Histopathology - Liver Flashcards
Portal triad
branches of the bile ducts, hepatic artery, portal vein
zone 1 closest to the portal triad
which zone has the most liver enzymes?
Zone 3
zone that gets less oxygen (further away from portal triad)
has the most metabolically active cells of the liver
that is also where the drug metabolising hepatocytes are
Flow of blood in the liver
reaches liver via hepatic portal vein (blood from gut) + hepatic artery (blood from heart)
blood travels in sinusoids –> drains in central vein –> goes to hepatic vein –> hepatic vein joins vena cava
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Liver marker that increases most in obstructive jaundice/ obstruction of bile duct/ damage to biliary epithelial cells
ALP
obstruction of the bile ducts also causes
also absence of urobilinogen in urine and presence of bile salts/acids in the blood
• Most representative of liver function
prothrombin time
PT affected by warfarin (extrinsic pathway)
APTT/PTTK affected by heparin (intrinsic pathway)
What is the van den Bergh reaction
van den Bergh reaction measures serum bilirubin via fractionation
A direct reaction measures conjugated bilirubin
Addition of methanol causes a complete reaction, which measures total bilirubin (conjugated plus unconjugated);
the difference measures unconjugated bilirubin (an indirect reaction).
What is the function of phototherapy?
Converts bilirubin to
lumirubin
photobilirubin
these compounds dont need conjugation for excretion
How is Gilberts disease inherited + pathophysiology + mx
Recessive
reduced activity of UDP (uridine 5 diphospho) glucuronyl transferase to 30%–> higher unconjugated bilirubin levels –> Unconjugated bilirubin tightly albumin bound and does not enter urine –> not excretes
Worsened by fasting
Phenobarbitone reduces levels
o if pt Anti-HBs + no Anti-HBe
o If pt Anti-HBs + Anti-HBe
• We only vaccinate people with HBsAg and no HBeAg
o if pt Anti-HBs + no Anti-HBe vaccinated
o If pt Anti-HBs + Anti-HBe infected
What are mallory denk bodies?
Mallory denk bodies (clumped cytoskeleton of hepatocytes) characteristic change in hepatocytes of alcoholic hepatitis
(2 step process: alcohol acetaldehyde, acetaldehyde acetic acid
acetaldehyde toxic to hepatocytes cross-links lysine residues causes cytoskeleton to clump Mallory denk bodies)
What kind of inflammation is present in alcoholic hepatitis?
Neutrophilic inflammation (acute)
ballooning of cells found in
steatohepatitis
commonest cause of fatty liver disease in the west
• NAFLD – associated with high BMI, diabetes etc
Vitamin deficiencies • D – • C – • B12 – • B1 – • B3 - • Folate –
Vitamin deficiencies • D – rickets • C – scurvy • B12 – pernicious anaemia (missing the intrinsic factor, need injections of B12) • B1 – beri-beri • B3 - pellagra • Folate – neural tube defects
Portal HTN triad
Caput medusae
Splenomegaly
Ascites
What is the intrahepatic shunting of blood?
Fibrous scar joins the portal tracts + the central vein blood flows through the fibrous scar, missing the hepatocytes and goes straight to the central vein intrahepatic shunting of blood this is the point at which the disease starts becoming non-reversible
Ischaemia of hepatocytes Toxins + poisons in blood not cleared out encephalopathy
Micronodular cirrhosis
Macronodular cirrhosis
Macronodular (nodules >3mm) – variable nodule size – viral hepatitis, Wilson’s disease, A1AT
Micronodular (nodules <3mm)– alcoholic/non-alcoholic, biliary tract disease
Portosystemic anastomoses
Oesophageal varices
Rectal varices
Umbilical vein recanalising
Spleno-renal shunt
gall bladder is palpable in a jaundiced patient…
The cause is gallstones
The cause is pancreatic Ca
The cause is pancreatic Ca
o If obstruction caused by stone in CBD gallbladder is likely to be thickened + fibrotic => not distended or palpable but rather shrivelled up
o If obstruction caused by tumour in CBD gallbladder is likely to be normal => will dilate due to back-pressure
Describe what happens during liver injury
Normally, endothelial cells are discontinuous + hepatocytes have microvilli
Liver injury
Hepatocytes lose microvilli
Stellate cells become activated to myofibroblasts – produce collagen
Changes in endothelial cells become continuous
Blood in the sinusoid doesn’t interact with hepatocytes because of 3 reasons
1) endothelial cells are joined together
2) collagen is produced by the myofibroblasts in the space of Disse
3) hepatocytes lose their microvilli
Acute vs chronic hepatitis + causes
Acute <6m
Drugs
Viruses - hep A+E
Chronic >6m
Drugs
VIruses - B, C ,D
Autoimmune
Stage vs grade of chronic hepatitis
stage = severity of fibrosis grade = severity of inflammation
stage more important than grade
Histology - portal inflammation vs interface hepatitis (piecemeal necrosis)
Portal inflammation
o All the lymphocytes are in the portal tract – Inflammation hasn’t crossed the limiting plate
Interface hepatitis
o Inflammation has crossed the limiting plate – hepatitis interfaces between portal tract + parenchyma
Features of alcoholic hepatitis
- Apoptosis
- Fat
- Pericellular fibrosis
- Mainly seen in zone 3
- (chronic hepatitis due to viruses – mostly seen around zone 1 – portal and periportal)
- Ballooned cells = hepatitis
Which scoring system is being used to assess the severity of liver cirrhosis
o Modified Child’s Pugh Score (ABCDE)
Albumin Bilirubin Clotting PT Ascites (Distension) Encephalopathy
PBC buzzwords
Epidemiology What is it Ix Association Mx
- Female
- Autoimmune
• Chronic inflammation with granulomas of the INTRAHEPATIC bile ducts
–> Granulomatous inflammatory destruction + loss of INTRAHEPATIC bile ducts
- Anti-mitochondrial antibodies = diagnostic test (anti-M2 antibodies)
- US = NO bile duct dilation
- Hx = bile duct loss with granulomas
- Raised cholesterol, xanthelasma, steatorrhea
- Chronic bile duct damage leading to fibrosis can eventually lead to cirrhosis if its treatment doesn’t stop its development
Mx - ursodeoxycholic acid
PSC buzzwords
Epidemiology
What is it
Ix
Association
- Males
- Inflammation + fibrosis of EXTRAHEPATIC and INTRAHEPATIC bile ducts
- Multifocal stricture formation with dilation of preserved segments
- ERCP = beading of the bile ducts (diagnostic)
- US = bile duct dilation
- Hx = onion skin fibrosis
• Associated with UC + cholangiocarcinoma
Haemochromatosis/ Bronzed diabetes
Inheritance Chromosome Pathophysiology Cirrhosis Histology
Fe, Ferritin, Transferrin saturation, TIBC/transferrin
AR
Chr 6
Increased iron absorption form the gut
Hepatomegaly with micronodular cirrhosis
Histology
Iron deposit in hepatocytes
Prussian blue stain
High Fe, ferritin, transferrin saturation
Low TIBC/transferrin
Haemosiderosis cause + complication
caused by blood transfusion - iron accumulation in macrophages (e.g. Kupffer cells of liver)
does NOT lead to cirrhosis
Wilson’s disease
Chromosome inheritance Protein affected Buzzwords Biochemistry Mx
Chr 13
AR
copper transporting ATPase
Kayser Fleischer rings
Mallory bodies
Rhodanine stain
low serum Cu, low serum ceruloplasmin
high urinary copper
Lifelong penicillamne
Autoimmune hepatitis
HLA association
Antibodies
Dx
HLA-DR3
Type 1 Anti-smooth muscle antibodies Anti nuclear antibodies Antti actin antibodies Anti soluble liver antigen
Type 2
Anti liver kidney microsomal Ig
Dx
Anti-smooth muscle antibodies in serum
Liver histology of A1AT
alpha 1 antitrypsin deficiency
intracytoplasmic inclusions of antitrypsin 1
stain with periodic acid schiff
Benign liver tumours
Liver cell adenoma
F>M, related to oestrogen levels, increased risk with COCP
Bile duct adenoma
Haemangioma
Most common benign lesion
Commonest liver tumours
Benign - haemangioma
Malignant - secondary metastases
Haemochromatosis symptoms
o Skin bronzing (melanin deposition) o DM o Hepatomegaly with micronodular cirrhosis o Cardiomyopathy o Hypogonadism o Pseudogout
