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Path: Liver 4 - Disease + Cirrhosis (iii) (iron metabolism (hepcidin…
Path: Liver 4 - Disease + Cirrhosis (iii)
iron metabolism
absorption in SI (controlled according to need)
loss limited (in women: menstruation, pregnancy, lactation)
transported in blood by transferrin
% saturation indicative of iron storage status - >55% = dx of iron overload)
storage form = ferritin (increase is suggestive but not reliable, better for measuring response to tx)
long term storage = haemosiderin (liver, macrophages, BM)
hepcidin
hormone secreted by liver
blocks iron entry into circulation from intestinal epithelium, macrophages, liver cells
inhibitory target = iron export protein ferroportin on cell surface
hereditary haemochromatosis involves genes that regulate hepcidin synthesis/activity - relative hepcidin deficiency
prolonged inflamm stims hepcidin - anaemia of chronic disease (e.g. RA)
Rare causes of chronic liver disease
both can manifest as chronic hepatitis (+/- flares) or cirrhosis, affect younger patients, consider if other causes excluded
Wilson's
A1AT deficiency
AI liver disease
autoAbs + elevated Ig levels
autoAb names have no link to pathological conditions + aren't named after their target (don't do damage, just markers, damage is cell mediated)
AIH
type 1 (classic): ANA/SMA +ve, AMA -ve
type 2: anti-LKM +ve (liver kidney microsomal)
in 5%
more aggressive
younger age of onset
elevated IgG
predominant transaminase elevation
chronic hepatocellular damage
necrosis + inflamm in hepatocytes
heterogenous presentation
jaundice/acute flare @ some point in 40%
resembles other forms of chronic hep
dx of exclusion
can be difficult to dx, scoring system used to help
F>M, 20-40 y/o, a/w other AI (e.g. thyroiditis)
T cells do the damage, autoAbs just markers
Tx = immunosuppression
steroids, azathioprine
effective
sometimes tx pre-emptively
portal inflamm with spillover into adjacent parenchyma
PBC
intrahepatic (destruction of intrahepatic bile ducts)
AMA +ve (>90%), SMA -ve, obstructive enzymes raised (v high ALP)
chronic cholestasis + possible liver damage
30% have granulomas on biopsy
F>M (10:1), middle age = typical onset, a/w other AI diseases
clinical features
asymptomatic
fatigue
pruritus (retained bile salts - hard to tx)
possibly cirrhosis (only @ end stage)
bili late to rise
elevated IgM
Tx
Ursodeoxycholic acid (UDCA aka Ursofalk)
bile salt analogue
v good prognosis if patient responds (life expectancy not reduced)
symptomatic
OLT(orthotopic)
NOT steroids
marked portal inflamm with damaged inflamed bile duct, epithelium containing lymphocytes, granulomas may be present
PSC
intra +/- extra hepatic (commonly both)
AMA -ve, obstructive enzymes raised
mimics PBC
often there is co-existing UC/Crohn's (strong a/w IBD esp UC)
UC present in 70% of patients with PSC (but <5% of UC sufferers have PSC)
increased cancer risk
cholangiocarcinoma
CRC with IBD
pANCA +ve
abnormal cholangiography
chronic fibro-obliterative destruction of bile ducts
if mainly intrahep: progressive cholestasis with clinical features similar PBC, progression to cirrhosis
if mainly extrahep: stricture with CBD obstruction, risk of ascending cholangitis
M>F (4:1)
much less common than PBC
dense fibrosis surrounds bile duct - will eventually obliterate duct
strictures + dilations of biliary tract - "beading"
Chronic Cholestatic diseases
chronic bile retention - harmful to hepatocytes
initial bile duct damage
inflamm, fibrosis + cirrhosis ('secondary biliary cirrhosis) in liver parenchyma if sustained
Causes
primary (AI)
cause inflamm/damage with ultimate loss of bile ducts
PBC
PSC
secondary (to other causes of chronic cholestasis)
rare childhood causes (e.g. CF)