Hepatic insufficiency

Before knowing any abnormality you should know about normal structure and functions.

Two type of cells in liver 

           1-  Hepatocyte

          2-Kupffer


Normal function of Liver

Hepatocyte
-Metabolism:   sugar,lipid,protein,vitamin, hormone
-Secretion and excretion: bile
-Synthesis: albumin, coagulation factors, profibrinolysin, anti-plasmin
-Catabolism: bate-oxidation of fatty acid
-Detoxication: toxin, drugs, hormones, metabolites

Kupffer
phagocytic and endocytic function in killing and clearing  bacterial, virus and endotoxins

1.   Metabolic dysfunction
Hypoglycemia(because of inhibit of gluconeogenesis)
 Hypoproteinemia:
     -   fibrinogen
     -   thrombinogen
     -   albumin
  Hypokalemia,  hyponatremia
      Energy crisis
2. Disturbed secretion and excretion
Hyperbilirubinemia ------Jaundice
3. Decreased detoxication and clearance
    poisons,  drugs,  hormones  
4. Decreased phagocytic and endocytic
    Dysfunction of Kupffer cells →Intestinal endotoxemia

Clinical manifestation of liver disorders

1. Portal hypertension
2. Ascites
3. Hepatic encephalopathy
4. Jaundice
5. Hapatorenal syndrome

1-Portal hypertension :                      

• Ascites
• Splenomegaly
• Hepatic encephalopathy
• Varices

2-Ascites

Ascites is the accumulation of fluid in the peritoneal cavity.

Reasons:
1. Serum albumin decrease.
2. Portal hypertension increases hydrostatic pressure.
3. Portal hypertension increases lymph production. 
4. Deranged liver metabolism permits the accumulation of hormones that regulate sodium and water balance.(ALD and ADH).
5. Mesenteric capillaries permeability increase.
6. Peripheral vasodilation.

3-Jaundice:
Jaundice is a yellow or green pigmentation of skin caused by hyperbilirubinemia(plasma bilirubin concentrations above 2.5 to 3.0mg/dl)

4-Hepatorenal syndrome:
Hepatorenal syndrome is a complication of advanced liver disease  with portal hypertension and functional renal failure.
Reasons:
1.Sudden decrease in blood volume
2.Inappropriate constriction of renal arterioles.

5-Portal hypertension
        Ascites         →       Effective circulatory
                                            blood volume↓
                                                   ↓
        
                   ↑  TxA2         → Renal vasoconstriction
Endotoxin → LTs                        ↓
                       Endothelin      Renal perfusion↓
                                                 GFR↓
                                                   ↓
                                    Functional renal failure

Disorders of the liver:

• Viral hepatitis
• Fulminant hepatitis
• Cirrhosis

Cirrhosis is an irreversible inflammatory disease that disrupts liver structure and function.

Causes:

1. Alcoholic liver disease
2. Non-alcoholic steatohepatitis
3. Chronic hepatitis C
4. Chronic hepatitis B
5. Auto-immune hepatitis
6. Primary biliary cirrhosis
7. Hereditary hemochromatosis
8. Wilson's disease
9. Cystic fibrosis
10. Hepatotoxic drugs or toxins

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