Medical liver diseases Flashcards
Jaundice definition
- First visible in sclera: white of eye
- Classified according to where the abnormality is in the metabolism of bilirubin
- Visible when bilirubin >40umol/l
- Commonest sign of liver disease
Pre-hepatic jaundice
- Too much bilirubin produced
- Haemolytic anaemia, Gilbert’s syndrome: enzyme deficiency
- Unconjugated: bound to albumin, insoluble, not excreted = patient notices yellow eyes/skin only
Hepatic jaundice
- Too few functioning liver cells
- Acute diffuse liver cell injury, End stage chronic liver disease, Inborn errors
- Mainly conjugated: soluble = patient notices yellow eyes and dark urine
Post-hepatic jaundice
- Bile duct obstruction
- Conjugated: soluble, excreted, but can’t get into gut = patient yellow eyes, pale stool and dark urine
Simplified Pathways of Bilirubin Metabolism
- Bilirubin produced by RBC breakdown = unconjugated
- Metabolised in liver: conjugated and excreted in bile
Investigation of Jaundice
- Ultrasound scan to check for dilated ducts – indicates an obstruction of biliary duct
- If no dilated ducts, biopsy to find cause of jaundice
Jaundice clinical features
- bile salts in the skin = patient itchy
- Jaundice in the skin, patient = yellow
- Over time, oedema reduces and fibrosis increases
- Characteristic appearance: Biliary Gestalt
Jaundice histopathological features
- bile in the liver parenchyma
- Bile salts and copper can’t get out: accumulate in hepatocytes
- Bile pigment is visible in bile plugs
- ## Swelling and irregularity of hepatocytes and inc activity of macrophages
Acute Hepatitis
- Inflammation in the liver
- acute liver injury caused by something that goes away
- Recent onset will resolve back to normal
Chronic hepatitis
- Inflammation in the liver
- chronic liver disease caused by something that doesn’t go away
- Results in ongoing liver cell injury and progressive structural liver damage of scarring and remodelling
- Persistence of abnormal liver tests for more than 6 months
Causes of acute hepatitis
- Damage hepatocytes, short term:
- Inflammatory injury: hepatitis: Viral, Drugs, Autoimmune, Unknown: seronegative
- Toxic/ metabolic injury: alcohol, drugs (paracetamol)
Commonest causes of severe liver cell injury in the UK =
alcohol and paracetamol toxicity
acute hepatitis pathogenesis
- Mild: death of individual hepatocytes
- Rare severe end: hepatocytes die faster than replaced; rapidly progressing organ failure and possibly death
Causes of Chronic Hepatitis
- Immunological injury: virus, autoimmune, drugs
- Toxic/ metabolic injury: fatty liver disease, alcohol, drugs – most common cause
- Genetic inborn errors: iron, copper, alpha 1 antitrypsin
- Biliary disease: autoimmune, duct obstruction
- Vascular disease: clotting disorders, drugs
Pathology of Chronic Liver disease
- Injury to liver cells, inflammation, formation of scar tissue and regeneration of hepatocytes
- Continuing liver damage is combined with the body’s attempts at regeneration of hepatocytes and repair: the wound healing of angiogenesis and fibrosis
Progression of Chronic Liver Disease
- Scarring gradually increases and starts to link vascular structures (bridging) eventually transforming the liver tissue into separate nodules = end stage = cirrhosis
- remodelling = bands of fibrosis that bridge between portal tracts and hepatic veins
- Remodelling becomes complete, and hepatocytes form nodules surrounded by fibrous tissue
- Portal blood entering the liver can flow through vessels in the fibrous tissue and not percolate through sinusoids, The cirrhotic liver therefore is inefficient in metabolic function
Viral Hepatitis
- Hepatotrophic viruses (Specifically affect hepatocytes)
- A, B, C
- D = delta, only in people with B
- E = waterborne
Alcohol and the liver
- steatophepatitis
- spectrum of fatty change associated with inflammation - can lead to cirrhosis
- Alcohol = major cause of liver disease
- Some patients with alcohol injury may just show fatty change: a reversible stage of liver injury that may or may not progress to steatohepatitis
Steatohepatitis =
collagen surrounds cells like chicken wire, increases as well as portal tract fibrosis
Obesity: NAFLD
- Non-alcoholic fatty liver disease
- Associated with metabolic syndrome: obesity, T2DM, hyperlipidaemia
- commonest cause of liver disease
NAFLD
- NAFLD = liver counterpart to metabolic syndrome
- Insulin resistance from excess of calorie intake over body’s demands means fat is stored in the body in various compartments including the liver:
- Stored in the liver = fatty liver or steatosis
- More serious complications include cirrhosis and steatohepatitis
Drug induced liver injury (DILI) classification
- Classified by its hepatotoxicity
- Intrinsic e.g. paracetamol - every time, predictable; Anyone taking this drug is likely to get liver damage
- Idiosyncratic: rare, unpredictable, metabolic and immunological input
Drug induced liver injury (DILI)
- Acute liver injury
- Raised liver enzymes
- Commonest symptom of DILI = jaundice
- Paracetamol toxicity = commonest cause of acute liver failure
- Paracetamol toxicity = necrosis of a high proportion of hepatocytes in a predictable, zonal distribution without any inflammation
Haemochromatosis
- Inborn error of iron metabolism: bronzed diabetes
- abnormality of HFE gene
- Failure of iron absorption regulation, excess iron stored in various organs: liver, pancreas, joints, skin, heart
Haemochromatosis diagnosis
- high serum levels of transferrin
- Large amounts of iron in hepatocytes cause liver injury
- Liver biopsies are stained with Perls’ stain for iron = blue
Haemochromatosis treatment
Treatment = easy, Frequent venesection
- remove blood to decrease iron usage in making more blood which will deplete iron stores to normal
Wilson’s Disease definition
- Inborn error of copper metabolism
- Causes little caeruloplasmin, a copper transport protein in blood = copper accumulation
Wilson’s Disease diagnosis
- CP levels in the blood can be tested
- low serum copper, high urinary copper (24hr urine collection) and high copper in liver tissue
- Rhodamine stain: copper = brown
Wilson’s Disease treatment
Treatment: to chelate copper - mineral supplement that may be better absorbed and easier on the stomach] and enhance its excretion
Alpha 1 Antitrypsin deficiency
- Inborn error of metabolism results in abnormal structure of A1AT, which folds wrongly and can’t be excreted from hepatocytes. There are many types, the commonest is PiZZ
Alpha 1 Antitrypsin deficiency diagnosis
- The accumulated A1AT forms globules of glycoprotein that stain positive with PAS diastase stain
- low levels of A1AT in the serum
Alpha 1 Antitrypsin deficiency pathogenesis
- This damages liver cells, may lead to fibrosis and cirrhosis
- low levels of A1AT in the serum make the patient susceptible to emphysema
Alpha 1 Antitrypsin
protein made in the liver excreted into blood where it functions to neutralise proteolytic enzymes, particularly from active polymorphs
Autoimmune hepatitis definition
chronic liver disease due to disturbance of the immune system with recognition of ‘self-antigens’ leading to chronic inflammation and destruction of hepatocytes
Autoimmune hepatitis features
- Autoimmune hepatitis
- Diagnosis based on auto-antibodies - raised IgG, ALT
- prominent interface hepatitis with lots of plasma cells seen on biopsy
Primary biliary cholangitis
- Anti-mitochondrial antibodies; IgM, raised alkaline phosphatase
- Commoner in women
- Bile duct injury characterised by granulomatous inflammation = destruction of bile ducts
Primary Sclerosing Cholangitis (PSC)
- More sinister
- Associated with ulcerative colitis, high ALP
- Commoner in men
- characteristic pruned tree on cholangiogram
- Periductal onion skin fibrosis
urso-deoxycholic acid
- A bile salt analogue which delays disease progression
- Used to treat primary sclerosing choloangitis
Cirrhosis definition
defined histologically as a diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules
Cirrhosis pathogenesis
- Liver cells still present, but portal vein blood bypasses sinusoids so liver cells cannot perform their functions
- Pressure inside the liver increases = portal hypertension
Cirrhosis aetiology
- Alcohol
- Non-alcoholic steatohepatitis
- Chronic viral hepatitis: B, C
- Autoimmune liver disease: AI hepatitis, PBC, PSC
- Metabolic: iron, copper, alpha 1 antitrypsin
Cirrhosis complications
Structural changes, fibrosis: - portal hypertension - increased blood flow - stiff liver - pressure rises in portal vein Oesophageal varices: - bleeding, can cause haemorrhage
Hepatic failure
- Liver so damaged it can’t function
- Acute hepatic failure = rare: severe rapid liver injury
- Chronic hepatic failure: end stage chronic liver disease
end stage chronic liver disease clinical features
- Ascites, Muscle wasting, Bruising, Gynaecomastia, Spider naevi
- Caput medusa = variceal umbilical vein collaterals (palm tree sign – portal hypertension so blood can’t get through so tries to go around periumbilical veins causing these large caput medusae)
