1. This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida, Chairman of the Department of Medicine. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Presented by: Weiam Al Maiman Medical Student December 22, 2008

3. LFT In general, liver blood tests are used to detect an injury or an inflammation to the liver.

4. Uses of LFTs: To establish a diagnosis. Monitor response to Rx or surgery. For prognosis. For screening.

5. LFT The values measured in liver blood tests are: Alanine aminotransferase.( ALT). Aspartate aminotransferase.( AST). Alkaline phosphatase. Gamma-glutamyltransferase (GGT) Albumin. Bilirubin. Prothrombin time (PT) 5’nucleotidase

6. LFT aminotransferases and alkaline phosphatase do not reflect the function of the liver. Strictly speaking, the true liver function tests (LFT's) include albumin, bilirubin, PT, and glucose. More specifically, AST, ALT, and alkaline phosphatase are called the liver enzymes and they typically are used to detect damage or injury to the liver (not its function).

7. LFT ALT & AST ------------------  rises in heptocyte damage Or necrosis of liver cells(( hepatetic picture)) ALP(with GGT) ------------------  rises with obstruction of bile flow (( cholestatic picture)) Bilirubin( total) ((direct + indirect)) ----------------  rises with excess Hb breakdown or failure to excrete bile. Albumin & PT ----------------  low Albumin & increased PT (( synthesis is affected))

8. LFT Normal values: ALT5-40 U/L AST12-40 U/L ALk.Ph39-117 U/L GGTMale (<50 U/L) Female (<32 U/L) Albumin35-50 g/L Bilirubin<17 µmol/L (0.3-1.5 mg/dL)

9. Alanine transaminase (ALT): Alanine transaminase (ALT), also called Serum Glutamic Pyruvate Transaminase (SGPT) or Alanine aminotransferase (ALAT) It is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN).

10. Aspartate transaminase (AST): Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) It is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver. The ratio of AST to ALT is sometimes useful in differentiating between causes of liver damage.

11. ALT & AST Hepatic causes of transaminase elevation: Alcoholic liver disease. Ch. Hep B Ch. Hep c Autoimmune hep Fatty liver Nonalcoholic steatohepatitis Cirrhosis Hemochromatosis Wilson’s disease A1 –antitrypsin deficiency Drug-induced liver disease Congestive hepatopathy Acute viral hep (EBV,CMV) Celiac disease.

12. AST:ALT RATIO > 2 Consider alcoholic liver disease.

13. Alkaline phosphatase (ALP): Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, kidney, intestine, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget's disease.

14. ALP Causes of high ALP: Cholestasis:  Intrahepatic: Medication induced Primary biliary cirrhosis Alcoholic hepatitis Viral hepatitis  Extrahepatic Stones Biliary stricture Malignancy (( pancreatic, duodenal, cholangiocarcinoma)) Pancreatitis & pseudocyst Primary sclerosing cholangitis.

15. Causes of high ALP: Infiltrative disease of the liver(( TB, sarcoidosis, etc)). Mass lesions of the liver(( tumor, cyst, abscess)) Parenchymal disease of the liver(( viral hep, alcoholic hep, autoimmune hep, cirrhosis)). Bone disease(( fractures, pagets disease, osteomalacia, bone growth)) Miscellaneous:  Malignancy (( renal cell ca, lymphoma))  Hyperthyroidism  Acromegaly  Hypervitaminosis D  Pulmonary infarct.  Renal infarction.

16. Bilirubin Total bilirubin (TBIL): Bilirubin is a breakdown product of heme (a part of haemoglobin in red blood cells). The liver is responsible for clearing the blood of bilirubin. It does this by the following mechanism: bilirubin is taken up into hepatocytes, conjugated (modified to make it water-soluble), and secreted into the bile, which is excreted into the intestine.

17. Bilirubin Increased total bilirubin causes jaundice, and can signal a number of problems: 1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage. 2. Hepatic: Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis. 3. Posthepatic: Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or in the bile duct.)

18. Bilirubin Direct bilirubin: The diagnosis is narrowed down further by looking at the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin, and the location of the problem is upstream of bilirubin excretion. Hemolysis, viral hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected.

19. Gamma glutamyl transpeptidase (GGT): Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP,(GGT) may be elevated with even minor, sub- clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic). In some laboratories, GGT is not part of the standard LFTs and must be specifically requested. There is a direct relation between alcohol intake & GGT level.

20. Albumine: It is synthesized exclusively by the liver. Dehydration can cause high albumen level.

21. Albumine: Causes of hypoalbuminemia: Malnutrition Malabsorption Malignancy Inflammation ( acute, ch) Increased loss:  Nephrotic syndrome  Protein losing enteropathy  Burns  Exudative skine disease Intravenous fluids Rapid hydration Overhydration Cirrhosis Ch. Liver disease Pregnancy.

22. Prothrombin time (PT) & (INR): The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function. It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.

23. Prothrombin time (PT) & (INR): PT: It will be normal until 80% of liver’s synthetic function is impaired. It is useful in acute liver disease {short half life of coagulation factors related to PT ((hours)) than albumin (3 wks) }.

24. Prothrombin time (PT) & (INR): Causes of high PT: Vit K deficiency Liver disease (( to defrentiate between v K deficiency & liver disease, give 10 mg vit K subcutaneously, decrease in PT of at least 30 % within 24 hrs suggest vit K deficiency)). Warfarin Factor VII deficiency ((rare)) False +ve result ((high hematocrit)).

25. 5' nucleotidase (5'NTD) 5' nucleotidase is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT.

26. 5' nucleotidase (5'NTD) When we order this test? If there is isolated increase in ALP. The high ALP is ether hepatobiliary or bone origin. So to differentiate we do 5’nucleotidase.

27. Other tests: Serum glucose: The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

28. Other tests: Lactate dehydrogenase (LDH) Lactate dehydrogenase is an enzyme found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage.

29. LFT ALT & AST ------------------  rises in heptocyte damage Or necrosis of liver cells(( hepatetic picture)) ALP(with GGT) ------------------  rises with obstruction of bile flow (( cholestatic picture)) Bilirubin( total) ((direct + indirect)) ----------------  rises with excess Hb breakdown or failure to excrete bile. Albumin & PT ----------------  low Albumin & increased PT (( synthesis is affected))

30. LFT Normal values: ALT5-40 U/L AST12-40 U/L ALk.Ph39-117 U/L GGTMale (<50 U/L) Female (<32 U/L) Albumin35-50 g/L Bilirubin<17 µmol/L (0.3-1.5 mg/dL)

31. Example 1 ALT -----  2010 AST----  2020 Bilirubin----  250 ALP-----  200

32. Example 1 hepatetic

33. Example 2 ALT------  400 AST------>1600 GGT----  70 ALP-----  300 Bilirubin----  150

34. Example 2 Alcoholic liver disease