Physiology: Cells, tissues, homeostasis, fluids and acid–base balance

Cellular physiology, tissues and homeostasis

• The cell: Cell Structure and Organelles | The Cell Membrane and Transport | Resting Membrane Potential | Cell Signalling and Receptors | The Cell Cycle, Growth and Cell Death
• Tissues: The Four Basic Tissues | Epithelium and Glands | Connective Tissue, Cartilage and Bone
• Body fluids and homeostasis: Homeostasis and Feedback | Body Fluid Compartments | Capillary Exchange and Oedema | Acid–base Physiology | Energy Metabolism | Temperature Regulation
• Revision: Cells and Homeostasis at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🧬 Cells, tissues, body fluids and homeostasis — page 1 of the Anatomy and Physiology chapter. Almost all disease is a failure of a cell, a tissue or a control system. Understanding how cells keep their internal environment, how fluid moves between compartments and how the body defends its pH and temperature explains oedema, hyponatraemia, acidosis, hyperkalaemia and fever — the bread and butter of clinical medicine.
Your four questions for every physiology topic: What is normal — and what keeps it there? Which sensor, control centre and effector are involved? What happens when the system fails (too much, too little)? How does this explain the patient's signs, results and treatment?

Cell Structure and Organelles

• The human body contains about 30–40 trillion cells of over 200 types; each (except red cells) has a nucleus, cytoplasm and organelles enclosed by a plasma membrane.
• Organelles:

  Organelle	Function	Clinical link
  Nucleus	Contains DNA (chromatin); transcription of RNA; nucleolus makes ribosomes	Nuclear changes in cancer (large nuclei, mitoses)
  Mitochondria	ATP production (oxidative phosphorylation); own DNA (maternal inheritance); apoptosis	Mitochondrial disorders (MELAS); cyanide and CO block the respiratory chain
  Rough endoplasmic reticulum	Protein synthesis for export and membranes (ribosomes attached)	Abundant in plasma cells and pancreatic acinar cells
  Smooth endoplasmic reticulum	Lipid and steroid synthesis; drug metabolism (cytochrome P450); calcium storage (sarcoplasmic reticulum in muscle)	Enzyme induction (rifampicin, carbamazepine)
  Golgi apparatus	Modifies, packages and sorts proteins (glycosylation)	I-cell disease (faulty lysosomal targeting)
  Lysosomes	Acid hydrolases digest worn-out material and engulfed particles	Lysosomal storage diseases (Gaucher, Tay–Sachs, Fabry)
  Peroxisomes	Fatty acid oxidation (very long chain), hydrogen peroxide breakdown	Zellweger syndrome, adrenoleukodystrophy
  Cytoskeleton	Microfilaments (actin), intermediate filaments, microtubules (cell division, transport, cilia)	Colchicine and vinca alkaloids act on microtubules; primary ciliary dyskinesia
  Ribosomes	Translate mRNA into protein	Target of antibiotics (bacterial 70S — macrolides, tetracyclines, aminoglycosides)

• From gene to protein — DNA → (transcription) → mRNA → (translation at ribosomes) → protein → (folding, modification in ER and Golgi).
• Cell junctions — tight junctions (seal epithelia — blood–brain barrier), adherens junctions and desmosomes (attach cells — pemphigus targets desmosomes), hemidesmosomes (attach to the basement membrane — bullous pemphigoid), gap junctions (direct electrical and chemical communication — heart muscle).

The Cell Membrane and Transport

• Structure — phospholipid bilayer (hydrophilic heads outside, hydrophobic tails inside) with cholesterol (stiffness) and proteins (channels, carriers, receptors, enzymes) — the "fluid mosaic" model; glycocalyx on the outer surface.
• What crosses easily — small, lipid-soluble molecules (O₂, CO₂, steroids, alcohol, many drugs); water crosses via aquaporins; ions and large polar molecules need proteins.
• Types of transport:

  Type	How it works	Examples
  Simple diffusion	Down a concentration gradient; no energy	O2, CO2 in the lung
  Facilitated diffusion	Down a gradient via a carrier or channel; saturable	Glucose via GLUT transporters (GLUT4 is insulin-dependent); ion channels
  Primary active transport	Against a gradient using ATP	Na+/K+-ATPase (3 Na+ out, 2 K+ in); H+/K+-ATPase (stomach — PPIs); Ca2+-ATPase
  Secondary active transport	Uses the Na+ gradient made by the Na+/K+-ATPase	SGLT (glucose with Na+ — gut and kidney; SGLT2 inhibitors); Na+/Ca2+ exchanger; NKCC2 (loop diuretics)
  Osmosis	Water moves to the side with more solute	Cell swelling in hyponatraemia
  Endocytosis and exocytosis	Vesicles take in or release large molecules	LDL uptake (receptor-mediated); hormone and neurotransmitter release

• Na⁺/K⁺-ATPase — uses about a quarter of resting energy; keeps intracellular K⁺ high and Na⁺ low; inhibited by digoxin; stimulated by insulin and beta-2 agonists (which is why they treat hyperkalaemia).
• Oral rehydration solution works because glucose–sodium co-transport (SGLT1) pulls water into gut cells even in secretory diarrhoea (cholera).
• Channelopathies — cystic fibrosis (CFTR chloride channel), long QT syndromes (K⁺ and Na⁺ channels), some epilepsies, periodic paralyses.

Resting Membrane Potential

• Resting membrane potential — the inside of a cell is negative compared with the outside — about –70 mV in neurons and –90 mV in skeletal and cardiac muscle.
• Why:
  • The Na⁺/K⁺-ATPase sets up gradients — K⁺ high inside (about 140 mmol/L vs 4 outside), Na⁺ high outside (about 140 vs 10 inside).
  • At rest the membrane is mainly permeable to K⁺ (leak channels) — K⁺ diffuses out, leaving negative charge (proteins) inside.
  • The resting potential is therefore close to the potassium equilibrium potential (about –90 mV) — calculated with the Nernst equation; the Goldman equation includes all permeable ions.
• Ion distribution:

  Ion	Outside (mmol/L)	Inside (mmol/L)	Equilibrium potential
  Na+	140	10–15	About +60 mV
  K+	4	140	About –90 mV
  Cl–	105	5–10	About –70 mV
  Ca2+ (free)	1.2	0.0001	About +120 mV

• Clinical consequences of potassium:
  • Hyperkalaemia — smaller K⁺ gradient → resting potential less negative (partially depolarised) → sodium channels inactivate → reduced excitability — peaked T waves, broad QRS, bradycardia, VF or asystole; calcium gluconate stabilises the membrane (raises threshold).
  • Hypokalaemia — hyperpolarisation and delayed repolarisation — muscle weakness, ileus, U waves, arrhythmias (especially with digoxin).
• Calcium and excitability — low extracellular calcium increases nerve excitability (lower threshold) — tetany, perioral tingling, Chvostek's and Trousseau's signs; high calcium reduces excitability (weakness, constipation, confusion).

Cell Signalling and Receptors

• Types of signalling — endocrine (hormones in blood), paracrine (to neighbouring cells — prostaglandins), autocrine (to itself — IL-2), neural (neurotransmitters across synapses), juxtacrine (direct contact).
• Receptor families:

  Receptor	Mechanism and speed	Examples
  Ligand-gated ion channel	Opens a channel — milliseconds	Nicotinic ACh receptor (neuromuscular junction), GABA-A (benzodiazepines), NMDA, 5-HT3 (ondansetron)
  G protein-coupled receptor (GPCR)	Activates G proteins and second messengers — seconds	Adrenoceptors, muscarinic, opioid, dopamine, histamine, angiotensin II, PTH, glucagon receptors — the largest drug target family
  Enzyme-linked (tyrosine kinase)	Receptor phosphorylates proteins — minutes	Insulin, growth factors (EGFR, VEGF); tyrosine kinase inhibitors (imatinib); JAK–STAT (cytokines — JAK inhibitors)
  Nuclear (intracellular) receptor	Lipid-soluble ligand alters gene transcription — hours to days	Steroids (cortisol, aldosterone, oestrogen), thyroid hormone, vitamin D, retinoids

• G proteins and second messengers:
  • Gs — ↑ adenylyl cyclase → ↑ cAMP → protein kinase A (β-receptors, glucagon, TSH, PTH, ADH V2).
  • Gi — ↓ cAMP (α2, M2, opioid, D2).
  • Gq — ↑ phospholipase C → IP₃ (releases intracellular Ca²⁺) and DAG (protein kinase C) (α1, M1 and M3, H1, angiotensin II AT1, V1).
  • Disease — cholera toxin (permanently activates Gs → watery diarrhoea), pertussis toxin (blocks Gi), McCune–Albright (activating Gs mutation).
• Agonists and antagonists — agonists activate receptors (efficacy and potency); antagonists block (competitive — surmountable; non-competitive); partial agonists (buprenorphine) produce a submaximal response.
• Receptor regulation — down-regulation with prolonged stimulation (tolerance — beta-agonists, opioids); up-regulation with blockade (rebound tachycardia when beta-blockers stop suddenly).

The Cell Cycle, Growth and Cell Death

• Cell cycle — G1 (growth) → S (DNA synthesis) → G2 (preparation) → M (mitosis) — G0 is a resting state; checkpoints (G1/S — p53 and Rb; G2/M) stop damaged cells dividing.
• Cell types by dividing ability:
  • Labile — divide continuously — skin, gut lining, bone marrow (affected by chemotherapy — mucositis, hair loss, neutropenia).
  • Stable — normally quiescent, can divide when needed — liver, kidney tubules, fibroblasts.
  • Permanent — can't divide — neurons, cardiac muscle, (most) skeletal muscle — heal by scarring.
• Mitosis (two identical diploid cells) vs meiosis (four haploid gametes; crossing over; non-disjunction causes trisomies) — see the Genetics chapter.
• Cellular adaptations:
  • Hypertrophy — bigger cells (left ventricle in hypertension; skeletal muscle with exercise).
  • Hyperplasia — more cells (endometrium, prostate, thyroid in Graves').
  • Atrophy — smaller cells (disuse, denervation, ischaemia, ageing).
  • Metaplasia — one mature cell type replaced by another (Barrett's oesophagus — squamous to columnar; bronchial squamous metaplasia in smokers) — can progress to dysplasia.
  • Dysplasia — disordered growth with atypical cells (cervical CIN) — precancerous.
• Cell death:

  	Apoptosis	Necrosis
  Nature	Programmed, energy-dependent ("cell suicide")	Uncontrolled death from injury
  Features	Cell shrinks, nuclear fragmentation, apoptotic bodies; no inflammation	Cell swells and bursts; inflammation
  Triggers	Development, DNA damage (p53), cytotoxic T cells, withdrawal of growth factors; caspases and Bcl-2 family	Ischaemia, toxins, infection, trauma
  Examples	Shaping fingers in the embryo; failure → cancer (Bcl-2 in follicular lymphoma — venetoclax)	Coagulative (MI), liquefactive (brain, abscess), caseous (TB), fat (pancreatitis), fibrinoid (vasculitis), gangrene

• Healing — regeneration (labile and stable tissue with an intact framework) or repair by scarring (fibrosis) — inflammation → granulation tissue → remodelling.

The Four Basic Tissues

• Types of muscle:

  	Skeletal	Cardiac	Smooth
  Appearance	Striated, multinucleate, long fibres	Striated, branched, 1–2 central nuclei, intercalated discs	Non-striated, spindle-shaped, 1 nucleus
  Control	Voluntary (somatic nerves)	Involuntary — intrinsic pacemaker, autonomic modulation	Involuntary — autonomic, hormones, stretch
  Ca2+ source	Sarcoplasmic reticulum; troponin	Extracellular entry triggers SR release ("calcium-induced calcium release"); troponin	Extracellular and SR; calmodulin and myosin light-chain kinase
  Regeneration	Limited (satellite cells)	Very limited — scar after MI	Good

• Glial cells — astrocytes (support, blood–brain barrier, scar — gliosis; astrocytoma), oligodendrocytes (myelin in the CNS — multiple sclerosis), Schwann cells (myelin in the PNS — Guillain–Barré; schwannoma), microglia (immune cells of the CNS), ependymal cells (line ventricles; CSF).

Epithelium and Glands

• Classification — by number of layers (simple — one layer; stratified — several; pseudostratified — one layer that looks layered) and cell shape (squamous, cuboidal, columnar).
• Types and locations:

  Epithelium	Where	Function
  Simple squamous	Alveoli, capillaries (endothelium), serosa (mesothelium)	Diffusion, filtration
  Simple cuboidal	Kidney tubules, thyroid follicles, small ducts	Secretion, absorption
  Simple columnar	Stomach, intestine (with microvilli and goblet cells), gallbladder	Absorption, secretion
  Pseudostratified ciliated columnar ("respiratory epithelium")	Nasal cavity, trachea, bronchi	Mucociliary clearance
  Stratified squamous (keratinised)	Skin	Protection, waterproofing
  Stratified squamous (non-keratinised)	Mouth, oesophagus, vagina, cornea, ectocervix	Protection from abrasion
  Transitional (urothelium)	Renal pelvis, ureters, bladder, proximal urethra	Stretch; barrier to urine

• Transition zones are where cancers often start — squamocolumnar junction of the cervix (HPV), gastro-oesophageal junction (Barrett's), anorectal junction.
• Cancer naming — epithelial cancers are carcinomas (squamous cell carcinoma, adenocarcinoma from glands, urothelial carcinoma); connective tissue cancers are sarcomas.
• Glands:
  • Exocrine — secrete through ducts (salivary, sweat, pancreatic acini, breast).
  • Endocrine — ductless, secrete into blood (thyroid, adrenal, islets).
  • Secretion types — merocrine (exocytosis — most), apocrine (part of the cell — axillary sweat, breast), holocrine (whole cell — sebaceous glands).
• Basement membrane — type IV collagen and laminin; invasion through it distinguishes invasive cancer from carcinoma in situ; antibodies against it — Goodpasture's (anti-GBM); Alport syndrome (type IV collagen mutation).

Connective Tissue, Cartilage and Bone

• Components — cells (fibroblasts, adipocytes, macrophages, mast cells) and extracellular matrix — fibres (collagen, elastin, reticulin) and ground substance (proteoglycans, glycosaminoglycans, water).
• Collagen — the body's main structural protein (triple helix; needs vitamin C for hydroxylation — scurvy):
  • Type I — bone, tendon, skin, scar (late) — osteogenesis imperfecta.
  • Type II — cartilage, vitreous.
  • Type III — blood vessels, early scar, skin — vascular Ehlers–Danlos.
  • Type IV — basement membranes — Alport, Goodpasture.
• Elastin — recoil in arteries, lungs and skin (fibrillin scaffold — Marfan syndrome; elastin breakdown in emphysema — alpha-1 antitrypsin deficiency).
• Adipose tissue — white fat (energy store, endocrine — leptin, adiponectin) and brown fat (heat production — infants).
• Cartilage — avascular (heals poorly):
  • Hyaline — articular surfaces, costal cartilage, trachea, growth plates (osteoarthritis — loss of hyaline cartilage).
  • Fibrocartilage — intervertebral discs, menisci, pubic symphysis.
  • Elastic — ear, epiglottis.
• Bone:
  • Cortical (compact) — outer shell, osteons (Haversian systems) — 80% of bone mass.
  • Trabecular (cancellous) — inner spongy bone; metabolically active — vertebrae, femoral neck and distal radius (osteoporotic fracture sites).
  • Cells — osteoblasts (build bone — alkaline phosphatase), osteocytes (mechanosensors — sclerostin), osteoclasts (resorb bone — from monocytes; activated by RANKL — denosumab blocks it; bisphosphonates inhibit them).
  • Ossification — endochondral (cartilage model replaced by bone — long bones, growth plates — achondroplasia) and intramembranous (skull vault, clavicle — cleidocranial dysplasia).
  • Remodelling — continuous; about 10% of the skeleton is replaced each year; controlled by PTH, vitamin D, calcitonin, oestrogen (menopause → bone loss), mechanical loading.
• Fracture healing — haematoma → inflammation → soft callus (cartilage) → hard callus (woven bone) → remodelling (lamellar bone) — slowed by smoking, diabetes, steroids, NSAIDs (possibly), poor blood supply (scaphoid, femoral neck, tibia).

Homeostasis and Feedback

• Homeostasis — keeping the internal environment (temperature, pH, glucose, blood pressure, osmolality, oxygen) within narrow limits (Claude Bernard's "milieu intérieur"; Cannon).
• Components of a control system — sensor (receptor) → control centre (integrator — often the hypothalamus or brainstem) → effector → response.
• Negative feedback (most systems) — the response opposes the change:
  • Blood pressure — baroreceptors (carotid sinus, aortic arch) → medulla → heart rate and vascular tone.
  • Blood glucose — insulin and glucagon.
  • Osmolality — hypothalamic osmoreceptors → ADH and thirst.
  • Hormone axes — hypothalamus → pituitary → target gland (e.g. cortisol suppresses CRH and ACTH — the basis of suppression tests; long-term steroids suppress the adrenals).
• Positive feedback (amplifies the change — usually to complete an event) — oxytocin in labour (Ferguson reflex), the LH surge before ovulation, blood clotting cascade, action potential upstroke (sodium channels).
• Feedforward — anticipatory responses (salivation before eating; increased breathing at the start of exercise).
• Disease as failed homeostasis — diabetes (glucose), hypertension (BP), heart failure (neurohormonal activation becomes harmful), shock (compensatory mechanisms overwhelmed).
• Normal ranges — defined as the central 95% of a healthy population — so 1 in 20 healthy people have a "normal" value outside the range; age, sex, pregnancy and ethnicity matter.

Body Fluid Compartments

• Total body water (TBW) — about 60% of body weight in adult men (about 42 L in a 70 kg man), 50–55% in women (more fat), 75% in term infants, and less in older people and obesity (fat contains little water).
• Distribution ("60–40–20"):

  Compartment	Fraction	Volume (70 kg)	Main ions
  Intracellular fluid (ICF)	Two-thirds of TBW (40% of body weight)	About 28 L	K+, phosphate, proteins, Mg2+
  Extracellular fluid (ECF)	One-third of TBW (20% of body weight)	About 14 L	Na+, Cl–, HCO3–
  — Interstitial fluid	Three-quarters of ECF	About 10.5 L	As plasma, little protein
  — Plasma	One-quarter of ECF	About 3.5 L	Na+, Cl–, proteins (albumin)
  — Transcellular	Small	About 1 L	CSF, synovial, pleural, GI secretions

• Blood volume — about 70 mL/kg in adults (about 5 L) and 80 mL/kg in children.
• Where IV fluids go:
  • 0.9% saline or Hartmann's (isotonic, sodium-containing) — stays in the ECF — only about a quarter stays in plasma (1 L raises plasma volume by about 250 mL).
  • 5% glucose — glucose is metabolised, leaving free water that spreads through all of TBW — only about 1/12 stays in plasma — useless for resuscitation; risk of hyponatraemia.
  • Colloids and blood — initially stay mainly in plasma.
• Osmolality — normal plasma osmolality 275–295 mOsm/kg; calculated osmolality = 2 × Na⁺ + glucose + urea; osmolar gap (measured – calculated) over 10 suggests unmeasured osmoles (methanol, ethylene glycol, ethanol, mannitol).
• Sodium and water — sodium content determines ECF volume (aldosterone, natriuretic peptides); water balance determines sodium concentration (ADH, thirst) — hyponatraemia is usually a water problem.
• Daily water balance (adult) — intake about 2.5 L (drink 1.5 L, food 0.8 L, metabolic water 0.3 L); output — urine 1.5 L, insensible losses (skin and lungs) about 0.8 L, faeces 0.1–0.2 L; insensible losses rise with fever (about 10% per °C) and tachypnoea.

Capillary Exchange and Oedema

• Starling forces govern fluid movement across capillary walls:
  • Hydrostatic pressure in the capillary (pushes fluid out) — higher at the arterial end.
  • Oncotic (colloid osmotic) pressure of plasma proteins — mainly albumin (pulls fluid in).
  • Interstitial hydrostatic and oncotic pressures (small).
  • Capillary permeability (reflection coefficient).
• Net filtration occurs along most capillaries; about 90% is reabsorbed and the rest (about 2–4 L a day) returns via the lymphatics (current understanding — the "revised Starling principle" and the endothelial glycocalyx mean little reabsorption happens in most capillaries, making lymph flow even more important).
• Causes of oedema:

  Mechanism	Examples
  Raised capillary hydrostatic pressure	Heart failure, fluid overload, venous obstruction (DVT), calcium channel blockers (arteriolar dilatation — ankle oedema), pregnancy
  Low plasma oncotic pressure (low albumin)	Nephrotic syndrome, liver cirrhosis, malnutrition (kwashiorkor), protein-losing enteropathy
  Increased permeability	Inflammation, sepsis (capillary leak), burns, anaphylaxis, ARDS
  Lymphatic obstruction	Lymphoedema — after axillary node clearance or radiotherapy, filariasis, congenital (Milroy) — non-pitting with time

• Pitting vs non-pitting — pitting (fluid displaced by pressure — most causes); non-pitting (lymphoedema, pretibial myxoedema, lipoedema).
• Pulmonary oedema — raised left atrial pressure (cardiogenic) or increased permeability (ARDS — non-cardiogenic).
• Effusions and ascites — fluid in serous cavities; transudates (pressure or protein problems) vs exudates (inflammation, malignancy — high protein, Light's criteria).

Acid–base Physiology

• Normal arterial pH 7.35–7.45 ([H⁺] about 40 nmol/L); the body produces about 15,000 mmol of CO₂ (volatile acid) and 50–100 mmol of non-volatile (fixed) acid a day.
• Three lines of defence:
  • Buffers (seconds) — bicarbonate (main extracellular buffer), haemoglobin, proteins, phosphate (intracellular and urine), bone.
  • Lungs (minutes to hours) — change CO₂ excretion by altering ventilation (central and peripheral chemoreceptors).
  • Kidneys (hours to days) — reabsorb filtered bicarbonate (proximal tubule), generate new bicarbonate and excrete H⁺ as ammonium and titratable acid (phosphate) (distal tubule).
• The bicarbonate buffer system — CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃^– (carbonic anhydrase speeds the first step).
• Henderson–Hasselbalch equation — pH = 6.1 + log ([HCO₃^–] ÷ (0.23 × PaCO₂ in kPa)) — pH depends on the ratio of bicarbonate (kidney) to CO₂ (lung).
• Four primary disorders and compensation:

  Disorder	Primary change	Compensation	Example
  Metabolic acidosis	↓ HCO3–	↓ CO2 (hyperventilation — Kussmaul)	DKA, lactic acidosis, AKI
  Metabolic alkalosis	↑ HCO3–	↑ CO2 (hypoventilation — limited)	Vomiting, diuretics
  Respiratory acidosis	↑ CO2	↑ HCO3– (renal — days)	COPD, opioid overdose
  Respiratory alkalosis	↓ CO2	↓ HCO3– (renal)	Anxiety, PE, altitude

• Acid–base and potassium — acidosis shifts K⁺ out of cells (hyperkalaemia); alkalosis shifts K⁺ into cells (hypokalaemia) — and hypokalaemia itself maintains metabolic alkalosis.
• Acid–base and calcium — alkalosis increases binding of calcium to albumin → lower ionised calcium → tingling and tetany in hyperventilation.
• Full blood gas interpretation and anion gap — see the Critical Care and Acute Medicine chapters.

Energy Metabolism

• ATP — the cell's energy currency; produced by:
  • Glycolysis (cytoplasm) — glucose → 2 pyruvate + 2 ATP; without oxygen, pyruvate → lactate (anaerobic — shock, exercise, red cells have no mitochondria).
  • Krebs (citric acid) cycle (mitochondria) — acetyl-CoA → CO₂, NADH, FADH₂; pyruvate dehydrogenase needs thiamine (deficiency → lactic acidosis, Wernicke's).
  • Oxidative phosphorylation (electron transport chain) — about 30–32 ATP per glucose; needs oxygen; blocked by cyanide and CO; uncoupled by salicylates (heat).
• Fed state (insulin dominant) — glucose uptake (muscle and fat — GLUT4), glycogen synthesis, fat storage (lipogenesis), protein synthesis; insulin also drives K⁺, phosphate and magnesium into cells (refeeding syndrome).
• Fasting state (glucagon, cortisol, adrenaline, growth hormone):
  • Glycogenolysis (liver) — first 12–24 hours.
  • Gluconeogenesis (liver and kidney) — from lactate (Cori cycle), amino acids (alanine) and glycerol.
  • Lipolysis → fatty acids → ketone bodies (liver) — the brain adapts to use ketones in prolonged starvation.
  • Ketoacidosis happens when insulin is absent (DKA) — unrestrained lipolysis and ketogenesis; alcohol and starvation ketoacidosis.
• Glucose-dependent tissues — brain (mostly), red cells, renal medulla, lens.
• Basal metabolic rate — about 1,400–1,800 kcal a day in adults (about 25 kcal/kg/day); raised by thyroid hormone, fever, sepsis, burns, pregnancy; total energy expenditure adds activity and digestion.
• Energy content — carbohydrate and protein about 4 kcal/g, fat about 9 kcal/g, alcohol about 7 kcal/g.

Temperature Regulation

• Normal core temperature — about 37°C (36.5–37.5°C); varies by about 0.5°C over the day (lowest early morning, highest late afternoon); rises after ovulation (progesterone).
• Control — thermoreceptors in the skin and core → hypothalamus (preoptic area — the thermostat) → effectors.
• Heat production — basal metabolism, muscle activity, shivering, non-shivering thermogenesis (brown fat — infants; thyroid hormone).
• Heat loss — radiation, conduction, convection, evaporation (sweating — sympathetic cholinergic fibres — anticholinergic drugs impair it).
• Responses:
  • Cold — skin vasoconstriction, shivering, piloerection, behaviour.
  • Heat — skin vasodilatation, sweating, behaviour.
• Fever vs hyperthermia:
  • Fever — the hypothalamic set point is raised by pyrogens (IL-1, IL-6, TNF → prostaglandin E2 in the hypothalamus) — the body feels cold and shivers (rigors) to reach the new set point; antipyretics (paracetamol, NSAIDs) work by reducing PGE2.
  • Hyperthermia — the set point is normal but heat production or gain exceeds loss (heat stroke, MH, NMS, serotonin syndrome, drugs) — antipyretics don't work — physical cooling is needed.
• Older people — blunted fever response in infection; reduced shivering and thirst; higher risk of hypothermia and heat illness.
• Environmental heat and cold — see the Emergency Medicine chapter.

Cells and Homeostasis at a Glance

Spot the Diagnosis

Exam-style Scenarios

1. A 70-year-old man on the ward has a potassium of 7.1 mmol/L with peaked T waves and widened QRS complexes.
Answer: Severe hyperkalaemia — explain the physiology of treatment.

• Calcium gluconate — doesn't lower potassium; restores the gap between resting potential and threshold (membrane stabilisation).
• Insulin with glucose and salbutamol — stimulate the Na⁺/K⁺-ATPase to shift K⁺ into cells (temporary).
• Remove K⁺ from the body — stop causes, potassium binders, dialysis if needed.

2. A 50 kg woman needs IV fluids. A colleague suggests 1 L of 5% glucose to treat her hypotension.
Answer: Wrong fluid for resuscitation.

• 5% glucose becomes free water and spreads through all body water — less than 100 mL of each litre stays in plasma.
• Use an isotonic crystalloid (Hartmann's or 0.9% saline) — stays in the ECF; about a quarter remains intravascular.
• Large volumes of hypotonic fluid risk hyponatraemia, especially after surgery (high ADH).

3. A 6-year-old has periorbital and leg oedema, frothy urine and serum albumin of 15 g/L.
Answer: Nephrotic syndrome (likely minimal change disease).

• Oedema from reduced plasma oncotic pressure (and sodium retention by the kidney).
• Other consequences — hyperlipidaemia, infection risk (immunoglobulin loss), thrombosis (antithrombin loss).
• Treatment — steroids; manage fluid and sodium.

4. A 20-year-old with type 1 diabetes has pH 7.12, bicarbonate 8 mmol/L and PaCO₂ 2.8 kPa. She is breathing deeply and rapidly.
Answer: Metabolic acidosis (DKA) with respiratory compensation.

• Lack of insulin → lipolysis → ketone bodies (fixed acids) consume bicarbonate.
• Kussmaul breathing — chemoreceptors drive hyperventilation to lower CO₂.
• Potassium shifts out of cells (total body K⁺ is low) — insulin will drive it back in, so replace potassium.

5. A 30-year-old man has a temperature of 41°C after a festival where he took ecstasy. Paracetamol hasn't helped.
Answer: Drug-induced hyperthermia, not fever.

• The hypothalamic set point is normal; heat production exceeds loss (muscle activity, serotonergic and sympathetic effects).
• Antipyretics don't work — need active cooling, benzodiazepines, fluids.
• Watch for hyponatraemia (MDMA increases ADH and water intake), rhabdomyolysis, DIC.

Key Points

• The Na⁺/K⁺-ATPase maintains ion gradients — digoxin blocks it; insulin and beta-agonists stimulate it.
• Resting membrane potential depends mainly on potassium — explaining the dangers of hyper- and hypokalaemia.
• Know the four receptor families and G protein second messengers — they explain most drug actions.
• Labile cells are hit by chemotherapy; permanent cells (neurons, heart) heal by scar.
• Metaplasia and dysplasia are steps towards cancer at transition zones.
• Learn collagen types and their diseases.
• Total body water is 60% of weight — two-thirds intracellular; 5% glucose spreads through all of it.
• Oedema — raised hydrostatic pressure, low oncotic pressure, leaky capillaries or blocked lymphatics.
• pH depends on the bicarbonate:CO₂ ratio — buffers, lungs and kidneys defend it.
• Insulin drives glucose, potassium and phosphate into cells — refeeding syndrome and hyperkalaemia treatment.
• Fever raises the set point (antipyretics work); hyperthermia doesn't (cooling needed).

Guidelines and Further Reading

• Guyton and Hall: Textbook of Medical Physiology
• Ganong's Review of Medical Physiology
• Wheater's Functional Histology
• Robbins and Cotran: Pathologic Basis of Disease (cell injury, adaptation and death)
• Rang and Dale's Pharmacology (receptors and signalling)
• NICE CG174: Intravenous fluid therapy in adults in hospital
• Medical Schools Council: Medical Licensing Assessment (MLA) content map — applied basic sciences
• BNF — for current doses