For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
Pathology: Haemodynamic disorders, thrombosis, embolism and atherosclerosis
🩻 Haemodynamic disorders, thrombosis, embolism and atherosclerosis. Disorders of blood flow and clotting - atherosclerosis, thrombosis, embolism, infarction, oedema and shock - are the commonest causes of death and disability in the UK (heart attack, stroke, pulmonary embolism, peripheral arterial disease). This chapter explains the pathology underlying these conditions so that their clinical presentations, investigation and prevention make sense. Your four questions: Which part of Virchow's triad is abnormal? Is the problem in an artery or a vein (different clots, different drugs)? Where can an embolus go from here? Is the tissue downstream able to survive (collateral or dual supply)?
Oedema and Effusions
Oedema - excess fluid in the interstitium or body cavities (effusion, ascites; anasarca = generalised). Explained by Starling forces.
Congestion (passive) - impaired venous outflow - blue (cyanotic). Chronic venous congestion of the liver in right heart failure → "nutmeg liver" (centrilobular congestion and necrosis) → cardiac cirrhosis; of the lungs in left heart failure → haemosiderin-laden macrophages ("heart failure cells").
Primary haemostasis (platelet plug) - platelets adhere to exposed collagen via von Willebrand factor (GPIb), activate, release ADP and thromboxane A₂, and aggregate via GPIIb/IIIa linked by fibrinogen. Defects → mucocutaneous bleeding (epistaxis, menorrhagia, petechiae): thrombocytopenia, von Willebrand disease (commonest inherited bleeding disorder), antiplatelet drugs, uraemia.
Secondary haemostasis (coagulation cascade) - tissue factor (extrinsic pathway - factor VII; PT/INR) and the intrinsic pathway (factors XII, XI, IX, VIII; APTT) converge on the common pathway (X, V, II - thrombin, fibrinogen → fibrin); factor XIII cross-links fibrin. Defects → deep bleeding (haemarthroses, muscle haematomas): haemophilia A (VIII) and B (IX) - X-linked; prolonged APTT, normal PT.
Natural anticoagulants - antithrombin (enhanced by heparin), protein C and protein S (inactivate Va and VIIIa; vitamin K-dependent), tissue factor pathway inhibitor.
Fibrinolysis - plasminogen → plasmin (by tPA) → breaks down fibrin → D-dimer. Tranexamic acid inhibits fibrinolysis; alteplase and tenecteplase activate it.
Drug targets: aspirin (COX-1/TXA₂), clopidogrel/prasugrel/ticagrelor (P2Y12 ADP receptor), heparins (antithrombin → IIa and Xa), DOACs (apixaban, rivaroxaban, edoxaban - factor Xa; dabigatran - thrombin), warfarin (vitamin K epoxide reductase → II, VII, IX, X, proteins C and S).
Arterial and venous thrombosis, recurrent miscarriage, thrombocytopenia, livedo reticularis; lupus anticoagulant (paradoxically prolongs APTT), anticardiolipin, anti-β2-glycoprotein I antibodies on two occasions 12 weeks apart; warfarin - DOACs are not recommended in triple-positive APS
Thrombophilia testing is not routinely recommended after a first provoked VTE (NICE NG158); it rarely changes management.
Embolus - a detached mass carried in the blood to a distant site. Most (>95%) are thromboemboli.
Pulmonary embolism - from DVT (mainly proximal leg and pelvic veins); small - pleuritic pain, haemoptysis, infarction; large or saddle - right heart strain, collapse, sudden death. Wells score → D-dimer or CTPA; anticoagulation; thrombolysis if haemodynamically unstable.
Systemic (arterial) emboli - from the left heart (AF - left atrial appendage; mural thrombus after MI; valve vegetations; prosthetic valves) or from aortic and carotid atheroma → stroke, acute limb ischaemia, mesenteric ischaemia, renal and splenic infarcts.
Paradoxical embolism - venous clot crosses to the systemic circulation through a patent foramen ovale or septal defect → stroke in a young person.
Other emboli:
Fat embolism - long bone (femoral) fractures, orthopaedic surgery: 24–72 hours later - hypoxaemia, confusion and petechial rash (axillae, conjunctivae).
Air embolism - central line insertion or removal (lie flat or head down; occlusive dressing), diving (decompression sickness - nitrogen), trauma; >100 mL can be fatal.
Amniotic fluid embolism - during labour or immediately after: sudden collapse, hypoxia, DIC; high mortality.
Cholesterol (atheroembolism) - after angiography or vascular surgery, anticoagulation: livedo reticularis, blue toes, AKI, eosinophilia, low complement.
Septic emboli - infective endocarditis (Janeway lesions, splinter haemorrhages, brain abscess, septic pulmonary emboli from tricuspid endocarditis), and tumour emboli.
Infarction - ischaemic necrosis due to obstruction of arterial supply (or venous drainage). Most are caused by thrombosis or embolism; others by vasospasm, external compression, torsion or rupture.
Factors determining outcome:dual or collateral circulation (lung - pulmonary and bronchial arteries; liver - hepatic artery and portal vein; hand; circle of Willis - more resistant), rate of occlusion (slow occlusion allows collaterals - chronic stable angina), tissue vulnerability (neurons > myocytes > fibroblasts), and oxygen content of blood (anaemia, hypoxaemia).
Watershed infarcts - boundary zones between arterial territories are vulnerable to hypotension (brain between ACA and MCA territories; splenic flexure of the colon - ischaemic colitis).
End-arteries with no collateral supply: central retinal artery, renal, splenic, coronary (functionally), terminal cerebral arteries.
Atherosclerosis - a chronic inflammatory disease of the intima of large and medium-sized arteries (aorta, coronary, carotid, iliac, femoral, cerebral), causing CHD, stroke, PAD, renovascular disease and AAA - the leading cause of death worldwide.
Risk factors: non-modifiable - age, male sex, family history (premature CVD in first-degree relative - men <55, women <65), ethnicity (South Asian), genetic (familial hypercholesterolaemia, raised Lp(a)); modifiable - smoking, hypertension, dyslipidaemia (LDL), diabetes, obesity, physical inactivity, CKD, inflammatory diseases (RA, SLE, psoriasis), HIV, severe mental illness, air pollution. QRISK3 estimates 10-year risk.
Pathogenesis (response to injury):
Endothelial dysfunction (shear stress at branch points, smoking, hypertension, hyperglycaemia) → increased permeability and adhesion molecule expression.
LDL enters the intima and is oxidised; monocytes migrate in and become macrophages, ingesting oxidised LDL via scavenger receptors → foam cells → fatty streaks (from childhood).
Cytokines and growth factors (PDGF) → smooth muscle cell migration and proliferation and collagen production → fibrous cap over a lipid-rich necrotic core → atheromatous plaque (fibrofatty plaque).
Complicated plaque - calcification, ulceration, haemorrhage into plaque, rupture or erosion → thrombosis.
Stable versus vulnerable plaque: thick fibrous cap and small lipid core → stable stenosis (stable angina, claudication); thin cap, large lipid core and many inflammatory cells → rupture → thrombosis → acute coronary syndrome, stroke. Most MIs arise from plaques that were <70% stenotic before rupture.
Statins lower LDL, stabilise plaques (reduce inflammation, thicken the fibrous cap), and reduce events.
Aneurysm - permanent abnormal dilatation of a vessel (≥50% of normal diameter). True (all three wall layers - abdominal aortic aneurysm - atherosclerosis, smoking, male, family history; berry aneurysms of the circle of Willis - ADPKD, Ehlers–Danlos, coarctation; syphilitic aortitis of the ascending aorta; mycotic) versus false (pseudoaneurysm) - a contained haematoma communicating with the lumen (femoral artery after catheterisation).
AAA - NHS screening of men at 65 (ultrasound); surveillance and repair at ≥5.5 cm or growth >1 cm/year or symptoms (NICE NG156); rupture risk rises with diameter.
Aortic dissection - blood tracks through an intimal tear into the media; hypertension (main risk), cystic medial degeneration (Marfan, Ehlers–Danlos type IV, Loeys–Dietz, bicuspid aortic valve, Turner's syndrome), pregnancy, cocaine, iatrogenic. Stanford A (ascending aorta - surgery) versus B (descending - usually medical blood pressure control).
Mönckeberg medial calcification - calcification of the media of muscular arteries in older people, diabetes and CKD; does not narrow the lumen but makes vessels incompressible - falsely high ABPI.
Haemorrhage classes (ATLS): class I <15% loss (minimal change), II 15–30% (tachycardia, narrowed pulse pressure), III 30–40% (hypotension, confusion), IV >40% (life-threatening). Young people and pregnant women maintain blood pressure until late; β-blockers mask tachycardia.
Scenario. A man with a DVT asks why his doctor did not test him for "clotting genes".
Answer: His DVT followed major surgery (a provoked event). NICE does not recommend thrombophilia testing after a provoked VTE as results rarely change management - treatment duration is set by the provoking factor (usually 3 months). Testing may be considered in unprovoked VTE with a strong family history, or when stopping anticoagulation is being considered.
Scenario. Why do statins reduce myocardial infarction even in people whose coronary stenoses are not severe?
Answer: Most MIs arise from rupture of vulnerable plaques that are not severely stenotic. Statins lower LDL and stabilise plaques - reducing the lipid core and inflammation and thickening the fibrous cap - making rupture and thrombosis less likely.
Scenario. A hypotensive patient after a road traffic collision has a raised JVP, absent breath sounds on the left and tracheal deviation to the right.
Answer: Obstructive shock from a tension pneumothorax - immediate needle or finger thoracostomy (fifth intercostal space, mid-axillary line in adults), followed by a chest drain.