Chemical Pathology - Liver disease CPC Flashcards
What is the inheritance pattern of Gilbert’s?
Autosomal recessive
What test measures bilirubin, and how does it work?
van den Bergh test
Fractionation
A direct reaction shows the conjugated bilirubin
Additional of methanol shows total bilirubin
Therefore you can calculate uncojugated bilirubin
How can normal paediatric jaundice be distinguished from pathological paediatric jaundice?
physiological jauncide in neonates- the bilirubin will be unconjugated and it is just due to liver immaturity
if not or doesnt go away - look for rare causes like congenital hypothyroidism
How can normal paediatric jaundice be treated?
phototherapy
What would make jaundice worse in Gilbert’s?
Fasting
What is the abnormally-functioning protein that causes Gilbert’s?
UDP glucoronyl transferase - it is reduced to 30% activity
What increases in Gilbert’s - conjugated bilirubin, unconjugated bilirubin or both?
ONLY unconjugated bilirubin
What is the best marker of liver function in acute liver injury?
Prothrombin time
How can you tell that a paracetamol OD is bad enough to need transplant?
PT in seconds is > hours since OD
How does acute alcoholic hepatitis present?
Nausea, abdominal pain and jaundice
Pain is due to inflammation
What are 3 key histological findings that is pathognemonic for alcoholic hepatitis?
Mallory denk bodies
Megamitochondria
Fibrosis
Which antibody to hep A will be the first to be produced, and for what time period post-exposure to the virus will it be present in serum?
IgM
Initial production at 3 weeks
Peaks at 5 weeks
Gone by 13 weeks
note in hep A virus will be in faecaes from 2-4 weeks
Which immunoglobulin class provides long-term hep A immunity, and how soon after exposure is it produced?
IgG
From 5 weeks
From when, and for how long, does hep A cause jaundice in an infected person?
From 4 weeks, potentially until 8 weeks, post-exposure
What are the 2 markers of hep B infection that can first be identified in an infected person,
HbS antigen - infectivity or vaccinatin
and HbE antigen- infectivity
Which hepatitis antigen is most infectious?
HbE antigen
In a patient who successfully fights off Hep B, for how long are HbS and HbE present in serum?
HbS = 4 months HbE = 2 months
what does anti-HBc or HBcAb mean in hep B
past or current hepatitis B infection.
core antibody does not provide any protection against the hepatitis B virus unlike the surface antibody
What are the 3 key signs of portal hypertension?
Caput medusae
Splenomegaly
Ascites
What sign may be indicative of liver failure?
Asterixis - flapping tremor
If a patient has scratch marks, what does this tell you about their jaundice?
It must be post-hepatic, as itching is called by bile salts and bile acids
What is courvoisier’s law?
If gallbladder is palpable but painless, it is almost always pancreatic cancer causing the jaundice
give 5 genetic causes of cirrhosis
haemochromastosis
wilsons
A1AT def
galactosemia
glycogen storage disease
what drug can cause cirrhosis
methotrexate
the 3 main alcoholic liver diseases that cause cirrhosis
hepatic steatosis (fatty liver)
alcoholic hepaitits
alcoholic cirrhosis
micronodular cirrhosis is seen in
alcoholic cirrhosis
steatosis is seen in
fatty liver
(fully reversible if alcohol avoided)
who is autoimmune hep more common in? what is the associated HLA
78% female
HLA DR3
linked to the other autoimmune’s
2 types of autoimmune hep and the antibodies
type 1 = ANA (antinuclear Ig), anti SMA etc
type 2 = anti LKM (liver, kidney, microsomal) Ig
2 biliary causes of cirrhosis
PBC AND PSC
outline the main differences between PBC & PSC
PBC = inflammation of intrahepatic bile ducts, PSC = intra & extra hepatic bile ducts, structure formation
PBC = 10X more in F, PSC = M> F
PBC scan = no bile duct dilation, PSC = bile duct dilation
PBC = treat w ursodeoxycholic acid, PSC = linked to IBD (UC)
PSC - linked to chalngiocarcinoma, histology shows onion skinning fibrosis
PSC increases risk of what cancer
cholangiocarcinoma
histology of PBC vs PSC
PBC = bile duct loss w granulomas PSC = onion skinning (concentric) fibrosis
are strictures are formed in PBS or PSC
strictures are in PSC, giving ending appearance of bile ducts
outline 3 zones of the liver
zone 1 - closest to portal triad - peri portal hepatocytes
zone 2 - mid zone
zone 3- close to terminal hepatic vein, perivenular hepatocytes are most mature and metabolically enzyme. most liver enzymes.
spotty necrosis on histopathology signifies
acute hepatitis (due to viruses a to e or drugs)
piecemeal necrosis on histology indicates
chronic hepatitis
is alcoholic hepatitis macro or micro nodular
micronodular
give 3 macronodular causes of hepatitis
viral hepatitis
Wilsons
A1AT
outline the 3 alcoholic liver diseases
- hepatic steatosis - fat droplets in hepatocytes
- alcoholic hepatitis - ballooning, mallory denk bodies
- alcoholic cirrhosis - micro nodular fibrosis
can reverse steatosis if alcohol avoided
which hepatitis virus tends to cause chronic infection more commonly
HCV> HBV
4 histopathological signs of cirrhotic liver
hepatocyte necrosis
fibrosis
nodules of regenerating hepaatocytes
disturbance of vascular architecture
what score indicated prognosis in liver cirrhosis
modified Childs Pugh score
higher score = worse
under 7 = child Pugh A = HALF SURVIVE 5 YEARS
7-9 = child Pugh B = 20% SURVIVE 5 YEARS
10+ = child Pugh C = UNDER 20% SURVIVE 5 YEARS
total out of 15, 3 points for each indicator
what are the 5 components of the child Pugh score
albumin
bilirubin
PT
ascites
encephalopathy
what are 3 genetic causes of cirrhosis & inheritance
haemachromatosis - AR
Wilsons - AR
A1AT def - AD
what gene is affected in haemachromatosis
HFE gene
what gene is affected in Wilsons
ATP7B on chromosome 13
histolgoical finding of haemochromatosis
iron deposits in liver stain w Prussian blue
main histo finding of Wilsons
copper stains w rhodaNine
histolgoical findings of A1AT def & what stain used
intracytopalmsic inclusions of A1AT which stain with periodic acid Schiff
3 main signs in haemochromatosis
skin bronzing (melanin deposition)
diabetes
hepatomegaly
triad of Wilsons signs
liver disease
neuro disease (basal ganglia involvement)
Kayser flesicher rings
presentation of A1AT in children vs adults
children = neonatal jaundice adults = emphysema and chronic liver disease
3 iron results in haemochromatosis
iron and ferritin increased
transferrin saturation over 45%
TIBC decreased
3 blood results in Wilsons
serum careuloplasmin decerased
serum copper decreased
urinary copper Increased
2 results of investigations in A1AT def
A1AT decreased
absent alpha globulin band on electrophoresis
2 treatments for haemochromatosis
venesection
desferrioxamine
drug for Wilsons
life long penicillamine
state 2 benign liver tumours? which is most common
haaemangioma (most common, no treatment needed) hepatic adenoma (linked to COCP)
state 4 malignant liver tumours
hepatocellular carcinoma
cholangiocarcinoma
haemangiosarcoma
hepatoblastoma
what is deposited in the space of disse in liver injury
collagen
what are liver macrophages called
kupffer cells
biomarker for HCC?
alpha fetoprotein
which malignant tumour tends to arise in those w chronic liver disease
HCC
which malignant tumour presents as an abdominal mass, originating from immature liver precursor cells
hepatoblastma
which malignant liver tumour is highly invasive
haemoangiosarcoma
cancer of vascular epithelium
what is the most common cause of malignant liver lesions
usually multiple secondary tumours from GIT, breast or bronchus
transmission of hep A & hep E plus type of infection
BOTH =
acute
fAeco-oral -
food (shellfish) or men or men sex
hep A - contaminated water
hep B- also uncooked pork
treatment of hep A
after jaundice and fever symptoms IgG is produced so cured and immune
hepatitis D requires co infection with
hepatitis B
what antigens are typically measured in hep B? what do they signify
HBsAg - Hepatitis B surface antigen = infected
HBeAg = infected & can spread
HBsAb - indicates that a person is protected/immune against the hepatitis B virus througb vaccination or naturally.
if vaccinated you’ll have anti HBs but NOT HBe
what % of hep B go on to be chronic compared to hep C
hep B only 10% go on to be chronic
hep C up to 80% go on to be chronic
HBV & HCV are associated w what liver cancer
HCC
give a risk factor for HCV
thalsscemia due to recurrent transfusions
transfusions/blood product spread are a MAJOR risk factor for HCV (much less so in HBV)
what types of viruses are hep B & C
hep B - DNA
hep C - RNA
is hep B or hep C more commonly transmitted through unprotected sex
hep B more so
give a drug that can cause chronic hep
methotrexate
3 signs of portal hypertension
caput medusae
ascites
spelnomegaly
4 signs of chronic stable (alcoholic) liver disease
palmar erythema
gynaecomastia (liver can’t break oestrdiol down)
spider nave > 5
duputryens contracture
3 vitamin to give in alcoholic hep
B1 - thiamine - beri beri
B3 -niacin - pellagra
B12 - cobalamin - B12 def/SCDC
what does courvoiseirs law state
if gallbladder is palpable in jaundiced patient, unlikely to be gallstones (ie probs pancreatic cancer which foot mets to liver)
itching is a sign of what type of jaundice
obstructive
