Endocrine System pt 3

Endocrine System – Key Organs

• Pineal
• Hypothalamus
• Pituitary
• Thyroid
• Parathyroids
• Thymus
• Adrenals (Suprarenal)
• Pancreas
• Gonads – Ovary & Testes
• Kidney (Renin-secreting Juxta-glomerular cells)
• Heart (Atrial endocrine cells)
• Adipose tissue (Leptin)

Adrenal (Suprarenal) Glands

• “Two glands in one”
  • Adrenal medulla – modified sympathetic neural tissue, makes catecholamines (Epi/Norepi).
  • Adrenal cortex – endocrine tissue producing steroid hormones (corticosteroids).
• Cortical layers & principal products
  • Zona glomerulosa → mineralocorticoids (chiefly aldosterone).
  • Zona fasciculata → glucocorticoids (chiefly cortisol).
  • Zona reticularis → gonadocorticoids (chiefly androgens – DHEA, androstenedione).

Aldosterone – Regulation (“Primary regulator of Na⁺ & K⁺ balance”)

• Stimuli that ↑ release
  • $\uparrow$ K⁺ in blood (direct membrane depolarisation).
  • $\downarrow$ Blood volume / pressure → $\uparrow$ Renin → $\uparrow$ $\text{Angiotensin II}$.
  • ACTH (stress-related, minor).
• Inhibitor
  • Atrial Natriuretic Peptide (ANP) from overstretched atria.
• Major actions on kidney distal tubule / collecting duct
  • ↑ Na⁺ and water reabsorption → ↑ blood volume/pressure.
  • ↑ K⁺ secretion.

Mineralocorticoid Disorders

• Hyposecretion (part of Addison’s disease / hypo-aldosteronism)
  • Severe dehydration, hypotension, hyponatremia, hyperkalemia, hypoglycemia.
• Hypersecretion (Aldosteronism)
  • Usually adrenal cortex tumour / glomerulosa over-activity.
  • Hypertension, oedema, accelerated loss of K⁺ → neuromuscular problems.

Cortisol (Principal Glucocorticoid)

• “Stress hormone” – clear circadian rhythm (peak early morning).
• HPA axis: Hypothalamus (CRH) → Anterior pituitary (ACTH) → Adrenal cortex (cortisol) → negative feedback at both higher levels.
• Physiological actions
  • Gluconeogenesis → ↑ blood glucose.
  • Protein catabolism (skeletal muscle).
  • Lipolysis & redistribution of fat (central deposition).
  • Anti-inflammatory / immunosuppressive.
• Hypersecretion
  • Cushing’s syndrome – excess glucocorticoid (any source).
  • Cushing’s disease – pituitary ACTH excess.
  • Features: $\uparrow$ glucose, muscle atrophy, bone loss, buffalo hump, moon face, poor wound healing, oedema.
• Hyposecretion (Addison’s disease – combined glucocorticoid & mineralocorticoid deficit)
  • Weight loss, hypotension, hypoglycaemia, hyperpigmentation (↑ACTH cross-binding to MSH receptors).

Gonadocorticoids (Adrenal Androgens)

• Main cortical products: DHEA & androstenedione.
• Insignificant vs gonadal sex steroids after puberty, but crucial before.
• Hypersecretion – Adrenogenital syndrome
  • Males: precocious puberty, exaggerated virility.
  • Females: masculinisation – hirsutism, enlarged clitoris, ↑ libido.

Androgen Biosynthesis Pathway (Cholesterol → Sex Steroids)

• Cholesterol → Pregnenolone → Progesterone →
  • Mineralocorticoid branch → Aldosterone
  • Glucocorticoid branch → Cortisol
  • Androgen branch → DHEA → Androstenedione ↔ Testosterone.
• Key enzymes
  • 5α-Reductase: Testosterone → Dihydrotestosterone (DHT) (potent androgen).
  • Aromatase: Androgens → Estrogens (estradiol, estrone, estriol).

Adrenal Medulla – Catecholamines

• Acute “fight or flight” response – Epinephrine (>80 %), Norepinephrine.
• Short-term actions: ↑ HR, ↑ BP, bronchodilation, glycogenolysis, lipolysis.
• Catecholamine deficiency rarely critical (SNS can compensate).
• Hypersecretion (Pheochromocytoma)
  • Paroxysmal hypertension, tachycardia, hyperglycaemia, sweating, weight loss (↑ BMR).

Pancreas – Glucose Homeostasis

Insulin

• Synthesised as preproinsulin → proinsulin → active insulin (A- & B-chains joined by disulphides).
• Major stimuli: $\uparrow$ blood glucose (post-prandial).
• Actions
  • ↑ glucose uptake (GLUT-4) in muscle & adipose.
  • ↑ glycogenesis (liver, muscle).
  • ↑ lipogenesis; ↓ lipolysis.
  • Promotes protein synthesis.

Glucagon

• Released by α-cells when glucose falls.
• Actions: glycogenolysis, gluconeogenesis, lipolysis → ↑ blood glucose.

Blood Glucose Set-point

• Homeostasis ≈ 90\ \text{mg·dL^{-1}} ( \approx 5\ \text{mmol·L^{-1}} ).
• Negative feedback loop: Rising glucose → insulin; Declining glucose → glucagon.

Diabetes Mellitus

• Absolute/relative insulin deficit → hyperglycaemia.
• Type 1 (juvenile, insulin-dependent): autoimmune β-cell destruction.
• Type 2 (adult onset): insulin resistance ± secretory defect (most common).
• Gestational: ~4 % pregnancies.
• Metabolic cascade
  • Liver: ↑ gluconeogenesis & ketogenesis → ketone bodies → metabolic acidosis.
  • Muscle: protein catabolism.
  • Adipose: lipolysis.
• Clinical triad: Polyuria, Polydipsia, Polyphagia.
• Other manifestations: glycosuria, ketosis/ketonuria, electrolyte loss (Na⁺, K⁺, H⁺), dehydration, Kussmaul breathing, acetone breath, arrhythmias, CNS depression/coma.

Pineal Gland

• Contains calcified deposits (“brain sand”) visible radiologically.
• Secretes melatonin (serotonin-derived).
• Functions
  • Regulates circadian rhythm – darkness ↑ secretion → sleep induction.
  • Potent antioxidant; potential ageing modulation.
• Light (especially in shift-workers) suppresses melatonin → sleep disturbances.

Gonads

Female – Ovaries

• Estrogen (alone)
  • Maturation of reproductive organs, development of secondary sex characteristics.
• Progesterone ± Estrogen
  • Breast development, regulation of menstrual/uterine cycle.
• Menopause = permanent cessation of menstruation (ovarian failure).

Male – Testes

• Testosterone – synthesized from cholesterol; converted to DHT (5α-reductase) or estradiol (aromatase).
• Developmental role: differentiation of Wolffian ducts, external genitalia, descent of testes; prevents Müllerian duct development.
• Post-pubertal actions
  • Hair pattern (facial, body, baldness predisposition).
  • Spermatogenesis & erectile function.
  • ↑ Muscle mass & strength.
  • ↑ Bone density, RBC production, libido, aggression.
• Andropause – age-related ↓ circulating testosterone.

Renin–Angiotensin–Aldosterone System (RAAS)

1. ↓ Renal perfusion/composition (↓BP, ↓Na⁺, SNS) → Juxtaglomerular cells secrete renin.
2. Renin converts angiotensinogen (liver) → Angiotensin I.
3. $\text{ACE}$ (lung endothelium) converts Ang I → Angiotensin II.
4. Ang II effects
   a. Potent vasoconstriction → ↑ BP.
   b. Stimulates aldosterone release (adrenal ZG).
   c. Triggers thirst (hypothalamus).
   d. ↑ ADH from posterior pituitary (water retention).
   e. ↑ Na⁺ reuptake in proximal tubule.
5. Result: restoration of blood pressure/volume.

• Therapeutics
  • ACE inhibitors, Ang II receptor blockers (ARBs) antagonise steps 3 & 4.

Leptin (Adipocytokine)

• Secreted by white adipocytes proportionally to fat mass.
• Targets hypothalamic nuclei (ARC, VMH, PVN).
• Actions
  • ↓ Appetite (anorexigenic).
  • ↑ Energy expenditure.
  • Overall ↓ body weight.
• Obesity often involves leptin resistance rather than deficiency.

Atrial Natriuretic Peptide (ANP)

• Produced by atrial myocytes in response to stretch/volume overload.
• Integrated actions

1. ↓ Renin release.
2. ↓ Ang II formation.
3. ↓ Aldosterone secretion.
4. Systemic vasodilation → ↓ BP.
5. Kidneys: natriuresis & diuresis → ↓ blood volume.

• Physiological antagonist to RAAS.

Comparative Feedback Examples (Exam Pointers)

• Negative feedback:
  • HPA (CRH → ACTH → cortisol).
  • HPT (TRH → TSH → T₃/T₄).
  • Blood glucose (insulin/glucagon).
  • RAAS (BP/volume).
• Positive feedback:
  • Estrogen ↑ → LH surge (ovulation).
  • Oxytocin during labour & milk let-down.
• Hormones with Similar Actions
  • Catecholamines & cortisol: both elevate glucose (different time courses).
  • Aldosterone & Ang II: both increase Na⁺ retention & BP (via different mechanisms).
  • ANP vs RAAS hormones: functional antagonists.

Practical / Ethical / Clinical Notes

• Long-term exogenous glucocorticoids → iatrogenic Cushing’s; taper slowly to avoid adrenal crisis.
• Doping: anabolic androgen derivatives (e.g., nandrolone decanoate) banned in sport.
• Shift work & screen light hygiene important for melatonin-related sleep disorders.
• ACE inhibitors & ARBs – cornerstone therapy for hypertension, heart failure, diabetic nephropathy (ethical issue: accessibility & cost).
• Insulin therapy: balance against hypoglycaemia; education, monitoring technologies improve outcomes.