Friday 3 October 2014

LIVER - functional anatomy, functions of liver, detoxification ( steps involved & mechanism), liver function test.


LIVER –STRUCTURE AND FUNCTION


INTRODUCTION

  •  It is the largest organ in the body.
  •  It is involved in secretory and excretory function.
  •   It weighs about 1.3 to 1.5 kg, it is pinkish-brown in color, “boomerang shaped” organ.
  •  It is located in upper and right side of the abdominal cavity, right side of the stomach, just below diaphragm.
  •  Liver holds 13 % of body’s blood at any given moment.

The liver is the largest parenchymal organ, lying just below the diaphragm.
The right lobe (at the left in the photograph) is larger than the left lobe.
The falciform ligament is the rough dividing line between the two lobes.

FUNCTIONAL ANATOMY

  •   Important function of liver is to serve as a filter between blood coming from the gastrointestinal tract and blood in the rest of body.
  •  Blood from intestines and other viceral organs reach the liver via the portal vein.
  •  Blood percolates in sinusoid between plates of hepatic cells and eventually drains into hepatic veins, which enter the inferior vena cava.
  •  Bile is formed on the other side at each plate. The bile passes to intestine via the hepatic duct.
 

 

1. HEPACATI LOBES:-
     Liver is made up of many lobes called hepatic lobes. Each lobe consists of many lobules called hepatic lobule.

2.  HEPATIC LOBULE:-
     It is the structural and functional unit of liver. there are about 50,000-100,000 lobules in the liver. The lobule is honey comb like structure. It is made up of liver cells called hepatocytes.

3.  HEPATOCYTES AND HEPATIC PLATES:-
     Hepatocytes are arranged in columns which form the hepatic plates. each plate is made up of 2 columns of cells. 

4.  HEPATIC ARTERY:-
      it arises directly from aorta and supplies  pure arterial blood to liver.it then enters portal triad.

5.  PORTAL VEIN:-
      It is formed by superior mesenteric vein and splenic vein.It brings deoxygenated blood from stomach, intestine, spleen and pancreas.

6.  HEPATIC VEIN:-
      The substances synthesized by hepatic cells, waste products and CO2 are discharged into sinusoide.


 FUNCTIONS OF LIVER


  • Carbohydrate metabolism
Glycolysis
Glycogenolysis –catabolism of glycogen
Gluconeogenesis-metabolic pathway that results in generation of glucose by non carbohydrate source.

  •  Lipid metabolism.
  •  Detoxification- removal of toxic property of harmful agent.
  •  Metabolism of vitamins A, D, K&B.
  •  Secretion of bile.
  •  Clotting factors, prothrombin- synthesis.
  •  Protein metabolism
anabolism
deamination – removal of amine group from molecule
Urea formation- urea cycle.

Excretory function-excretion of cholesterol, bile pigments, heavy metals, toxins.
Hemolytic function- the senile RBCs after the life span of 120 days are destroyed in kuffer’s cells.
Inactivation of hormones-liver categorizes hormones such as cortisol, insulin, glucogon, estrogen, parathormone.
OTHER FUNCTIONS

**   Breakdown of insulin and other hormones.
**   Liver breaks down hemoglobin, creating metabolites that are added to bile pigment.
**   In first trimester fetus, the liver is the main site of red blood cell production.
**   Liver stores multitude of substances, including glucose in the form of glycogen, vitamin B12, iron and copper.

Detoxification

The removal of toxic property of the harmful agent is known as detoxification.
**  Liver plays an important role in detoxification of blood originating from the gut or elsewhere in the body.
**  The reticuloendothelial cells (Kuffer’s cells) of the liver play an important role in defense of body.

Detoxification occurs by 2 ways
1) By total destruction of substances by means of metabolic degradation.
2) By converting toxic substances into non toxic materials by means of conjugation with glucoronic acid or sulphates.





Steps involved in detoxification:

 * The foreign bodies like bacteria or antigens are swallowed and digested by reticuloendothelial cells of liver by means of phagocytosis.
 * In phase I large number of cytochrome P450 enzyme is expressed in hepatocytes, these convert xenobiotic and other toxins to inactivate. it includes oxidation, hydroxylation and reactions mediated by cytochrome P450s.
* In phase II ultimately metabolites are secreted into bile for elimination via gastrointestinal tract.




LIVER FUNCTION TESTS

Steps involved
1.  Detect the presence of liver diseases
2.  Distinguish among the different types of liver diseases
3.  Gauge the extent of known liver damage
4.   Follow response to treatment.

TESTS BASED ON DETOXIFICATIONS AND EXCRETORY FUNCTIONS:

1. SERUM BILIRUBIN – a breakdown product of porphyrin ring of heme containing proteins (conjugated, unconjugated)

 unconjugated/indirect – insoluble in water; bound to albumin in the blood   

 conjugated/direct – water soluble; excreted in kidneys.
Normal serum bilirubin concentration: <17 micromol/L.Up to 30% of the total is direct-reacting.
Elevation of unconjugated fraction of bilirubin: rarely due to liver disease.

Hemolytic disorder-genetic conditions: Crigler-Najjar,Gilbert Syndrome
Elevation of conjugated bilirubin: almost always implies liver or biliary tract disease.

2. URINE BILIRUBIN:
 presence of bilirubinuria à liver diseases à almost 100% accurate

3. BLOOD AMMONIA: elevated  in advanced liver diseases with significant muscle wasting à Hyperammonimea.
There is a poor correlation between either the presence or the degree of acute enceph and elevation of blood ammonia
There is a poor correlation of the blood serum ammonia and hepatic function.

4.     SERUM ENZYMES
      2 categories of serum enzymes:

§  Enzymes whose elevation in serum reflects damage to hepatocytes
§  Enzymes whose elevation in serum reflect cholestasis
§  Enzymes that do not fit precisely into either patterns.                  

ENZYMES THAT REFLECT DAMAGE TO HEPATOCYTES

AMINOTRANSFERASES:
Sensitive indicator of liver cell injury and most helpful in recognizing acute hepatocellular diseases such as hepatitis. These enzymes are normally present in the serum in low concentrations. They are released in the blood in greater amounts when there is damage to the liver cell membrane resulting in increased permeability.

AST (Aspartate aminotransferase): liver, cardiac, skeletal, kidneys, brain, pancreas, lungs, leukocytes and erythrocytes.

ALT (Alanine aminotransferase): found primarily in the liver.

ENZYMES THAT REFLECT CHOLESTASIS

* Alkaline phosphatase and 5’ nuleotidase: found near the bile canalicular membrane of hepatocytes
Gamma Glutamyl Transpeptidase: Endoplamic reticulum and in bile duct epithelial cells à lacks specificity.

Alkaline phosphatase:
Liver, bone, placenta, less commonly small intestine
Elevation of liver-derived alkaline phosphatase is not totally specific for cholestasis and a less than 3 fold elevation can be seen in any type of liver disease.

TESTS THAT MEASURE BIOSYNTHETIC FUNCTION OF THE LIVER

SERUM ALBUMIN: synthesized exclusively by hepatocytes has a slow turn over not a good indicator of acute or mild hepatic dysfunction

 SERUM GLOBULINS: group of proteins made up of gamma globulins (immunoglobulins) produced by B lymphocytes and alpha and beta globulins produced primarily in hepatocytes
Increases in the IgM levels are common in primary biliary cirrhosis
Increases in the IgA levels occur in alcoholic liver diseases.

COAGULATION FACTORS:
With the exception of Factor VIII, the blood clotting factors are made exclusively in hepatocytes.Because of their rapid turnover, measurement of the clotting factors is the single best acute measure of hepatic synthetic function and helpful in both the diagnosis and assessing the prognosis of acute parenchymal liver disease

v Serum prothrombin time: collectively measures factors II, V, VII, and X
Marked prolongation of prothrombin time, >5s above control is a poor prognostic sign in acute viral hepatitis and other acute and chronic liver diseases.


RELATED PICTURE:



MORPHOLOGICAL & ANATOMICAL FEATURES OF LIVER











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