1. LABORATORY DIAGNOSIS IN LIVER DISEASES

2. The metabolic pathways of glycolysis,the Krebs cycle,amino acid synthesis and degradation and the process of oxidative phosphorylation are all carried out in hepatocytes,which are well endowed with mitochondria.
The liver contains an extensive reticuloendothelial system for the synthesis of blood cells.

5. Protein synthesis in liver
Albumin
Transthyretin(prealbumin)
Igs
Ceruloplasmin
α1-antitrypsin
Haptoglobulin
β2-microglobulin
Transferrin
α-fetoprotein
Some coagulation factors

6. Albumin is the major protein product of the liver.
İt has a long biological half-life in plasma
(about 20 days )
Hypoalbuminemia is a feature of advanced chronic liver disease.

7. Metabolic liver diseases
Clinical conditions associated with abnormal concentrations of liver_produced proteins in plasma :

8. 1. Genetic Deficiency Of Α1-antitrypsin
Alpha 1-antitrypsin deficiency (A1AD) is a genetic disorder that causes defective production of alpha 1- antitrypsin leading to its decreased activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells
Hepatic α1-antitrypsin belongs to the serpins, one of the family of serine protease inhibitors
This can cause cirrhosis, severe liver damage and scarring, and liver cancer. And because the proteins aren't traveling to your lungs like they should, it can also cause lung problems.

9. Wilson's disease
Wilson's disease is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease (acute hepatitis- cirhosis).
It is the result of inadequate copper excretion into bile and blood resulting in decreased serum ceruloplasmin, and increased copper in the urine and blood. 
Copper then accumulates in the liver, brain, cornea, kidneys, joints.
It is treated with chelation with penicillamine.

10. Neuropsychiatric changes include behavioral changes + psychosis .
Cupper accumulates in liver, brain,cornea, kidney and joints
Corneal rings(Kayser_Fleischer)
Hemolysis + proximal renal tubular dysfunction + osteopenia

11. LAB & TREATMENT LAB: Serum ceruloplasmin: Urinary Cu>100 μg/d
Hepatic Cu>250 μg/d
AST>ALT
Untreated Wilson’s disease is fatal
TREATMENT:
Chelation therapy with D-penicillamine(1-2g/d

12. 3. Liver Cancer Is Associated With Particularly High Plasma Α-fetoprotein (AFP) Concentrations
AFP and albumin have sequence homology
in the fetus, AFP appears to serve physiologic functions similiar to albumin in adult
By the end of first year of life, AFP in plasma is replaced by albumin

13. Hemochromatosis
Hemochromatosis, is a genetic disorder characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues.
The most important cause is a mutation of the HFE gene.
It can also be caused by transfusional iron overload, which can result from repeated blood transfusions.

14. Hemochromatosis…….
The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arth ritis, or hyperpigmentation.
Routine treatment in an otherwise-healthy person consists of regularly scheduled phlebotomies.
For those unable to tolerate routine blood draws, there is a chelating agent available for use.

15. Alcoholic liver disease
Alcoholic liver disease is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.

16. Alcoholic liver disease…….
Fatty liver known steatosis

17. Alcoholic liver disease……..
alcohol dehydrogenase Alcohol acetaldehyde Acetaldehyde will form adducts with other important macromolecules that inhibit their function and cause disturbance of immune system and neutrophil infiltration to clean these foreign adducts and lead to hepatocyte death. Reactive oxygen species will be produced that will destroy DNA and proteins
Alcoholic hepatitis
(mallory bodies)

18. Alcoholic liver disease……..
hepatomegaly
Neutrophilic leukocytosis
Enzyme leak↑ ALT & ↑ ↑ AST
↑ ALP, ↑ GGT
Thrombocytopenia, hyopglycemia
Treatment: stop alcohol, corticosteroides will supress immune system
Liver cirrhosis and failure

19. Liver function tests: Bilirubin Aminotransferases (AST and ALT )
Alkaline phosphatase (ALP )
Gamma- glutamyl transpeptidase ( γ GT )
Plasma proteins
Prothrombin time

21. High ucb Gilbert syndrome: low UGT (uridinglucoronyl transferase)
In the presence of hemolysis for any reason, UCB will increase
Crigler Najjar syndrome: no UGT enzyme, very high UCB in blood

22. High cb
Dubin-jonson syndrome: autosomal recessive, CB transport defect that prevents CB to go bile canaliculi, and thus accumulated in the liver and bcz of another upregulated transport protein it allows CB to go to blood, high CB
OBSTRUCTIVE JUINDICE: high CB
Block of bile in bile canaliculi, that will increase the pressure in the canaliculi, so bile including bile salts, bilirubin, cholesterol will leak to blood via gap junctions of hepatocytes. Steatorrhea (fat excretion), xanthomas, pruritis itching of the skin no absorption of fat soluble vitamins
VIRAL HEPATITIS:HIGH CB plus UCB:

25. AST-ALT Sensitive, non-specific index of
Acute damage to hepatocytes irrespective of aetiology
Hepatitis,toxic injury,drug overdose

26. Cholestatic liver disease
Cholestasis is a condition where bile cannot flow from the liver to the duodenum.
The two basic distinctions are obstructive cholestasis where there is a mechanical blockage in the duct system, and
metabolic cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired (estrogen inhibit the bile pump protein into canaliculi and thus bile accumulates in hepatocytes).
Jaundice and pruritis in both types of cholestasis: yellow and itchy skin
Xanthomas bcz of high cholesterol
ALT & ALP will be high
Low nutrient absorption

27. ALP İntra-or extrahepatic cholestasis Tumours Cirrhosis
Liver is not the sole source of ALP activity
Substantial amounts are present in bone,small intestine,placenta and kidney.
In normal blood,ALP activity is derived mainly from bone and liver,with small amounts from intestine.
The liver and bone isoenzymes can be separated by electrophoresis

28. Post-hepatic jaundice
Diagnostic tests[20]
Function test
Pre-hepatic jaundice
Hepatic jaundice
Post-hepatic jaundice
Total bilirubin
Normal / increased
Increased
Conjugated bilirubin
Normal
Unconjugated bilirubin
Urobilinogen
Decreased
Decreased / negative
Urine color
Normal[21]
Dark (urobilinogen + conjugated bilirubin)
Dark (conjugated bilirubin)
Stool color
slightly pale
Pale
Alkaline phosphatase levels
Alanine transferase and aspartate transferase levels
Conjugated bilirubin in urine
Not present
Present
Large spleen
Absent

29. Post-hepatic jaundice
Diagnostic tests[20]
Function test
Pre-hepatic jaundice
Hepatic jaundice
Post-hepatic jaundice
Alanine transferase and aspartate transferase levels
Normal
Increased
Alkaline phosphatase levels
Conjugated bilirubin
Conjugated bilirubin in urine
Not present
Present
Large spleen
Absent
Stool color
slightly pale
Pale
Total bilirubin
Normal / increased
Unconjugated bilirubin
Urine color
Normal[21]
Dark (urobilinogen + conjugated bilirubin)
Dark (conjugated bilirubin)
Urobilinogen
Decreased
Decreased / negative

30. γ GT
Microsomal enzyme,widely distributed in tissues including liver and renal tubules
A very sensitive index of liver pathology
İncreases in cholestasis
Alcohol and pheytoin induce enzyme activity.

31. Prothrombin time (PT )
A measure of the activities of certain coagulation factors,made by the liver
A very short half-life
İncreased PT may be the earliest indicator of reduced hepatic synthesis.