Home β€Ί Anaesthesia β€Ί Chronic Liver Disease (Cirrhosis) β€Ί Pathophysiology

🧩 Cirrhosis, Portal Hypertension & Systemic Effects

Portal HTNHVPGHRS Β· HPS Β· POPHCoagulopathy
🧩 3 · Pathophysiology

Cirrhosis & Portal Hypertension

"Cirrhosis is the end-stage of chronic liver injury: the normal architecture is distorted by fibrosis and regenerative nodules, causing loss of hepatocellular function and a rise in intrahepatic vascular resistance. The resulting portal hypertension, together with splanchnic vasodilatation, drives the whole clinical syndrome β€” varices, ascites, encephalopathy and the hepatorenal, hepatopulmonary and portopulmonary complications."

Synthesised from Stoelting's Co-Existing Disease & Barash β€” Clinical Anesthesia.

Causes β€” where the block is

Causes of cirrhosis / portal hypertension by site
Pre-hepaticPortal / splenic / SMV thrombosisHaemoglobinopathies (thalassaemia, sickle cell)
HepaticCirrhosis (commonest)Pre-sinusoidal: schistosomiasis, sarcoidosis, PBC Β· Sinusoidal: alcohol, viral, NASH Β· Post-sinusoidal: veno-occlusive disease
Post-hepaticBudd–Chiari, RHFConstrictive pericarditis, TR
Cirrhosis / Portal hypertension
πŸ“‹ Common aetiologies (hepatic causes)
  • Infections: Hepatitis B & C (Β± Hep D superinfection with B).
  • Alcoholic liver disease.
  • NASH (non-alcoholic steatohepatitis β€” part of the metabolic syndrome).
  • Autoimmune: autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis.
  • Storage disorders: Wilson's disease, haemochromatosis, Ξ±1-antitrypsin deficiency.
  • Drugs/toxins: paracetamol toxicity, Amanita phalloides (death-cap), herbal remedies, methotrexate.

Portal hypertension β€” the numbers (HVPG)

Hepatic venous pressure gradient (HVPG)Meaning
1–5 mmHgNormal
>5 mmHgPortal hypertension
β‰₯10 mmHgClinically significant portal hypertension β€” varices & ascites can form
β‰₯12 mmHgThreshold for variceal bleeding
>16–20 mmHgAssociated with acute-on-chronic decompensation / high mortality

↑ Resistance to portal blood flow β†’ ↓ portal flow β†’ formation of porto-systemic collaterals (varices) to decompress the system.

Compensated β†’ decompensated

Natural history
Chronic liver disease↑ Liver fibrosis
Compensated cirrhosisHVPG 6–10 mmHg Β· often asymptomatic
hyperdynamic circulation develops
Decompensated cirrhosisHVPG >10 mmHg β†’ ascites Β· variceal bleeding Β· encephalopathy Β· jaundice
End-stageAcute-on-chronic liver failureHVPG >16–20 mmHg Β· high perioperative mortality

Acute liver failure (contrast): hepatic dysfunction with coagulopathy (↑ PT/INR) and encephalopathy in the absence of pre-existing chronic liver disease, evolving in <26 weeks β€” a different entity from decompensated cirrhosis.

🫁 4 · Multisystem Effects

Systemic Effects of Cirrhosis β€” Organ by Organ

The unifying mechanism is splanchnic & peripheral vasodilatation (excess endogenous vasodilators β€” chiefly nitric oxide β€” plus reduced clearance) producing a hyperdynamic circulation and a fall in effective circulating volume (central hypovolaemia despite splanchnic hypervolaemia). Every downstream complication flows from this.

β‘  Cardiovascular β€” the hyperdynamic circulation & cirrhotic cardiomyopathy

❀️ CVS changes
  • ↑ Cardiac output, ↑ stroke volume, ↓ SVR β€” a chronically vasodilated, hyperdynamic state. Effective blood volume is reduced, so these patients are preload-dependent and drop their pressure with induction, PEEP, haemorrhage or neuraxial block.
  • Blunted baroreceptor reflexes & chronotropic incompetence β€” down-regulation of Ξ²-adrenergic receptors β†’ a poor heart-rate response to hypovolaemia and vasopressors.
  • Bilirubin deposition in the SA & AV nodes β†’ prone to arrhythmias.
  • Cirrhotic cardiomyopathy: impaired systolic & diastolic function that is masked at rest by the low afterload, unmasked by stress (surgery, fluid, TIPS), plus QT prolongation. Manage with sodium restriction / diuretics and avoid QT-prolonging drugs.

β‘‘ Respiratory β€” HPS vs POPH

🫁 Hepatopulmonary syndrome (HPS)

Triad: liver dysfunction + intrapulmonary vascular dilatation (IPVD) + arterial hypoxaemia (A–a gradient β‰₯15 mmHg; PaOβ‚‚ <70). Dilated capillaries at the lung bases β†’ shunt.

  • Orthodeoxia: SpOβ‚‚/PaOβ‚‚ falls on standing (>5% drop) β€” more blood diverts to the bases β†’ worse V/Q mismatch & shunt.
  • Dx: contrast (bubble) echo or Tc-99m MAA perfusion lung scan.
  • Rx: supplemental Oβ‚‚; definitive = liver transplant.

🩺 Portopulmonary hypertension (POPH)

Imbalance of vascular mediators β†’ vasoconstriction + endothelial damage β†’ pulmonary smooth-muscle proliferation.

  • Dx (RHC): mPAP >25 mmHg at rest, PCWP <15, PVR >240 dynΒ·sΒ·cm⁻⁡ (>3 Wood units).
  • Severity: mild 25–35 Β· moderate 35–50 Β· severe >50.
  • mPAP >50 with PVR >250 = contraindication to transplant.
  • Rx: inhaled NO, prostacyclin (epoprostenol), endothelin antagonist (bosentan), PDE-5 inhibitor (sildenafil).

DDx of hypoxaemia in cirrhosis: β‘  ascites β†’ basal compression atelectasis; β‘‘ hepatic hydrothorax (Rx: salt restriction + diuretics); β‘’ HPS; β‘£ POPH. Also ↓ diffusion capacity and ↑ extravascular lung water.

β‘’ Central nervous system β€” hepatic encephalopathy (HE)

Pathogenesis of hepatic encephalopathy
↑ Ammonia produced in the gut
Shunted into the systemic circulation (porto-systemic shunts + ↓ hepatic clearance)
Crosses the blood–brain barrier β†’ taken up by astrocytes
↑ Glutamine β†’ astrocyte swelling & dysfunction β†’ altered neurotransmission
EncephalopathyMild confusion β†’ cerebral oedema & raised ICP (net inhibitory / depressant effect)
West Haven gradeClinical features
IMild confusion, change in behaviour, day–night reversal
IIAsterixis (flapping tremor), moderate confusion, lethargy
IIIMarked confusion, arousable, incoherent speech, stupor
IVComa, unresponsive to pain
⚑ Precipitants (memorise β€” you can cause these in theatre)
  • ↑ Nitrogen load: GI bleed, constipation, excess dietary protein.
  • Drugs: sedatives, opioids/narcotics (avoid or minimise!).
  • Metabolic: hypoxia, hypotension/hypovolaemia, hyponatraemia, hypokalaemia, alkalosis.
  • Miscellaneous: sepsis, surgery, TIPS.

Rx: identify & correct the precipitant β†’ protein restriction β†’ lactulose 30–40 mL TID (gut bacteria β†’ lactate/acetate β†’ ↓ pH β†’ traps ammonia as non-absorbable NH₄⁺) β†’ non-absorbable oral antibiotics (rifaximin) β†’ zinc supplementation.

β‘£ Renal β€” hepatorenal syndrome (HRS)

From portal HTN to HRS
↓ Effective (central) blood volume
Activation of vasoconstrictor & antidiuretic systems (RAAS, SNS, ADH)
Na⁺ retentionβ†’ plasma volume expansion β†’ ascites
Water retention→ dilutional hyponatraemia
Renal vasoconstriction→ hepatorenal syndrome (functional, pre-renal)
Diagnostic criteria for HRS (functional, diagnosis of exclusion)
Cirrhosis + ascites Β· rising serum creatinine Β· no improvement after 2 days of diuretic withdrawal + albumin volume expansion Β· absence of shock Β· no current/recent nephrotoxins Β· no structural kidney disease (bland urine, no proteinuria).
Type 1 HRS (HRS-AKI)Type 2 HRS (HRS-NAKI)
CourseRapidly progressiveModerate, stable impairment
CreatinineRapid ↑ (β‰₯0.3 mg/dL in 48 h or β‰₯50% from baseline)Slower, stable rise
PrognosisPoor β€” median ~2 weeks~6 months
TriggerOften a precipitant (SBP, GI bleed, over-diuresis, large-volume paracentesis)Refractory ascites

Rx of HRS: stop nephrotoxins & remove the trigger β†’ albumin (volume expansion) β†’ splanchnic vasoconstrictors to raise MAP & renal perfusion: terlipressin (an ADH analogue β†’ splanchnic vasoconstriction β†’ ↑ MAP, ↑ GFR) or midodrine + octreotide Β± noradrenaline. Definitive treatment is liver transplant.

β‘€ Haematological β€” the rebalanced coagulopathy

🩸 Coagulation

  • ↓ Pro-coagulant factors (vitamin-K-dependent & independent) and ↓ anticoagulants (protein C/S, antithrombin) β€” a rebalanced but fragile system.
  • Dysfunctional clotting factors; ↑ thrombin generation potential β†’ cirrhosis can be pro-thrombotic (e.g. PVT, DVT) as easily as it bleeds.

πŸ”» Anaemia & thrombocytopenia

  • Anaemia: nutritional deficiency, chronic GI blood loss, hypersplenism, marrow suppression by alcohol, Zieve's syndrome.
  • Thrombocytopenia: hypersplenism (pooling), ↓ thrombopoietin synthesis, immune destruction, plus platelet dysfunction.
⚠️ The single most important coagulation teaching point
  • Because pro- and anti-coagulant deficits offset each other, the INR does NOT predict bleeding risk in cirrhosis and does not need "correcting" before every procedure. Assess whole-blood clotting with TEG/ROTEM, treat fibrinogen and platelets, and transfuse to the clinical picture β€” over-transfusing FFP raises portal pressure and worsens variceal bleeding.

β‘₯ Endocrine & metabolic

Prone to hypoglycaemia (depleted glycogen stores + reduced insulin degradation) β†’ check glucose intra-operatively. ↑ Plasma glucagon & growth factor; abnormal sex-hormone metabolism (β†’ gynaecomastia, testicular atrophy, spider naevi, palmar erythema).

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