1. Clinical diagnostic biochemistry - 9 Dr. Maha Al-Sedik 2015 CLS 334

2. 1-Excretory function Bilirubin. Bile acids. 2-synthetic function Protein (mainly albumin and coagulation factors). Lipids and lipoprotein. Urea. 3- metabolic function Ammonia. Carbohydrate. 4- storage function LIVER FUNCTIONS

3. Bilirubin synthesis

4.  RBCs life span is 120 days and are destructed and this releases hemoglobin, which is broken down to heme and globin which turned to amino acids cycle.  The heam is then turned into unconjugated bilirubin.  This unconjugated bilirubin is not soluble in water and it can cross blood brain barrier, it is carried by albumin to liver.  Each gram of albumin can carry 6 – 8 mg of indirect bilrubin.  In the liver, bilirubin is conjugated with glucuronic acid making it soluble in water.

5.  In the intestinal tract, conjugated bilirubin are hydrolyzed and reduced by bacteria to form colorless urobilinogens, which undergo an enterohepatic circulation.  A small fraction (2% to 5%) escapes the liver and is excreted in urine.  In the colon, urobilinogens spontaneously oxidize to stercobilinogen then stool pigments stercobilin.

7. (i)Protein Synthesis: The liver is the primary site of the synthesis of plasma proteins. Although disturbances of protein synthesis occur as a consequence of impaired hepatic function: Other factors affect plasma protein concentrations include:  Decreased availability of amino acids (malnutrition, maldigestion, and malabsorption).  Catabolic states (hyperthyroidism, burns, postsurgery recovery).  Protein losing states (nephrotic syndrome ) Hepatic Synthetic Function:

8. Albumin: Albumin is the most commonly measured serum protein and is synthesized exclusively by the liver. The rate of synthesis varies, depending on the colloidal osmotic pressure of the blood.

9.  These proteins interact to produce a fibrin clot.  Inhibitors of the coagulation system, including antithrombin, protein C, and protein S, are also synthesized in the liver. Activated protein C in plasma inhibits coagulation by inactivating factors V and VIII.  Parenchymal liver disease of sufficient severity to impair protein synthesis or obstructive liver disease sufficient to impair intestinal absorption of vitamin K is there­fore a potential cause of bleeding disorders. Coagulation Proteins:

10. The prothrombin time (PT):  Measures activity of fibrino­gen (factor I), prothrombin (factor II), and factors V, VII, and X ( extrinsic pathway ).  Normally from 10 – 15 seconds.  Since all of these factors are made in the liver and several are vitamin K dependent, a prolonged PT often indicates the presence of significant liver disease.

11.  In cholestasis, vitamin K deficiency may also cause an increase in PT. In this case, the coagulation abnormality is corrected within a few days by parenteral injection of l0mg of vitamin K.  In con­trast, if PT is prolonged because of hepatocellular disease, factor synthesis is decreased and administration of vitamin K does not typically correct the problem.

12.  Patients with severe hepatocellular disease have decreased synthesis of the vitamin K-dependent clotting factors, especially factor VII.  Patients with cholestatic disease have decreased bile salt secretion, which is necessary for the absorption of vitamin K, leading to failure of activation of factors II, VII, IX, and X. In these patients, unlike those with hepatocellular disease, the prothrombin time can be cor­rected with an injection of vitamin K.

13. Prothrombin time: A sample of the patient's blood is obtained by venipuncture. The blood is decalcified (by collecting it into a tube with oxalate or citrate ions) to prevent the clotting process from starting before the test. The blood cells are separated from the liquid part of blood (plasma) by centrifugation. The PT test is performed by adding the patient's plasma to some source of Tissue Factor (e.g.: a protein, thromboplastin, from homogenized brain tissue) that converts prothrombin to thrombin. The mixture is then kept in a warm water bath at 37°C for one to two minutes. Calcium chloride (excess quantities of ionized calcium) is added to the mixture in order to counteract the sodium citrate and allow clotting to start. The test is timed from the addition of the calcium chloride until the plasma clots. This time is called the Prothrombin Time.

14.  Catabolism of proteins and amino acids results in the formation of ammonia then in the liver urea is formed from ammonia, which is predominantly cleared from the body by the kidneys. Urea Synthesis:

15. Protein Proteolysis, principally enzymatic Amino acids Transamination and oxidative deamination Ammonia Enzymatic synthesis in the “urea cycle” Urea

16.  Patients with end-stage liver disease may have low concentrations of urea in plasma.  In addition, plasma concentrations are elevated for ammonia.  These findings suggest that patients with liver disease have an impaired ability to metabolize protein nitrogen and to synthesize urea.

17. Inflammation of the liver which causes damage of liver cells with reduced the liver’s ability to perform life preserving functions. What is Hepatitis ?

18. Infection Non-Infection Autoimmune Toxic: (drug, Alcohol) Traumatic Bacterial leptospira (Weil's disease) mycoplasma - rickettsia (typhus fever) Parasitic Amoeba and schistosome Viral: A, B, C, D, E. chickenpox, Rubella & cytomegalovirus

21. Individuals infected with a hepatitis virus tend to have generalized symptoms, which in the early stages are similar to the flu: Fatigue Loss of appetite Nausea Fever Jaundice. Ascites. Esophageal varies. Hepatic encephalopathy. Bleeding tendency.

23. Hepatitis Viruses are Highly Infectious, Particularly HBV 50-100 times More than HIV.

24. A E B D C Enterically Transmitted Parenterally Transmitted

26. Acute hepatitis May range from asymptomatic (without any signs or symp.) to severe fatigue, jaundice, nausea, vomiting or diarrhea. The acute infection cleared within 6 months. Symptoms often subside without treatment within a few weeks or months.

27. Chronic hepatitis About 5 % of cases develop into an incurable form of the disease > 6 months, called chronic hepatitis, which may last for years causing slowly progressive liver damage that lead to cirrhosis, a condition in which healthy liver tissue is replaced with dead, nonfunctional fibrous tissue. In some cases, cancer develops.

28. A and E (feco-oral) through: Ingestion of contaminated water supplies or food (most common) Close contact. B C D  Blood: Drug abuse, tattoo, Stick injury, Hemodialysis, Blood transfusion, transplantation.  Sexual: sexual Contact with infected household objects. It is not sure about virus C.  Placental: Mother to neonate. Routes of transmission

29. Chronicity EDCBA NoYes No Hepatocellular Carcinoma EDCBA NoneYes None

30. Reference: Burtis and Ashwood Saunders, Teitz fundamentals of Clinical Chemistry, 4th edition, 2000.