Liver and biliary pathology Flashcards
Deescribe the basic structure of the liver
Basic structural unit is the hepatic lobule – thought of as a hexagon.
At the centre are the terminal branches of the hepatic vein (= centrilobular vein). The points of the hexagon are formed by the portal tracts, which contain 3 structures (portal triad): branches of the bile ducts, hepatic artery and portal vein. The liver cells can be split into three zones.
• Zone 1 (closest to the portal triad) – periportal hepatocytes receive more oxygen and
• Zone 2 – mid zone
• Zone 3 (close to terminal hepatic vein) – perivenular hepatocytes are the most mature
and metabolically active. Zone 3 has most liver enzymes
Which zone receives the most oxygen?
Zone 1- closest to the portal triad
Which zone is the most metabolically active?
Zone 3- closest to the central vein
Which protein is NOT synthesised by the liver?
Gamma globulin
Where is the space of Disse?
Between the hepatocytes and endothelieal cells
Where are the stellate cells?
In the space of disse
What is the function of stellate cells?
store vitamin A
Usually lie quiescent in the space of disse
when activated due to injurt to the hepatocytes, they produce collagen
They become myofibroblasts–>deposit collagen in the space of disse
Myofibroblasts contract constricting sinusoids and increasing vascular resistance
What causes acute hepatitis? + define acue hepatitis
Viruses or drugs
Hepatitis last <6 months
Histology of acute hepatitis
Spotty necrosis
small foci of inflammation + infiltration
lymphocytes and macrophages with damaged hepatocytes
Grade vs stage of chronic inflammation
Grade- severity of inflammation
Stage - severity of fibrosis - this is more important in chronic hepatitis
Histopathology of chronic hepatitis
- Portal Inflammation: inflammation has not crossed the limiting plate
- Interface hepatitis (PEICEMEAL NECROSIS) – cannot see the border between the portal tract and parenchyma
- Lobular inflammation- looks similar to spotty necrosis in acute hepatitis
- Fibrosis: Bridging from the portal vein to central vein due to fibrosis- intraheptic shunting- (critical stage in the evolution of hepatitis to cirrhosis)
What is the key stage in evolution of hepatitis to cirrhosis?
Bridging between the portal vein and central vein
Histopathology of cirrhotic liver
whole liver is affected
Hepatocyte necrosis
Fibrosis
Nodules of regenerating hepatocytes with surrouding fibrosis
Disturbance of vascular architecture (formation of intrahepatic and extrahepatic shunts)
Explain intrahepatic and extrahepatic shunting
Major causes of cirrhosis
- Alcoholic liver disease
- Non-alcoholic fatty liver disease
- Chronic viral hepatitis (hep B+/-D and C)
- Autoimmune hepatitis
- Biliary causes: Primary biliary cirrhosis & Primary sclerosing cholangitis
- Genetic causes:
a) Haemochromatosis- HFE gene Chr 6 b) Wilson’s disease- ATP7B gene Chr 13 c) Alpha 1 antitrypsin deficiency (A1AT) d) Galactosaemia e) Glycogen storage disease - Drugs e.g. methotrexate
Haemochromatosis gene mutation
HFE gene Ghr 6
Wilson’s disease mutation
ATP7B gene Chr 13
Alpha 1 antitrypsin: gene mutation
A1At gene
Micronodular vs macronodular cirrhosis
Micro: <3mm and uniform nodules throughout the liver
Maco: >3mm, variable nodule size throughout the liver
What causes micronodular cirrhosis?
alcoholic hepatitis, biliary tract disease
(a, b)
non alcoholic Fatty liver disease
Haemchromatosis
**think haemachromatosis is bronzed diabetes; diabetes, NAFLD all similar pathology…**
Causes of macronodular cirrhosis
viral hepatitis, Wilson’s disease, alpha1 antitrypsin deficiency
VWA
Outline the child’s pugh score
Outline the spectrum of alcoholic liver disease
What type of cirrhosis is alcoholic cirrhosis?
Micronodular
Most common cause of chronic liver disease in the West
NAFLD
Spectrum of NAFLD
a) simple steatosis - fatty change
b) non-alcoholic steatohepatitis (NASH) - progressed to inflammation
HLA association of Autoimmune hepatitis
HLA-DR3
Antibodies seen in autoimmune hepatitis
Type 1: ANA (antinuclear Ig), anti-SMA (anti-smooth muscle Ig), anti-actin Ig, anti- soluble liver antigen Ig
Type 2: Anti-LKM Ig (anti liver-kidney-microsomal Ig)
PBC biochemical features
↑serum ALP, ↑cholesterol, ↑IgM, hyperbilirubinaemia (late)
Anti-mitochondrial antibodies
PBC
Bile duct loss with granulomas secondary to chronic inflammation
PBC
- Hallmark: granulomatous inflammatory destruction of bile ducts.
signs & symptoms of PBC
Fatigue, pruritis, abdominal discomfort
skin pigmentation, xanthelasma (part. eyelid),
steatorrhoea, vitamin D malabsorption, inflammatory arthropathy.
Which bile ducts are affected in PBC vs PSC?
PBC- intrahepatic
PSC- intrahepatic and extrahepatic
Treatment of PBC
ursodeoxycholic acid
Male vs female incidence of PBC vs PSC
PBC: F>M
PSC: M>F
Association of PSC
UC
Biochemical features of PSC
↑ serum ALP, several associated auto-Ig, particularly p-ANCA
USS of PSC vs PBC
PBC- no dilatation of bile ducts
PSC - dilatation of bile ducts: beading of the bile ducts (multi-focal strictures with dilation of preserved segments)
ERCP findings of PSC
beading of bile ducts (due to multifocal strictures)
What type of fibrosis do you get in PSC?
Onion skinning - concentric fibrosis
Which cancer is associated with PSC?
Cholangiocarcinoma
What is the most common benign liver lesion?
Haemangioma
3 benign liver tumours
Liver cell adenoma
Bile duct Adenoma
Haemangioma
What is the main risk factor of hepatic adenoma?
OCP use, associated with to oestrogen levels
Treated with stopping OCP; if doesn’t resolve –> resection
Malignant liver lesions
HCC
Chlangiocarcinoma
Haemangiosarcoma
Hepatoblastoma
Secondary tumours
Causes of HCC
Most commonly occurs in patients with chronic liver
disease – closely linked with viral hepatitis, alcoholic cirrhosis,
haemochromatosis, NAFLD, Aflatoxin, androgenic steroids
IVx of HCC
AFP and USS
RF for cholangiocarcinoma
primary sclerosing cholangitis
(worm)parasitic liver disease
chronic liver disease-Cirrhosis
congenital liver abnormalities
Lynch syndrome type II
when are hepatic adenomas resected
when symptomatic
>5mm
non shrinkage despite stopping OCP
Most common malignant liver lesion
Secondary tumours - GI tract, breast or bronchus
Genetic causes of cirrhosis
haemochromatosis
Wilson’s
Alpha 1 antitrypsin deficiency
Haemochromatosis mode of inheritance
Autosomal recessive mutation of HFE gene on chrmosome 6
Wilson’s disease mode of inheritance
Autosomal recessive mutation of ATP7B gene on chr 13
Alpha 1 antitrypsin deficiency mode of inheritance
Autosomal dominant
mutation of A1AT
Histology of haemochromatosis
Fe deposits in liver – stains with Prussian blue stai
micronodular cirrhosis
Liver turns chocolatey brown colour
Wilson’s disease histology
Cu stains with Rhodanine stain
Mallory bodies and fibrosis on microscopy
A1AT deficiency histology
Intracytoplasmic inclusions of A1AT which stain with Periodic acid Schiff
Ivx of haemochromatosis
↑ Fe, ↑ Ferritin
● Transferrin saturation > 45% ● ↓ TIBC
Treatment of haemochromatosis + prognosis
Venesection
iron chelation
Desferrioxamine
30% with cirrhosis → HCC
Biochemical findings of wilson’s disease
↓ serum caeruloplasmin ●
↓ serum copper (as it’s depositing everywhere else)
↑ urinary copper
Treatment of wilson’s disease
Lifelong pencillamine
Absent α-globulin band on electrophoresis
Alpha 1 antitrypsin deficiency
in drug injury which zone of the liver is most affected/damaged
- The damaged hepatocytes are in zone 2 and 3- mostly zone 3
Zone 3 is most affected because that is where the most drug metabolising hepatocytes are so where most of the toxic metabolites of drug metabolism is formed
Difference between PBC and PSC
PBC: intrahepatic and bile duct loss secondary to inflammation
PSC: Extrahepatic and intrahepatic: bile duct loss due to peridcutal fibrosis
which liver conditions cause granulomas
PBC
Drugs
sturcture of hepatic adenoma
round circumscribed lesion
Sharply demarcated borders
HCC- main causes in the west and developing countries
west- cirrhosis
developing countries -viruses
difference between haemchromatosis and haemsiderosis
haemchromatosis: Fe accumulation in hepatocytes, develops into cirrhosis and HCC
HAemosiderosis: Fe accumulation in macrophages, does not develop into cirrhosis, secondary to repeated blood transfusions, not somethign to be worried about
whihc malignancy is common in thailand and due to worms
cholangiocarcinoma
Which of these is NOT associated with fatty change in the liver?
- Diabetes
- Hepatitis B
- Hepatitis C
- Alcohol
- Answer: Hep B
- Diabetes and alcohol are classic causes of fatty change
- There is a genotype of Hepatitis C which can cause fatty change so it is also technically correct
3 Cirrhosis defining features
WHOLE liver is involved
Characterised by scarring and fibrosis surrounding nodules of regenerating hepatocytes
Distortion of liver vascular architecture: development of intra- and extrahepatic shunts
3 Complications of Cirrhosis
Portal hypertension:oesophageal varices + splenomegaly: palpable slpeen due to backlog of blood into spleen
Hepatic encephalopathy
Liver cell cancer
is cirrhosis reversible
cirrhosis may be REVERSIBLE If the underlying cause is aggressively treated
which stages of alcoholic liver disease are reversible and irreversible
Fatty liver disease- reversible
Alocohlic hepatits- irreversible
in alcolhilic liver disease, which zone is alcoholic hepatits mostly affecting
changes are MAINLY seen in Zone 3
cells that get damaged are the ones that contain the most alcohol dehydrogenase that convert alcholic in toxic metabolise of acetaladehyde
what type of firbosis is very characteristic of alcoholic liver disease
and what else do you see (cell types)
Pericellular fibrosis: Fibrosis around individual cells
inflammation: lots of inflammatory cells will be seen but the most characteristic inflammatory cell seen is the neutrophil polymorph but can be lymphocytic too.
features of haemchromatosis
deposition in:
testes: fertility
pancreas: Bronzed diabetes
Liver: hepatocyte damage >> HCC
cardiovascular: cardiomyopathy
skin: tanned complexion
what is Haemosiderosis
is a type of iron overload
accumulation of iron in macrophages
usually occurs as a result from repeated blood transfusion
presentation of Wilson’s disease
depositio of copper in:
lentiform nucleus of the basal ganglia: Parkinsonian features, dementia, psychosis
iris- Kayser-Fleischer rings
liver- liver disease: : acute hepatitis, fulminant liver failure or cirrhosis
other associated conditons of autoimmune hepatits:
autoimmune conditions: SLE, rheumatoid arthritis, thyroiditis, UC etc.
what type of cell accumulaiton do you find in autoimmune hepatitis + why
active form of chronic hepatits: lots of inflammatory cells + plasma cells
lots of plasma cells
Lots of plasma cells because lots of autoantibodies are secreted
treatment for autoimmune hepatits:
Responds to STEROIDS
a1-Antitrypsin Deficiency clinical features:
hepatocyte can make a1-antitrypsin but cannot secrete it so deficinecy in blood but excess in liver causes:
emphysema in the lung
COPD in NON SMOKERS
A1AT: deficiency can present in neonates as giant cell hepatitis (giant cell hepatocytes are multinuclear)
what can the skin look like in haemochromatosis?
bronzed or slate grey
