Liver Disease + Gall Bladder + Pancreas Flashcards
What does excessive bilirubin level in blood cause
Jaundice
What is the prehepatic cause of jaundice
Haemolytic anaemia - excess breakdown of RBC, releasing excess bilirubin
Sickle cell disease
What organs breakdown RBC
spleen
How is bilirubin metabolised
Metabolised in the liver, undergoes phase 2 metabolism - glucoronidation, making bilirubin more water soluble so it can be excreted in bile
What is glucoronidation
Addition of glucuronic acid by glucuronosyltransferase (UGT1A1)
Two types of hepatic causes of jaundice
Unconjugated - abnormal metabolism of bilirubin
Conjugated - abnormal excretion of conjugated bilirubin
What are the unconjugated hepatic causes of jaundice
Gilbert’s syndrome
hyperthyroidism
high serum levels of gentamicin
What are the conjugated hepatic causes of jaundice
hepatocellular injury - viral hepatitis / autoimmune hepatitis / alcoholic hepatitis / non-alcoholic fatty liver disease/ drug induced liver injury
Cholestatic liver disease - PBC, PSC
Sarcoidosis / amyloidosis / tuberculosis
What are the post hepatic causes of jaundice
Cholestatic liver diseases (PBC, PSC, malignancy, gallstones)
biliary atresia
strictures of biliary duct
What are cholestatic liver diseases
Decrease in bile flow due to abnormal excretion or obstruction of the bile ducts
Examples of cholestatic diseases
Malignancy at head of pancreas
primary sclerosing cholangitis
primary biliary cholangitis
gallstones
What is acute liver failure
Loss of liver function due to acute massive necrosis of hepatocytes
In absence of chronic liver disease
Causes of acute liver failure
Drug induced liver injury
viral hepatitis
alcohol
Budd chiari syndrome
What is the most common cause of acute liver failure
Drug induced liver injury
What drugs can cause drug induced liver injury
Paracetamol overdose
Co-amoxiclav / flucloxacillin / NSAID
Statins, ecstasy
What are the characteristic findings of acute liver failure
Hepatic encephelopathy + coagulopathy + hypoglycaemia + jaundice
What is hepatic encephelopathy
Altered mental state
Confusion
Asterixis (liver flap)
Due to build up of toxic ammonia
Symptoms of ALF
Jaundice HE easy bruising (due to coagulopathy) Abdominal pain Infection circulatory failure
What causes circulatory failure
Massive necrosis leads to massive inflammation, massive vasodilation -> very low SVR
Diagnosis of ALF
INR - coagulability Blood glucose level Ammonia level LFT - albumin / ALP / gGT / bilirubin Imaging
Treatment of ALF
IV fluids
Vitamin K and fresh plasma with clotting factors
Transplant
Sepsis 6 bundle if indicated
Complications of acute liver failure
Infections Circulatory failure High output HF Cerebral injury Haemorrhage
Why does circulatory failure occur in ALF
Because massive necrosis -> inflammation -> vasodilation -> low SVR
What is the end stage of liver disease
Cirrhosis
Timeline of liver disease
Chronic liver disease -> persistent inflammation -> fibrosis -> cirrhosis -> acute liver failure / decompensated cirrhosis
What does decompensated cirrhosis mean
The point where there is so much fibrosis and scarring causing the liver to fail ultimately
Examples of chronic liver diseases (conditions that can develop into chronic liver disease)
Alcoholic hepatitis Non-alcoholic fatty liver disease Viral hepatitis Autoimmune hepatitis Malignancy Primary biliary cholangitis / primary sclerosing
Development of alcoholic liver disease
Alcoholic fatty liver -> alcoholic hepatitis -> fibrosis -> cirrhosis
Disease progresses as you continue drinking
Why should you treat alcoholic fatty liver / alcoholic hepatitis as soon as possible
Because they are reversible; once you stop drinking, they can resolve and not develop into cirrhosis
What causes alcoholic fatty liver
Metabolism of alcohol leads to excess fat deposits in the liver
What will be seen on histology of alcoholic fatty liver
fat vacuoles (steatosis)
What products from alcohol metabolism are toxic to the liver
Ethanol and acetaldehyde
How long does it usually take for alcoholic hepatitis to develop
Weeks or months of excessive alcohol consumption
What happens in alcoholic hepatitis
Toxic ethanol and acetaldehyde -> necrosis -> inflammation
What immune cells infiltrate the liver in alcoholic hepatitis
Neutrophils
What stain is used to identify collagen fibres
Masson Trichome
How long does it take for fibrosis to occur in alcoholic hepatiits
months to years of excessive alcohol consumption
Histological features of cirrhosis
Collagen fibres surrounding regenerative nodules of hepatocytes, cutting off blood supply
How does cirrhosis make the hepatocytes no longer functional
Because the collagen fibres surrounding the hepatocytes cuts off the blood supply to the hepatocytes, meaning that
- the hepatocytes cannot receive portal blood from portal vein = cannot filter the nutrient rich blood
- the hepatocytes cannot receive blood from hepatic artery = no oxygen so dies
Why are there regenerative nodules in cirrhosis
Because of the persistent liver injury and necrosis in that area, causing the hepatocytes have to proliferate
Symptoms of alcoholic hepatitis
Jaundice Pain tender on palpation hepatomegaly signs of decompensated cirrhosis / liver failure
What are the signs of decompensated cirrhosis
Ascites
Portal hypertension
Easy bruising - coagulopathy
HE
Management of alcoholic hepatitis
Stop alcohol consumption
Ensure good nutrition and hydration
corticosteroid therapy for severe hepatitis
Complication of chronic liver disease
Cirrhosis
Malnutrition
Increase risk of hepatocellular carcinoma
What is NAFLD
Fatty liver in absence of excess alcohol consumption
Risk factors for NAFLD
Obesity
Metabolic syndrome - hypertension / hyperlipidaemia / low HDL
Diabetes
Genetic changes
Changes in what genes are associated with NAFLD
PNPLA3
TM6SF2
When should you suspect that the patient’s NAFLD is caused by genetic changes
When the patient is young and lean
Symptoms of NAFLD
Usually asymptomatic
Hepatomegaly
Signs of decompensated cirrhosis / liver failure
Pathogen for hepatitis A
Ebstein Barr virus
Pathogen for hepatitis B
yellow fever virus
Pathogen for hepatitis C
Herpes simplex virus
Pathogen for hepatitis E
cytomegalovirus
Which type of viral hepatitis is least likely to cause chronic liver disease
Hepatitis A and E
Which type of viral hepatitis has a high chance of developing into chronic liver disease
Hepatitic B (the younger the patient is, the greater the risk) Hepatitis C
What is considered as chronic viral hepatitis B
Failure to clear hepatitis B, causing presence of HBsAg antigen for over 6 months
Does hepatitis B have a short or long incubation period
Long - takes 1 - 4months to develop symptoms
Transmission of hepatitis B
By blood or sexual fluids
Can hepatitis B be transmitted from mother to child? And why is it bad?
Yes (vertical transmission); bad because the younger the patient gets hepatitis B, the more likely it is to develop into chronic liver disease and eventually cause cirrhosis
How long is the incubation period of hepatiits C
2 to 12 weeks
Chronic hepatitis caused by which virus is more associated with increased risk of hepatocellular carcinoma
Hepatitis B
What may be a histological finding for hepatitis caused by hepatitis C
Steatosis
Infiltration of inflammatory cells
What is the LFT pattern for cholestatic disease
Raised ALP and gGT
What would the LFT result be for viral hepatitis
Raised ALT and AST, normal ALP and gGT
Low albumin
Which hepatitis causes chronic hepatitis
Hepatitis C
Hepatitis B
Symptoms of acute hepatitis
Fever Jaundice Abdominal pain Nausea/vomiting Diarrhea
What is the most common cause of cirrhosis
Alcoholic hepatitis
Symptoms of chronic hepatitis
Usually asymptomatic till develop decompensated cirrhosis / ALF or exacerbations (symptoms of acute hepatitis)
Signs of deceompensated cirrhosis: HE, ascites, easy bruising
What conditions increases the risk of hepatocellular carcinoma
Chronic viral hepatitis B
Alcoholic hepatitis
NAFLD
PBC
Transmission of hepatitis A
Faecal-oral
Which age group does hepatitis A more commonly affect
young people
What needs to be done to confirm diagnosis for Hepatitis A
clotted blood for HAV IgM
Which group of hepatitis B patients need to be treated
Those with hepatitis B for more than 4 weeks
Those with coagulopathy
Those with acute liver failure
Diagnosis of hepatitis B
Serology and LFT
What would serology for active hepatitis B infection be
HBsAg positive
HBeAg positive
HBV DNA PCR positive
IgM anti-HBc positive
What signifies a chronic hepatitis B
HBsAg for more than 6 months
Serology for chronic hepatitis B
IgM anti HBc negative IgG anti HBc positive HBsAg positive anti-Hbs negative HBV DNA PCR positive
How long will IgM anti HBc be present
6 months
Which anti HBc will be present after 6 months of infection (in chronic hepatitis)
IgG HBc
What does HBeAg indicate
Indicates high viral replication / infectivity
What does anti-HBs indicate
clearance of disease or vaccinated
What does anti HBe indicate
decrease in viral replication
Serology for hepatitis B vaccinated person
anti HBs positive
others negative
Risk factors for Hepatitis B
Infected mother
Multiple sex partners
IV drug usage (repeated use of needle / contaminated needle)
What type of PCR is used in hepatitis C
RNA PCR
Which hepatitis are detected by RNA PCR
Hepatitis C
Hepatitis D
Treatment for hepatitis B
Anti-virals:
tenofovir / entecavir
PegIFN-alpha
Examples of anti virals
tenofovir / entecavir
PegIFN-alpha
How is hepatitis C transmitted
By blood
Why is hepatitis C serious
Because there is low level of spontaneous clearance, most develop into chronic hepatitis
Diagnosis of Hepatitis C
HCV RNA PCR
presence of HCV IgG
What can HCV IgG indicate
If positive -> can be active or past infection
Then test for HCV RNA by PCR
If HCV RNA PCR is positive -> active infection
If HCV RNA PCR is negative -> past infection
Management for hepatitis C
8-12 weeks of combination DAA (direct acting antivirals)
Which hepatitis cause acute hepatitis only
Hepatitis A
Hepatitis E
Transmission of hepatitis E
Faecal oral
Incubation period of Hepatitis E
15 to 60 days
What does hepatitis D need in order to be present
HBsAg, so it needs the presence of Hepatitis B as well
Treatment for hepatic encephalopathy
Lactulose - increases excretion of ammonia
Rifaximin
Cirrhosis mechanism
Liver injury -> activating Hepatic stellate cells -> HSC proliferate and cause fibrosis
Where are HSC found
space between hepatocytes and sinusoids
How does cirrhosis cause portal hypertension
Massive structural change, causing increase in vascular resistance
Hepatic portal vein carries blood from which organs back to liver
Spleen Small and large intestines Pancreas Stomach Oesophagus
What vessels drain into hepatic portal vein
superior and inferior mesenteric vein
splenic vein
gastrin vein
Blood flow from hepatic portal vein to right atrium
Hepatic portal vein -> sinusoids -> Central vein -> IVC -> right atrium
Location of anastamosis between portal and circulatory sytem
Oesophageal plexus
Umbilical vein
Haemorrhoidal venous plexus
Retroperitoneal collateral vessels
What is the significance of the anastamoses between portal and systemic circulation
During portal hypertension, because there is an increased resistance of blood flowing into liver then back into the circulatory system, blood will flow to the collateral vessels, bypassing the liver, flowing back to circulatory system (so basically, blood is finding an alternate way to go back to the heart)
What occurs due to portal hypertension
Ascites
Oesophageal varices
Haemorrhoids
How does ascites occur
Portal hypertension; increase in pressure forces fluid out of vessels
What is the vicious cycle of portal hypertension
1) Portal hypertension
2) Formation of collateral vessels, increase in blood flow in collateral vessels
3) sphlanchic vasodilation to increase blood flow into portal vein to compensate the loss of portal blood to collateral vessels
4) decrease in MAP, SVR -> stimulate baroreceptors and RAAS
5) RAAS increases water and sodium retention
6) increases blood flow in portal system = worsening portal hypertension
What are the other causes of portal hypertensionW
Portal embolism / portal thrombosis
Budd Chiari syndrome
What are the common causes of cirrhosis
Alcoholic hepatitis
NAFLD
Chronic viral hepatitis (HCV , sometimes HBC)
Why do patients with cirrhosis need to be on heparin
Because they are likely to bleed or clot (imbalance)
If they are not bleeding, they are likely to clot hence need to be on anti-coagulant to prevent clotting
What is Budd Chiari syndrome
Blockage of hepatic vein that drains the liver
What is decompensated cirrhosis
When the extent of cirrhosis is so great, the liver fails to function normally anymore
Symptoms of compensated cirrhosis
Mostly asymptomatic Hepatomegaly Splenomegaly Varices Clubbing Gynaecomastia
Signs of decompensated cirrhosis
HE
Coagulopathy - easy bruising
Ascites
Jaundice
Causes of ascites
Most commonly cirrhosis - portal hypertension
Peritonitis
Malignancy in peritoneal cavity
Types of ascitic fluid
Exudate = presence of proteins, immune cells; usually due to infection increasing vascular permeability Transudate = without presence of proteins and only a few cells; usually due to high pressure forcing fluid out of vessels
What type of ascitic fluid would portal hypertension cause
Transudate
Diagnosis of ascites
Dullness in percussion
Ascitic tap
Albumin level / WCC
Ultrasound
Ascitic tap procedure
Insert small needle to get a sample of ascitic fluid and send for microbiological sampling.
What does elevated neutrophil in ascitic fluid mean
Spontaneous bacterial infection
Management of ascites without spontaneous bacterial infection
First line: Spironalactone
Second line: Spironalactone + loop diuretics
Paracentesis - drain fluid
TIPSS
Management of ascites with spontaneous bacterial infection
Broad spectrum antibiotics
IV terlipressin
What drug is used to prevent varices from bleeding
Non selective Beta blockers - carvedilol / propanolol
What is cholelithiasis
Gall stones within gall bladder
What is choledocholithiasis
Gallstones escaped the gallbladder, lodges within biliary tree
Components of bile
Bile acids, cholesterol, water, bilirubin, phospholipid
How do cholesterol galltones form
Due to excess cholesterol in bile
Supersaturation in gallbladder causes crystallization of the cholesterol -> gallstone
Types of gallstones
Cholesterol
Bilirubin
Mixed cholesterol and bilirubin
Calcium bilirubinate and calcium salts
What causes black gallstones
Gallstones formed due to excess bilirubin
What causes brown gallstones
Calcium bilirubinate and calcium salts
Risk factors for gallstones
Female Fat Middle age Crohn's disease family history of cholelithiasis Rapid weight loss / prolonged fasting diabetes Oral contraceptive pill
What is biliary colic
It is abdominal pain caused by gallbladder contracting while gallstone blocking the cystic duct, increasing pressure in gallbladder
No infection
Symptoms of biliary colic
RUQ pain - colicky
Worse after eating / eating fatty meal
Pain may radiate to shoulder or interscapular region
Nausea and vomiting
Biliary colic is commonly seen in
Fair (caucasian), Fat, Forty, Female
LFT for biliary colic
Normal, no signs of infection
Are gallstones usually symptomatic
No, usually asymptomatic till they cause other conditions
Imaging for symptomatic gallstones
USS (ultrasound)
MRCP
What does MRCP show
special type of MRI that shows the gallbladder, cystic duct, pancreas and pancreatic duct
Management for biliary colic
Analgesia (avoid morphine)
Lifestyle modification
Cholecystectomy
Why is cholecystectomy commonly performed in patients with biliary colic
Because once a gallstone forms, more will form so it is better to just remove the GB to prevent recurrence
What conditions can gallstones cause
Biliary colic Ascending cholangitis Cholecystitis Acute pancreatitis empyema Gallstone ileus
What is cholecystitis
Inflammation of the GB due to gall stones blocking the cystic duct
How do gallstones cause cholecystitis
Gallstones block cystic duct -> causing impaired drainage -> inflammation
Complications of cholecystitis
Empyema
Rupture of GB
Infection backing up to the liver
What may a GB with chronic cholecystitis look like
Thickened wall due to fibrosis
Symptoms of cholecystitis
RUQ pain Fever Nausea + vomiting Malaise Murphy's sign
What is Murphy’s sign
inspiratory arrest upon palpation of RUQ
Ask the patient to hold in a deep breath then palpate the RUQ, if pain occurs -> Murphy’s sign
Diagnosis of Cholecystitis
USS + Murphy’s sign is diagnostic
MRCP
What may USS show for cholecystitis
Cholelithiasis
Thickening of gall bladder wall
Pericholecystic fluid
management of Cholecystitis
IV antibiotics IV fluids Analgesia Cholecystectomy within 1 week of diagnosis Percutaneous cholecystostomy
When is percutaneous cholecystotomy used
to drain pus (empyema) / fluid
What should be done before cholecystectomy
Remove gallstones via ERCP
What can rupture of GB cause
release of contents into peritoneal cavity -> peritonitis
What is ascending cholangitis
Infection of the biliary tree
secondary to gallstones or biliary stricture
Is ascending cholangitis common
No
Causes of biliary strictures
PSC / malignancy at head of pancreas / cholangiocarcinoma
Symptoms of ascending cholangitis
Charcot’s triad or Reynold’s pentad
Malaise
Vomiting and nausea
What is Charcot’s triad
RUQ pain
Fever
Jaundice
What is Reynold’s pentad
RUQ pain fever jaundice Hypotension Confusion
When will shock and confusion show in ascending cholangitis
in Sepsis
Common pathogen causing ascending cholangitis
E.coli
LFT result for ascending cholangitis
Raised bilirubin , ALP
Raised CRP
Raised inflammatory markers
What would Ultrasound for ascending cholangitis show
Dilated bile duct
Gallstones at bile duct
Management of acute cholangitis
IV antibiotics
IV fluids, analgesia
ERCP for drainage / relieve obstruction (remove stones)
What antibiotics are used for cholecystitis
IV augmentin
What antibiotics are used for ascending cholangitis
IV augmentin or tazocin
What is primary biliary cholangitis (Primary biliary cirrhosis)
An autoimmune cholestatic liver disease that causes destruction of own bile ducts
How is cholestasis caused in PBC
Autoimmune destruction of bile ducts mediated by T cells -> bile duct loss -> cholestasis
How does cholestasis in PBC cause cirrhosis
Cholestasis -> build up of toxic substances in liver -> persistent inflammation -> fibrosis, cirrhosis
Characteristics of PBC
Anti-mitochondrial autoantibodies
Increased IgM
LFT and serology findings of PBC
Cholestatic pattern LFT = raised ALP, gGT, albumin
Increased IgM
PBC is commonly seen in which group of people
Middle aged females
Risk factors of PBC
Age - 30-60
Female
Family history of PBC
Symptoms of PBC
Pruritus (itchy skin) Fatigue RUQ pain Xanthomas, xanthelasmas Clubbing Hepatomegaly / splenomegaly Jaundice
Management of PBC
Ursodeoxycholic acid
Obeticholic acid
Liver transplantation
What is used to treat pruritus
cholestyramine (bile acid sequestrant)
Complications of PBC
Increases risk for HCC
Osteoporosis
Osteomalacia
Decompensated cirrhosis
What is primary sclerosing cholangitis
Autoimmune disorder causing cholestatic liver disease due to persistent inflammation hence fibrosis of intra and extrahepatic bile ducts
What condition is associated to Primary sclerosing cholangitis
Ulcerative colitis
HIV
Risk factors for PSC
UC
HIV
Men
Between 30-40 years old
Symptoms of PSC
Pruritus
Jaundice
Recurrent bacterial cholangitis
LFT of PSC
Raised ALP, gGT
Difference between PSC and PBC
PBC has raised IgM and presence of anti-mitochondrial antibodies whereas PSC does not
PSC may have positive p-ANCA and anti-smooth muscle antibodies
PBC only affects intrahepatic bile ducts whereas PSC affects intra and extra hepatic ducts
PBC is more common among middle aged females whereas PSC is more common among middle aged males
Test for PSC
LFT
p-ANCA
What is p-ANCA
Test for Antineutrophil cytoplasmic antibodies
What may be seen on MRCP or ERCP in primary sclerosing cholangitis
Multiple biliary strictures - looks like beads
Management of PSC
Liver transplant
Primary sclerosing cholangitis increases the risk of
Cholangiocarcinoma
Cholangiocarcinoma type of carcinoma
Adenocarcinoma
Risk factors of cholangiocarcinoma
Cholelithiasis PSC UC smoking Obesity
Is the prognosis for cholangiocarcinoma good
No
Symptoms are often only presented at late stage
Symptoms of cholangiocarcinoma
Palpable mass at RUQ
Persistent biliary colic symptoms
Weight loss
Anorexia
What is courvoisier sign
Palpable mass at RUQ, occurs in cholangiocarcinoma
How to obtain biopsy for cholangiocarcinoma
via ERCP
Management of cholangiocarcinoma
Cholecystectomy
Palliation
Signs of cholestasis
Darker urine
Pale stool
Pale stool is a sign of
not enough bile produced
Secretion of bile is blocked / reduced
What can amiodarone cause
It is toxic to hepatocytes, can cause hepatic jaundice
Characteristics of primary sclerosing cholangitis
Anti smooth muscle antibodies
ANCA (anti nuclear antibodies)
Characteristics of autoimmune hepatitis
Anti smooth muscle antibodies
Maybe antinuclear antibodies
What conditions are at higher risk if the patient has primary sclerosing cholangitis
Cholangiocarcinoma
Colorectal cancer
What are the drugs that can cause prehepatic jaundice
Rifampicin (used in IE)
What are the drugs that can cause hepatic jaundice (drug induced liver injury)
Paracetamol overdose Statins Ecstasy Co-amoxiclav Flucloxacillin NSAID Amiodarone
What are the drugs that can cause post hepatic jaundice (cholestatic jaundice)
Co-amoxiclav
Nitrofurantonin
steroids
Flucloxacillin
What is a marker for hepatocellular cancer
AFP
What may low albumin level indicate
Liver disease
Inflammation
Kidney disease