Abnormal Liver Function Tests Flashcards

1
Q

Describe the liver

A

-Approx 1.5 kg
-in ‘chest`
-2 blood supplies;
-art ^ press+low O2, PV low press,low O2

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2
Q

Overview of liver function tests

A

Not sensitive or specific
reflect damage rather than function
BUT clinically useful
AND patterns give clues

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3
Q

Describe bilirubin

A

-difficult to assay and non-specific
-haem–biliverdin–bilirubin——>
-mono then diglucuronide–bile–stool—->
-some reabsorbed as urobilinogen
-Isolated rise in Gilberts synd. Or haemolysis

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4
Q

Describe the pathway of bilirubin excretion

A

-Because of its poor solubility in physiologic
aqueous solution, unconjugated bilirubin circulates in the blood as a noncovalent complex with albumin.
-The pores in the hepatic sinusoids are
sufficiently large so that the bilirubin-albumin complex readily diffuses to the plasma membrane of the hepatocyte as blood flows through the liver.
-It is there unconjugated bilirubin dissociates from albumin and enters the cytosol. This dissociation occurs by facilitated transport.
-Within the hepatocyte cytosol, unconjugated bilirubin is bound to the protein ligandin (glutathione-S-transferase).
-The bilirubin molecule is subsequently conjugated with one or two molecules of glucuronic acid by the enzyme uridine diphosphate-glucuronyl
transferase, which is located in the interior of the endoplasmic reticulum
-Conjugated bilirubin is excreted across the canalicular membrane into bile.
-Conjugated bilirubin remains largely intact during passage through the biliary tract and the small intestine, but it is degraded by colonic bacteria to a series of tetrapyrroles that are collectively termed urobilinogen.
-These compounds partially account for the colour of stool. A portion of urobilinogen is absorbed and excreted in bile; less than 2% is excreted in urine under normal circumstances.

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5
Q

Describe ALT

A

-Alanine transaminase (ALT), more liver specific than aspartate transaminase (AST).
-half-life hours
-increased when hepatocytes die
-all dead=10,000, 10%=1000, 1%=100,
-0,5%=N (20 yrs min injury–> cirrhosis)
-AST>ALT in ALD or advancing fibrosis

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6
Q

Describe ALP

A

-Alkaline Phosphatase, liver only one of 4 isoenzymes (ie not specific)-check GGTP
-from biliary system-new enz production
-little reflects completeness of bile obstr

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7
Q

Describe GGT

A

-Gamma Glutamyltranferase, not just in liver ie not specific.
-Increases by induction not damage
-from liver and biliary system
-^ alcohol, obesity, phenytoin, carbamazipine, NAFLD cirrhosis

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8
Q

Describe Albumin

A

-Large amount in blood
-Important for osmotic effect, carries non-water soluble subst incl uncon bil
-High in dehydration
-Low due to dilution or reduced synth
-Often normal in cirrhosis until liver failing

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9
Q

Describe prothrombin time

A

-Good marker of synthetic function of the liver
-Very good in acute liver failure
-Rarely very abnormal in cirrhosis

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10
Q

What do patterns in liver function tests reflect?

A

-Bil only–Gilbert’s or haemolysis
-ALT mild–common eg NASH, hepC, ALD incl Alc Hep.
-ALT high– hepatitis incl drug damage
-GGTP only– induction eg drug, inactive cirrhosis
-ALK Phos+GGTP biliary dis eg stones, panc ca, PBC

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11
Q

What other tests are done in response to abnormal liver function tests?

A

-In practice triggers a ‘liver screen’ with
-Hepatitis viruses
-Autoantibodies ANA, AMA and AntiSMAb
-Ferritin
-Caeruloplasmin and Alpha-1-antitrypsin
-Immunoglobulins
-And an ultrasound scan and referral

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12
Q

Raised bilirubin

A

-Occurs earlier in natural history of biliary disease (PBC) than in disease of liver parenchyma (cirrhosis)
-Swelling of liver within capsule in inflammation can impair bile flow (disproportionate rise to degree of liver damage)

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13
Q

Low serum albumin

A

-Liver disease
-Change in the volume of distribution of albumin, and reduced synthesis
-Can be normal in acute liver failure (plasma half-life 2 weeks)
-Reduced in chronic liver failure

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14
Q

ALT and AST

A

-Located in cytoplasm of hepatocyte (AST also in hepatocyte mitochondria)
-Expression of ALT outside the liver is relatively low= more specific for hepatocellular damage
-Hepatic LTFT pattern

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15
Q

ALP

A

-Alkaline phosphatase= enzymes that hydrolyse phosphate esters at alkaline pH
-Main sites of production are in liver, GI tract, bone , placenta and kidney
-Cell membranes of hepatic sinusoids and biliary canaliculi
-Levels rise with intrahepatic and extrahepatic biliary obstruction, sinusoidal obstruction (infiltrative liver disease)

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16
Q

GGT

A

-Gamma-glutamyl transferase= microsomal enzyme
-Highest concentrations located in liver, produced by hepatocytes and epithelium lining small bile ducts
-Cholestatic/ obstructive pattern with ALP
-Isolated= alcohol/ NAFLD

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17
Q

Biliary obstruction LFT pattern

A

+AST/ALT (x2)
++GGT (2-5x)
+++ALP (marked elevation x5)

18
Q

Hepatitis LFT pattern

A

+++AST/ALT
+GGT
+ALP

19
Q

Alcohol/enzyme-inducing drugs LFT pattern

A

N/+ AST/ALT
++GGT
N ALP

20
Q

Drugs that increase levels of GGT

A

-Barbiturates
-Carbamazepine
-Ethanol
-Griseofulvin
-Rifampicin
-Phenytoin

21
Q

Sodium in liver disease

A

-Hyponatraemia in severe liver disease
=Increased production of vasopressin (ADH)

22
Q

Urea in liver disease

A

-Serum urea reduced in hepatic failure
-Increased urea following GI haemorrhage
-High urea + raised bilirubin, high creatinine, low urinary sodium= hepatorenal failure

23
Q

Ferritin in liver disease

A

-Elevated significantly= haemochromatosis
-Modest elevation= inflammatory disease, NAFLD, alcohol excess

24
Q

Mean cell volume in GI disease

A

-Normochromic normocytic anaemia= recent GI haemorrhage
-Hypochromic microcytic anaemia secondary to iron deficiency= chronic blood loss
-High MCV (macrocytosis)= alcohol misuse (persist for long period of time following cessation so not a good marker for ongoing consumption), target cells in jaundice

25
Leukocytes in GI disease
-Leukocytopenia= complicate portal hypertension and hypersplenism -Leucocytosis= cholangitis, alcohol hepatitis and hepatic abscesses -Atypical lymphocytes= infectious mononucleosis (can be complicated by an acute hepatitis)
26
Platelets in GI disease
-Thrombocytopenia= cirrhosis (reduced production and increase breakdown due to hypersplenism) -Falls with worsening liver function -More depressed than white cells and haemoglobin in presence of hypersplenism in cirrhosis -Indictor of chronic liver disease, hepatomegaly -Thrombocytosis= active GI haemorrhage, rarely in hepatocellular carcinoma
27
Coagulation tests in liver disease
-Abnormal -Normal half-lives of vitamin K-dependent coagulation factors short (5-72 hrs) so changes in PT occur quickly following liver damage -Increase PT= severe liver damage in chronic liver disease, not reversible by vitamin K -Vitamin K corrects PT in biliary obstruction due to non-absorption of fat-soluble vitamins
28
Immunological tests in liver disease
-Liver-related autoantibodies= autoimmune liver disease (false positives in non-autoimmune inflammatory disease like NAFLD) -Elevation in overall serum immunoglobulin levels can indicate autoimmunity (IgG and IgM) -Elevated IgA can be seen in more advanced alcoholic liver disease and NAFLD
29
What is tested in chronic liver disease screen?
-Hep B surface antigen -Hep C autobody -Liver autoantibodies (ANA, smooth muscle antibody, antimitochondrial antibody) -Immunoglobulins -Ferritin -a1-antitrypsin -Caeruloplasmin
30
Alcoholic liver disease diagnosis
-History -AST>ALT -High MCV -Random blood alcohol
31
NAFLD diagnosis
-Metabolic syndrome (central obesity, diabetes, hypertension) -LFTs -Liver biopsy
32
Chronic hep B diagnosis
-Injection drug use; blood transfusion -HBsAg -HBeAg, HBeAb, HBV-DNA
33
Chronic hep C diagnosis
-Injection drug use; blood transfusion -HCV antibody -HCV-RNA
34
Primary biliary cholangitis diagnosis
-Itching, raised ALP -AMA -Liver biopsy
35
Primary sclerosing cholangitis diagnosis
-Inflammatory bowel disease -MRCP -ANCA
36
Autoimmune hepatitis diagnosis
-Other autoimmune disease -ASMA, ANA, LKM, immunoglobulin -Liver biopsy
37
Haemochromatosis diagnosis
-Diabetes/ joint pain -Transferrin saturation, ferritin -HFE gene test
38
Wilson's disease diagnosis
-Neurological signs; haemolysis -Caeruloplasmin -24hr urinary copper
39
a1-antitrypsin diagnosis
-Lung disease -a1-antitrypsin level and genotype
40
Drug-induced liver disease
-Drug/herbal remedy history -LFTs -Liver biopsy
41
Coeliac disease diagnosis
-Malabsorption -Tissue transglutaminase -Duodenal biopsy
42
What also increases AST levels?
-Haemolysis -Rhabdomyolysis -MI