN → ↑ STN → ↑ GPi/SNr → ↑ Inhibition on Thalamus → ↓ Motor cortex

Net effect: LESS movement
Dopamine D2 receptors on striatum INHIBIT indirect pathway

Dopamine balance: SNc sends dopamine to striatum. Dopamine FACILITATES movement overall (excites direct via D1, inhibits indirect via D2). Loss of dopamine → Parkinson's disease.

Diseases:

Disease	Pathology	Features
Parkinson Disease	Degeneration of SNc (dopamine loss)	Resting tremor, bradykinesia, rigidity (cogwheel), shuffling gait, mask-like face. Tx: L-DOPA, dopamine agonists (bromocriptine)
Huntington Disease	Destruction of striatal cholinergic + GABAergic neurons (hereditary, CAG repeat on chromosome 4)	Chorea (writhing movements), dementia. No cure

(Costanzo Physiology 7e)

3. PAIN PATHWAY

Pain receptors (nociceptors): Free nerve endings. Stimulated by tissue damage, chemicals (bradykinin, substance P, prostaglandins).

First-order neurons (afferents):

Aδ fibers (myelinated, fast) → sharp, well-localized, acute pain
C fibers (unmyelinated, slow) → dull, burning, chronic pain

Spinal cord entry: Dorsal horn. Synapse in substantia gelatinosa (Rexed laminae I, II, V).

Second-order neurons: Cross the midline in the anterior white commissure → ascend in Anterolateral (spinothalamic) tract.

Pathway summary:

Nociceptor → Aδ/C fiber → Dorsal horn (laminae I, II, V) → Cross to contralateral side → Lateral spinothalamic tract → Thalamus (VPL nucleus) → Somatosensory cortex (S1, S2)

Trigeminal Pain Pathway (face/head): Trigeminal nerve → Spinal trigeminal nucleus (brainstem) → Cross midline → Trigeminal lemniscus → Thalamus → Somatosensory cortex

Modulation of Pain - Gate Control Theory:

Aβ fibers (light touch) can REDUCE pain by activating inhibitory interneurons in dorsal horn
Explains why rubbing an injury reduces pain
Basis of TENS (transcutaneous electrical nerve stimulation)

Descending pain modulation: Periaqueductal grey (PAG) → raphe nuclei → releases serotonin and enkephalins (endogenous opioids) → inhibit dorsal horn transmission.

Endogenous opioids: Enkephalins, endorphins, dynorphins → act on μ, δ, κ receptors → inhibit pain transmission.

(Neuroscience: Exploring the Brain 5e)

4. CORTICOSPINAL TRACT (Pyramidal Tract)

Origin: Primary motor cortex (area 4) + premotor cortex (area 6) + somatosensory cortex

Course:

Motor cortex → Internal capsule (posterior limb) → Cerebral peduncles
Pons (scattered fibers in basilar pons)
Medulla - forms pyramids → 85% decussate at pyramidal decussation (lower medulla)
Lateral corticospinal tract in contralateral spinal cord → synapse on lower motor neurons (LMN) in anterior horn

15% that DON'T cross → Anterior corticospinal tract → cross at spinal cord level.

Function: Voluntary, fine skilled movements especially of distal limbs (hands, fingers).

Somatotopic organization (homunculus): Leg fibers are medial, arm fibers are lateral in the cortex and spinal cord.

5. UPPER vs. LOWER MOTOR NEURON LESIONS

Feature	UMN Lesion	LMN Lesion
Location	Above anterior horn (cortex, internal capsule, brainstem, spinal cord)	Anterior horn cell, nerve root, peripheral nerve, NMJ, muscle
Tone	Increased (spasticity - velocity-dependent)	Decreased (flaccid)
Reflexes	Hyperreflexia (exaggerated DTRs)	Hyporeflexia/areflexia
Plantar reflex	Extensor (Babinski sign positive)	Flexor (normal)
Muscle wasting	Mild, disuse atrophy (late)	Severe, early atrophy
Fasciculations	Absent	Present (denervation)
Clonus	Present	Absent
Weakness pattern	Contralateral, extensors in arm/flexors in leg	Same side, same distribution as nerve
Fibrillations (EMG)	Absent	Present

Examples:

UMN: Stroke, MS, spinal cord compression above lesion level, ALS (upper component)
LMN: Poliomyelitis, Guillain-Barré, peripheral neuropathy, ALS (lower component)

6. HYPOTHALAMUS

Location: Ventral to thalamus, forms floor and lateral walls of third ventricle.

Functions (mnemonic: TAN HATS):

Temperature regulation (anterior hypothalamus = cooling; posterior = heat conservation)
Autonomic control (sympathetic and parasympathetic)
Neurohypophysis control (produces ADH and oxytocin)
Hunger/satiety (lateral = hunger/feeding center; ventromedial = satiety center)
Adenohypophysis control (releases TRH, CRH, GnRH, GHRH, dopamine, somatostatin)
Thirst and water balance (osmoreceptors trigger ADH release)
Sexual behavior/circadian rhythms (suprachiasmatic nucleus = biological clock)

Portal system: Hypothalamic hormones travel via hypothalamo-hypophyseal portal blood to anterior pituitary to control its secretion.

Posterior pituitary (neurohypophysis): Does NOT produce hormones - stores and releases ADH (vasopressin) and oxytocin which are made in hypothalamic paraventricular and supraoptic nuclei.

(Costanzo Physiology 7e)

7. SLEEP

EEG stages:

State	EEG Pattern	Features
Awake (eyes open)	Beta rhythm (13-30 Hz), low voltage, high frequency, desynchronized	Alert
Awake (eyes closed)	Alpha rhythm (8-13 Hz), synchronous	Relaxed
Stage 1 (NREM)	Alpha + theta waves	Light sleep, hypnic jerks
Stage 2 (NREM)	Sleep spindles + K complexes	True sleep onset
Stage 3 (NREM)	Delta waves + sleep spindles	Deep sleep
Stage 4 (NREM)	Delta waves (slow-wave sleep)	Deepest sleep; sleepwalking, night terrors here
REM sleep	Desynchronized, low voltage, fast (resembles awake EEG)	Dreams, loss of muscle tone, rapid eye movements

REM sleep features:

"Paradoxical sleep" - EEG looks awake but person is hardest to arouse
Loss of muscle tone (atonia)
Rapid eye movements
Penile erection
Loss of thermoregulation
Fluctuating HR, BP, respiration
Most vivid dreaming occurs here

Sleep cycle: REM occurs every ~90 minutes. First REM periods are short; later ones are longer.

Age: Newborns = 50% REM. Young adults = 25% REM. Elderly = little REM.

Sleep centers:

VLPO (ventrolateral preoptic nucleus) in hypothalamus → promotes sleep (inhibits arousal systems)
Reticular activating system (RAS) → promotes wakefulness
Raphe nuclei (serotonin), Locus coeruleus (noradrenaline) - both wakefulness promoting but shut off in REM

(Costanzo Physiology 7e)

8. SPEECH PATHWAY AND DISORDERS

Key cortical areas:

Broca's area (Area 44, 45) - Inferior frontal gyrus (left hemisphere, dominant) → Motor production of speech
Wernicke's area (Area 22) - Posterior superior temporal gyrus → Comprehension of speech
Arcuate fasciculus - White matter tract connecting Wernicke's to Broca's area

Speech pathway:

Wernicke's area (comprehension) → Arcuate fasciculus → Broca's area (motor planning) → Primary motor cortex → Corticobulbar tract → Motor nuclei of CN VII, IX, X, XII → Muscles of speech (lips, tongue, larynx)

Aphasia Types:

Type	Location	Fluency	Comprehension	Repetition	Key feature
Broca's (Expressive)	Broca's area (frontal)	Non-fluent	Intact	Impaired	Patient aware, frustrated; "telegraphic" speech
Wernicke's (Receptive)	Wernicke's area (temporal)	Fluent	Impaired	Impaired	Unaware; word salad, neologisms
Conduction	Arcuate fasciculus	Fluent	Intact	Impaired	Cannot repeat sentences
Global	Both Broca's + Wernicke's	Non-fluent	Impaired	Impaired	Severe, large MCA territory
Anomic	Angular gyrus	Fluent	Intact	Intact	Can't find words (tip-of-tongue)

Dysarthria = Motor problem with articulation (not a language problem) - slurred, nasal, or explosive speech. Dysphonia = Problem with voice production (larynx/vocal cords).

9. VISUAL PATHWAY

Pathway:

Photoreceptors (retina) → Bipolar cells → Retinal ganglion cells → Optic nerve → Optic chiasm → Optic tract → Lateral Geniculate Nucleus (LGN) of thalamus → Optic radiation → Primary visual cortex (V1, Area 17, calcarine sulcus)

At the optic chiasm:

Nasal (medial) fibers from each retina CROSS to opposite optic tract
Temporal (lateral) fibers stay ipsilateral
Result: Each optic tract carries information from the CONTRALATERAL visual hemifield

Visual field defects (classic exam):

Site of Lesion	Visual Defect
Optic nerve (before chiasm)	Monocular blindness (same eye)
Optic chiasm (center)	Bitemporal hemianopia (tunnel vision - pituitary tumor)
Optic tract (after chiasm)	Contralateral homonymous hemianopia
Meyer's loop (temporal lobe)	Contralateral superior quadrantanopia ("pie in the sky")
Parietal optic radiation	Contralateral inferior quadrantanopia ("pie on the floor")
Occipital cortex (V1)	Contralateral homonymous hemianopia with macular sparing

Two streams of visual processing:

Dorsal "Where" pathway → Parietal lobe → guides movement (visually guided reaching)
Ventral "What" pathway → Temporal lobe → object recognition, face recognition

(Kandel Principles of Neural Science 6e)

10. TASTE (GUSTATORY) PATHWAY

Five basic tastes: Sweet, sour, salty, bitter, umami.

Receptors: Taste buds on tongue (papillae: fungiform, circumvallate, foliate).

Cranial nerves carrying taste:

CN VII (chorda tympani branch) → anterior 2/3 of tongue
CN IX (glossopharyngeal) → posterior 1/3 of tongue
CN X (vagus) → epiglottis and pharynx

Central pathway:

Taste receptors → CN VII/IX/X → Nucleus of Solitary Tract (NTS) in medulla → Thalamus (VPM nucleus) → Primary gustatory cortex (Insula + frontal operculum)

11. OLFACTORY PATHWAY

Only sensory pathway that does NOT relay through thalamus first.

Pathway:

Olfactory receptor neurons (nasal epithelium, CN I) → Cribriform plate → Olfactory bulb (glomeruli, mitral cells) → Olfactory tract → Piriform cortex / Primary olfactory cortex (medial temporal lobe, amygdala, entorhinal cortex) → Thalamus (mediodorsal nucleus) → Orbitofrontal cortex (conscious smell)

Clinical: Anosmia (loss of smell) = head trauma (shearing of CN I at cribriform plate), frontal meningioma, COVID-19.

Foster Kennedy syndrome: Ipsilateral anosmia + optic atrophy, contralateral papilledema (frontal lobe tumor).

12. COLOUR VISION, RODS AND CONES

Photoreceptors:

Feature	Rods	Cones
Number	~120 million	~6 million
Location	Peripheral retina	Concentrated in fovea/macula
Pigment	Rhodopsin (opsin + retinal)	Photopsins (red/green/blue)
Function	Night vision, low light (scotopic)	Color vision, fine detail, bright light (photopic)
Sensitivity	Highly sensitive (single photon)	Less sensitive, need bright light
Acuity	Low	High (fovea = maximum acuity)
Convergence	High (many rods → one bipolar cell)	Low (1 cone → 1 bipolar at fovea)

Color vision - Trichromatic theory (Young-Helmholtz):

Three types of cones: S (short, blue ~420nm), M (medium, green ~530nm), L (long, red ~560nm)
Color perception results from ratio of activation of these three cone types

Opponent-process theory (Hering): At the ganglion cell level, signals are processed in opponent pairs: Red-Green, Blue-Yellow, Black-White. Explains afterimages.

Color blindness: Usually X-linked recessive (red-green deficiency). More common in males.

Deuteranopia = green cone absent
Protanopia = red cone absent
Tritanopia = blue cone absent (autosomal, rare)

Dark adaptation: Rods slowly regenerate rhodopsin in dark (takes ~20-30 min for full dark adaptation). Cones adapt faster but less sensitively.

13. HEARING LOSS

Two types:

Type	Mechanism	Rinne Test	Weber Test
Conductive	Problem in outer/middle ear (wax, otitis media, otosclerosis)	BC > AC (negative Rinne)	Lateralizes to affected ear
Sensorineural	Problem in cochlea or CN VIII (noise damage, presbycusis, Meniere's)	AC > BC (positive Rinne, but reduced)	Lateralizes to normal/better ear

Rinne test: Tuning fork on mastoid (bone conduction = BC) then next to ear (air conduction = AC). Normal: AC > BC.

Weber test: Tuning fork on forehead/vertex. Normal: heard equally in both ears.

Auditory pathway:

Cochlea (hair cells, organ of Corti) → CN VIII (vestibulocochlear) → Cochlear nuclei (medulla) → Superior olivary nucleus (bilateral) → Lateral lemniscus → Inferior colliculus (midbrain, auditory reflex) → Medial geniculate nucleus (thalamus) → Primary auditory cortex (A1, Heschl's gyrus, area 41, temporal lobe)

Key: Auditory pathway is bilateral after cochlear nuclei (hence unilateral cortical lesions rarely cause complete deafness).

ENDOCRINOLOGY SECTION

14. THYROID HORMONES

Synthesis steps:

Iodide trapping - Na/I symporter actively transports I⁻ into follicular cells
Oxidation - TPO (thyroid peroxidase) oxidizes I⁻ → I₂
Organification - TPO iodinates tyrosine residues on thyroglobulin (Tg) → MIT (monoiodotyrosine) and DIT (diiodotyrosine)
Coupling - TPO couples: DIT + DIT = T4 (thyroxine), DIT + MIT = T3 (triiodothyronine)
Secretion - TSH stimulates follicular cells to endocytose colloid, lysosomal enzymes cleave T4/T3 from Tg → released into blood

Transport: >99% bound to TBG (thyroxine-binding globulin), albumin, transthyretin. <1% free (active).

T3 vs T4:

T4 is the main secreted form (prohormone)
T3 is 4× more potent, formed by peripheral deiodination of T4 (mainly in liver, kidney)

Mechanism of action: T3 enters cell → binds nuclear thyroid hormone receptor (TR) → homodimer or heterodimer with RXR → binds thyroid response elements (TRE) on DNA → stimulates gene transcription (genomic action).

HPT Axis:

Hypothalamus (TRH) → Anterior pituitary (TSH) → Thyroid (T3/T4) → Negative feedback on hypothalamus and pituitary

Actions of thyroid hormones:

↑ Basal metabolic rate (BMR), O₂ consumption, heat production (calorigenic)
↑ Cardiac output and heart rate (↑ β-adrenergic receptor expression)
Essential for fetal/childhood neurological development and growth
↑ Metabolism of carbohydrates, lipids, proteins
Required for normal reproductive function

(Sabiston Textbook of Surgery)

15. HYPOTHYROIDISM vs HYPERTHYROIDISM

Feature	Hypothyroidism	Hyperthyroidism
Common cause	Hashimoto's thyroiditis (autoimmune, anti-TPO Ab), iodine deficiency	Graves' disease (TSI/TRAb autoantibody), toxic nodule
TSH	High ↑ (primary)	Low ↓ (primary)
T3/T4	Low ↓	High ↑
Metabolic rate	Decreased	Increased
Weight	Gain	Loss
Heart rate	Bradycardia	Tachycardia, palpitations, AF
Temperature	Cold intolerance, hypothermia	Heat intolerance, sweating, fever
Skin/hair	Dry skin, coarse hair, myxedema	Warm moist skin, hair loss
GI	Constipation	Diarrhea
Neurology	Lethargy, depression, delayed reflexes	Anxiety, tremor, hyperreflexia
Specific signs	Periorbital edema, hoarse voice, macroglossia, carpal tunnel	Exophthalmos (Graves'), pretibial myxedema, thyroid bruit
Congenital	Cretinism (if untreated) - mental retardation, short stature	-
Crisis	Myxedema coma	Thyroid storm
Treatment	Levothyroxine (T4)	PTU, methimazole, β-blockers, radioiodine, surgery

Myxedema: Non-pitting edema due to accumulation of glycosaminoglycans in tissues. Cretinism: Severe hypothyroidism in infancy/childhood → irreversible mental retardation + stunted growth.

16. MECHANISM OF HORMONE ACTION

Three main types:

Type 1: Lipid-soluble hormones (steroid hormones, thyroid hormones)

Cross cell membrane freely
Bind intracellular/nuclear receptors
Receptor-hormone complex acts as transcription factor
Binds to hormone response elements (HRE) on DNA
Stimulates/inhibits gene transcription → new protein synthesis
Slow onset (hours), long duration
Examples: Cortisol, Aldosterone, Estrogen, Testosterone, T3

Type 2: Water-soluble hormones (peptide hormones, catecholamines)

Cannot cross cell membrane
Bind to cell surface receptors (GPCRs, receptor tyrosine kinases)
Activate second messengers:
- cAMP pathway (via Gs protein → adenylyl cyclase): LH, FSH, TSH, ACTH, ADH (V2), PTH, Glucagon, Epinephrine (β)
- IP3/DAG/Ca²⁺ pathway (via Gq protein → phospholipase C): TRH, GnRH, Oxytocin, Angiotensin II, ADH (V1)
- cGMP pathway: ANP, NO
- Tyrosine kinase (JAK-STAT or receptor itself): Insulin (RTK), GH, Prolactin, Cytokines
Fast onset (seconds-minutes), short duration

Type 3: Eicosanoids (prostaglandins, leukotrienes)

Act locally (autocrine/paracrine)
Bind G-protein coupled receptors

17. GLUCOCORTICOIDS (Cortisol)

Synthesis: Adrenal cortex, zona fasciculata.

Regulation: Hypothalamus (CRH) → Pituitary (ACTH) → Adrenal cortex (Cortisol). Cortisol feeds back negatively on both.

Diurnal variation: Peak cortisol in early morning (~8 am), lowest at midnight.

Mechanism: Binds intracellular glucocorticoid receptor (GR) → translocates to nucleus → GRE binding → gene transcription changes.

Actions:

Metabolic: ↑ Gluconeogenesis (liver), ↑ Protein catabolism (muscle), ↑ Lipolysis → net: RAISE blood glucose (anti-insulin, diabetogenic)
Anti-inflammatory: ↓ Phospholipase A2 (via lipocortin) → ↓ Arachidonic acid → ↓ Prostaglandins + Leukotrienes; ↓ Cytokines; ↓ Histamine release; ↑ Neutrophils, ↓ Lymphocytes, eosinophils, basophils
Immunosuppressive: ↓ T-cell and B-cell activity
Cardiovascular: ↑ Vascular tone (permissive effect on catecholamines)
Bone: ↓ Osteoblasts, ↑ Osteoclasts → osteoporosis (long-term use)
CNS: Mood elevation, euphoria (excess) or depression
Fetal: Stimulates surfactant production in fetal lungs

Cushing's syndrome (excess cortisol):

Central obesity, moon face, buffalo hump
Striae (purple)
HTN, hyperglycemia
Osteoporosis
Thin skin, easy bruising
Hypokalemia, muscle weakness
Cause: pituitary tumor (Cushing's disease), adrenal tumor, ectopic ACTH, iatrogenic

Addison's disease (adrenal insufficiency):

Weakness, hypotension, hypoglycemia
Hyperpigmentation (↑ ACTH/MSH)
Hyponatremia, hyperkalemia
Salt craving, nausea
Treat: Hydrocortisone + Fludrocortisone

18. INSULIN

Source: β-cells of islets of Langerhans, pancreas.

Structure: 51-amino acid peptide; A chain + B chain connected by disulfide bonds; derived from proinsulin (cleaved to insulin + C-peptide).

Stimuli for secretion:

↑ Blood glucose (primary) - via KATP channel closure in β-cells
↑ Amino acids (arginine)
GLP-1, GIP (incretins)
Vagal stimulation (acetylcholine)
β-adrenergic stimulation (epinephrine → ↑ insulin)
Sulphonylureas (drug)

Inhibition: α-adrenergic stimulation (stress), somatostatin, fasting, diazoxide.

Mechanism (β-cell):

Glucose enters β-cell via GLUT2 → Glycolysis → ↑ ATP/ADP ratio → Closes KATP channels → Membrane depolarization → Voltage-gated Ca²⁺ channels open → Ca²⁺ influx → Insulin granule exocytosis

Mechanism of action on target cells:

Insulin binds receptor tyrosine kinase (RTK) → Autophosphorylation → IRS-1 phosphorylation → PI3K → PKB/Akt → Multiple downstream effects

Metabolic actions:

Tissue	Effect
Liver	↑ Glycogen synthesis, ↑ Glycolysis, ↑ Lipogenesis; ↓ Gluconeogenesis, ↓ Glycogenolysis
Muscle	↑ Glucose uptake (GLUT4), ↑ Glycogen synthesis, ↑ Protein synthesis
Adipose	↑ Glucose uptake (GLUT4), ↑ Lipogenesis, ↓ Lipolysis

Overall effect: ANABOLIC - lowers blood glucose, promotes energy storage.

Type 1 Diabetes: Autoimmune destruction of β-cells → absolute insulin deficiency. Type 2 Diabetes: Insulin resistance + relative insulin deficiency.

19. PARATHYROID HORMONE (PTH)

Source: Chief cells of parathyroid glands (4 glands, usually posterior thyroid).

Stimulus: ↓ Serum Ca²⁺ (detected by calcium-sensing receptor, CaSR).

Mechanism: Binds GPCR → ↑ cAMP (PTH-1R) → PKA activation.

Actions - Raises serum Ca²⁺ and lowers phosphate:

Site	Action
Bone	↑ Osteoclast activity (via RANKL on osteoblasts) → bone resorption → ↑ Ca²⁺ + ↑ PO₄ release
Kidney	↑ Ca²⁺ reabsorption (DCT), ↓ PO₄ reabsorption (proximal tubule - phosphaturia); ↑ 1α-hydroxylase → ↑ active Vit D (1,25-dihydroxyvitamin D)
Gut	Indirect (via Vit D activation) → ↑ Ca²⁺ and PO₄ absorption

Net result: ↑ Ca²⁺, ↓ PO₄ (phosphate wasted in urine).

Hyperparathyroidism: Stones (kidney), Bones (osteitis fibrosa cystica), Groans (GI), Psychic moans.

Hypoparathyroidism: Hypocalcemia → tetany (Chvostek's sign, Trousseau's sign), perioral tingling, muscle cramps, prolonged QT.

Calcitonin (from thyroid C-cells): Opposes PTH; ↓ serum Ca²⁺ by inhibiting osteoclasts, increasing renal excretion of Ca²⁺.

20. PITUITARY HORMONES (Focus on Posterior Pituitary)

Pituitary gland: Two lobes:

Anterior pituitary (adenohypophysis): True gland; controlled by hypothalamic releasing/inhibiting hormones via portal blood.
Posterior pituitary (neurohypophysis): Extension of hypothalamic neurons (not true gland); STORES and releases hormones made in hypothalamus.

Posterior Pituitary Hormones:

1. ADH (Vasopressin, AVP)

Made in: Supraoptic nucleus (mainly) of hypothalamus
Stimulus for release: ↑ Plasma osmolality (main), ↓ blood volume/pressure, pain, nausea, nicotine
Inhibition: ↓ Osmolality, ↑ blood volume, ethanol (major inhibitor)
Mechanism: V2 receptor (kidney collecting duct) → cAMP → PKA → Inserts aquaporin-2 (AQP2) water channels → ↑ water reabsorption → concentrated urine
V1 receptor (blood vessels) → Gq/IP3 → vasoconstriction (hence "vasopressin")
Diabetes Insipidus (DI):
- Central DI: ADH deficiency (head trauma, pituitary surgery) → dilute urine, polydipsia, polyuria → Treat with desmopressin (DDAVP)
- Nephrogenic DI: Kidney unresponsive to ADH (lithium, hypercalcemia, V2 receptor mutation)
SIADH: Excess ADH → ↑ water retention → dilutional hyponatremia → confusion, seizures

2. Oxytocin

Made in: Paraventricular nucleus of hypothalamus
Actions:
- Uterine contraction during labour (Ferguson reflex - positive feedback loop)
- Milk ejection (let-down reflex) during breastfeeding
- Bonding and social behaviour
Clinical: Synthetic oxytocin (Pitocin) used to induce/augment labour

Anterior Pituitary Hormones (brief):

Hormone	Hypothalamic control	Target	Action
GH	GHRH ↑ / Somatostatin ↓	Liver → IGF-1	Growth, lipolysis, anti-insulin
TSH	TRH ↑	Thyroid	T3/T4 synthesis
ACTH	CRH ↑	Adrenal cortex	Cortisol synthesis
LH/FSH	GnRH ↑	Gonads	Sex hormone synthesis, gametogenesis
Prolactin	Dopamine ↓ (main inhibitor) / TRH ↑	Breast	Milk production

21. ALDOSTERONE

Source: Adrenal cortex, zona glomerulosa.

Stimuli (via RAAS - Renin-Angiotensin-Aldosterone System):

↓ Blood pressure / ↓ Na⁺ → JGA cells release Renin
Renin converts Angiotensinogen → Angiotensin I
ACE (lung) converts Ang I → Angiotensin II
Ang II acts on adrenal cortex → releases Aldosterone
Also stimulated by: ↑ K⁺ (direct), ACTH (minor)

Mechanism of action: Steroid hormone → intracellular receptor → nuclear → ↑ transcription of ENaC (epithelial Na channels) and Na/K-ATPase on principal cells of collecting duct.

Actions (kidney - collecting duct):

↑ Na⁺ reabsorption → water follows → ↑ blood volume and pressure
↑ K⁺ excretion (principal cells)
↑ H⁺ excretion (intercalated cells) → metabolic alkalosis

Net effect: ↑ Na⁺ and water retention, ↓ K⁺, ↓ H⁺ → ↑ Blood pressure.

Hyperaldosteronism (Conn's syndrome):

HTN, hypokalemia, metabolic alkalosis
Primary: adrenal adenoma or bilateral hyperplasia
Secondary: ↑ Renin (renal artery stenosis, heart failure, cirrhosis)

Hypoaldosteronism (Addison's):

Hypotension, hyperkalemia, metabolic acidosis, hyponatremia

Drugs:

Spironolactone / Eplerenone = aldosterone antagonists (K⁺-sparing diuretics)
ACE inhibitors (e.g., lisinopril) = block Ang II formation → ↓ Aldosterone

QUICK SUMMARY TABLE: Key Hormones, Sources, and Second Messengers

Hormone	Source	Receptor/2nd Messenger	Key Action
Insulin	Pancreas β-cells	RTK (tyrosine kinase)	↓ Blood glucose
Glucagon	Pancreas α-cells	GPCR → cAMP	↑ Blood glucose
TSH	Anterior pituitary	GPCR → cAMP	Thyroid hormone synthesis
PTH	Parathyroid	GPCR → cAMP	↑ Ca²⁺
ADH (V2)	Posterior pituitary	GPCR → cAMP	↑ Water reabsorption
ADH (V1)	Posterior pituitary	GPCR → IP3/Ca²⁺	Vasoconstriction
Oxytocin	Posterior pituitary	GPCR → IP3/Ca²⁺	Uterine contraction, milk ejection
Cortisol	Adrenal fasciculata	Intracellular → nuclear	Anti-inflammatory, ↑ glucose
Aldosterone	Adrenal glomerulosa	Intracellular → nuclear	↑ Na⁺ retention, ↓ K⁺
T3	Thyroid/peripheral	Intracellular → nuclear	↑ BMR
GH	Anterior pituitary	RTK/JAK-STAT	Growth, anti-insulin

This covers the full NMC exam list. The main sources are Costanzo Physiology 7e, Kandel's Principles of Neural Science 6e, Neuroscience: Exploring the Brain 5e, and Sabiston's Textbook of Surgery.

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