Liver Flashcards
What is the brief pathogenesis of chronic liver disease?
Cause of chronic liver disease –> recurrent inflammation & process of fibrosis –> cirrhosis compensated –> cirrhosis non compensated; chronic liver failure –> acute onset chronic liver failure
How does non-alcoholic fatty liver disease show on histology?
Hepatocytes are larger than they should be, and there is inflammatory cell infiltrate
What is simple steatosis?
An accumulation of fat in the liver, making a ‘fatty liver’. It corresponds to the accumulation of lipids (triglycerides) in the liver cells (hepatocytes) and may complicate alcoholic intoxication or metabolic disorders such as Type 2 diabetes, obesity, and dyslipemia.
- Diagnosis by ultrasound
- No liver outcomes
- Increased cardiovascular risks
- Treatment is weight loss exercise
What is NASH?
What is the typical patient?
How is it diagnosed?
What are the associated risks?
Non-alcoholic steatohepatitis - increased fat in hepatocytes and inflammation
Middle aged and obese
Diagnosis is by liver biopsy
Risk of progression to cirrhosis
Name five autoimmune lives diseases
- Primary Biliary Cholangitis (Cirrhosis)
- Auto-immune Hepatitis
- Primary Sclerosing Cholangitis - diseases with auto-immune features
- Alcohol related liver disease
- Drug Reactions
What is primary biliary cholangitis (cirrhosis)? Aetiology? Typical patient? Symptoms? Associated conditions? Diagnosis? Outcome?
CD4+ T cell mediated chronic autoimmune granulomatous inflammation, causing progressive destruction of the SMALL bile ducts, eventually leading to cirrhosis
Female around 50
Symptoms - often asymptomatic, but may itch, jaundice, fatigue, xanthelasma
Associated with other autoimmune conditions e.g. Sjogren’s syndrome, thyroid disease and dry eyes and mouth are frequently found
Diagnosis - antimicrobial antibody (AMA), cholestatic LFTs, high ALP, serum IgM, liver biopsy
Treatment - ursodeoxycholic acid
Majority nothing major, but some develop liver failure and it’s still a common cause of liver transplant, complications are those of cirrhosis
Auto-immune hepatitis Type 1 (most common) What is it? Who gets it? Presentation? Tests and dianosis? Biopsy?
Inflammatory liver disease of unknown cause whith suppressor T cell defects and autoantibodies directed at hepatocytes
Young or middle aged women
Some present with acute hepatitis and signs of autoimmune disease e.g. fever, malaise, rash, polyarthritis, while others with gradual jaundice
ANA, ASMA, elevated IgG, anaemia, low WBC and platelets
Liver biopsy - chronic hepatitis with necrosis
Auto-immune hepatitis Type 2
Who gets it?
What do bloods show?
Children & teenagers
Antibodies +ve
ANA and ASMA -ve
Primary Sclerosing Cholangitis What is it? Typical patient? Symptoms? Histology? Diagnosis? Associated with which cancers? Treatment?
Autoimmune destructive disease of LARGE AND MEDIUM sized bile ducts, giving progressive cholestasis and bile duct inflammation with strictures
Male, 40s, IBD - typically UC
Pruritus, fatigue, recurrent cholangitis
Histology shows scar tissue described as onion skin
Diagnosis is ERCP to differentiate between large duct and small duct disease - shows irregularities of the hepatic ducts
Bile duct, gall bladder, liver, colon
Liver transplant
Ursodeoxycholic acid may protect aganst colon cancer and improve LFT
Hereditary Haemochromatosis What is it? What gene? Symptoms? Bloods? Imaging? Biopsy? Treatment?
Autosomal recessive genetic defect leading to increased intestinal iron absorption, leading to iron deposits in joints, liver, heart, pancreas and skin
HFE gene
Arthralgia, slate grey/bronze skin pigmentation, signs of chronic liver disease, hepatomegaly, diabetes
Increased LFT and serum ferritin; transferrin saturation >45%
Chondrocalcinosis; liver MRI
Liver biopsy - Perl’s stain quantifies iron loading and assesses severity
Venesection
Wilson's disease What is it? Presentation? Tests? Treatment?
Autosomal recessive disease causing massive deposition of copper in liver and basal ganglia (CNS)
Children present with liver disease (hepatitis, cirrhosis, fulminant liver failure) and adults with CNS disease (tremor, dysarthia, dysohagia, random stereotyped movements, dementia)
Other presentation include change in mood, increased libido, bad memory, grey skin, blue nails, brown rim around iris
Cu in urine, increased LFTs, serum copper
Treatment is penicillamine
Alpha-1-Anti Trypsin deficiency What is it? Associated with? Presentation? Tests? Treatment?
An autosomal recessive disease commonly affecting lung (emphysema) and liver (cirrhosis and hepatocellular cancer)
Associated with asthma, pancreatitis, gall stones, Wegener’s
Dyspnoea, cirrhosis, cholestatic jaundice
Serum A1AT is decreased; phenotyping, prenatal diagnosis
Supportive; liver transplant
Budd-Chiari syndrome What is it? Causes? Presentation? Test? Treatment?
Hepatic vein outflow obstruction by thrombosis or tumour causing congestive ischaemia and hepatocyte damage
Caused by hypercoagulable states - pill, pregnancy, malignancy, TB, etc
Abdominal pain, hepatomegaly, ascites and increased ALT; high protein content in the ascitic fluid
USS + dopplers, CT or MRI
Anticoagulate and consider liver transplant
Methotrexate
What is it used to treat?
What does it cause in the liver?
Rheumatoid arthritis and psoriasis
Causes progressive fibrosis without symptom - requires monitoring
Name the four collateral pathways of anastomoses between the portal and systemic venous system.
What does portal hypertension do to these?
- Oesophageal and gastric venous plexus
- Umbilical vein from the left portal vein to the epigastric venous system
- Retroperitoneal collateral vessels
- The hemorrhoidal venous plexus
Portal hypertension causes these anastomoses to become engorged, dilated or varicosed, and subsequently rupture
What is the normal portal vein pressure?
5-8 mmHg
What are the two main classes of portal hypertension according to site?
- Prehepatic - blockage of the portal vein before the liver; due to portal vein thrombosis or occlusion secondary to congenital portal venous abnormalities
- Intrahepatic - due to distortion of the liver architecture, either presinusoidal (e.g. schistosomiasis, or non cirrhotic hypertension) or postsinusoidal (e.g. cirrhosis)
Give some common signs of compensated cirrhosis and decompensated cirrhosis
Compensated - Spider naevi - Palmar erythema - Clubbing - Gynaecomastia Decompensated - Jaundice - Ascites - Encephalopathy - Bruising
What are two bone related common complications of cirrhosis?
What causes this?
Osteoporosis and osteomalacia
Due to poor intake and absorption of calcium, vitD, malnutrition and steroid use
What causes ascites?
What is diagnosis based on?
The first step is development of portal hypertension, which causes release of local vasodilators. These act on the splanchnic arteries, decreasing the arterial blood flow and pressures.
Progressive vasodilation leads to activation of vasoconstrictor mechanisms, e.g. RAAS, sympathetic, anti-diuretic.
The knock on effect is Na and H2O retention.
Diagnosis based on ultrasound
How do you treat ascites?
Improve underlying liver disease No NSAIDs Reduce salt intake Diuretic plan: 1. Spironolactone first 2. Increase dose of spironolactone 3. Add a loop diuretic 4. Increase the dose Paracentesis Transplant
Spontaneous bacterial peritonitis
What is it?
Investigation?
Treatment?
Translocated bacterial infection of ascites - very serious
Do a tap in ass ascites and cell count - neutrophil count >250
Antibiotics and alba; terlipressin for vascular instability, maintain renal perfusion
Encephalopathy
What is it and what is it caused by?
Diagnosis?
Treatment?
As the liver fails, nitrogenous waste (as ammonia) builds up in the circulation and passes into the brain, where astrocytes clear it, releasing glutamine, causing an osmotic imbalance and a shift of fluid into these cells, causing cerebral oedema
Diagnosis is based on flap confusion; any neurology; alcohol withdrawal
Small, frequent meals; think about transplant
What two circulation changes occur in liver disease?
- Low albumin creates a low plasma volume the adrenal glands release more renin, which converts angiotensinogen into angiotensin I, and consequently angiotensin II, increasing blood volume and causing some type of hypertension.
- Aldosterone manufacture is impaired, causing secondary aldosteronism.
Other hormonal effects include some problems with endothelin and oestrogen, resulting in increased production of endothelin and oestrogen.
The middle hepatic vein separates what lobes of the liver?
Right lobe (contains caudate and quadrate lobes) and the left lobe
What three vessels enter the liver at the porta hepatis?
Portal vein
Hepatic artery
Bile duct
What is special about the blood supply to the caudate lobe?
It receives an independent blood supply from the portal vein and hepatic artery, and its hepatic vein drains directly into the IVC
What is the functional hepatic unit?
What parts of the acinus are most and least susceptible to damage?
The acinus
Least susceptible = zone 1, near the portal triad
Most susceptible = zone 3, near the terminal (central) hepatic veins
What three vessels are contained within the portal triad?
Portal vein radicles
Hepatic arterioles
Bile ductules
What vessels do the right and left hepatic ducts combine with to get to the duodenum?
Right and left hepatic ducts (from right and left lobes respectively) join at the porta hepatis to form the common hepatic duct.
The cystic duct connects the gall bladder to the lower end of the common hepatic duct.
The common bile duct is formed at the junction of the cystic duct (from the gall bladder) and common hepatic duct.
This then passes through the head of the pancreas, narrowing at its lower end to pass into the duodenum.
Opens into the 2nd part of the duodenum through a common channel at the ampulla of Vater, which contains the muscular sphincter of Oddi.
- What is the main protein found in plasma?
- What are the main functions of this molecule?
- What happens if there is reduced synthesis of this?
- What other proteins does the liver make?
- Albumin
- Maintains the intra-vascular oncotic pressure; transports H2O-insoluble substances e.g. bilirubin
- Reduced synthesis produces hypoalbuminaemia
- Other proteins - transferring, A1AT, most factors involved in coagulation
How does the gall bladder concentrate bile?
The gall bladder mucosa absorbs 85% of the water and electrolytes and cholesterol
Describe the processes involved in bilirubin metabolism to form stercobilin
Bilirubin is produced mainly from the breakdown of RBCs by Kupffer cells (macrophages)
Hb is broken down into haem and globin
The haem is converted into biliverdin, which is converted into unconjugated bilirubin, which is transported to the liver by albumin
In the liver it is conjugated with glucuronic acid and secreted into bile
This conjugated bilirubin is water soluble and is secreted into the small intestine within bile
In the terminal ileum, enzymes convert this into stercobilin, which gives faeces (and urine) its characteristic colour
What immunological functions does the liver have?
Acts as a sieve for bacterial and other antigens carried to it by the portal vein from the GI tract
These antigens are phagocytosed
Serum albumin
What is it a marker of?
Acute or chronic liver disease?
Synthetic function of the liver
Marker of severity of chronic liver disease
May be normal in acute liver disease
Prothrombin time (PTT)
What is it a marker of?
Acute or chronic liver failure?
What should be excluded as a cause of increased PTT?
Synthetic function of the liver
Marker of both acute and chronic liver disease
Vitamin K deficiency should be excluded by giving an IV bolus of VitK
AST
What does it stand for and what is it?
High levels are seen in?
Why is it not that great?
Aspartate aminotransferase - a mitochondrial enzyme
Hepatic necrosis, MI, muscle injury
Not specific to the liver
ALT
What does it stand for and what is it?
What does it reflect?
Why is it better than AST?
Alanine aminotransferase - a cytosol enzyme
Reflects hepatocellular damage
Specific to the liver
ALP
What does it stand for and what is it?
If gamma-GT is also raised, what does it indicate?
Alkaline phosphatase - an enzyme
Raised in both intrahepatic and extrahepatic cholestatic disease of any kind
gamma-Glutamyl transpeptidase
What induces its intake?
Drugs and alcohol
If ALP is normal can be a useful guide to alcohol intake
What serum immunoglobulin is increased in:
(i) Primary biliary cirrhosis
(ii) Autoimmune hepatitis
(i) PBC –> IgM
(ii) Autoimmune hepatitis –> IgG
