Liver Disease Flashcards
Normal liver functions
- Protein, carbohydrate and fat metabolism
- Plasma protein and enzyme synthesis
- Production of bile
- Detoxification
- Storage of proteins, glycogen, vitamins and metals
- Immune functions
Normal structure of the liver
- Vasculature: Incoming portal vein and hepatic artery. Outgoing hepatic vein to IVC
- Parenchymal liver cells (limiting plate (interface)-sheet of hepatocytes lying against the peri-portal connective tissue). Damage to the interface = interface hepatitis, can lead to fibrosis.
- Biliary system
- Connective tissue matrix
- All arranged as portal tracts (portal vein, hepatic artery and bile duct) with surrounding parenchyma in acini structure
Portial triad components
Bile Duct
Hepatic artery
Hepatic portal vein branch
Causes of liver injury
Vascular (portal hypertension) Infection (hep C& ) Traumatic (obstruction to bile or blood flow) Autoimmune - ALD M- metabolic (drugs, toxins, alcohol), fatty liver disease Iatrogenic/idiopathic Neoplastic Congenital - genetic (haemochromatosis) Degenerative Enviromental
Inflammation
body’s response to injury
Acute inflammation
agent causes injury but its then removed
Chronic inflammation
agent causes injury but then persists
Presentation of acute
Days to weeks. N.B.
“Fulminant” = severe acute, rapidly progressing towards liver failure
Presentation of chronic
Months to years
Acute on chronic presentation
Chronic liver disease often presents with acute exacerbation of disease but with evidence of underlying chronicity e.g. fibrosis. Common presentation in autoimmune conditions also.
Inflammation target
- Injurious agent causes cell damage and sometimes death, often with inflammatory cell infiltrate e.g. alcohol, virus.
- Liver injury often mainly to parenchyma (hepatocytes); but bile ducts or rarely blood vessels can be the main target
- Parenchyma, bile ducts, blood vessels and connective tissue are inter-dependent, so damage to one damages the others
- Chronic inflammation common in liver and may increase connective tissue (fibrosis)
Cirrhosis 3 parts
- Diffuse process with
- Fibrosis &
- Nodule formation
= end-stage liver disease
Main treatment and diagnosis aim -acute not to chronic -chronic not to cirrhosis 0cirhosis not to portal hy[ertension -
Liver signs
hepatomegaly
Portal hypertension
ascites and encephalopathy
Chronic dysfuncion
pruritis, spider naevvi, jaundce
Non specific symptoms
nausea, falls, tremor (liver flap)
Abnormal biliary systen
o Accumulation of bilirubin (esp. acute cholestasis); jaundice
o Accumulation of bile acids (esp chronic cholestasis); pruritis
Abnormal parenchyma
o Right upper quadrant pain (RUQ)
o In chronic diseasehormone changes (gynaecomastia)
o Liver failure only occurs once
Liver investigations - blood
• LFTs:
Transaminases- ALT, AST, Alkaline phosphatase- ALK P, Gamma glutamyl transferase-GGT,
Bilirubin and albumin
• Liver-related haematology test e.g. Prothrombin time- tests synthetic function
• Synthetic function PPT and Albumin
Other tests
• Viral serology
• Autoimmune serology
• Liver metabolic/genetic diseases- iron, copper and alpha-1-antitrypsin
• Alpha-fetal protein hepatocellular carcinoma
• Radiology- especially useful for masses: Ultrasound of abdomen, CT of abdomen. ERCP/MRCP
• Biopsy - only in few cases due to significant morbidity.
Modes of presentation with liver disease
Modes of Presentation with Liver disease
- Asymptomatic- abnormal LFTs, abnormal imaging (Abnormalities incidental or on screening: increasingly common presentations esp. to GP)
- Symptomatic- classic signs (jaundice or ascites) or more general (malaise, itch, anorexia)
Two diagnosis of liver disease
Diffuse liver disease
space-occupying lesion
Liver disease falls into broad patterns
acute hepatitis, acute cholestasis, fatty liver disease, chronic hepatitis, chronic biliary disease, hepatic vascular disease and deposition/genetic disease.
Acute hepatitis Presentation
short history of RUQ pain
tendereness
malaise
Elevated AST/ALT
paracetemol overdose AST/ALT in thousands, massive necrosis
Causes of acute hepatitis
viral hepatitis
autoimmune
drug injury
(Viral, drug, autoimmune)
Histology of acute hepatitis
diffuse hepatocyte injury seens as swelling throughout the liver (portal tracts, interface and parenchyma)
Hepatocyte death - acidophil body
Management of acute hepatitis
remove or treat cause
liver support if severe dysfunction e.g confluent necrosis
Acute cholestasis presentation
Acute onset of jaundice.
Elevated bilirubin, alk P, GGT also possibly alt/ast
Causes of acute cholestasis
extra-hepatic biliary obstruction
Drug injury e.g Ab, NSAIDS, Steroids
Histology of acute cholestasis
Brown bile (bilirubin)pigment with +/- acute hepatitis
Fatty liver disease presentation
Acute or chronic “hepatitis” or
Asymptomatic abnormal LFTS
Fatty liver disease Causes
Alcohol
Non alcholic (
Drugs (methotrexate, amiodarone, steroids)
Chronic hepatitis definition
Liver inflamamtion (abnormal LFTS) for at least 6 months
Presentation of chronic hepatitis
Chronic hepatitis or acute exacerbation
Causes of chronic hepatitis
Viral (ep B or C)
Drugs
Autoimmune
Aims in chronic hepatitis
Hep B&C have classical features. Assess grade and stage.
Liver support if severe disease. Specific treatment where possible
Histology of chronic hepaittis
appears like acute combined with fibrosis (masson stain) -often appears mainly at portal tracts with lymphoid aggregates
In viral hepatitis B- ground glass cytoplasm in hepatocytes due to accumulation of sAg (one of three main HB viral antigens)
Chronic hepatitis pathology reporting
- Activity (grade); degree of inflammation and sites: Portal, interface & parenchymal inflammation. Guides treatment
- Yields histological summary and numerical score e.g. chronic hepatitis with mild activity and mild fibrosis, Ishak score grade 4/18 and stage 2/6
- Facilitates follow-up and monitoring of treatment including clinical trials
Chronic biliary cholestatic disease
Chronic liver diseasepruritus due to excess bile acid
OR Abnormal LFTs- mainly alk P and GGT (for over 6 months)
Causes of chhronic biliary cholestatic disease
Primary biliary cirrhosis:
Primary sclerosing cholangitis
Histology of chronic biliary cholestatic disease
Focal, Portal predominant inflammation and fibrosis with bile duct injury
(granulomas in PBC).
PBC
- Middle aged woman
- Autoimmune disease with serum anti-mitochondrial antibodies (AMA) and high IgM
- Despite the name is not cirrhotic from the outset, it is progress from fibrosis to cirrhosis
- No cure but ursodeoxycholic acid eases symptoms and slows progression; liver transplant at end stage.
PSC
- Rare, assoc with ulcerative colitis
* Risk of progression to cholangiocarcinoma
Genetic deposition liver disease
Haemochromatosis - Iron
Wilsons disease - coppper
Alpha-1-anti-trypsin deficiency-lack of secretion from an accumulated in liver
• May mimic other forms of liver disease
• Due to uncontrolled iron or copper accumulation in liver and other organs; easily treatable by increased removal
Hepatic vascular disease
• Main form= hepatic vein outflow obstruction
- Major form = budd-chiari syndrome causing hepatic vein thrombosis
a. Often fatal due to pro-thrombotic
tendency
b. Early identification permits anti-coagulant therapy - Lesser degrees are more common and milder e.g. nodular regenerative hyperplasia
Drug induced disease
- Drugs can cause almost any pattern of liver disease so usually enter differential diagnosis, esp. acute hepatitis and acute cholestasis/cholestatic hepatitis
- Most drug hepatotoxicity is idiosyncratic (rare but usually single clinical pattern) thus hard to investigate Augmentin, co-amoxiclav (cholestatic)
- Occasionally predictable liver damage e.g. methotrexate, paracetemol
- Don’t forget non-perscribed drugs
Masses Liver disease
- for masses (space-occupying lesions and focal lesions) the main differential diagnosis is inflamm, benign or cancer
- cancers include: metastases and primaries (HCC)
Focal liver disease symptoms
- Symptomatic- hepatomegaly, RUQ pain, jaundice
* Asymptomatic- incidental discovery by imaging or abnormal LFTs
Focal liver disease investigations
imaging by- u/s, CT +/- a biopsy
Types of focal liver lesions
Non neoplastic
- development/degererative e,g cysts
- inflammatory e.g abscess
Neoplastic
- benigh
- malignant
Cysts
• Usually developmental or degenerative
• Single or multiple (if many, normally part of a syndrome e.g.polycystic kidnay disease)
• Commonest= Von Meyenberg complex= simple biliary hamartoma
o Important as it can resemble a metastases but no treatment is required
Liver abscess
- May arise from ascending cholangitis
* Also from Hydatid and other parasites
Benign types of liver neoplasms
Benign 5%
Hepatocyte - Hepatocellular adenoma
Bile duct -bile duct adenoma
Blood vessel- haemangioma
Malignant types of liver neoplasms
Hepatocyte - Hepatocellular carcinoma
Bile duct -cholangiocarcinoma
Blood vessel- Angiosarcoma
Haemangioma
- Benign blood vessel tumour
* Biopsy avoided because of bleeding risk
Hepatic adenoma
- Relatively rare
- Mainly in young women, often associated with hormonal therapy esp. OCP
- No background cirrhosis
- Risk of bleeding and rupture
- Treatment: excision if large
Hepatocellular carcinoma
- Most common primary liver tumour
* Usually rises in cirrhosis and associated with elevated alpha feto protein
Cholangiocarcinoma
- Adenocarcinoma of the bile ducts- intra or extra hepatic
- Diagnosis on imaging and cytology (hard to distinguish from metastatic adenocarcinoma)
- Poor prognosis
- Curative surgery or palliate
Liver metastases
- Common
- Mainly metastatic carcinoma especially adenocarcinoma
- Especially from GI, Lung and Breast
- Metastatic neuroendocrine and melanoma also common
- Treatment usually standard chemo etc.
How to tell the difference between intrahepatic jaundice and extra hepatic jaundice?
In hepatic jaundice or liver disease ALT>AST, with a high bilirubin
In post hepatic jaundice ALP>AST with a high bilirubin (obstructive jaundice)
Remember ALT is predominantly found in the in the liver hepatocytes
