Endocrine, Renal & Musculoskeletal Physiology — Endocrine I–III (pituitary/thyroid, adrenal/pancreas/calcium, reproduction), Renal I–II (GFR, tubular reabsorption, RAAS, acid-base), and Bone & Muscle (contraction, bone cells, calcium regulation), condensed to the highest-yield facts.
| Topic | One-glance facts |
|---|---|
| Hormone classes | Peptides/proteins (3–200 aa): water-soluble, stored in vesicles, exocytosed, bind membrane receptors, fast (GH, ACTH, TSH, FSH/LH, ADH, oxytocin, insulin/glucagon, PTH). Steroids: cholesterol-derived, lipid-soluble, made on demand, bind intracellular receptors (cortisol, aldosterone, sex steroids, vitamin D). Tyrosine derivatives split: thyroid hormone (T3/T4) lipid-soluble/nuclear; catecholamines water-soluble/membrane. |
| Feedback control | Negative feedback is dominant (cortisol inhibits CRH + ACTH). Positive feedback is rare/self-limited (estrogen surge → LH surge; oxytocin in labor). Cyclic variation overlays both (cortisol circadian rhythm, menstrual cycle). |
| Anterior vs. posterior pituitary | Adenohypophysis (from Rathke's pouch) synthesizes its own hormones — GH, ACTH, TSH, prolactin, FSH, LH — under hypothalamic releasing/inhibiting hormones delivered via portal blood. Neurohypophysis is neural tissue that only stores/releases ADH and oxytocin, which are made in the hypothalamus and delivered by axons. |
| Hypothalamic releasing hormones | GHRH → GH; somatostatin (GHIH) inhibits GH and TSH. TRH → TSH (and prolactin). CRH → ACTH. GnRH → FSH/LH. Dopamine (PIH) tonically inhibits prolactin — the one hormone under default inhibition rather than stimulation. |
| Growth hormone | Anabolic for protein (↑ amino acid transport/synthesis), mobilizes fat, and is "diabetogenic" (↓ glucose uptake by muscle/fat, ↑ hepatic gluconeogenesis). Growth effects mostly indirect via liver IGF-1. Stimulated by sleep, exercise, stress, hypoglycemia, ghrelin; inhibited by ↑ glucose/FFA, obesity, aging. Falls with age (~6 → ~1.6 ng/mL). |
| ADH and oxytocin | ADH (supraoptic nucleus): 9-aa peptide, acts on collecting duct (aquaporin insertion) and vasculature (vasoconstriction); released by ↑ osmolality or ↓ blood volume/pressure. Oxytocin (paraventricular nucleus): 9-aa peptide, causes milk let-down and uterine contraction; classic positive-feedback hormone. |
| Thyroid hormone synthesis | NIS traps iodide → pendrin moves it into colloid → peroxidase organifies it onto thyroglobulin (MIT/DIT → T4/T3), stored extracellularly in colloid. TSH triggers pinocytosis/proteolysis, releasing ~90% T4/10% T3. T3 acts faster (6–12h) and more potently than T4 (2–3 days, t½ ~6–7 days). ~99% protein-bound (TBG); only free hormone is active. Raises BMR, O2 use, heart rate/cardiac output. |
| Topic | One-glance facts |
|---|---|
| Adrenal cortex zones | "GFR → Salt, Sugar, Sex": zona Glomerulosa → aldosterone (~15%), zona Fasciculata → cortisol (fasciculata + reticularis ~75%, under ACTH), zona Reticularis → androgens (DHEA, androstenedione, ~10%). All synthesized from cholesterol via the rate-limiting, ACTH-stimulated step cholesterol → pregnenolone. |
| Aldosterone | Made in zona glomerulosa; acts on collecting-duct principal cells (basolateral Na+/K+-ATPase, apical ENaC, ROMK) → ↑ Na+ reabsorption, ↑ K+/H+ secretion. Driven mainly by ↑ plasma K+ and angiotensin II; suppressed by ↑ ECF volume; ACTH only permissive. |
| Cortisol | Made in zona fasciculata, ~90% bound to CBG. ↑ gluconeogenesis and blood glucose ("adrenal diabetes"), ↓ protein everywhere except the liver, mobilizes fat, anti-inflammatory/immunosuppressive. HPA axis (CRH → ACTH → cortisol, negative feedback) with circadian peak ~6–8 AM. 11β-HSD2 inactivates cortisol → cortisone to protect the mineralocorticoid receptor (licorice blocks it → apparent mineralocorticoid excess). |
| Adrenal medulla | Modified sympathetic tissue — chromaffin cells act like postganglionic neurons without axons, driven directly by preganglionic sympathetic fibers. Secretes epinephrine (~80%) and norepinephrine, reinforcing fight-or-flight: ↑ HR/contractility, ↑ blood glucose, ↑ lipolysis, bronchodilation. |
| Insulin | Beta cells (~60% of islet), t½ 6 min; C-peptide marks endogenous production. Glucose → GLUT2 → glucokinase → ↑ ATP → closes K+ channel → depolarization → Ca2+ influx → exocytosis (sulfonylureas act at this same K+ channel). ↑ glucose uptake via GLUT4 (muscle/fat) and glycogen/fat/protein synthesis; brain glucose entry (GLUT1) is insulin-independent. |
| Glucagon and somatostatin | Glucagon (alpha cells, ~25%) → ↑ glycogenolysis and gluconeogenesis, opposing insulin; stimulated by hypoglycemia, amino acids, fasting/exercise. Somatostatin (delta cells, ~10%) is a paracrine brake inhibiting both insulin and glucagon (also the hypothalamic GH-inhibiting hormone). |
| Calcium regulation | PTH (chief cells, sensing low Ca2+ via CaSR) raises plasma Ca2+: bone resorption (via osteoblasts → osteoclasts, which have no PTH receptor), ↑ renal Ca2+ reabsorption + ↓ phosphate reabsorption, and stimulates 1α-hydroxylase. Vitamin D activation: skin → liver (25-OH) → kidney (1,25-OH, PTH-driven) → ↑ gut Ca2+/phosphate absorption. Calcitonin (parafollicular C cells) is released by high Ca2+ and inhibits osteoclasts — a minor, transient opponent of PTH. |
| Topic | One-glance facts |
|---|---|
| Male HPG axis | Pulsatile GnRH (every 1–3h) is essential — continuous GnRH shuts the axis down. LH → Leydig cells → testosterone; FSH → Sertoli cells → support spermatogenesis + secrete inhibin (selectively suppresses FSH). Testosterone feeds back negatively on hypothalamus/pituitary. |
| Testosterone vs. DHT | Testosterone (~98% bound to albumin/SHBG) drives internal ducts, muscle, and libido. Converted to DHT by 5α-reductase in target tissues; DHT drives external genitalia, testicular descent, prostate, and male-pattern hair/balding. Puberty: voice deepening, body/facial hair, ↑ muscle/bone, ↑ RBCs, eventual epiphyseal closure. |
| Spermatogenesis | Continuous from puberty (up to ~120 million sperm/day), taking ~64–74 days. Spermatogonia (mitosis) → primary spermatocyte → meiosis I → 2 secondary spermatocytes → meiosis II → 4 haploid spermatids → spermiogenesis → spermatozoa. One primary spermatocyte yields 4 sperm, vs. one oocyte yielding a single ovum. |
| Two-cell estrogen model | LH acts on theca cells to make androgens (theca lacks aromatase); FSH induces aromatase in granulosa cells, which convert those androgens to estrogen — both gonadotropins are required. In the luteal phase, the corpus luteum makes so much progesterone that it predominates over conversion. |
| Menstrual cycle | Follicular phase: rising estrogen = negative feedback, rebuilds proliferative endometrium. Pre-ovulatory estrogen peak flips to positive feedback → LH surge → ovulation (~day 14). Luteal phase: corpus luteum makes estrogen + progesterone (secretory endometrium), suppressing the axis. No pregnancy → corpus luteum dies (~day 26) → menses (~40 mL blood). |
| Pregnancy hormones | Fertilization occurs in the ampulla; blastocyst reaches the uterus in ~3–5 days, implants ~1–3 days later. hCG (syncytiotrophoblast) rescues the corpus luteum, peaking ~10–12 weeks (basis of pregnancy testing); the placenta then makes rising estrogen and progesterone to term. Progesterone quiets the uterus; estrogen enlarges the uterus/breasts and softens the pelvis. |
| Parturition and lactation | Rising estrogen:progesterone ratio + more uterine oxytocin receptors + fetal cortisol/prostaglandins + cervical stretch (positive feedback via oxytocin) drive labor (dilation → expulsion → placental delivery → involution). Postpartum, falling estrogen/progesterone unblock prolactin, which drives milk synthesis via suckling-triggered bursts; oxytocin drives let-down; suckling suppresses GnRH (and ovulation). |
| Topic | One-glance facts |
|---|---|
| Bladder innervation | Parasympathetic pelvic nerves (S2–S4) contract the detrusor to empty ("P = Pee") and carry stretch afferents. Sympathetic hypogastric nerves (L1–L2) relax the detrusor/tighten the neck to store. Somatic pudendal nerve controls the voluntary external sphincter. |
| Micturition reflex | Stretch receptors → pelvic afferents → sacral cord → parasympathetic efferents → detrusor contraction (bladder pressure 40–60 mmHg); the reflex is self-regenerative. Pons facilitates, cerebral cortex mainly inhibits, until voiding is convenient. Normal residual urine 5–10 mL. |
| Glomerular filtration barrier | Fenestrated endothelium (negatively charged glycocalyx) + basement membrane (negative proteoglycans) + podocyte foot processes/filtration slits. Blocks by both size and negative charge — albumin (~6 nm) is smaller than the ~8 nm pores but is electrostatically repelled. Filters ~180 L/day. |
| GFR and clearance | GFR ≈ 125 mL/min (≈180 L/day). Clearance C = (U × V)/P. Inulin is the gold standard (freely filtered, not reabsorbed/secreted); creatinine clearance slightly overestimates true GFR (minor tubular secretion) but is the practical clinical marker. Filtration fraction = GFR/renal plasma flow ≈ 125/650 ≈ 0.2. GFR ~10% lower in women, declines with age. |
| Starling forces / GFR equation | GFR = Kf × (PG − PB − πG + πB). PG ≈ 60 mmHg favors filtration; PB ≈ 18 mmHg and πG ≈ 32 mmHg oppose it; net filtration pressure ≈ 10 mmHg outward. PG is the main lever the body regulates. |
| Afferent vs. efferent arterioles | ↑ afferent resistance → ↓ PG, ↓ renal blood flow, ↓ GFR. ↑ efferent resistance → ↑ PG and ↑ GFR while renal blood flow still falls — the mechanism angiotensin II uses to preserve GFR under low perfusion. Over-constricting the efferent eventually drops GFR too (via ↑ filtration fraction/πG). |
| Autoregulation | Myogenic mechanism: ↑ arterial pressure stretches the afferent arteriole → reflex constriction. Tubuloglomerular feedback: macula densa senses NaCl delivery — high GFR → more NaCl → adenosine/ATP constrict the afferent; low GFR → renin → angiotensin II preserves GFR. Together these hold GFR/RBF nearly constant over ~80–180 mmHg; kidneys receive ~22% of cardiac output. |
| Topic | One-glance facts |
|---|---|
| Nephron segments | Proximal tubule reabsorbs ~65% of filtered Na+/water/glucose/amino acids/HCO3−. Thin descending limb is water-permeable (concentrates filtrate). Thick ascending limb = "diluting segment" (Na-K-2Cl transporter, water-impermeable, loads the medulla with salt). Early distal tubule holds the macula densa and is the major site of Ca2+ reabsorption (PTH-enhanced). Late distal/collecting duct: ADH-controlled water permeability, aldosterone-controlled Na+/K+. |
| ADH mechanism | Made in supraoptic/paraventricular nuclei; released by ↑ plasma osmolality (osmoreceptors) or ↓ blood volume/pressure (baroreceptors). Binds V2 receptors on collecting-duct principal cells → inserts aquaporin-2 → water reabsorption → concentrated urine. No ADH → duct stays impermeable → dilute urine. |
| Kidney hormone mnemonic | ADH Adds water; Aldosterone Adds sodium (↑ Na+ reabsorption/↑ K+ secretion via Na+/K+-ATPase, ENaC, ROMK, driven by angiotensin II + high K+); Angiotensin II Assists Na+/water retention (plus efferent constriction, preserving GFR); ANP Allows Na+/water to leave (natriuresis, opposes RAAS); PTH Preserves calcium, Tosses phosphate. |
| RAAS cascade | Low perfusion pressure, low NaCl delivery (macula densa), or sympathetic β1 stimulation → JG cells release renin → angiotensinogen (liver) → angiotensin I → (ACE, lungs) → angiotensin II → efferent constriction + ↑ Na+ reabsorption + ↑ ADH + ↑ thirst + aldosterone release → Na+/water retention → ↑ blood volume and pressure. |
| Countercurrent multiplier | Single effect: the water-impermeable ascending limb actively pumps NaCl out, making the interstitium ~200 mOsm more concentrated. Fluid displacement: the water-permeable descending limb loses water into that salty interstitium. Repeating these steps multiplies the gradient from ~300 mOsm (cortex) to ~1200 mOsm (deep medulla/papilla); the vasa recta act as a countercurrent exchanger that preserves the gradient. |
| Sodium reabsorption distribution | Proximal tubule ~65%, thick ascending limb ~25%, distal tubule ~5%, collecting duct ~3% — the small but hormonally (aldosterone) fine-tuned fraction. All powered by the basolateral Na+/K+-ATPase, which keeps intracellular Na+ low and the cell interior negative (~−70 mV). |
| Acid–base handling | Proximal tubule reabsorbs ~80–90% of filtered HCO3− (requires carbonic anhydrase). Type A intercalated cells (collecting duct) secrete H+ via H+-ATPase/H+-K+-ATPase and generate new HCO3−; type B cells secrete HCO3−. Ammonium buffer (NH3 + H+ → NH4+) excretes acid and regenerates bicarbonate — key for handling a chronic acid load. |
| Topic | One-glance facts |
|---|---|
| Neuromuscular junction | Motor neuron synapse at the motor end plate (one per fiber). Action potential → voltage-gated Ca2+ opens at dense bars → ~125 vesicles release acetylcholine (exocytosis). Nicotinic receptor is a nonselective cation channel (Na+/K+/Ca2+), net inward Na+ → end-plate potential → opens neighboring voltage-gated Na+ channels → muscle action potential. Acetylcholinesterase in the 20–30 nm cleft terminates it (one impulse = one response). |
| Excitation–contraction coupling | Action potential travels the T-tubule → dihydropyridine receptor (voltage sensor) mechanically opens the ryanodine receptor → Ca2+ out of the sarcoplasmic reticulum → contraction; Ca2+ pump returns it, calsequestrin buffers storage. Skeletal = voltage-triggered (VACR, no extracellular Ca2+ needed); cardiac = calcium-triggered (CACR, needs extracellular Ca2+). |
| Sarcomere & sliding filaments | Z disc to Z disc; thin (actin) anchors at Z, thick (myosin) at center, titin tethers/recoils. Ca2+ binds troponin C → tropomyosin uncovers actin active sites → myosin "walk-along" power stroke (ATP detaches/re-cocks the head). A band stays constant; I band and H zone narrow (filaments slide, don't shorten). Length–tension peaks at optimal overlap. |
| Fiber types & motor units | Speed set by myosin ATPase Vmax. Slow (Type I, red): oxidative, high myoglobin/mitochondria/capillaries, fatigue-resistant, recruited first. Fast (Type II, white): glycolytic, large diameter, powerful, fatigable. Motor unit = one neuron + all its fibers (all one type); small units = precise (extraocular ~10 fibers), large units = coarse/powerful (quadriceps ~1000). Denervation → loss of tone → flaccid → atrophy. |
| Smooth muscle | Mononucleate, no striations. Unitary/visceral (gap-junction syncytium, often spontaneously active) vs. multiunit (discrete, densely innervated). Myosin-based regulation: no troponin — Ca2+ binds calmodulin → myosin light chain kinase phosphorylates myosin (1 ATP) → contraction; myosin light chain phosphatase dephosphorylates → relaxation. 60–75% shortening, very energy-efficient, latch state holds force; "diffuse junction" innervation; poorly developed SR (uses extracellular Ca2+). |
| Bone cells & ossification | Osteoblast secretes type I collagen (90% of bone protein, needs vitamin C) + osteocalcin (bonds hydroxyapatite to collagen, needs vitamin K) → osteoid; hydroxyapatite + Ca/phosphate salts calcify it (~70% inorganic). Osteocyte = osteoblast trapped in a lacuna, senses load (piezoelectric) via canaliculi. Osteoclast = fused hemopoietic (monocyte/macrophage) progenitors, multinucleated, resorbs bone in Howship's lacuna via acid + cathepsin K. |
| Calcium regulation | PTH raises Ca2+: binds osteoblasts → they make RANKL + M-CSF to mature osteoclasts (and PTH lowers osteoprotegerin, the RANKL decoy); ↑ renal Ca2+ reabsorption (distal), ↓ phosphate reabsorption (proximal → excreted), ↑ active vitamin D → ↑ gut Ca2+. Only free ionized Ca2+ (~60%) is active; Ca and phosphate move inversely. Calcitonin lowers Ca2+ (inhibits osteoclasts; from thyroid C-cells in hypercalcemia). GH/IGF-I drive growth-plate chondrocytes. |