Evaluation of liver function tests ppt
-
Upload
dhiraj-kumar -
Category
Health & Medicine
-
view
141 -
download
22
Transcript of Evaluation of liver function tests ppt
![Page 1: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/1.jpg)
EVALUATION OF LIVER FUNCTION
TESTSGuide - Dr. Manohar Lal Prasad Presenter - Dr. Dhiraj Kumar
Source - Harrison’s principles of internal medicine 19th edition.Sleisenger and Fortrans textbook of gastrointestinal and liver disease.
![Page 2: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/2.jpg)
LIVER FUNCTION TEST USED TO:
Detect presence of liver disesase
To know the extent of known liver diseases
Distinguish among different types of liver diseases
Follow the response to treatment
![Page 3: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/3.jpg)
Liver function tests
Can be normal in pt. with serious liver diseases
Rarely suggests specific
diagnosis rather suggest
general categories of liver disease
Hepatocellular
Cholestatic , or infiltrative
They detect –liver cell damge,
interference with bile flow
![Page 4: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/4.jpg)
Functions of liver
Metabolic functions
Excretory functions
Synthetic functions
Storage functions
Detoxification functions
![Page 5: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/5.jpg)
Tests based on detoxification function:
Blood ammonia level
![Page 6: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/6.jpg)
Tests based on excretory functions:
Sr. bilirubin Urine bilirubin
Urine and fecal
urobilinogen
Urine bile salts
![Page 7: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/7.jpg)
Tests based on synthetic functions:
Plasma protein Prothrombin time
![Page 8: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/8.jpg)
Tests based on metabolic functionsCarbohydrate metabolism• G
alactose tolerance test
Lipid metabolism• Sr
Cholesterol
Protein metabolism• S
r Protein
• Aminoaciduria
![Page 9: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/9.jpg)
Enzymes in diagnosis of liver diseses
ENZYMES
•AST(SGOT)•ALT(SGPT)
ENZYMES•ALP•GGT•5’NT
![Page 10: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/10.jpg)
Tests used in clinical practice
Sr . Bilirubin ALT(SGPT)
AST(SGOT) Alkaline phosphatase
Serum Albumin
Prothrombin time
![Page 11: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/11.jpg)
Sr. Bilirubin• Breakdown product of porphyrin ring of heme containing
protein( myoglobin, cytochrome, peroxidase)• Two fractions:• Conjugated(Direct)(water soluble)(excreted by kidney)• Unconjugated (indirect)(water insoluble) (bound to
albumin)• Normal value- 1- 1.5mg/dl• In case of hyperbilirubinemia, if direct fraction <15% -
Unconjugated hyperbilirubinemia• Direct fraction- Upper limit of normal range is 0.3mg/dl
![Page 12: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/12.jpg)
![Page 13: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/13.jpg)
![Page 14: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/14.jpg)
CAUSES OF HYPERBILIRUBINEMIA Isolated increase in unconjugated bilirubin is due to –1. Hemolytic disease2. Genetic disorders – crigler najjar and gilbert’s syndrome3. Neonatal jaundice/physiological jaundice
Isolated increase in conjugated bilirubin is due to –4. Cholestasis5. Genetic disorders – Dubin johnson syndrome and rotor’s
syndrome
Increase in both conjugated and unconjugated bilirubin is due to –
1. Intrahepatic /liver disorders
![Page 15: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/15.jpg)
![Page 16: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/16.jpg)
![Page 17: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/17.jpg)
Degree of elevation of Sr bilirubin significant in:
Viral hepatitis
Alcoholic hepatitis
Drug induced liver disease
![Page 18: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/18.jpg)
Model for End Stage Liver Disease(MELD) Score
• Criteria for listing a pt. for liver transplantation• Range of MELD score is 6 to 40• Liver tansplantation done in those pt who
have >15 MELD score• MELD score – bilirubin, creatinine, PT as INR• MELD score >= 21 high mortality in alcoholic
hepatitis
![Page 19: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/19.jpg)
Urine Bilirubin:
Any bilirubin in urine- Conjugated bilirubin
Unconjugated fraction is water insoluble and albumin bound, hence not filtered
Phenothiazine give false positive
Recovering from jaundice urine bilirubin clears prior to Sr bilirubin
![Page 20: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/20.jpg)
Bile salts:
• Are products of cholesterol metabolism• Facilitate absorption of fat from intestine• Primary bile salts- cholate & chenodeoxycholate,
produced in liver
• Metabolised by bacteria in intestine
• Produces secondary bile salts-lithocholate & deoxycholate
![Page 21: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/21.jpg)
Bile salts
In cirrhosis- decreased ratio of primary to secondary bile salts
In cholestasis - secondary bile salts not formed – increased ratio of primary to secondary bile salts
Normally renal excretion of bile salt is negligible
Cholestasis increase renal excretion of bile salt
Measured by- Hay’s test, HPLC
![Page 22: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/22.jpg)
BLOOD AMMONIA:Detoxification of ammonia
In liver – get converted to urea-excreted in kidney
In striated muscles- combines with glutamine – glutamic acid
![Page 23: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/23.jpg)
Advanced liver disease •Significant muscle wasting•Contributes to hyperammonemia
Increased blood ammonia •Detect occult liver disease with mental status change
Increased blood ammonia •In severe portal hypertension•Portal blood shunts around liver
Increased arterial ammonia •Correlates with fulminant hepatic failure outcome
![Page 24: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/24.jpg)
ENZYMES IN LIVER DISEASES
• Sr transaminases• Aspartate
aminotransferases (AST)(SGOT)
• Alanine aminotransferases (ALT)(SGPT)
• Alkaline phosphatase(ALP)• Gamma glutamyl
transpeptidase(GGT)• 5’ Nucleotidase(5’NT)
![Page 25: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/25.jpg)
![Page 26: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/26.jpg)
Sr enzyme test grouped in two categories:
Enzymes whose elevation reflect damage to hepatocytes
Enzyme whose elevation reflect cholestasis
Enzyme showing infiltrative pattern
![Page 27: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/27.jpg)
Enzymes that reflect damage to hepatocytes:
Aspartate aminotransfersase(AST)(SGOT)
Alanine aminotransferases(ALT)(SGPT)
AST(SGPT) is found in liver > cardiac muscles > skeletal muscles> kidney> brain >pancreas> lungs> WBC >RBC
ALT(SGPT) is found primarily in liver.( more liver specific)
Normal range is 10-40 IU/L
![Page 28: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/28.jpg)
• Sr aminotransferases upto 300 IU/L are non specific
• Minimal ALT elevation Fatty liver disease• If levels >1000 IU/L reflects extensive
hepatocellular injury seen in:1. Viral hepatitis2. Ischemic liver injury( prolonged hypotension
or acute heart failure3. Toxin/drug induced liver injuryIn most acute hepatocellular disorder ALT >=AST
![Page 29: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/29.jpg)
AST/ALT Ratio:• Normal ratio 0.7 to 1.4• Useful in 1. Wilson disease 2. Chronic liver disease 3. Alcoholic liver disease• AST/ALT <1 seen in 1.Chronic viral hepatitis 2.NAFLD • AST/ALT >2:1 suggestive & 3:1 is highly suggestive of alcoholic
liver disease• In alcoholic liver disease : ALT rarely >300 & ALT often
normal( alcohol induced deficiency of PYRIDOXAL PHOSPHATE)
![Page 30: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/30.jpg)
Aminotransf-erases
not increased
in obstructive jaundice
except
During the
acute phase
of biliary
obstruction
Due to passage of gall
stone into CBD
In this aminotran-sferases
1000-2000 IU/L
![Page 31: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/31.jpg)
AST(SGOT)
• 2 forms 1. Cytosolic 2. Mitochondrial (mAST) – synthesized in precursor
form( pre-mAST)
converted to mature form• Account for 80% of total AST activity in liver cells• mAST/ total AST ratio- marker of chronic alcohol
consumption
![Page 32: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/32.jpg)
• Isolated rise of ALT is seen in1. Chronic HepC infection2. Fatty liver• Isolated AST elevation1. Alcohol related 2. Drug induced liver injury3. Hemolysis4. Myopathic processesThese enzymes distinguish hepatocellular from cholestatic
jaundice• Increase in ALT and AST (>500 IU/L) in hepatocellular
jaundice than in cholestatic jaundice(>200 IU/L)• Persistence of elevated AST & ALT beyond 6 month in
case of hepatitis – chronic hepatitis
![Page 33: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/33.jpg)
![Page 34: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/34.jpg)
Enzymes showing cholestasis:• 3 enzymes are elevation in cholestasis 1. Alkaline phosphatase(ALP)2. 5’Nucleotidase(5’NT)3. Gamma glutamyl transpeptidases(GGT)
ALP & 5’NT – in or near bile canalicular membrane of hepatocytes
GGT located in ER & bile duct epithelial cells(less specific for cholestasis)
GGT (sometimes) used to identify occult alcohol use
![Page 35: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/35.jpg)
• ALP isoenzyme is found in 1. Liver 2. Bone 3.Placenta 4. Small intestine• Physiological rise in ALP 1. Age >60 years ( 1-1.5 times)2. Blood type O & B (after eating a fatty meal
due to influx of intestinal ALP in blood)3. Children and adolescents ( rapid bone growth)4. Late in normal pregnancies( placental ALP)
![Page 36: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/36.jpg)
• ALP < 3 times – any liver disease• ALP> 4 times 1. Cholestatic liver disease 2. Infiltrative liver disease(cancer & amyloidosis) 3. Pagets disease of bone( rapid bone turnover)If ALP is raised – source of isoenzyme by:1. Fractionation of ALP by electrophoresis2. Measure GGT &5’NT –elevated only in liver disease3. Different isoenzymes have different heat susceptibilityi. Increased heat stable fraction – MC from placentaii. Sensitive to heat inactivation- Bone ALP
![Page 37: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/37.jpg)
![Page 38: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/38.jpg)
Normal levels
Sr GGT 10 to 47 IU/L
Sr 5’ NT 2 to 17 IU/L
Sr ALP 39 to 117IU/L
![Page 39: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/39.jpg)
Tests based on Biosynthetic function
Plasma proteins
Coagulation factors(Prothrombin time P.T.)
![Page 40: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/40.jpg)
Plasma proteins• Liver is the sole source of plasma proteins except for
immunoglobulins( by plasma cells)• Sr albumin comprises 60% of all plasma proteins• Tests of plasma protein include:1. Total Sr protein2. Sr albumin 3. Sr globulin4. Sr A/G ratio5. Pre albumin6. Pro collagen III peptide 7. Ceruloplasmin
![Page 41: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/41.jpg)
Albumin• Synthesized exclusively by hepatocytes• Long half life 18 – 20 days; 4% is degraded per day• Slow turn over – not a good indicator of acute or mild hepatic
dysfunction• In hepatitis , albumin < 3 mg/dl – Chronic liver disease like
cirrhosis, reflects liver damage and decreased albumin synthesis• Non hepatic cause of low albumin:1. Protein malnutrition2. Protein losing enteropathy3. Nephrotic syndrome4. Chronic infection(increased levels of IL-1, TNF, Cytokines- inhibit
albumin synthesis
![Page 42: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/42.jpg)
Sr Globulin
• Made of alpha, beta , gamma globulin• Alpha & beta globulin produced primarily in hepatocytes• Gamma globulin produced by B lymphocytes• In Cirrhosis and Chronic hepatitis – gamma globulin is
increased ( Cirrhotic liver fails to clear bacterial antigen from intestine which come through hepatic circulation)
• Diffuse polyclonal IgG – Auto immune hepatitis• Increased IgM – Primary biliary cirrhosis• Increased IgA- Alcoholic liver disease
![Page 43: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/43.jpg)
• Pre Albumin1. Level falls in liver diseases2. Half life 2 days3. Sensitive indicator of change in synthetic & catabolic function4. Useful in drug induced hepato toxicity• Ceruloplasmin 1. Acute phase protein2. Normal plasma level 0.2 – 0.4g/l• Decreased in Increased in 1. Wilson disease 1.Copper toxicity2. Menke’s disease 2. Pregnancy3. Aceruloplasminemia 3. OCPs4. Copper deficiency
![Page 44: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/44.jpg)
Pro collagen III peptide
• Cleavage product of type III procollagen molecule• Radioimmuno assay• Increased when there is transformation of viable
hepatic tissue into connective tissue / fibrosis• Used in evolution of liver disease like:1. Chronic active hepatitis2. Liver fibrosis 3. Liver cirrhosis
![Page 45: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/45.jpg)
Coagulation factors• Except factor VIII, clotting factors synthesized in
liver• Half life ranges 6 hrs( factor VII) to 5 days
(fibrinogen)• Measurement is single best measure of hepatic
synthetic function• Diagnosis and prognosis of acute parenchymal liver
diseases• Test – Prothrombin time(PT)• PT measures II, VII, IX, X activity - Vit K dependent
![Page 46: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/46.jpg)
PT & INR• INR- Degree of anti coagulation on warfarin therpy• International Sensitivity index(ISI): INR standardise PT
measured according to thromboplastin reagent used in any lab expressed as ISI.
• ISI is used to calculate INR• PT is increased in 1. Hepatitis2. Cirrhosis3. Vit k deficiency- obstructive jaundice, fat malabsorption4. If PT > 5 times , not corrected by parenteral Vit k - poor
prognostic sign in acute viral hepatitis & other liver diseaseINR is part of MELD Score
![Page 47: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/47.jpg)
LFT in Anti TB treatment• LFT should be preferred before starting anti TB treatment• With use of rifampicin & isoniazid , onset of liver damage
may be as soon as 10 days or may be upto 1yr after commencing therapy
• So LFT should be repeated routinely• High risk groups are –1. Malnourished 2. Children and elderly3. Known liver disease - Alcoholic liver disease - Hepatitis B &C
![Page 48: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/48.jpg)
Percutaneous liver biopsyCan be performed bedside with LADone in• Hepatocellular disease of uncertain cause• Prolonged hepatitis with possibility of auto immune hepatitis• Unexplained hepatitis• Fever of known origin• Staging of malignant lymphomaContradiction of percutaneous liver biopsy• Significant ascites• Prolonged INRIn these conditions transjugular approach is done.
![Page 49: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/49.jpg)
Transient Elastography (FibroScan)
• Ultra sound waves to measure hepatic stiffness non invasively
• Useful for early fibrosis in1. Chronic Hep C2. Primary Biliary Cirrhosis3. Hemochromatosis4. NAFLD5. Recurent chronic hepatitis after liver
transplantation
![Page 50: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/50.jpg)
![Page 51: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/51.jpg)
Evaluation of chronically abnormal liver tests
![Page 52: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/52.jpg)
![Page 53: Evaluation of liver function tests ppt](https://reader033.fdocuments.in/reader033/viewer/2022061417/58f9b159760da3da068bbfde/html5/thumbnails/53.jpg)