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LIVER DYSFUNCTION

CLINICAL BIOCHEMISTRY II (SBD 0113)

MISS SUZAILA BT.ARSAD

Liver Functions:
Metabolism Carbohydrate, Fat & Protein

Secretory bile, Bile acids, salts & pigments

Excretory Bilirubin, drugs, toxins

Synthesis Albumin, coagulation factors

Storage Vitamins, carbohydrates etc.

Detoxification toxins, ammonia, etc.

FUNCTION OF LIVER
Making bile to help digest foods
Bile acid synthesis & secretion

Stopping cuts from bleeding (coagulation)

Responsible for the synthesis of prothrombin, factor VII, IX, and X from vitamin K absorption.

Filtering toxic chemicals from the body

Remove waste products of nutrient breakdown

 Helps with disposing of bilirubin

excretes bilirubin into the small bowel so that bowel bacteria can change it into the safe green colored biliverdin.

Helping to build muscles/ proteins

Plasma protein synthesis Lipid & lipoprotein synthesis

Glucose homeostasis Albumin is synthesized exclusively in the liver

albumin is essential for carrying molecules (and drugs), and for keeping fluid in the blood vessels. Hypoalbuminemia causes fluid shift into tissue and patient will show signs of edema.
albumin decreases in malabsorption & tumor necrosis, or any form of chronic liver disease.

Role of the liver (cont)

Storing energy
Store vitamins A, D, E and K, & B12

Liver blood supply

Blood enters the liver from the hepatic artery and the portal vein and leaves the liver from the hepatic vein.

The blood from the artery carries oxygen while the portal vein carries nutrients from the intestine.

Liver regeneration
If individual hepatocytes are destroyed but the architecture of the lobule is not destroyed, the remaining hepatocytes will totally regenerate the liver parenchyma. If whole lobules are destroyed, the remaining lobules will expand. They will function normally, though bile may not be drained quite so well. Of course, if scar tissue alters the flow of blood through the liver (i.e., cirrhosis has occurred), regeneration will only produce less-than-fullyperfused nodules of liver cells.

Hepatic failure biochemical changes

Electrolyte imbalance Eg. Na and Cl fall Severe metabolic acid-base imbalance Hyperglycaemia Renal failure exposure of glomeruli to toxin Increaseblood NH3 failed to detoxify Hypoalbuminemia - Edema/ascites Hemorrhage

Ascites

Alcoholic Fatty Liver

Alcoholic Hepatitis Diagnostic Studies

A. Laboratory Test:
The SGOT (AST) 2-10xs normal
SGPT (ALT) is less elevated Bilirubin mild to moderate Alk phos is usually 2-3xs normal Globulins elevated with reverse A/G ratio

Prothrombin time elevated (poor prognosis)

Leukocytosis Blood NH3 (Ammonia) level

Other causes of Chronic Hepatitis

Inherited Chronic Liver Disorders

A. Wilsons disease B. Hemachromatosis C. Alpha 1-antitrypsin deficiency

D. Reye syndrome

 Wilsons disease
genetic disorder of copper metabolism. abnormal accumulation of copper in the hepatocytes. The defect is in the ceruloplasm which carries the copper.

Haemachromatosis
A group of disorders with excessive absorption of iron.

 Primary cause unknown Secondary- Iron overload :

anemias cirrhosis Dietary

Diagnosis:

Lethargy, weakness in men 40-60 yo

Skin hyperpigmentation Diabetes 30-60% of pts arthopathy

 Alpha 1-Antitrypsin Deficiency

Alpha 1-antitrypsin is potent protease inhibitor found in the serum, body fluids, & tissues It is synthesized by the liver to protect from tissue injury resulting from protease like trypsin

Reyes syndrom
only happens in kids less than 15 years old.

The cause is unknown, but it is strongly associated with Aspirin use during flu's (fever). Symptoms: Nausea, vomiting, hyperactivity, confusion, seizures, & coma, Increasing drowsiness, fatty infiltration Chemistry: elevated liver enzymes, NH3

CIRRHOSIS
Terminal stage of chronic liver damage

Most common cause:

Chronic excess alcohol ingestion

Hepatitis -particularly Hep B

Autoimmune ds

Difficult in coping with food,esp fatty meals Reduced capacity to metabolize drugs Itch

Fibrotic bands of connective tissue change the structure of the liver

Inflammation causes degeneration and destruction of liver cells

Tissue becomes nodular

Blood flow changes occur from compression by the fibrous tissue

Nodules block bile ducts and normal blood flow throughout the liver

Pathogenesis:
Hepatocyte injury leading to necrosis.
Alcohol, virus, drugs, toxins, genetic etc..

Chronic inflammation - (hepatitis). Bridging fibrosis. Regeneration of remaining hepatocytes Proliferate as round nodules. Loss of vascular arrangement results in regenerating hepatocytes ineffective.

Cirrhosis

Cirrhosis

Fibrosis

Regenerating Nodule

Ascitis in Cirrhosis

Micronodular cirrhosis:

Liver Biopsy Cirrhosis

Cirrhosis Clinical Features

Signs of liver ds and causes

Jaundice- diminished bilirubin secretion Fetor hepaticus- sulfur compounds produced by intestinal bacteria, not cleared by liver Spider angiomas, palmar erythema, & gynecomastiaelevated estrogen levels Ecchymoses- decreased synthesis of clotting factors Xanthomas- elevated cholesterol levels

 Hypoglycemia- decreased glycogen stores

Hypersplenism- portal hypertension

Encephalopathy, asterixis- portosystemic shunt, NH3 Hepatorenal syndrome (rapid decline of GFR)renal failure of unknown pathogenesis, kidneys are normal (may be transplanted), assoc c ascites, almost always fatal

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