Liver and friends Flashcards
Liver tests
ALT/AST
ALP
GGT
Generally associated with hepatocellular damage, ALT more specific for liver
Ratio is important:
AST:ALT = 1 - Ischaemia
AST:ALT > 2.5 - Alcoholic hepatitis
AST:ALT < 1 - High ALT for hepatocellular damage e.g. paracetamol OD with hepatocellular necrosis, viral hepatitis, ischaemic necrosis, toxic hepatitis
Elevated with cholestasis
ALP associated with cholestasis and malignant hepatocellular damage + marker of bone turnover
GGT is sensitive to alcohol ingestion, it is non-specific marker of HC damage
Metabolic causes of liver disease (3)
Hereditary haemochromatosis
Wilson’s disease
Alpha-1 antitrypsin deficiency
Hereditary haemochromatosis
Inheritance
Pathology
Presentation
Autosomal recessive
Increased intestinal absorption of iron leading to accumulation in tissues: liver (fibrosis, cirrhosis, HCC), heart, skin, joints (arthropathy), pancreas (diabetes)
Early: fatigue, weakness, arthralgia, erectile dysfunction
Late: skin bronzing, diabetes, cirrhosis (liver signs), impotence, cardiac arrhythmia, arthropathy 2nd and 3rd metacarpophalangeal joints
Hepcidin
Transferrin
Ferritin
Produced by hepatocytes in response to high iron levels. It blocks iron absorption by blocking ferroportin at enterocytes and reduces iron exit from liver and macrophages (storage sites) in same way
Binds iron reversibly in blood
Stores iron intracellularly, an acute phase protein
Haemochromatosis
Ix
Mx
*Iron studies
-Serum ferritin (high) - lots of iron in cells - low specificity as acute phase pro
-Transferrin saturation (>45%) - lots of iron in blood specific
LFTs
MRI - iron overloaded liver
Liver biopsy with Perl’s stain
ECG/ECHO for cardiomyopathy
Tests for other causes of hyperferritinaemia e.g. inflammation (CRP), alcohol, metabolic syndrome (BP, BMI, glucose, triglycerides
Venesection/phlebotomy 4-500ml weekly
Low Iron diet
Wilsons disease Inheritance Pathology Features: Hepatic/Psychiatric/Neurological/Opthalmological
Autosomal recessive
Disorder of biliary excretion of copper. This is deficient in Wilson’s leading to copper retention in liver and basal ganglia
Acute liver failure, chronic hepatitis and cirrhosis @ younger
Severe depression (50%)
Asymmetrical tremor, ataxia, mask-like facies, clumsiness, excess salivation, choreiform movement - Parkinsonian @ older
Kayser-Fleischer ring (95%) + sunflower cataracts
Wilsons disease
Ix
Mx
Copper studies: low serum caeruloplasmin, high 24 hour urine copper excretion, high free copper, slit-lamp kayser-fleisher, liver biopsy (copper), MRI (density at basal ganglia)
Chelation agents binds copper for excretion in urine- penicillamine (oral)
Stop absorption of copper - zinc compounds
Avoid foods with copper: mushrooms, liver, chocolate, nuts
Monitor hepatic function, renal function, FBC and clotting
Avoid alcohol and hepatotoxic drugs
A1AT deficiency
Inheritance
Pathology
Presentation
Autosomal recessive very common, consider in young person with COPD
A1AT is a glycoprotein produced in the liver. It is a serine protease inhibitor and controls inflammatory cascades and balances the action of neutrophil elastase in the lung (cigs/inflammation). NE will break down elastin leading to alveolar destruction. In A1ATd an abnormal protein is produced which cannot leave, congests in liver cells and causes destruction.
Lung disease at 30s/40s
Dyspnoea, wheezing, cough i.e. COPD (lung bases commonly)
Hepatitis, cirrhosis (HCC), fibrosis
A1AT deficiency
Ix
Mx
Serum A1AT (low) -> phenotyping required
CXR and LuFT
LFT and biopsy
Asymptomatic - smoking and alcohol advice
Lung symptoms - as COPD
Liver disease - regular LFTs , treat cirrhosis, screen for HCC
4 main characteristics of liver failure
Hepatic encephalopathy
Jaundice
Abnormal bleeding - Haematemesis & Melaena - Varices
Ascites
Causes of liver failure (5 groups)
Toxin - Paracetamol, alcohol, medications (co-amoxiclav, cipro, doxy, erythro, methotrexate, gold) Infection - Viral hepatitis, EBV, CMV Neoplastic - HCC Metabolic - Wilson’s A1ATd vascular - Ischaemia, Budd-Chiari AI liver disease
Pathology of hepatic encephalopathy
In liver failure ammonia builds up in circulation and crosses BBB. Astrocytes clear this turning glutamate to glutamine. Glutamine excess causes fluid shift to cells -> cerebral oedema.
- Altered mood, drowsiness, restless, coma
Signs of liver failure
Finger clubbing/fetor hepaticus
Leukonychia
Asterixis (liver flap)
Palmar erythema
Spider naevi/scratch marks
Ascites - Shifting dullness, fluid thrills, due to hypoalbuminaemia
Bleeding - Deficient in: Factor 10, 9, 7, 2 (with vitamin K), fibrinogen (factor 1), 5, 8, 11, 12
Liver failure blood Ix
FBC - Thrombocytopenia LFT - Raised ALT + AST Bilrubin - Raised Ammonia - Raised Glucose - Dangerously low Copper high - ?Wilson’s Paracetamol - ?High Creatinine - Raised at hepatorenal syndrome PT/INR - Raised
Ascites What Causes Ix Management
Collection of fluid in peritoneal cavity
- 1500ml on exam or 500ml on USS
Transudate
Mostly cirrhosis - 50% cirrhosis develop ascites + peripheral oedema + pleural effusions
Decreased albumin (decreased oncotic) and portal hypertension (increased hydrostatic)
15% malignancy - GI tract, ovarian (Meig’s)
Heart failure
Exudate
Nephrotic syndrome - protein lost in urine
Pancreatitis
Peritoneal TB
Albumin levels, WCC, GS&C, amylase.
Treat cause
Restrict salt intake
Diuretics - spironolactone in cirrhosis - beware hyperkalaemia - Aim to lose approx 500ml per day
Spontaneous bacterial peritonitis What Presentation Ix Bacteria causing Mx
Fever, mild abdominal pain, vomiting. Abdominal pain + fever
Triad of peritonism: guarding, rebound tenderness, pain on palpation
FBC - *leuocytosis
LFT, *U+E (renal impairment), blood cultures
*Diagnostic paracentesis - for culture and amylase
Imaging - upright AXR and CXR
E.coli, streptococci, enterococci
IV 3rd generation cephalosporins if >250 cells/mm3
Hepatic encepalopathy
Causes
Ix
Mx
Develops in 50% of patients with cirrhosis and is a feature of decompensated cirrhosis
AKI, infection, constipation, sedatives, diuretics
Arterial/serum ammonia, EEG triphasic waves, MRI/CT for other cause of encephalopathy
Avoid sedatives and diagnose early
Decrease nitrogen load - lactulose removes nitrogen from gut, neomycin (ABX) lowers nitrogen forming gut bacteria
Hepatorenal syndrome
What
Criteria
Mx
A complication of end-stage liver disease (40%) Impaired renal function often precipitated by events lowering BP e.g. spontaneous bacterial peritonitis, GI bleed, pneumonia.
Criteria is a diagnosis of exclusion
Triad - Cirrhosis, ascites, Cr > 133 micromol
+ no shock, no hypovolaemia, no nephrotoxics
General:
Admit to HDU + monitor fluids (urine output), treat infections + stop nephrotoxics/diuretics
Specific:
Splanchnic vasoconstrictors e.g. terlipressin with albumin - increases blood pressure and GFR + TIPS (transjugular intrahepatic shunt) - reduces ascites in portal HTN
Cirrhosis
What
Features
Causes
Diffuse hepatic process characterised by fibrosis and conversion of normal liver architecture to nodules.
Distortion of hepatic vasculature -> increased intrahepatic resistance and portal hypertension (oesophageal varices, hypoperfused kidneys, increased cardiac output)
Hepatocyte damage -> impaired liver function and decreased synthesis clotting factors
Common: alcohol, hep B/C, NAFLD and NASH - non-alcoholic fatty liver/steatohepatitis
Signs and Symptoms of cirrhosis
Fatigue, malaise, anorexia, nausea, weight loss
Advanced/decompensated: oedema, ascites, bruising, poor memory, bleeding varices, SBP
Signs: FLAPS (finger clubbing, leukonychia, asterixis, palmar erythema, spider naevi, scratch (pruritus), jaundice, dupuytren’s
Other - Hepatomegaly, oedema, gynaecomastia (increased production androstenedione by adrenals and conversion to oestrogen), hypogonadism (toxicity of alcohol/iron)
Ix for causes of cirrhosis
AST + ALT raised with hepatocyte damage, GGT raised in alcohol, ALP, bilirubin
Albumin low in advanced cirrhosis
FBC - Bleeding - anaemia, low platelets (hypersplenism), macrocytosis (alcohol abuse)
U&E -Hepatorenal syndrome
Coag- Increased PT in advanced
Ferritin - Raised in HH, low in iron deficiency/blood loss
Viral - Hep B/C
NASH - Fasting glucose, insulin, triglycerides and uric acid levels
AAb screen - Anti-mitochondrial at primary biliary cirrhosis
A1AT level, caeruloplasmin, urinary copper, fasting transferrin saturation
Portal hypertension What Pre hepatic causes Hepatic causes Post hepatic causes
Abnormally high pressure in hepatic portal vein (significant if hepatic venous pressure gradient >10mmHg)
Portal vein thrombosis, splenic vein thrombosis, extrinsic compression e.g. tumour
Cirrhosis, hepatitis, schistosomiasis, granuloma (sarcoid)
Budd-Chiari, RHF/CHF, constrictive pericarditis
Portal hypertension
Signs
Ix
Mx
Ascites, splenomegaly, dilated umbilical veins
*Haematemesis/melaena -> bleeding varices
Signs of cirrhosis/liver failure
AUSS for liver/spleen/ascites Doppler ultrasound - blood flows Spiral CT for portal vasculature Endoscopy for oesophageal varices Portal pressure by hepatic venous pressure gradient (normal < 5, varices > 10)
Treat cause ± liver transplantation
Reduce portal venous pressure (beta blockers ± nitrates or shunts - TIPS (also treatment for big varices)) - Non specific beta blockers e.g. carvedilol
Location of varices in portal hypertension (4)
Gastro-oesophago junction
Anterior abdominal wall
Anorectal junction
Retroperitoneum
Budd-Chiari syndrome
What
Presentation
Rare syndrome with obstruction of hepatic veins
Sudden RUQ pain + rapidly developing ascites + hepatomegaly + jaundice + renal involvement (50%)
Liver cancer Primary vs Secondary occurance Cause Associations Presentation
10% are primary, 90% are secondary cancers (stomach, colon, lung, breast)
90% of primary are HCC, 10% are cholangiocarcinoma (flukes, PSC, biliary cysts, early jaundice)
HepC is the leading cause in the UK
Worldwide - HBV
8x more common in men
Occurs 20 years after initial insult
90-95% of HCC patients have cirrhosis
Alcoholism, HH, PBC, metabolic syndrome
Anorexia, wt loss, night sweats, RUQ pain + symptoms of liver disease/cirrhosis/failure
Liver cancer screening
Screen high risk i.e. HBV ± cirrhosis and HCV/alcoholic cirrhosis
6-12 monthly USS + AFP (alpha fetoprotein levels >400 n.b. If <4cm may be normal)
Steatosis/steatohepatitis What Alcoholic vs non alcoholic distinction Causes (4) Presentation
Accumulation of fat in the liver. If this is associated with inflammation it is called steatohepatitis (or NASH - non-alcoholic steatohepatitis)
Based on alcohol consumption (>2U/day women/ 3U/day men)
Metabolic syndrome, PCOS, alcohol excess, starvation, HBV/HCV, metabolic disorders (Wilson’s, glycogen storage disorder…) medications (amiodarone, tamoxifen, glucocorticoids, methotrexate)
Steatosis generally is asymptomatic (fatigue/RUQ pain). Advanced disease may have cirrhosis symptoms ascites, oedema, jaundice
Hepatomegaly is common
