9. Liver and Biliary System Flashcards
Pre-Hepatic Jaundice
Excessive amount of bilirubin is presented to the liver due to excessive haemolysis
Elevated unconj. BR in serum
Liver Jaundice
Impaired cellular uptake, defective conj, or abnormal secretion by the liver cell.
Both unconj and conj bilirubin may be elevated in serum
Biliary Jaundice
Impaired excretion due to mechanical obstruction to flow
Elevated conj. BR in serum
Signs of portal HTN
Oesophageal varices --> coffee ground vomiting Splenomegaly Caput medusae Ascites Hemorrhoids
Signs of liver cell failure
Asterixis Bruising Clubbing Dupuytren’s contracture Erythema (palmar) Fetor hepaticus Gynaecomastia Have portal hypertension (see left) Itching (Pruritis) Jaundice Spider naevi + testicular atrophy
A 26 y/o male returns from holiday in India. He has had diarrhoea after eating at a seafood restaurant on his last night. He is feverish and nauseous. You notice that the whites of his eyes are yellow.
A. Hepatitis A B. Hepatitis B C. Hepatitis C D. Hepatitis D E. Hepatitis E
A. Hepatitis A
A 64 y/o male with thalassaemia is investigated under the two-week wait for jaundice and weight loss. His blood tests show a raised αFP. Which chronic infection is he most likely to have?
A. Hepatitis A B. Hepatitis B C. Hepatitis C D. Hepatitis D E. Hepatitis E
C. Hepatitis C
aFP- raised in liver cancer, for which Hep C chronicity is a risk factor
A 32 y/o male returns from holiday in Thailand, feeling ‘under the weather’ with RUQ pain, fevers and nausea. He is jaundiced. He reveals he has used IV drugs and had unprotected sex with a stranger while on holiday. Which test is most likely to give the correct diagnosis?
A. Liver function tests B. HIV serology C. Hepatitis B serology D. Hepatitis C PCR E. CXR
C. Hepatitis B serology
A 43 y/o confused man is brought to A&E by police after being found wandering the streets. He is disorientated and unable to give a clear history. You notice the a brownish-yellow ring around in his eyes. What is he likely to have?
A. Alcohol intoxication B. Wilson’s disease C. Opiate overdose D. Haemochromatosis E. Hypoglycaemia
B. Wilson’s disease
72 y/o man with cirrhosis presents to A&E with diffuse abdominal pain and fever. He is nauseous and has vomited. His abdomen is distended and there is shifting dullness on examination. Which investigation would be most urgent?
A. Paracentesis B. Stool sample MC&S C. Abdominal USS D. LFTs E. Blood cultures
A. Paracentesis
Although it’s important to diagnose the underlying condition, this is suggestive of bacterial peritonitis (secondary to cirrhosis) which much be treated quickly as a priority.
Hep A: Transmission Incubation Period Areas of high risk Risk factors Chronic?
Faecal-oral 2 weeks Africa/Asia Poor hygiene Rare
Hep B: Transmission Incubation Period Areas of high risk Risk factors Chronic?
Bodily fluids 4-12 weeks Africa Health workers Likely in children, 5% adults
5% of people with chronic Hep B have Hep D too.
Hep C: Transmission Incubation Period Areas of high risk Risk factors Chronic?
Bodily fluids 2 weeks -6 months Eastern Mediterranean Injecting drugs Yes, 60-80%
Hep D: Transmission Incubation Period Areas of high risk Risk factors Chronic?
Bodily fluids 4-12 weeks Africa ONLY co-infects with Hep B Rare
Hep E: Transmission Incubation Period Areas of high risk Risk factors Chronic?
Faecal-oral 5-6 weeks Poor water supply Immunocompromised patients Pregnancy Rare
Viral Hepatitis: Symptoms and Signs
Fever + Jaundice (+ High AST/ALT)
Other symptoms likely:
- Reduced appetite (anorexia),
- Nausea and vomiting, lasting for a few days
- Abdominal pain
- Itching (without skin lesions), skin rash
- Joint pain
- Dark urine and pale stools
- Tender hepatomegaly
Viral Hepatitis: Investigations
Liver function tests (first line) - indicate whether the jaundice is a liver or biliary cause
FBC
U+Es
Antibodies (diagnostic)
NAAT - Nucleic Acid Amplification Test can indicate viral load- useful to measure treatment response.
Hepatitis B Serology Interpretation
Anti-HBc IgM: Acute
Anti-HBc IgG: resolved acute, or chronic ongoing
HBsAg: Acute/Chronic ongoing infection
Anti-HBs (surface): Resolved acute, prior vaccination (after infection has passed)
Viral Hepatitis: Management
A: supportive care
B: supportive care for acute, antivirals +peginterferon for chronic.
C: supportive care for acute, antivirals for chronic.
Liver transplant if worsening.
Prognosis and complications of Viral Hepatitis
A: nearly all resolve by 6 months
B: viral suppression in 90% of chronic cases
C: mortality at 79% at 10 years for chronic cases.
One complication apart from chronicity is fulminant liver failure - very rare but requires an emergency transplant.
NASH - Non-Alcoholic Steatohepatitis/FLD
Aetiology, RF and Epidemiology
Aetiology: insulin resistance –> increased triglycerides –> steatosis–> inflammation –> steatohepatitis.
Risk factors: T2DM, metabolic syndrome, some medications. WITHOUT significant alcohol use.
Epi: 20-40% of the Western world are likely to have this to an extent.
NASH: Signs and Symptoms
Metabolic syndrome WITHOUT alcohol use
RUQ Pain
Hepatosplenomegaly
Usually no jaundice (not serious enough)/fever
NASH: Investigations
Liver function tests
- AST:ALT ratio will be <1
- (NB ALD: >2)
- GGT <96.5 (above = fibrosis/ALD)
FBC
Metabolic panel (NA, K, U&Es, serum glucose - comorbid T2DM in up to 50%) and lipid profile
Hepatic US (every 6 months ?progression to cirrhosis)
(No Dx test - clinical)
Prognosis of NASH
1/3s reverse the condition
1/3 stay stable throughout life
1/3 progress to cirrhosis.
Complications: –> cirrhosis: HCC, ascites, portosystemic thrombosis and haemorrhage etc etc.
Low albumin, very high bilirubin would indicate the liver failure.
Alcoholic hepatitis Aetiology
Alcohol metabolism in the liver produces excess NADH which inhibits gluconeogenesis and fatty acid oxidation –> same pathology as NASH.
Epidemiology: 10-15% heavy drinkers
ETOH > 40-80 g/day in men and 20-40 g/day in women for 10-12 years to cause alcoholic hepatitis or cirrhosis
RF: co-morbid obesity, metabolic syndrome, viral hepatitis
Alcoholic hepatitis: Signs and Symptoms
RUQ pain
Hepatosplenomegaly
WITH a background of heavy alcohol use
Other symptoms increase with severity
Alcoholic Hepatitis Investigations
Liver function tests - AST:ALT ratio >2 - GGT should be elevated - if not, reconsider Dx FBC U+Es Vitamins screen (?Deficiencies) Hepatic Ultrasound
Alcoholic Hepatitis Management
- Abstinence support
- Metabolic syndrome addressed if needed
- Steroids, nutritional supplementation may be added
- Liver transplant if in failure.
Cirrhosis Definition and aetiology
Hepatocytes death –> scarring –> fibrosis
The end stage of all chronic hepatitis
Decompensated liver failure gives symptoms (other systems are no longer able to COMPENSATE for its lack of function)
Cirrhosis: Signs and Symptoms
Symptoms - prevents normal BF through liver system => portal vein HTN
Abdominal distension
Pruritis
Coffee-ground vomit (oe varices)
Signs Jaundice Ascites Asterixis Dupeytren’s Contracture Sparse Body Hair Musc Wasting Encephalopathy etc
Cirrhosis: Investigations
LFTS - Albumin low - PT prolonged (Synthetic function - more affected by fibrosis than fat build up) Electrolytes, U+Es - Na may be low due to ascites US/CT/MRI - Not necessary but useful to see atrophy/fibrotic nodules
Management, Prognosis and Complications of Cirrhosis
Treat underlying cause.
Liver transplant if severe.
Prognosis: median survival of patients with fibrosis is 10 years, shortened by oesophageal varices.
Complications: portosystemic encephalopathy, hepatorenal and hepatopulmonary syndrome.
Wilson’s disease: Definition, Aetiology, Epidemiology
Disease of impaired copper excretion (AR)
Mutation in ATP7B gene –> impaired excretion of copper in the bile.
Accumulates in the liver –> cirrhosis and basal ganglia –> neuropsychiatric disorder.
30/million - rare
Wilson’s disease: Symptoms and Signs
Hepatitis symptoms
Ataxia
Tremor
Dysdiadochokinesia
Wilson’s disease: Investigations
LFTS
- Abnormal
Urinary copper
- High (only way of excreting)
Serum caeruloplasmin
- Low (used up by high copper)
Kayser-Fleischer Ring
Accumulation of copper
Seen under slit-lamp investigation
Haemochromatosis:Definition, Aetiology, Epidemiology
Haemochromatosis (AR) is a multisystem disorder of dysregulated dietary iron absorption and increased iron release from macrophages.
Autosomal recessive inheritance.
The most common mutations of the haemochromatosis gene (HFE) are C282Y and H63D for hepcidin (protein regulating iron intake) –> mutation = continued duodenal absorption from the diet.
Deposits in liver, pancreas and pituitary gland.
Haemochromatosis: Signs, Symptoms,
Tanned skin T1DM Liver symptoms - Hepatomegaly - Fatigue - Pruritis
Haemochromatosis: Investigations
Haematinics
- Transferrin LOW (transport protein for iron – when iron is low, it increases to compensate )
- Ferritin HIGH
- Transferrin saturation HIGH
A 41 y/o female presents with a history of colicky, right sided abdominal pain. She states the pain is worse after eating fish and chips and Indian takeaways. On examination her abdomen is soft and non-tender. Which is the best investigation to confirm her diagnosis?
A. Abdominal X-ray B. ERCP C. Liver biopsy D. USS of biliary tree E. CT-KUB
D. USS of biliary tree
A 41 y/o female presents to A&E with a history of severe, continuous, RUQ pain. She feels feverish and complains of an occasional pain in her right shoulder. On examination she displays RUQ tenderness and a positive Murphy’s sign. What is the most likely diagnosis?
A. Biliary colic B. Ascending cholangitis C. Acute cholecystitis D. Primary biliary cirrhosis E. Cholangiocarcinoma
C. Acute cholecystitis
While waiting to be admitted, her RUQ pain becomes worse and she starts shaking uncontrollably. You notice she now looks jaundiced. What is the most likely diagnosis?
A. Biliary colic B. Ascending cholangitis C. Acute cholecystitis D. Primary biliary cirrhosis E. Cholangiocarcinoma
B. Ascending cholangitis
A 35 y/o man presents with a two week history of jaundice and RUQ pain. He is taking mesalazine for a “bowel condition”. What is the most likely cause of his jaundice?
A. Autoimmune hepatitis B. Haemochromatosis C. Primary sclerosing cholangitis D. Primary biliary cirrhosis E. Drug side effect
C. Primary sclerosing cholangitis
Gallstones: Management
Cholelithiasis- Cholecystectomy
Choledocholithiasis - ERCP:
Endoscope Retrograde Choleo-pancreotography – endoscope down inti the small intestine to the opening of the bile duct- can view and remove stones.
Gallstones: Management
Cholelithiasis- Cholecystectomy
Choledocholithiasis - ERCP:
Endoscope Retrograde Choleo-pancreotography – endoscope down inti the small intestine to the opening of the bile duct- can view and remove stones.
Gallstones: Two important complications
Ascending Cholangitis:
CBD –> Bile Stasis –> Bacteria from gut to BD
Acute Cholecystitis
GB/Cystic duct –> Bile Stasis, Inflammation + bacteria
Acute Cholecystitis Symptoms and Signs
Constant (DDx to Gallstones) RUQ pain May radiate to R scapula (Boas’ sign) Fever Nausea & vomiting Rebound tenderness Murphy’s sign +ve
Ascending Cholangitis
Symptoms and Signs
Charcot’s triad
RUQ pain
Fever
Jaundice
If septic:
Reynold’s pentad
+ Hypotension
+ Confusion
Jaundice + sepsis risk much more prevalent compared to acute cholecystitis
PBC: Definition, aetiology, epidemiology
Primary biliary cirrhosis/cholangitis
An auto-immune condition resulting in damage to, and progressive destruction of, the biliary epithelial cells lining the small intrahepatic bile ducts.
Peak diagnosis ages 55-65.
10:1 Female to Male Ratio.
Risk factors: previous autoimmune disease and/or hypocholesteraemia (irritates the intrahepatic bile ducts)
PBC: Signs and Symptoms:
- Pruritis
- Fatigue
- Often comorbid Sjogren’s: dry eyes and mouth
Investigations:
LFTs AMA antibodies (Anti-mitochondrial) Diagnostic Abdo US Obstructive duct lesion MUST be excluded.
PSC: Definition, Aetiology, Epidemiology
Inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts, resulting in diffuse, multi-focal stricture formation.
Aetiology: unknown - may be AI (high serum Ab)
Peak incidence in 40-50s; rare - 13/100,000
Risk factors: male gender and concurrent IBD (2/3rds).
PSC Symptoms and Signs
RUQ pain
Pruritis
Fatigue
Vague - based on RF
PSC Investigations:
LFTs (first line) - GGT elevated MRCP (diagnostic) - Beading AMA antibodies - Should be negative
Differences between PBC and PSC
Site of disease involvement:
PSC: BD inside and outside liver (10% have small duct PSC)
PBS:
Pancreatic Cancer
6th most common cause of cancer- related death.
Technically pancreatic ductal adenocarcinoma.
Peak incidence 65-75 years old.
Risk factors: smoking, FH.
Key symptoms: jaundice, non-specific abdo pain, FLAWS.
Investigations: LFTs, ultrasound CT if suspicious.
Differences between PBC and PSC
Site of disease involvement:
PSC: BD inside and outside liver (10% have small duct PSC)
PBS: Small bile ducts inside liver
Mode of Dx:
PSC: MRI of bile ducts. Liver Biopsy or ERCP
PBC: Raised ALP, +ve Ab (AMA), Dx Liver Biopsy
Pancreatic Cancer
6th most common cause of cancer- related death.
Technically pancreatic ductal adenocarcinoma.
Peak incidence 65-75 years old.
Risk factors: smoking, FH.
Key symptoms: jaundice, non-specific abdo pain, FLAWS.
Investigations: LFTs, ultrasound –> CT if suspicious.
Pancreatic Cancer
6th most common cause of cancer- related death.
Technically pancreatic ductal adenocarcinoma.
Peak incidence 65-75 years old.
Risk factors: smoking, FH.
Key symptoms: jaundice, non-specific abdo pain, FLAWS.
Investigations: LFTs, ultrasound –> CT if suspicious.
A 58 year old woman is referred on from her GP as a result of abnormal laboratory tests. She is well does, does not smoke or drink; but does lead a sedentary lifestyle, suffers from hypertension and has a BMI of 33.
Laboratory results show:
Elevated AST and ALT. Elevated Triglycerides.
ALP, Bilirubin, INR within normal limits; Fasting glucose normal;
Total cholesterol, LDL, HDL normal;
Hepatitis serology, autoimmune screen: negative; Ferritin levels: normal
Possible differentials
Chronic Viral Hepatitis, Alpha 1 Anti-Trypsin Deficiency, Non Alcoholic Fatty Liver Disease (NAFL), Wilson’s Disease, Haemochromatosis
