o Occurs in cytoplasm.
o Anaerobic breakdown of glucose to pyruvate → 2 ATP per glucose.
o End product: lactate in anaerobic conditions.
o In mitochondria.
o Pyruvate → acetyl-CoA → CO₂, NADH, FADH₂.
o Central hub for amino acid and fatty acid catabolism.
o Inner mitochondrial membrane.
o Uses NADH/FADH₂ to generate ATP via electron transport chain (ETC).
o O₂ is final electron acceptor.
o Anabolic hormone; promotes glycogenesis, lipogenesis, protein synthesis.
o Increases glucose uptake (via GLUT-4 in muscle/adipose).
o Inhibits gluconeogenesis and glycogenolysis.
o Catabolic; stimulates gluconeogenesis, glycogenolysis, lipolysis.
o Acts primarily on liver.
o Cortisol, catecholamines, growth hormone → increase glucose (stress response).
• Location: Liver (part mitochondrial, part cytoplasmic).
• Converts ammonia (NH₃) (toxic) into urea, excreted by kidneys.
• Hyperammonaemia → encephalopathy (e.g., liver failure, inherited enzyme deficiencies).
• 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.
• 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).
• 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).
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
