Alcoholic liver disease Flashcards
List some DDx for a presentation of:
- bilat pitting oedema
- tense abdomen, shifting dullness
- splenomegaly
- bleeding haemorrhoids
- hx ETOH abuse
• Hepatic:
o Cirrhosis
o Hepatitis – viral (HBV, HCV, HIV)
o ETOH
o NASH
o Drug induced (paracetamol, aspirin, isoniazid)
o AI hepatitis
o Metabolic- haemochromatosis (iron overload), Wilson’s disease (Cu overload), steohepatitis
o Vascular- Budd-Chiari syndrome (occluded hepatic veins -> hepatomegaly, abdo pain, ascites)
o HCC- portal vein thrombosis, mets (colon, breast, lung)
• Obstructive- cholecystitis, cholelithiasis, primary sclerosing cholangitis, pancreatitis, pancreatic ca
• Cardiac: CCF
• GIT: poor protein absorption (hypoalbuminaemia)
• Neuro: stroke, Wernicke-Korsakoff syndrome (lack of B1/thiamine)
• Bleeding diathesis- thrombocytopenia, platelet dysfunction, coagulation deficiency, mixed platelet and coagulation deficiency
• Neoplastic- leukaemia, CRC (with mets), lung ca (with mets)
Describe the clinical manifestations of liver disease?
- Hands: leukonychia, clubbing palmar erythema, bruising, asterixis (poor ammonia metabolism)
- Face: jaundice, scratch marks, spider naevi, fetor heptaticus (portal HTN -> portosystemic shunting allows thiols/sulfur analogue of ETOH to pass directly into the lungs), xanthalesma
- Chest: gynaecomastia, loss of body hair, spider naevi, angioma, bruising, pectoral muscle wasting
- Abdo: hepatosplenomegaly, ascites, portal HTN signs, testicular atrophy
- Legs: oedema, muscle wasting bruising
What are the signs of portal hypertension?
Portal HTN signs:
- splenomegaly,
- peripheral pitting oedema
- engorged vasculature (caput medusae, chest veins)
- ascites (>500ml)
- haemorrhoids
- oesophageal varices
- hepatic encephalopathy
What investigations would you order for liver disease?
• Blood tests:
o FBC- WBC (infection), RBC (anaemia of chronic disease), platelets (coagulation)
o ESR/CRP- inflammation
o LFT- liver function, albumin (oedema), obstructive pattern (GGT, ALP)
o EUC- kidney function, electrolyte, ammonia (hepatic encephalopathy)
o Coagulation- liver synthesis function
o Serology- HBV, HCV, HIV
o PCR- HCV-RNA, CMV, EBV
• Imaging:
o Hepatic US- masses (cysts, tumour, abscesses), cirrhosis, fatty liver
o Doppler hepatic US- portal HTN, tumour vascularity
o CT abdo- HCC, mets
• Liver biopsy- micro (cirrhosis) or macronodular (hepatitis) patter
What lab findings might you expect in cirrhosis?
- Macrocytic anaemia- due to nutritional deficiency (B12 or folate) secondary to ETOH, also ETOH toxicity on BM
- Low WCC- reduced BM production (ETOH BM toxicity), possible sequestration
- Poikilocytes (abnormally shaped RBC)- possible due to nutritional deficiency
- Thrombocytopenia- reduced thrombopoeitin production, suppressed haemopoiesis, increased platelet breakdown (due to portal HTN hypersplenism)
- Elevated Br- obstruction (due to fibrosis) -> indicates severe cirrhosis (usually compensated)
- Elevated ALP and GGT – obstructive pattern (due to fibrosis)
- Hypoalbuminaemia- hepatic synthesis dysfunction (causing peripheral pitting oedema)
- Elevated globulin- portal-systemic shunting of blood -> bacterial toxins from GIT bypass liver and enter systemic circulation -> increased Ig production (via activation of B-cells in spleen and LNs) to provide immunity
Describe the changes in transminase levels in liver disease?
- Acute: transaminases normally elevated in hepatitis (AST > ALT in ETOH)
- Chronic: transaminase levels normal as cirrhotic liver has fewer hepatocytes -> fever enzymes released
How does alcohol cause a raised GGT?
y-Glutamyltransferase (GGT):
• Location: hepatocytes and bile duct epithelium
• Function: aid transference of amino acids across cellular membrane, leukotriene metabolism and glutathione metabolism
ETOH metabolism:
• ETOH meatbolised-> toxic acetylaldehyde -> acetate
• Increase in acetylaldehyde -> hepatocyte injury -> raised GGT
Describe the electrolyte changes seen in cirrhosis?
Hepatorenal syndrome:
• Portal HTN -> NO and vasculo-endothelial growth factor (VEGF) -> progressive splanchnic vasodilation -> reduced cirulating volume
⇒ Decreased stretch at carotid and renal baroreceptors
⇒ Activation of RAAS and ADH -> Na and H2O retention
⇒ Dilutional hyponatraemia (both Na and H2O absorbed) and hypokalaemia (more severe hepatic impairment)
- note worse hyponatraemia poor prognostic indicator
• Increased nitrogen waste products
What other tests can you do to determine the liver’s synthetic function?
• Coagulation studies
o PT and INR: extrinsic pathway (note: PT has short half life)
o aPTT: extrinsic pathway
• EUC: hyperuricemia (liver convert ammonia to urea for excretion), dilutional hyponatraemia (due to portal HTN -> vasodilation -> RAAS -> Na and H2O retention)
• Fat soluble vitamins (bile salts requird for fat absorption)
• Serum Alb or total protein – hepatic synthesis
• Urine protein- exclude underlying nephrotic syndrome
Why would you find bruising in cirrhosis?
- Hepatic failure -> reduced protein synthesis -> reduced coag factor and thrombopoietin -> impaire haemostasis -> bleeding
- Malnutrition -> vit K deficiency
- ETOH intake -> malnutrition -> reduced protein intake -> poor collagen stores -> weak BVs
- Malnutrition -> vit C deficiency -> poor collagen synthesis -> impaired healing
Describe the pathogenesis of cirrhosis?
Steps:
1) ETOH -> oxidises to form ROS, toxic acetyaladehyde and lipid perioxidases
2) Liver parenchyma fibrosis -> nodular, brown, hardened and shrunken macroscopic appearance
⇒ Vascular smooth muscle contraction and myofibroblast -> scarring and parenchymal nodule formation -> disrupt blood flow
3) Portal HTN:
⇒ Increased resistance to portal flow at sinusoids -> compression of central veins (by perivenular fibrosis and expandable parenchymal nodules)
⇒ Increased intrahepatic pressure
⇒ Sinusoidal epithelial cells release vasoconstrictive enzymes (enthothelin-1, angiotensinogen, eicosanoids) -> further increase intrahepatic pressure
⇒ Sinusoid remodelling and anastamosis -> intrahepatic shunting between arterial and portal system in fibrous septa
⇒ Imposing arterial pressures on low pressure portal venous system (no longer small BVs to dissepate arterial pressure)
⇒ Backflow and HTN in portal system
What causes pitting oedema?
Steps:
1) Reduced Alb production (normally accounts for 50% serum proteins)
⇒ reduced oncotic pressure -> alters Starling’s forces
⇒ extravasation of fluid into interstitium
⇒ gravity dependent (ankles)
2) Portal HTN -> Na and H2O retention -> fluid overload
⇒ portal HTN -> mediators released (PG, NO) -> splanchnic vasodilation -> reduced circulating blood volume -> activated baroreceptors (carotid and kidney)
⇒ activated RAAS and ADH -> Na and H2O retention -> fluid overload -> generalised oedema
What causes ascites in cirrhosis?
Steps:
1) hepatic obstruction (cirrhosis) -> portal HTN -> increased intravascular hydrostatic pressure
2) hypoproteinaemia -> decreased intravascular oncotic pressure
3) RAAS activation -> Na and H2O retention -> increased interstitial capillary pressure -> fluid extravasation
4) extravasation of intravascualr fluid into extravacular space of Disse (normally goes through hepatic lymphatics to thoracic duct, but sheer vol of lymph overwhelms thoracic duct and perocolates to peritoneal cavity)
⇒ ascites
What causes splenomegaly in cirrhosis?
1) Portal HTN -> shunting from portal to systemic circulation -> dilated collateral vessels -> formation of portal-systemic anastamoses
2) Splenic vasodilation (increased splenic vein pressure) -> hyperaemia and oedema of spleen
List some complications of cirrhosis?
- Porto-sytstemic hepatic encephalopathy (ammonia damages brain astrocyes)
- Hepatorenal syndrome (poor renal perfusion causes AKI)
- Hepatopulmonary syndrome (hepatic vasodilators causes intrapulmonary arteriovenous dilations and VQ mismatch)
- Variceal haemorrhage
- Bacterial peritonitis
