HBP Pathology Flashcards
Anatomy of the Liver: location, structure, vascular supply, portosystemic anastomoses and clinical significance
Location: right 5th intercostal space to just below the costal margin at the mid clavicular line
Structure: 2 lobes, 8 segments, covered by Glisson’s capsule (contains pain fibres)
Vascular supply: portal vein deO2 (66%), hepatic artery O2 (33%)
Portosystemic anastomoses (clinically significant consequences in portal hypertension)
- oesophageal vein (systemic) – left gastric vein (portal) –> oesophageal varices and bleeding
- inf/middle rectal vein – superior rectal vein –> haemorrhoids (controversial)
- superficial epigastric vein – paraumbilical vein –> caput medusae
Basic histology of the liver: model, 6 features
Lobular model (hexagonal) - centrilobular region (terminal hepatic venule/ central vein) --> least O2 therefore more susceptible to metabolic stress and toxins
- periportal region (portal triad) –> most O2, more susceptible to blood borne infections
- trabeculae –> arrangement of hepatocytes between central vein and portal tracts; in “plates” 1-2 cells thick
- sinusoids between plates where blood traverses to exit at central vein
- bile canaliculi –> 1-2 micrometer channels formed by grooves in membrane of adjacent hepatocytes; drains into periportal bile ductules then terminal bile ducts
- kupffer cell and stellate cell
Functions of the liver (6)
Nutrient metabolism, protein synthesis, drug/ hormone/ toxin metabolism, excretion (bile), storage, immunity (increase acute phase reactants e.g. CRP, SAA, Hepcidin)
Bilirubin metabolism
Haemoglobin –> globin + haem
Haem –> iron + bilirubin
Unconjugated Bilirubin carried by albumin to liver
Bilirubin conjugated and excreted in bile into gut
Gut bacteria convert bilirubin to urobilinogen
Urobilinogen then either
- further converted to stercobilin and ejected in stool
or
- enter portal vein via enterohepatic circulation to return to liver or to go to kidneys to be excreted in urine
Liver biopsy: indications (5), routes (3), complications (3)
Indications:
- Diagnosis
- liver mass with inconclusive imaging (30-60% cases), abnormal LFT with unknown aetiology, pyrexia of unknown origin, multiple possible parenchymal liver diseases (exclude common conditions)
- Prognosis
- staging and grading of known liver disease - Management
- treatment plans based on histological analysis; distinguish between primary and metastatic CA
Route:
- percutaneous (risk of tumour seeding, bleeding, injury to adjacent organs)
- transjugular (IJV-SVC-IVC) – safer
- open wedge (laparoscopy)
Complications:
- bleeding
- puncture of adjacent organs
- tumour seeding along needle track
Hepatocyte Injury: general changes, regeneration, scar formation
Potentially reversible changes e.g. fat and bilirubin accumulation
Irreversible = cells die by apoptosis or necrosis –> widespread death leads to confluent necrosis
Regeneration of hepatocytes is mainly by mitotic replication of hepatocytes adjacent to those that died; stem cell-proliferation and differentiation in long standing CLD
Scar formation by perisinusoidal stellate cells activation
Stigmata of Chronic Liver Disease: general, impaired liver functions, complications
General:
- malaise, fatigue, RUQ pain, hepatomegaly, weight loss
Impaired liver function:
- protein synthesis –> leukonychia + ascites; bruising
- biliary excretion –> jaundice + pruritus
- waste metabolism –> hepatic flap, fetor hepaticus
- estrogen metabolism –> gynaecomastia, spider naevi, palmar erythema, testicular atrophy
Complications:
- liver failure –> encephalopathy, hepatorenal syndrome
- portal hypertension –> formation of portosystemic shunts: haematemesis, varices, splenomegaly (congestive, platelets sequestered in expanded red pulp), caput medusae, ascites
Jaundice: cause, classifications (2)
Hyperbilirubinaemia (normally first presenting as yellow sclera)
Pre-hepatic, hepatic and post-hepatic
Unconjugated vs Conjugated
Unconjugated Hyperbilirubinaemia: presentation (2), causes (2), Gilbert’s syndrome cause/ prevalence/ bilirubin levels
Normal coloured urine and stool
Clinically detectable jaundice at >35 micro mol/L
Pre-hepatic:
- increased production of bilirubin
e. g. Haemolytic Anemia, Ineffective erythropoiesis, resorption of internal bleeding
Hepatic:
- decreased uptake and conjugation of bilirubin
e. g. Gilbert’s syndrome*, physiological jaundice of newborn, drugs such as rifampicin
Gilbert’s syndrome is UGT1A1 mutation causing defective glucuronosyltransferase activity
- common
- mild defect, usually bilirubin <100, rarely clinical jaundice
(vs. Crigler-Najjar with more severe jaundice - type I has absent enzyme, very rare, bilirubin >340, early manifestation, kernicterus; type II bilirubin 100-340, rare, moderately decreased enzyme)
Conjugated Hyperbilirubinaemia: presentation (2), causes
Tea-coloured urine, pale stool
Clinically detectable jaundice at >45 micro mol/L
Hepatic:
- intrahepatic cholestasis (if there is insufficient compensatory drainage)
e. g. inherited hepatocellular injury (hepatitis), intrahepatic bile duct disease (PBC), drugs such as OCP/anabolic steroid/ augmentin
Post-hepatic:
- extra hepatic cholestasis
e. g. intraluminal gallstone, mural cholangiocarcinoma or PSC, extraluminal CA pancreas or lymphoma
Portal hypertension: causes (3 classes), pathogenesis of cirrhosis causing portal HT (2)
Pre-hepatic:
- portal vein thrombosis/ congenital stenosis/ compression by mass
Hepatic:
- cirrhosis
- non cirrhotic schistosomiasis, diffuse granulomatous disease
Post-hepatic:
- heart – right HF or TR (c.f. nutmeg liver)
- IVC thrombosis
- Budd Chiari syndrome (obstruction of >2 hepatic veins)
Portal HT secondary to cirrhosis
- Increased vascular resistance: mechanical obstruction by portal, perisinusoidal and perivenular fibrosis and increased endothelin with decreased NO from sinusoid endothelial cells = vasoconstriction
- Increased blood flow: anastomosis of hepatic arteries and portal veins through fibrous septa and increased splanchnic arteriolar vasodilation by increased NO production in gut (decreased clearance of gut bacteria material by liver)
Liver congestion: pathophysiology, histology (3), clinical presentations (3)
Heart failure increases CVP which is transmitted backwards to IVC and hepatic veins –> dilation of hepatic sinusoids and central veins
Nutmeg appearance (alternating dark sinusoids and pale parenchyma) Centrilobular zone necrosis (red/brown) with atrophy and fatty change, surrounded by uncongested periportal zone (tan-coloured)
Clinical:
- hepatomegaly
- RUQ tenderness
- CCF signs
Ascites: pathophysiology (3), potential treatment
Excessive fluid accumulation in peritoneal cavity
Caused by
- increased hydrostatic pressure in portal HT increasing the venous pressure at peritoneal capillary beds
- decrease in osmotic pressure due to hypoalbuminaemia
- decrease in ECV due ascites and splanchnic vasodilation (decreased CO) leads to activation of RAAS (and ADH) –> increase water retention –> further increase portal HT (and causes dilutional hypoNa)
(liver also unable to metabolise aldosterone)
Aldosterone antagonist (spironolactone) can break vicious cycle
Hepatorenal syndrome: definition, pathophysiology
Pre-renal renal failure due to excessive vasoconstriction of afferent arterioles (decrease renal perfusion pressure and GFR)
Portal HT causes splanchnic arteriolar vasodilation –> decrease ECV –> strong RAAS and SNS activity –> intense renal vasoconstriction overwhelming renal vasodilator system
Hepatic encephalopathy: cause, pathophysiology (2), precipitating factors (1), presentations (5)
Hyperammonaemia
Pathophysiology:
- decrease functional hepatocytes for urea cycle
- portosystemic shunt of ammonia to systemic circulation – physiological, pathological (I.e. portal HT), iatrogenic (trans jugular intrahepatic portosystemic shunt TIPS for portal HT)
Precipitated by variceal bleeding (resorption of internal bleed –> Hb degradation –> protein)
Clinically presents as:
- behavioural abnormalities, insomnia –> confusion/ stupor –> coma, death
- develop over days/wks/mths with fluctuating neurological signs (rigidity, hyperreflexia, asterixis)
Liver failure: definition of acute liver failure, fulminant liver failure, clinical course, histology, biochemical levels, acute-on-chronic examples
Acute liver failure is the presence of encephalopathy within 6 months of disease diagnosis
- usually due to paracetamol overdose, Hep B/E
Fulminant liver failure = encephalopathy within 2 weeks of jaundice onset
Nausea, vomiting, jaundice, fatigue followed by encephalopathy, coagulation defects, portal HT (although more of a chronic feature) and ascites
AST very high, swelling and oedematous liver initially then shrink dramatically and AST decrease
- massive hepatic necrosis with small and shrunken liver; large zones of destruction with loss of architecture microscopically (very pink)
Multiorgan failure eventually
Acute on Chronic liver failure:
- established cirrhosis and extensive vascular shunting/ borderline vascular supply –> liver vulnerable to insults
e.g. Hep D superimposed on Hep B
Ascending bacterial chlangitis in PSC
Primary or metastatic CA
Resistance to medical therapy for viral hepatitis
Definition of Cirrhosis** and classification
**Definition: disrupted architecture of liver with diffuse, regenerative nodules that are separated by bridging fibrous septa
- dynamic and bidirectional (potentially reversible with regression of fibrosis with cure of CLD)
(fibrous septa formed by activation of stellate cells when underlying reticulin collapses in severe injury)
Classified into macro-nodular (e.g. viral hepatitis) and micro-nodular (e.g. AFLD, haemochromatosis) with 3mm as limit – not clinically useful