LFTs and cases Flashcards
Enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components is ___?
intermediary metabolism
which are the most abundant proteins syntheissed in the liver?
- enzymes
- protein binding
- nucleic acid binding
- transporters
- signal transduction
- structural
what are some reactions and components involved in xenobiotic metabolism?
- Chemical Modification:
P450 Enzyme System
Acetylation / de-acetylation
Oxidation / Reduction - Conjugation
glucuronate
sulphate - Excretion
what components due we look at to assess ACUTE LIFVER DYSFUNCTION?
INR
PT
Which hormones are metabolised in liver?
give details of the reaction?
Vitamin D:
hydroxylation - 25OHD3 -> 1,25OHD3
Steroid Hormone :
conjugation
excretion
Peptide Hormone:
catabolism
List some constituents of bile.
list some functions of bile?
constituents: Water Bile salts/acids Bilirubin Phospholipids Cholesterol Proteins Drugs and Metabolites
functions:
Excretion - of waste products eg bilirubin into faeces
Micelle formation
Digestion - of fats and fat soluble vitamins
how is bilirubin created?
how is it transported around the body?
- Red cells are broken down releasing heme, iron and globin
- The heme then goes on to form bilirubin
- Bilirubin is then bound to albumin in the plasma
- This unconjugated bilirubin goes to the liver and becomes glucuronidated
- The conjugated bilirubin is released into the bile
describe the Reticuloendothelial (immune) Function of the liver?
1.Erythropoesis
- Kupffer Cells:
a phagocytic cell
which forms the lining of the sinusoids of the liver and is involved in the breakdown of red blood cells.
are adhesive to their endothelial cells which make up the blood vessel walls.
Clearance of infection and LPS
Antigen presentation
Immune modulation
-cytokines etc.
list some Serum markers of liver cell damage?
ALT
AST
ALP
GGT
list some markers of Synthetic function?
Albumin
Pro-thrombin time (PT)
Bilirubin
describe the hepatic archictecture?
made of subunits called lobules - hexagonal structure
- central vein in middle
- hepatic artery, portal vein and bile duct in corners of hexagon (portal triad)
- sinusoids flowing from central vein to portal arteriole/vein
interlobular veins connected to hepatic vein
nutmeg appearance
describe heaptic sinusoids
fenestrated endothelial lining
also lined by kupffer cells
what are the functoins of AST and ALT
where are they found?
enzymes contained within cytoplasm of hepatocytes
“catalyzes the transfer of the alpha-amino groups of alanine and aspartate, respectively, to the alpha-keto group of ketoglutarate, which results in the formation of pyruvate and oxaloacetate…..”
AST: ALT ratio >2.0, suggestive of —-? why?
alcoholic liver disease
because AST rises more
In absence of alcohol AST:ALT ratio >0.8 suggest ___?
? advanced fibrosis or cirrhosis
which hormone :
catalyzes the transfer of the gamma-glutamyl group from gamma-glutamyl peptides such as glutathione to other peptides and to L-amino acids…”
GGT
Where is ggt found?
found in liver, kidney, pancreas, spleen, heart, brain, seminal vesicles
in liver found in hepatocytes and epithelium of small bile ducts
when is GGT elevated?
elevated in chronic alcohol use
also raised in bile duct disease and hepatic metastasis
which hormone :
a group of enzymes that catalyze the hydrolysis of a large number of organic phosphate esters at an alkaline pH
ALP
where is ALP located ?
liver version - located in sinusoidal and canalicular membranes
other sources bone, small intestine, kidney, WBC’s, placenta etc
when is ALP elevated?
markedly - obstructive jaundice or bile duct damage
less elevated in viral hepatitis or alcoholic liver disease i.e. hepatocyte damge
bone disease (especially metastatic and pregnancy)
function of albumin?
contributes to oncotic pressure and binds steroids /drugs/bilirubin/calcium etc
half life of albumin?
20 days
albumin is low in?
low production (chronic liver disease, malnutrition)
loss (eg gut, kidney- nephrotic syndrome)
sepsis (“3rd spacing”) - *into interstitial tissue
which hasa higher molecular weight afp or albumin?
AFP - is part of albumin superfamily though
what is normal afp level?
causes of raised afp?
in adult concentration low / no known function
used in diagnosis of hepatocellular carcinoma (but may rise too late or not at all)
also raised in hepatic damage/regeneration
raised in pregnancy and testicular cancer
what is the normal site for conjugated bilirubin?
urine
if you see conjugated bilirubin in post hepattic blood, this suggests?
Bile duct obstruction
Drugs
jaundice/ raised bilirubin with Normal enzymes /absence of other elevated markers refers to?
Haemolysis
Gilbert’s
raised bilirubin with a cholestatic picture ie raised ALP refers to?
Dilated ducts ie.obstruction. gallstones/cancer etc.
Undilated ducts, drugs / PBC-PSC, pregnancy etc.
when is Urobilinogen detected in urine?
– normally detected in small amounts in urine
Absent in obstructive jaundice
Increased in haemolysis, hepatitis, sepsis
pale stools, dark urine is seen in?
obstructive jaundice so
raised alp, jaundice/ increased bilirubin
Diagnostic tool for PSC - cholangitis?
what would you see and why?
MRCP
you will see a beading appearance of the biles ducts including the common bilee duct due to the formation of strictures?
Diaignostic tool for PBC - cholangitis?
AMA
- anti-mitochondrial antibodies against pyruvate
dehydrogenase complex (PDC-E2)
- 95% accuracy
Liver biopsy
what is the aetiology and inheritance of alpha 1 antitrypsin deficiency? epidemiology ?
what clinical syndromes is it associated with?
Mutation in gene found on chromosome 14
Autosomal recessive inheritance with codominant expression
Manifests in childhood
Concomitant panlobular pulmonary emphysema
misfolded insoluble globular proteins accumulate leading to hepatic fibrosis and even hepatocellular carcinoma (HCC).
what is caeruloplasmin ?
Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism.
deficiencies and excesses in caeruloplasmin are associated with which conditions?
deficiency;
Wilson disease - excess copper deposited in hepatocytes
Menkes
Acearuloplasminaemia
excess;
copper toxicity - excess
pregancy
cocp
lymphoma
acute and chronic inflammation - its an acute phase
protein
positive ASMA and/or LKM may indicate?
Anti-smooth muscle antibodies (ASMAs) attack several structural proteins in smooth muscle, affecting the liver and other tissues.
The presence of ASMA in the blood indicates that a person may have autoimmune hepatitis
Anti-liver-kidney-microsomal antibodies (anti-LKM) inidcates same
what are ANCAs and what are they used to investigate?
Antineutrophil Cytoplasmic Antibodies (ANCA)
- target proteinis inside neutrophils
- used to check for autoimmune vasculitis
investigate :
Microscopic polyangiitis (MPA)
Granulomatosis with polyangiitis (GPA) - wegners
Eosinophilic granulomatosis with polyangiitis (EGPA)
Polyarteriitis nodosa
whats a positive pANCA and cANCA mean?
pANCA, which targets a protein called MPO (myeloperoxidase)
cANCA, which targets a protein called PR3 (proteinase 3)
positive pANCA:
- mainly -> PSC
- others -> EGPA, Ulcerative colitis..
Positive cANCA:
- GPA : wegners granulomatosis
How do Serum bile acids change in different conditions?
Elevated esp. in cholestasis
10-100x in cholestasis of pregnancy
25X in PBC/PSC
what is the following test useful for;
Breath tests: Aminopyrine / Galactose (carbon 14)
measure residual functioning liver cell mass
? predict survival in alcoholic hepatitis
? distinguish cirrhosis without biopsy (70-80%sensitivity)
what is the following test useful for;
Dye tests Indocyanine green / Bromsulphalein
Measure excretory capacity of liver
Meaure hepatic blood flow
what is Courvoisier’s Sign/law?
in the presence of a painless palpable gallbladder, jaundice is unlikely to be caused by gall stones
which markers are prognostically important in acute and chronic liver disease?
Albumin / pro-thrombin time-INR
what are the tests of liver function?
Bilirubin
Albumin / pro-thrombin time-INR - synthetic function
what is INR?
is a laboratory measurement of how long it takes blood to form a clot.
1.1 or less is normal.
if taking anticoagulants, they aim for between 2-3 therapeutic range, because it is understood that clotting is taking longer perhaps due to less clotting factors.
Name a major culprit in drug induced cholestasis?
Augmentin;
Amoxicillin / Clavulanic acid
How does wilsons present and ivx findings ?
symptoms of chronic liver failure.
LFTs - abnormally high levels of transaminases
normal alk phos & bilirubin levels.
There’s marked accumulation of copper-associated protein in hepatocytes obtained from a biopsy.
SERUM copper levels and caeruloplasmin are abnormally low.
PSC is associated with which condition?
Ulcerative colitis
what does PBC stand for?
Primary biliary cholangitis
due to the leak of bile into liver, there is risk of developing cirrhosis. guess thats where the other term came from.
