1. Major Energy Pathways

•    Glycolysis

o    Occurs in cytoplasm.

o    Anaerobic breakdown of glucose to pyruvate → 2 ATP per glucose.

o    End product: lactate in anaerobic conditions.

•    TCA (Krebs) cycle

o    In mitochondria.

o    Pyruvate → acetyl-CoA → CO₂, NADH, FADH₂.

o    Central hub for amino acid and fatty acid catabolism.

•    Oxidative phosphorylation

o    Inner mitochondrial membrane.

o    Uses NADH/FADH₂ to generate ATP via electron transport chain (ETC).

o    O₂ is final electron acceptor.

2. Hormonal Control of Glucose Metabolism

•    Insulin

o    Anabolic hormone; promotes glycogenesis, lipogenesis, protein synthesis.

o    Increases glucose uptake (via GLUT-4 in muscle/adipose).

o    Inhibits gluconeogenesis and glycogenolysis.

•    Glucagon

o    Catabolic; stimulates gluconeogenesis, glycogenolysis, lipolysis.

o    Acts primarily on liver.

•    Other hormones

o    Cortisol, catecholamines, growth hormone → increase glucose (stress response).

3. Urea Cycle

•    Location: Liver (part mitochondrial, part cytoplasmic).

•    Converts ammonia (NH₃) (toxic) into urea, excreted by kidneys.

•    Hyperammonaemia → encephalopathy (e.g., liver failure, inherited enzyme deficiencies).

4. Starvation and Fasting Metabolism

•    Short-term fasting (up to ~24h)

o    Glycogenolysis (liver) main glucose source.

•    Prolonged fasting (>24h)

o    Gluconeogenesis: amino acids, lactate, glycerol used.

o    Ketogenesis: fatty acid-derived ketone bodies (acetoacetate, β-hydroxybutyrate) → brain energy source.

•    Key features

o    ↓ insulin, ↑ glucagon.

o    Muscle protein breakdown → amino acids → gluconeogenesis.

5. Acid-Base Physiology

•    Henderson–Hasselbalch equation

o    pH = 6.1 + log([HCO₃⁻] / (0.03 × pCO₂))

o    Respiratory (CO₂) and metabolic (HCO₃⁻) components.

•    Buffers

o    Bicarbonate (major extracellular), phosphate, proteins (e.g., Hb).

•    Compensation

o    Metabolic acidosis → hyperventilation (↓ CO₂).

o    Respiratory acidosis → renal HCO₃⁻ retention (days).

6. Electrolyte Balance Principles

•    Sodium (Na⁺)

o    Major extracellular cation.

o    Hyponatraemia: often due to excess water (e.g., SIADH, polydipsia).

o    Hypernatraemia: water loss > Na⁺ loss.

•    Potassium (K⁺)

o    Major intracellular cation.

o    Hypokalaemia: diuretics, GI loss, insulin shift.

o    Hyperkalaemia: renal failure, acidosis, tissue breakdown.

•    Calcium (Ca²⁺)

o    50% ionised (active), rest protein-bound.

o    Hypocalcaemia: hypoparathyroidism, Vit D deficiency.

o    Hypercalcaemia: malignancy, hyperparathyroidism.

•    Magnesium (Mg²⁺)

o    Cofactor in ATP reactions.

o    Low Mg²⁺ → refractory hypokalaemia, hypocalcaemia.

•    Phosphate (PO₄³⁻)

o    Important for ATP, bone mineralisation.

o    Hypophosphataemia: refeeding syndrome, DKA recovery.

o    Hyperphosphataemia: renal failure.

Extra Revision Pearls

•    In DKA, ketone production contributes to anion gap metabolic acidosis.

•    In alkalosis, K⁺ shifts intracellularly → hypokalaemia.

•    Serum calcium correction for albumin: ↓ albumin → falsely low total Ca²⁺, ionised usually normal.

•    Severe hypoMg²⁺ can mimic hypocalcaemia neurologically (tetany).