Liver Flashcards
Hypoalbuminaemia found in
Liver dysfunction
Hyper catabolic states - sepsis, chronic inflammation
Increased loss due to nephrotic syndrome
Determine liver synthetic function by measuring…
Prothrombin time - clotting factors are synthesised in liver, increases if impaired function
Serum albumin decreases if impaired function
Prolonged prothrombin time can be due to
Liver dysfunction
Vit K deficiency in biliary obstruction (iv v.K improves clotting)
Gilbert’s disease
Increased bilirubin, other biochemistry normal
Due to inherited defect in bilirubin metabolism
Isolated rise in serum bilirubin - causes
Gilbert’s disease
Haemolysis
Ineffective erythropoiesis (premature RBC death in bone marrow)
Very high bilirubin levels most common in…
Biliary tract obstruction
Aminotransferases are…
Enzymes in hepatocytes, leak if damage
High levels aminotransferases in
Acute hepatitis - 20-50 times normal
Aspartate aminotransferases (AST)
Found in liver, heart, skeletal muscle
Raised serum conc on hepatitis, myocardial infarct, skeletal muscle damage
Alanine aminotransferases (ALT’s)
More specific to liver damage than ASTs
Alkaline phosphatase is situated in
Canalicular and sinusoid all membranes of liver
Alkaline phosphatase is increased in
Cholestasis - impaired bile flow from any cause
Pregnancy - as produced in placenta
Produced in bone, so growing children, bony metastases, Paget’s disease
Gamma - GT is a..
Liver microsomal enzyme induced by alcohol and enzyme inducing drugs
Gamma-GT raised in
Alcohol abuse
Enzyme inducing drugs eg phenytoin
In cholestasis rises in line with serum alkaline phosphatase (similar pattern of excretion)
Predominant elevation of serum aminotransferases indicates…
Hepatocellular injury
Predominant elevation of serum bilirubin and alkaline phosphatase indicates…
Cholestatic disorder
Eg primary biliary cirrhosis, primary sclerosing cholangitis, extra hepatic bile duct obstruction
Isolated rise in bilirubin most likely due to…
Gilbert’s disease
Use of ultrasound in hepatobiliary disease
Usually first imaging investigation
Useful tests for lesions in gall bladder, bile duct
Endoscopic US (ultrasound probe at scope tip) used for…
Detect and stage pancreatic carcinomas
Assess bile ducts
Confirm malignancy
MRI use…
Investigate focal liver disease
Allergies to iodine based contrast, so no contrast CT
MRCP
Magnetic Resonance Cholangiopancreatography
High quality images pancreatic and bile ducts
Similar to ERCP - replacing its diagnostic, not therapeutic use
ERCP
Endoscope to second part duodenum, image pancreatic and bile ducts with radio graphic contrast via ampulla of vater
Percutaneous transhepatic Cholangiopancreatography (PCT)
Inject contrast into biliary system via intrahepatic duct
Performed if biliary dilatation if ERCP failed
If obstruction, bypass stent can be inserted
Acute liver disease presentation
May be asymptomatic
Early stages - lethargy, anorexia, malaise
Later - Jaundice
Chronic liver disease complications
Ascites
Oesophageal varices - haematemesis, melaena
Hepatic encephalopathy - confusion, drowsiness
Pruritus (itching) found in
Cholestatic jaundice - any cause
Especially - primary biliary cirrhosis
Signs in compensated chronic liver disease
Xanthelasma Spider naevi Gyanaecomastia Small/large liver Splenomegaly Testicular atrophy Hands - clubbing, dupuytrens contracture
Decompensated liver disease signs
Neurological - disorientation, drowsy, coma Hepatic flap Ascites Dilated veins on abdomen (caput medusa) Oedema
General liver signs
Jaundice
Fever
Loss of body hair
Bilirubin is derived predominantly from…
Haemoglobin breakdown in spleen Carried in blood bound to albumin Conjugated in liver Excreted in bile to small intestine Terminal ileum - converted to urobilinogen and excreted, or re absorbed, excreted by kidneys
3 clinical categories of jaundice
Haemolytic jaundice Congenital hylerbilirubinaemia (impaired conjugation) Cholestatic jaundice (failure of bile excretion - abnormal LFTs)
Haemolytic jaundice
Increased breakdown RBCs, increased bilirubin
Mild
Causes = haemolytic anaemias
Congenital hylerbilirubinaemia
Most common Gilbert’s syndrome, 5% population
Asymptomatic, often incidental finding
Reduced conjugation
Other LFTs normal
Two types Cholestatic jaundice
Intrahepatic cholestasis - hepatocellular swelling / abnormalities at a cellular level of bile excretion
Extrahepatic cholestasis - obstruction of bile flow distal to bile canaliculi
Both - conjugated bilirubin so pale stools, dark urine
Causes intrahepatic cholestatic jaundice
Viral / alcoholic hepatitis
Drugs
Cirrhosis
Pregnancy
Causes extrahepatic jaundice
Common duct stones Carcinoma - bile duct, head of pancreas, ampulla of vater Biliary stricture Sclerosing cholangitis Pancreatitis
Investigating jaundice - three things plus some
Serum liver biochemistry - confirm jaundice
US examination
Serum viral markers
Also - prothrombin time, serum autoantibodies
Serum biochemistry in jaundice
Confirms jaundice, larger rise AST - hepatitis, larger rise alkaline phosphatase - extra hepatic obstruction
Hepatitis serum viral markers
Hepatitis A and B - serum viral markers present in acute viral hepatitis
Hepatitis C - antibodies develop late, RNA detectable by 2 weeks
US examination shows dilated bile ducts in…
Extra hepatic cholestasis
May identify level of cause eg gall stones, tumours
Acute hepatitis causes
Mostly viral
Acute hepatitis progression
Usually self limiting
Occasional progression to massive cell necrosis
Acute hepatitis - clinical features
May be jaundiced
Enlarged, tender liver
Lab evidence of raised aminotransferases
Acute hepatitis assess disease severity by…
Prothrombin time
Serum bilirubin
Chronic hepatitis is…
Sustained inflammation of liver >6 months
Most common cause chronic liver disease world wide is…
Viral hepatitis
Causing chronic liver disease, cirrhosis, hepatocellular carcinoma
Hepatitis A epidemiology
Most common Particularly children and young adults Faeco-oral transmission route Ingestion contaminated food - shellfish Most infectious just before onset jaundice
Clinical features hepatitis A
Average incubation period 28 days
Nonspecific nausea, anorexia, distaste for cigarette
Then some jaundiced, dark urine, pale stools, prodrome improves
Moderate hepatomegally, spleen palpable 10%
Self limiting 3-6 weeks
Rare - coma and death
Drug causes chronic hepatitis
Methyl dopa
Nitrofurantoin
Isoniazid
Ketoconazole
Investigation findings Hep A
Raised ALT, then raised bilirubin
Bloods - leucopenia, lymphocytosis, high ESR
Severe cases - prothrombin time prolonged
Antibodies in HAV
Acute HAV - IgM anti-HAV
Past infection - IgG anti-HAV
HAV prophylaxis
Active immunisation with inactivated strain given to travellers, people with chronic liver disease, occupational risk, haemophilia patients treated with clotting factors
HAV passive immunisation
With immunoglobulin
Given to close contacts of confirmed HAV cases
HBV epidemiology
Vertical transmission most common
Also blood, blood products, sexual intercourse
Acute HBV infection immune response
Penetrates hepatocyte, strong cellular immune response
Clearance of infection in 99% infected adults
Anti HBs antibodies develop
Immunity to subsequent infection
Fulminant liver failure
Occasional effect of HAV / HBV infection
Hepatic failure with encephalopathy in less than 2 weeks
Due to massive cell necrosis
Presents - hepatic encephalopathy, jaundice, coagulopathy
Complications - hypotension, renal failure, cerebral oedema, hypoglycaemia
HBsAg
Appears in blood from about 6 weeks to 3 months after an acute infection, then disappears
If chronic hepatitis, persists and indicates chronic infection / carrier state
HBeAg
Rises early, declines rapidly in acute disease
Chronic - persists, correlates with increases severity / infective ty
Anti HBe correlates with decreased HBeAg
Anti HBc
First antibody to appear, high titres suggest acute ongoing infection
HBV DNA
Suggests continued viral replication
Chronic HBV progression
Persistence of HBsAg for >6 months after acute infection = chronic
Progression depends on virulence, age, immunocompetence
Acquisition of HBV at / near birth
Immune tolerant phase 20-30 years, high levels replication
Normal ALT, positive HBeAg
Then immune clearance phase active hepatitis, high ALT
Ends with clearance of HBeAg, development anti-HBe
HBV treatment given to…
Patients most likely to develop progressive liver disease - high HBV DNA,
HBV / HIV co-infection
10-20%
Test all chronic HBV for HIV
Hepatitis C epidemiology
UK - iv drug use
Worldwide - blood products, poorly sterilised instruments
Clinical features HCV
Acute often mild, jaundice rare, most progress to chronic liver disease
Present with elevated aminotransferases or signs/symptoms CLD
Px with cirrhosis secondary to HCV are at increased risk of…
Hepatocellular carcinoma
Diagnosis of HCV
HCV antibody in serum
8 weeks to appear after acute infection
Positive HCV RNA suggests active disease
HCV treatment
Aims for viral clearance
Depends on genotype (2&3 more responsive so even treat mild)
1&4 less responsive so treat moderate/ severe
IFN-Alfa and ribavirin
Autoimmune hepatitis what, who
Progressive liver disease
Often associated with autoimmune eg pernicious anaemia, thyroiditis
Most common in young-middle aged women
Autoimmune hepatitis aetiology
Unknown
Disease characterised by hypergammaglobulinaemia
High IgG, circulating autoantibodies
Clinical features autoimmune hepatitis
Insidious onset, anorexia, malaise, nausea, fatigue
25% present acute hepatitis - rapid progressive liver disease
Treatment autoimmune hepatitis
Prednisolone 2-3 weeks
Maintenance dose may be required, and azathiopene as steroid sparing agent
Autoimmune hepatitis prognosis
Steroid and azathiopene induce remission in over 80% cases
Liver transplant may be necessary
Non-alcoholic fatty liver disease
Liver biopsy finds changes indistinguishable from alcohol excess
But no heavy drinking
Non alcoholic fatty liver disease is associated with..
Obesity, T2DM, hypertension, hyperlipidaemia
Considered the liver component of ‘metabolic syndrome’
NAFLD pathogenesis
Not entirely known
Thought that insulin resistance is key, then ‘second hit’ oxidative injury, progresses to inflammatory component - steatohepatitis (NASH)
Clinical features non-alcoholic fatty liver disease
Most asymptomatic
Mild elevation aminotransferases picked up
Hepatomegaly common
Management non alcoholic fatty liver disease
No proven effective therapy
Treat risk factors
Transplant may be needed for end stage disease
Cirrhosis
Results from necrosis of liver cells
Then fibrosis, nodule formation
Therefore impairment of liver cell function, gross distortion anatomy, portal hypertension
Aetiology cirrhosis
Alcohol, viral hepatitis
Histologically two types cirrhosis
Micronodular - small, uniform, ongoing alcohol/ biliary tract disease
Macronodular - variable size, normal acini in larger nodules, chronic viral hepatitis
Some is mixed.
Clinical features hepatitis
Secondary to portal hypertension / liver cell failure
Decompensated cirrhosis has…
Encephalopathy, ascites, varicella haemorrhage
Compensated cirrhosis has NO
Ascites, encephalopathy, varicella haemorrhage
Liver biochemistry in cirrhosis
May be normal
Often some increase serum alkaline phosphatase and aminotransferases
FBC in cirrhosis
Thrombocytopenia at most diagnoses
Leukopenia, anaemia develop later
Measure liver function in cirrhosis with
Prothrombin time and serum albumin
Serum electrolytes in cirrhosis
Low sodium - severe liver disease secondary to impaired free water clearance / excess diuretic therapy
Elevated serum creatinine associated with worse prognosis
Serum alpha-fetoprotein (AFT) in cirrhosis
Usually undetectable post partum
May be raised in chronic liver disease
High level suggests hepatocellular carcinoma
Aetiology of cirrhosis
Response to any chronic liver injury
Liver biopsy to confirm severity, type
Further investigations in cirrhosis
Seek and treat oesophageal varices - endoscopy
US for HCC and assess patency portal and hepatic veins
Cirrhosis management
Manage complications Underlying problems - halt progress Screen for HCC End stage consider transplant Flu vaccine
Portal vein formed from union of
Superior mesenteric (gut) Splenic vein (spleen)
Portal vein carries blood to
Liver
Accounts for 75% hepatic vascular inflow
Blood vessel passage in liver
enter liver via hilum (porta hepatis)
Passes into hepatic sinusoids via portal tracts
Leaves liver through hepatic veins to join IVC
Normal portal pressure
5-8mmHg
Three types blockage hepatic blood flow
Prehepatic - due to blockage portal vein before liver
Intrahepatic - from distortion of liver architecture
Post hepatic - venous blockage outside liver - rare
Most common cause portal hypertension
Cirrhosis
1cause prehepatic portal hypertension
Portal vein thrombosis
3 causes intrahepatic portal hypertension
Cirrhosis
Alcoholic hepatitis
Schistosomiasis
Two causes post hepatic portal hypertension
Right heart failure
Constrictive pericarditis
Common signs portal hypertension
Splenomegaly
GI bleeding
Ascites
Hepatic encephalopathy
Management bleeding oesophageal varices
Endoscopic therapy - eg band ligation
Pharmacological - emergency control bleeding
Balloon tamponade if endoscopy fails - inflate gastric balloon, pull back to block blood G-O junction !aspiration pneumonia, oesophageal rupture!
Ascites is
Presence of fluid in peritoneal cavity
Commonest cause ascites is
Cirrhosis
Pleural effusion in ascites
Usually right sided
Causes ascites - transudate
Portal hypertension
Hepatic outflow obstruction
Cardiac failure
Causes ascites - exudate
Peritoneal carcinomatosis
Peritoneal TB
Pancreatitis
Nephrotic syndrome
Cirrhotic ascites and high neutrophil count (>250)
Bacterial peritonitis
Management ascites - cirrhotic
Dietary sodium restriction, plus spironolactone
Frusemide added if poor response
Maybe paracentesis, plus albumin infusion
Aim of ascites treatment
Lose 0.5kg weight/day
Too rapid diuresis - intravascular depletion, encephalopathy
Rising creatinine / hyponatraemia in management ascites…
Inadequate renal perfusion
So temporary cessation diuretic therapy
Spontaneous bacterial peritonitis in cirrhotic ascites patients
Occurs in 8%
Mortality rate 10-15%
Mostly E-Coli
Perform diagnostic aspiration and empiric antibiotics
Portosystemic (hepatic) encephalopathy
Occurs in advanced chronic/acute hepatocellular disease
Also following TIPS shunts
Failure of toxin breakdown
Clinical features hepatic encephalopathy
Drowsy, comatose
Increased tone, hyperreflexia
Chronically - irritable, slurred speech, reversed sleep
Signs hepatic encephalopathy
Fetor hepaticus - sweet smelling breath
Asterixis
Constructional apraxia
Hepatic encephalopathy investigations
EEG
Arterial blood ammonia
Factors precipitating hepatic encephalopathy
High dietary protein
GI haemorrhage
Constipation
Infection…
Management hepatic encephalopathy
Laxatives - lactulose, limits ammonia absorption
Antibiotics decrease bowel flora therefore ammonia production
Initially restrict protein
Hepatorenal syndrome
Development AKI if advanced liver disease
Due to peripheral vasodilatiation, hypovolaemia
Decreased renal perfusion
Diagnosis - oliguria, rising serum creatinine, low urine sodium
Hepatopulmonary syndrome
Inteapulmonary vascular dilatation in chronic liver disease, hypoxaemia, can be breathless on standing
Diagnose by echo, improve with liver transplant
Liver transplantation
Liver failure, any cause Psychological assessment Education Few over 65 years 6 month abstinence if alcohol related
Primary biliary cirrhosis
Type of chronic liver disease
Destruction of bile ducts, cholestasis, cirrhosis
Predominantly women middle age
Abnormal immuneregulation inherited anti-mitochondrial antibodies often present
Primary biliary cirrhosis features
Pruritus, sometimes jaundice Advanced - hepatosplenomegaly, xanthelasma Raised serum alkaline phosphatase Autoantibodies Steatorrhoea
Primary billiard cirrhosis investigations
Raised alkaline phosphatase, IgM
Often anti mitochondrial antibodies, antinuclear factor
Liver biopsy - loss of bile ducts, later cirrhosis (staging)
Primary biliary cirrhosis prognosis
Asymptomatic - near normal
Jaundiced - poor, death in 5 years without transplant
Secondary biliary cirrhosis
Cirrhosis due to prolonged large duct biliary obstruction
Eg bile duct strictures, CBD stones, sclerosing cholangitis
Hereditary haemochromatosis
Autosomal recessive, 1in400 prevalence (Caucasian)
Approx 10% population carriers
Excess iron deposition - fibrosis - organ failure
Aetiology haemochromatosis
Increased iron absorption from small intestine
HFE gene mutation
Few cases due to defects in metabolism
Clinical features haemochromatosis
Often incidental finding increased iron / ferritin or screening
Less overt disease in women do to iron loss
Symptoms due to iron deposition
Symptoms of iron deposition in organs
Liver - hepatomegally, lethargy Pancreas - diabetes Myocardium - cardiomegally, heart failure, conduction disturbances Pituitary - loss of libido, impotence Joints - arthralgia Skin - hyperpigmentation
Investigations hereditary haemochromatosis
Serum liver biochemistry often normal
Serum iron increased, iron binding capacity reduced
Serum ferritin elevated
Genotyping - mutation HFE gene
Non invasive assessment fibrosis/cirrhosis
Management haemochromatosis
Venesection - 500ml blood removed twice weekly till normal
Then three or four venue sections / year maintenance
If cirrhosis, surveillance for HCC required
Screen relatives HFE mutations
Prognosis haemochromatosis
Major complication development HCC if cirrhosis
Life expectation fairly normal
Wilson’s disease (hepatolenticular degeneration)
Rare, recessive inheritance, mutations ATP7B gene
Decreased secretion of copper into biliary system
Copper accumulates in liver - fulminant hepatic failure, cirrhosis
Basal ganglia - Parkinsonism, dementia
Cornea - Keyser-Fleischer rings
Renal tubules
Diagnosis Wilson’s disease
Demonstrate low serum copper and caeruloplasmin
Increased urinary copper excretion
Increased copper in liver specimen
Alpha-1 anti trypsin deficiency
Rare cause of cirrhosis
Abnormal protein accumulates in liver
Treat for chronic lung and liver disease - stop smoking!
Alcohol and liver…
Most common cause liver disease western world
Alcohol is hepatotoxic
Only 15% excessive drinkers develop cirrhosis
3 major findings - fatty change, alcoholic hepatitis, alcoholic cirrhosis
Three major clinical illnesses associated with excessive alcohol intake
Fatty change
Alcoholic hepatitis
Alcoholic cirrhosis
Fatty liver change
Most common biopsy finding in alcoholics
Can be caused by just a few weeks - macro vascular lipid in hepatocytes
Symptoms often absent, may be hepatomegally
Often normal lab tests
Increased MCV may suggest heavy drinking
Gamma GT usually elevated
REVERSIBLE
Alcoholic hepatitis
Years of heavy drinking
May coexist with cirrhosis
Swollen hepatocytes contain Mallory bodies, surrounded by neutrophils.
May be fibrosis, degeneration of hepatocytes
Alcoholic hepatitis clinical features
Rapid onset jaundice
Also nausea, annorexia, RUQ pain
Fever, ascites, encephalopathy, tender hepatomegally
Full blood results in alcoholic hepatitis
Leukocytosis
Raised MCV
Often thrombocytopenia
Liver biochemistry in alcoholic hepatitis
Elevated AST, ALT, disproportionate rise AST, but <500
Bilirubin may be markedly elevated
Serum albumin low
Prothrombin time prolonged
Management severe alcoholic hepatitis
Nutritional input, support
Corticosteroids for inflammation
Steroids contraindicated in renal failure, infection, bleeding
Alcoholic cirrhosis
Final stage liver disease form alcohol abuse
Fibrosis, destruction liver architecture
May be symptomatic, or cirrhotic presentation
Primary sclerosing cholangitis
Chronic liver disease, progressive fibrosis of intra and extra hepatic ducts, -> cirrhosis
Unknown cause, link ulcerative colitis
Often diagnosed while asymptomatic but with IBD
Raised alkaline phosphatase
Symptomatic - pruritus, jaundice, cholangitis
Budd-Chiari syndrome
Occlusion hepatic vein- stasis and liver congestion - hypoxia, necrotic damage hepatocytes
Often due to hypercoagulable state - myeloproliferative disorders, thrombocytopenia, OCP, malignancy, inherited thrombophillias
Clinical features Budd-Chiari syndrome
RUQ pain, hepatomegally, jaundice, ascites
Acute - may -> fulminant hepatic failure
Chronic - cirrhosis, portal hypotension etc
Differentials ! Right heart failure, IVC obstruction, constrictive pericarditis!
Budd-Chiari investigations
Doppler US - abnormal flow, IVC thickening
Plus non specific signs hepatomegally etc
Biopsy not often necessary
Treatment Budd-Chiari syndrome
Three aims:
Restore venous drainage, if acute - thrombolysis, stent, angioplasty
Treat portal hypertension ascites complications
Detect underlying hypercoagulable disorder, treat
Causes liver abscesses
Biliary sepsis, portal pyaema from intra-abdominal sepsis
Trauma, bacteraemia, peri euphoric access
Most common is E Coli
Also strep milleri and anaerobes - bacteriodes
Amoebic liver abscess
Spread of entamoeba histolytica from bowel to liver via portal vein
Serological tests eg compliment / ELISA
Often recent travel endemic country
Single access right lobe liver
Clinical features liver abcess
Fever, lethargy, weight loss, abdominal pain
Liver - enlarged, tender,
Right side chest - consolidation/effusion
Investigations in liver abcess
Non specific infection signs inc low albumin
Raised alkaline phosphatase
US lesions, CT - non enhancing cavities with surrounding rim inflammation
Pyogenic liver abcess management
Aspirate under radiological control
Pigtail catheter for further drainage
Initial empirical antibiotics, then check
Liver tumours
Most are metastatic - GI tract, breast, bronchus
Can be confused with cysts
Hepatocellular carcinoma
5th most common tumour worldwide
Most due to hepB, hepC, pathogens
In patients with CLD / cirrhosis
Clinical features HCC
Weight loss, abdo pain, anorexia, fevers ascites - rapid development suggests HCC
Focal lesion in cirrhotic liver very likely HCC
Hepatocellular carcinoma investigations
Serum AFP can be raised (alpha fetoprotein)
US / CT show large filling defects
Biopsy / MRI if diagnostic doubt
Management hepatocellular carcinoma
Sometimes resection or transplant possible
Percutaneous ablative therapies - high frequency US or ethanol injection can produce tumour necrosis
Transarterial chemoembolisation in large tumours
Iv chemo not much use
Prognosis hepatocellular carcinoma
Median survival 6-20 months
Most common benign liver tumours
Haemangiomas - incidental finding
Hepatic adenomas - resect if symptomatic
