Haemodynamic disorders

Oedema: four forces and a pump

Fluid leaves capillaries when hydrostatic pressure pushes it out faster than plasma oncotic pressure (mainly albumin) pulls it back and lymphatics clear it.

• Burns oedema is mainly from increased capillary permeability, with a contribution from the fall in plasma protein as it leaks out.
• Nephrotic oedema (periorbital in the morning, proteinuria over 3.5 g/day) is from low albumin and secondary salt retention.
• Hereditary angioedema: deficiency of C1 esterase inhibitor (autosomal dominant) lets bradykinin rise, giving recurrent swelling of lips, larynx and gut without urticaria or itch; C4 is low even between attacks. It does not respond to antihistamines or adrenaline.
• Pulmonary oedema (left heart failure) starts in alveolar walls then fills alveoli. Cerebral oedema is dangerous because the skull cannot expand.

Hyperaemia and congestion

• Hyperaemia is active arteriolar dilatation (inflammation, exercise): red and warm.
• Congestion is passive, from impaired venous outflow: blue and cool.
• Chronic passive congestion of the liver (right heart failure) congests and kills centrilobular (zone 3) cells around central veins, leaving paler periportal zones: nutmeg liver, which can progress to cardiac cirrhosis.
• Chronic lung congestion thickens alveolar walls and fills alveoli with haemosiderin-laden macrophages (heart failure cells): brown induration.

Haemorrhage

• Petechiae (1–2 mm), purpura (3 mm or more), ecchymoses (bruises), haematoma (a collection).

• Effect depends on volume, rate and site. Rapid loss of more than about 20% of blood volume causes shock; a small bleed in the pons or pericardium kills. Pontine haemorrhage in a hypertensive patient gives sudden coma, pinpoint pupils, quadriplegia and high fever, not reversed by naloxone.
• In the newborn, a cephalohaematoma is subperiosteal, so it stops at the suture lines; a subgaleal haemorrhage crosses sutures and can cause shock.
• After acute blood loss, plasma volume is restored first (fluid shift from interstitium within hours, then renal salt retention); red cell mass recovers over weeks.

Thrombosis and Virchow's triad

• Endothelial injury: dominant in the heart and arteries (atheroma, MI, vasculitis, smoking).
• Abnormal flow: stasis (veins, atrial fibrillation, aneurysm, immobility) or turbulence (arteries).
• Hypercoagulability: inherited (factor V Leiden, the commonest inherited cause; prothrombin G20210A; antithrombin, protein C or S deficiency) or acquired (surgery, immobility, cancer, pregnancy and puerperium, oestrogen, nephrotic syndrome, antiphospholipid syndrome, heparin-induced thrombocytopenia).
• Thromboangiitis obliterans (Buerger disease): inflammatory thrombosis of medium and small arteries and veins of the limbs, almost confined to young male smokers; leads to rest pain and gangrene of digits; stopping smoking is the key treatment.

• Arterial thrombi are pale and grow backwards from the attachment; venous thrombi are red and grow with the flow.
• Fates: propagation, embolisation, dissolution, organisation and recanalisation.
• DVT usually begins in the valve pockets and soleal sinuses of the calf, where flow is slowest; propagation into popliteal and femoral veins produces most clinically important pulmonary emboli.

Embolism

• A patient who dies days after a pelvic fracture with multiple small brain infarcts has had fat embolism.

Infarction

• Infarcts are wedge-shaped, apex at the occlusion, base at the surface.
• Necrosis is coagulative in most organs but liquefactive in the brain. Over 1–2 weeks a brain infarct fills with foamy macrophages (from microglia and blood monocytes) that ingest myelin lipid; astrocytes form the gliotic scar later.
• Vulnerability: neurons die in 3–5 minutes, myocardium in 20–30 minutes, fibroblasts survive hours.
• Watershed infarcts form between two arterial territories when perfusion falls: between anterior and middle cerebral arteries; splenic flexure of the colon (SMA and IMA).
• Sheehan syndrome: the pituitary enlarges in pregnancy but its portal supply does not; massive postpartum haemorrhage infarcts the anterior pituitary, giving failure of lactation, amenorrhoea and later hypothyroidism and adrenal insufficiency.
• Mesenteric thrombosis of an atherosclerotic SMA gives dark purple, haemorrhagic small bowel.

Gangrene

• Dry: arterial occlusion without infection; black, shrivelled, clear line of demarcation (toes in arterial disease).
• Wet: infection on top of necrosis, often with venous obstruction; swollen, foul, spreading (bowel, diabetic foot).
• Gas gangrene: Clostridium perfringens alpha toxin (lecithinase); crepitus and rapid spread.

Shock

Shock is inadequate tissue perfusion: hypovolaemic (haemorrhage, burns; a femoral fracture can hide 1–1.5 L), cardiogenic, obstructive (tension pneumothorax, tamponade, massive PE) and distributive (septic, anaphylactic, neurogenic).

• Septic shock from Gram-negative bacteria (E. coli, Pseudomonas) is triggered by lipopolysaccharide (endotoxin); its lipid A binds TLR4 (with CD14) on macrophages, which release TNF-α, IL-1 and IL-6. These cause vasodilatation (NO), leaky capillaries, endothelial activation and DIC. Gram-positive shock uses cell-wall components and superantigens.
• After splenectomy, overwhelming sepsis is most often from Streptococcus pneumoniae (encapsulated organisms: also Haemophilus influenzae type b, meningococcus), hence vaccination before elective splenectomy.
• Compensation to haemorrhage is led by baroreceptor-driven sympathetic activation (tachycardia, vasoconstriction), then RAAS and ADH. Adequate resuscitation is judged by urine output (above 0.5 mL/kg/hour in adults).
• Stages: compensated, progressive (lactic acidosis), irreversible. Morphology: acute tubular necrosis, centrilobular liver necrosis, diffuse alveolar damage, adrenal haemorrhage, gut mucosal necrosis.

Remember Oedema: pressure up, protein down, leaky vessels, blocked lymph, salt kept.

Exam trap Red infarcts occur in organs with dual supply (lung, gut) or venous occlusion; pale infarcts in solid organs with end-arteries.

Exam trap TTP and DIC both give schistocytes and low platelets, but clotting times are normal in TTP and prolonged in DIC.

How FCPS asks about this

• Oedema in burns: increased capillary permeability; in nephrotic syndrome: low oncotic pressure.
• Commonest cause of lymphoedema worldwide: filariasis.
• Proof a thrombus formed before death: lines of Zahn.
• Where leg DVT begins and where the embolus lodges: calf soleal sinuses and valve pockets; pulmonary arteries.
• Breathless, confused, petechial rash 2 days after femoral fracture: fat embolism.
• Haemorrhagic infarct site: lung (dual supply); pale infarcts in heart, kidney, spleen.
• Key trigger of Gram-negative septic shock: LPS (lipid A) binding TLR4 on macrophages.