LIVER & FRIENDS Flashcards
Give 4 functions of the liver
- Glucose and fat metabolism
- Detoxification and excretion
- Protein synthesis (e.g. albumin, clotting factos)
- Bile production
Name 3 things that liver function tests measure
- Serum bilirubin
- Serum albumin
- Pro-thrombin time
Name an enzyme that increases in the serum in cholestatic liver disease (duct and obstructive disease)
Alkaline phosphate (ALP)
What enzymes increase in the serum in hepatocellular liver disease?
Transaminases - e.g. AST and ALT
What tests give no index of liver function and why?
Liver enzymes - alkaline phosphate, GGT, AST, ALT Released by damaged cells
Define jaundice
Raised serum bilirubin
Name the 3 broad categories of jaundice
- Pre-hepatic (unconjugated)
- Hepatic (conjugated)
- Post-hepatic (conjugated)
Give 2 causes of pre-hepatic jaundice
Excess bilirubin production
- Haemolytic anaemia
- Gilberts disease
Give 4 causes of hepatic jaundice
- Liver disease
- Hepatitis - viral, drug, immune, alcohol
- Ischaemia
- Neoplasm - HCC, mets
- Congestions - CCF
Give 3 causes of post-hepatic jaundice
Duct obstruction
- Gallstones
- Stricture - Malignancy, ischaemia, inflammatory
- Blocked stent
What colour is the urine and stools in pre-hepatic jaundice?
Both are normal
No itching and the LFTs are normal
What colour is the urine and stools in someone with cholestatic jaundice (hepatic and post hepatic)?
Dark urine
Pale stools
Itching
LFTs are abnormal
What can cause raised unconjugated bilirubin?
A pre-hepatic problem (haemolysis, hypersplenism)
What can cause raised conjugated bilirubin?
Indicated cholestatic problem
[liver disease (hepatic) or bile duct obstruction (post hepatic)]
Give 3 symptoms of jaundice
- Biliary pain
- Rigors - indicate an obstructive cause
- Abdomen swelling
- Weight loss
Why are liver patients vulnerable to infection?
- Impaired reticuloendothelial function
- Reduced opsonic activity
- Leucocyte function
- Permeable gut wall
Give 3 causes of Gallstones
- Obesity and rapid weight loss
- DM
- Contraceptive pill
- Liver cirrhosis
what are the risk factors for gallstones
- Female
- Fat
- Fertile
- Forty
- Family history
Name 2 types of gallstones
- Cholesterol (70%)
2. Pigment (30%)
Describe the pathophysiology of cholesterol gallstones
Excess cholesterol/lack of bile salts –> cholesterol crystals –> gallstone formation, precipitated by reduced gallbladder motility
Describe the pathophysiology of pigment gallstones
Excess bilirubin –> polymers and calcium bilirubinate –> stones
seen in haemolytic anaemia
Give 4 symptoms of gallstones
Most are asymptomatic
- Biliary colic (sudden RUQ pain radiating to the back and epigastrium +/- nausea/vomiting) - AFTER EATING FATTY MEALS
- Acute cholecystitis (gallbladder distension –> inflammation, necrosis, ischaemia)
- Obstructive jaundice
- Cholangitis
- Pancreatitis
How can gallstones be removed from the gallbladder?
Laparoscopic cholecystectomy
ERCP with removal or destruction (mechanical lithotripsy) or stent placement
Bile acid dissolution therapy (for people not suitable for surgery)
What is liver failure?
When the liver has lost the ability to regenerate to repair, so that decompensation occurs
Name 3 types of liver failure
- Acute = sudden failure in previously healthy liver
- Chronic = liver failure on the background cirrhosis
- Fulminant = massive necrosis of liver cells –> severe liver function impairment
Give 5 causes of acute liver disease
- Viral hepatitis
- Drug induced hepatitis
- Alcohol induced hepatitis
- Vascular - Budd-Chiari
- Obstruction
Give 2 possible outcomes of acute liver disease
- Recovery
2. Liver failure
Give 5 causes of chronic liver disease
- Alcohol
- NAFLD
- Viral hepatitis (B,C,E)
- Autoimmune diseases
- Metabolic
- Vascular - Budd-Chairi
Give 2 possible outcomes of chronic liver disease
- Cirrhosis
2. Liver failure
Give 5 signs of acute liver failure
- Jaundice
- Fetor hepaticus (smells like pears)
- Coagulopathy
- Asterixis - liver flap
- Malaise
- Lethargy
- Encephalopathy
Give 5 signs of chronic liver disease
- Ascites
- Oedema
- Bruising
- Clubbing
- Depuytren’s contracture
- Palmar erythema
- Spider naevi
What investigations are conducted on someone on with liver failure?
Blood tests - FBCs, U+Es, LFTs, clotting factors, glucose
Imaging - EEG, USS, CXR, doppler USS
Microbiology - blood and urine culture and ascitic tap
What do the blood tests show in someone with liver failure?
Raised bilirubin Low glucose High AST and ALT Low levels of coagulation factors Raised prothrombin time High ammonia levels
Describe the treatment for liver failure
- Nutrition
- Supplements
- Treat complications
- Raised intracranial pressure = mannitol
- PPI = reduce GI bleeds
- bleeding = vitamin K
- encephalopathy = lactulose
- ascites = diuretics
- sepsis = sepsis 6, antibiotics - Liver transplant
Give 4 complications of of liver failure
- Hepatic encephalopathy
- Abnormal bleeding
- Jaundice
- Ascites
What drugs should be avoided in liver failure?
Constipators
Oral hypoglycaemics
Warfarin has enhanced effects
Opiates
What is cirrhosis?
Loss of normal hepatic architecture with fibrosis - liver injury causes necrosis and apoptosis- irreversible
Give 3 causes of cirrhosis
common:
- chronic alcohol abuse
- non-alcoholic fatty liver disease
- hepatitis
others
- haemochromatosis
- Wilson’s disease
- alpha-antitrypsin deficiency
Give 4 signs of cirrhosis
- ascites
- clubbing
- palmar erythema
- xanthelasma
- spider naevi
- hepatomegaly
- peripheral oedema
What investigations are done in someone with cirrhosis?
- Bloods = low platelets, high INR, low albumin
- US and CT - hepatomegaly
- liver biopsy - diagnostic
What is the treatment for liver cirrhosis?
- Good nutrition and alcohol abstinence
- Treat underlying cause
- Fluid and salt restriction for ascites –> spironolactone, furosemide, prophylactic ciprofloxacin
- liver transplant = definitive
- Screen for HCC - increased AFP
Give 4 complications of cirrhosis
Ascites
portal hypertension
- Decompensation
- SBP
- Increased risk of HCC
Approximately what percentage of blood flow to the liver is provided by the portal vein?
75%
Give 3 causes of portal hypertension
- Pre-hepatic = blockage of hepatic portal vein before the liver (portal vein thrombosis)
- Hepatic = distortion of liver architecture (cirrhosis, schistosomiasis, Budd Chiari syndrome)
- Post-hepatic = venous blockage outside the liver (RHF, IVC obstruction)
what is the clinical presentation of portal hypertension?
- often asymptomatic
- splenomegaly
- spider naevi
- GI bleeding
- ascites
- hepatic encephalopathy
Why can portal hypertension lead to varices?
Obstruction to portal blood flow
Blood is diverted into collaterals and so causes varices
What are the potential consequences of varices?
If they rupture –> haemorrhage
blood is then digested -> melaena
What is the primary treatment for varices?
Variceal banding – band put around varices using endoscope – after few days the banded varix degenerates and drops off leaving a scar
Describe the pathophysiology of hepatic encephalopathy
Ammonia accumulates and crosses the BBB causing cerebral oedema
Name 4 conditions that can develop as a result of having hepatic encephalopathy
SAVE
- Splenomegaly
- Ascites
- Varices
- Encephalopathy
What is ascites?
Chronic accumulation of fluid in the peritoneal cavity that leads to abdominal distension
Give 4 causes of ascites and an example for each
- Local inflammation - peritonitis
- Leaky vessels - imbalance between hydrostatic and oncotic pressures
- Low flow - cirrhosis, thrombosis, cardiac failure
- Low protein - hypoalbuminaemia
Describe the pathophysiology of ascites
- Increased intra-hepatic resistance leads to portal hypertension –> ascites
- Systemic vasodilation leads to secretion of RAAS, NAd and ADH –> fluid retention
- Low serum albumin also leads to ascites
Transudate = blockage of venous drainage
Exudate = inflammation
Give 3 signs of ascites
- Distension
- Dyspnoea
- Shifting dullness on percussion
- Signs of liver failure
What investigations might you do in someone who you suspect has ascites?
- USS
2. Ascitic tap
Describe the treatment for ascites
- Restrict sodium and fluids
- Diuretics - spirolactone
- Paracentesis
- Albumin replacement
Describe the effects of alcoholic liver disease
- Fatty liver –> hepatitis –> cirrhosis and fibrosis
- GIT –> gastritis, varices, peptic ulcers, pancreatitis , carcinoma
- CNS –> Degreased memory and cognition, wernicke’s encephalopathy
- Folate deficiency –> anaemia
- Reproduction –> testicular atrophy, reduced testosterone/progesterone
- Heart –> dilated cardiomyoapthy, arrhythmias
What might be seen histologically that indicates a diagnosis of alcoholic liver disease?
Neutrophils and fat accumulation within hepatocytes
What type of anaemia do you associate with alcoholic liver disease?
Macrocytic anaemia
What blood test might show that someone has alcoholic liver disease?
Serum GGT will be elevated
What distinctive feature is often seen on biopsy in people suffering form alcoholic liver disease?
Mallory bodies
What are the CAGE questions?
- Cut down?
- Annoyed at criticism?
- Guilty about drinking?
- Eyeopener?
How do you treat alcoholic liver disease?
● Stop alcohol – treat delirium tremens with diazepam
● IV thiamine to prevent Wernicke-Korsakoff encephalopathy
● High vitamin and protein diet
● Fatty liver – if alcohol stopped fat disappears
● Hepatitis
o Nutrition maintained with enteral feeding and vitamin supplements
o Steroids show short term benefit – reduce inflammation
o Infections treated and prevented
● Cirrhosis
o Reduce salt intake, stop drinking for life
o Avoid aspirin and NSAIDS
o Liver transplant
How does alcoholic hepatitis present?
Jaundice Anorexia Nausea and vomiting Fever Encephalopathy Cirrhosis Hepatomegaly Ascites, bruising, clubbing
How long does hepatitis persist for to be deemed chronic?
6 months
Give 4 types of hepatitis?
- Viral - A,B,C,D,E
- Drug induced
- Alcohol induced
- Autoimmune
Give 3 infective causes of acute hepatitis
- Hepatitis A-E infections
- EBV
- CMV
Give 3 non-infective causes of acute and chronic hepatitis
- Alcohol
- Drugs
- Toxins
- Autoimmune
Give 3 symptoms of acute hepatitis
- General malaise
- Myalgia
- GI upset
- Abdominal pain
- Raised AST, ALT
- +/- jaundice
What are the potential complications of chronic hepatitis?
Uncontrolled inflammation –> fibrosis –> cirrhosis –> HCC
If HAV a RNA or DNA virus?
RNA virus - PicoRNAvirus
How is HAV transmitted?
Faeco-oral transmission - contaminated food/water, shellfish
Who could be at risk of HAV infection?
Travellers and food handlers
Is HAV acute or chronic?
Acute 100% immunity after infection
How might you diagnose someone with HAV infection?
bloods - ALT/AST raised
raised IgG and IgM
Describe the management of HAV infection
- Supportive
- Monitor liver function to ensure no fulminant hepatic failure
- Manage close contacts
What is the primary prevention of HAV?
Vaccination
Is HBV a RNA or DNA virus?
DNA virus Replicates in hepatocytes
How is HBV transmitted?
Blood borne transmission - blood products and bodily fluids
IVDU, needle-stick, sexual, vertical
Highly infectious
Vertical transmission from mother to child during parturition is most common method of transmission
Describe the natural history of HBV in 4 phases
- Immune tolerance phase: unimpeded viral replication –> high HBV DNA levels.
- Immune clearance phase: the immune system ‘wakes up’ = liver inflammation and high ALT
- Inactive HBV carrier phase: HBV DNA levels are low = ALT levels are normal, no liver inflammation
- Reactivation phase: ALT and HBV DNA levels are intermittent and inflammation is seen on the liver –> fibrosis
What HBV protein triggers the initial immune response?
The core proteins
How might you diagnose someone with HBV?
HBV assay- HBs-Ag - present 1-6 months after exposure. Presence for >6 months implies carrier status- anti-HBs
Describe the management of HBV infection
vaccination pegylated interferon alpha 2a nucleotide analogue (tenofovir) - inhibits viral replications
How would you know if someone had acute or chronic HBV infection?
Follow up appointment at 6 months to see if HBsAg still present
still present = chronic hepatitis
What are the potential consequences of chronic HBV infection?
- Cirrhosis
- HCC
- Decompensated cirrhosis
How can HBV infection be prevented?
Vaccination - injecting a small amount of inactivated HbsAg
Give 3 side effects of alpha interferon treatment for HBV
- Myalgia
- Malaise
- Lethargy
- Thyroiditis
- Mental health problems
Give 2 HBV specific symptoms
Arthralgia
Urticaria (hives)
If HCV a RNA or DNA virus?
RNA virus - flavivirus
How is HCV transmitted?
Blood borne
Give 4 risk factors for developing HBV/HCV infection
- IVDU
- People who have required blood products - blood transfusion
- Needle stick injuries
- Unprotected sex
- Vertical transmission
How might you diagnose someone with current HCV infection?
HCV RNA - indicates current infection
Anti-HCV serology
Describe the treatment for HCV
Direct acting antivirals
NS5A inhibitor - Ritonavir
NS5B inhibitor - Sofosbuvir
What percentage of people with acute HCV infection will progress onto chronic infection?
Approximately 70%
What percentage of people with acute HBV infection will progress onto chronic infection?
Approximately 5%
How can HCV infection be prevented?
- Screen blood products
- Lifestyle modification
- Needle exchange
No vaccination, and previous infection doesn’t confer immunity
Is HDV a RNA or DNA virus?
Incomplete RNA virus Needs Hep B for assembly
How is HDV transmitted?
Blood borne transmission - particularly IVDUit is transmitted in the same way as HBV
Is HEV a RNA or DNA virus?
Small RNA virus
How is HEV transmitted?
Faeco-oral transmission
Is HEV acute or chronic?
Usually acute but there is a risk of chronic disease in the immunocompromised
How might you diagnose someone with HEV infection?
HEV RNA - HEV IgM, IgGanti-HEV
Describe the primary prevention of HEV
Good food hygiene
Vaccine is in development
What types of viral hepatitis are capable of causing choric infection?
Hepatitis B (+/- D), C and E in the immunosuppressed
What is non alcoholic steatoheptitis (NASH)?
An advanced form of non-alcoholic fatty liver disease
Give 3 causes of non-alcoholic fatty liver disease
- T2DM
- Obesity
- Hypertension
- Hyperlipidaemia
How do you manage NAFLD?
Lose weight
Control HTN,
DM and lipids
What is Budd-Chiari syndrome?
Hepatic vein occlusion –> ischaemia and hepatocyte damage –> liver failure or insidious cirrhosis
Name 3 metabolic disorders that can cause liver disease
- Haemochromatosis - iron overload
- Alpha 1 anti-trypsin deficiency
- Wilson’s disease - disorder of copper metabolism
90% of people with haemochromatosis have a mutation in which gene?
HFE - chromosome 6
Haemochromatosis is a genetic disorder, how is it inherited?
Autosomal recessive inheritance
Describe the pathophysiology of haemochromatosis
Uncontrolled intestinal iron absorption –> deposition of iron in liver, heart, pancreas, joins, skin –> fibrosis and functional organ failure
Give 4 signs of haemochromatosis
- Fatigue, arthralgia, weakness
- Hypogonadism – eg erectile dysfunction
- SLATE-GREY SKIN (brownish/bronze)
- Chronic liver disease, heart failure, arrythmias
How might you diagnose someone with haemochromatosis?
- bloods - Raised ferritin, LFTs
- HFE genotyping - C282Y
- Liver biopsy - gold standard
What is the treatment for haemochromatosis?
- Iron removal - venesection
- Monitor DM
- Low iron diet
- Screening for HFE
- iron-chelating drugs
Give 2 complications of haemochromatosis?
Liver cirrhosis –> failure/cancer
DM due to pancreatic depositions
How is alpha 1 anti-trypsin deficiency inherited?
Autosomal recessive mutation in serine protease inhibitor gene
How does Alpha 1 anti-trypsin deficiency present?
Liver disease in the young - cirrhosis, jaundice Lung disease in the old (smokers) - emphysema
What is the treatment for Alpha 1 anti-trypsin deficiency?
Smoking cessation
Liver/lung transplant
What is Wilson’s disease?
An autosomal recessive disorder of copper metabolism
Excess deposition of copper in the liver
Describe the pathophysiology of Wilson’s disease
Impaired incorporation of Cu into caeruloplasmin –> Cu accumulation in liver
How does Wilson’s disease present?
Children = liver disease - hepatitis, cirrhosis, fulminant liver failure
Adults = CNS problems, mood changes, and Kayser-Fleischer rings