Disorders of liver disease - USMF failure-converted...liver destruction • Alcoholic cirrhosis •...
Transcript of Disorders of liver disease - USMF failure-converted...liver destruction • Alcoholic cirrhosis •...
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Patho physiology of liver
disease
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Major hepatic
functions
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Metabolic Functions of
the Liver
• Carbohydrate Metabolism
• Protein synthesis and
Conversion of Ammonia to
Urea
• Lipid Metabolism
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Defects in Amino Acid
Metabolism
• Oxydative deamination
• Transamination
• Diminution of the blood urea nitrogen level
• Increase in the amount of circulating ammonia
• Hepatic coma
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Ketoacid
• It can be modified and cycled
through the Krebs cycle,
producing ATP;
• It can be converted into glycogen,
fatty acids, or transaminated;
• It can be transaminated,
converting it to another kind of
keto
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Impaired Production of
Clotting Factors
• Fibrinogen, prothrombin,
Factors 5, 7, 10
• Coagulation defects
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Defects in Carbohydrate
Metabolism
• Glucose tolerance like in
diabetus mellitus
• Hyperglycemia
• Hepatic diabetes
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Defects in Lipid
Metabolism
• Deposition of triglycerides –
”fatty liver”
• Diminution in the rate of
synthesis of cholesterol
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Bile production and
cholestasis
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Bilirubin formation, circulation, and
elimination
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Cholestasis
• 1. Intrahepatic disorders
• Cystic fibrosis
• Granulomatosis
• Drug side effects (allopurinol,
sulfonamides)
• High estrogen concentration
(pregnancy, contraceptive pill)
• 2. Extrahepatic bile duct
occlusion
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Cholestasis
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Types of jaundice
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General features of
hepatic diseases
• 1. metabolic
• 2. toxic
• 3. microbial
• 4. circulatory
• 5. neoplastic insults
• Major primary diseases
• viral hepatitis
• alcoholic liver disease
• nonalcoholic fatty liver disease
(NAFLD)
• hepatocellular carcinoma (HCC)
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General features of
hepatic diseases
• Secondary diseases:
• cardiac failure
• disseminated cancer
• extrahepatic infections
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PATTERNS OF HEPATIC INJURY
• Hepatocyte degeneration and
intracellular accumulations
• Hepatocyte necrosis and apoptosis
• Inflammation
• Regeneration
• Fibrosis
• Clinically:
• hepatic failure
• cirrhosis
• portal hypertension
• jaundice
• cholestasis
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Hepatic failure
The destruction of overall
hepatic function
2000 cases per year US
80-90% of HF
Mortality is 80%
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Alterations that cause LF:
• Acute liver failure (fulminant LF)
• Chronic liver disease
• Hepatic dysfunction without overt
necrosis
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Hepatic failure
• Sudden and massive
liver destruction
• Alcoholic cirrhosis
• End stage of
progressive chronic
damage
• Hematologic
disorders
• Endocrine
disorders
• Skin Disorders
• Hepatorenal
Syndrome
• Hepatic
Encephalopathy
• Hepatopulmonary
syndrome
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Causes of acute (fulminant) hepatic
failure
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Hepatic failure
• Jaundice
• Hypoalbuminemia
• Hyperammonemia
• Fetor hepaticus
• Portosystemic shunting
• Palmar erythema
• Spider angiomas
• Hypogonadism
• Gynecomastia
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Hematologic Disorders
• Anemia (blood loss, excessive
red blood cells destruction,
impaired formation of red blood
cells)
• Thrombocytopenia
(splenomegaly)
• Coagulation defects (decline of
factors 5, 7, 9, 10, prothrombin,
fibrinogen)
• Mal absorbtion of the fat-
soluble vitamin K
• Leucopenia
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Endocrine Disorders
• Disturbances in gonadal sex
hormone function
• Menstrual irregularities , loss of
libido, sterility
• Testes atrophy, loss of libido,
impotence, gynecomastia
• Salt and water retention
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Skin disorders
• Vascular spiders
• Telangiectases
• Spiders angiomas
• Spider nervi
• Palmar erythema
• Clubbing of the fingers
(cirrhosis)
• Jaundice
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Hepatic
encephalopathy
• Lack of mental
alertness to
confusion, coma,
and convulsions
• Flapping tremor
called asterixis
• Euphoria
• Irritability
• Anxiety
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Hepatic
encephalopathy
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Hepatorenal Syndrome
• Azotemia
• Increased
serum
creatinine
levels
• Oliguria
• Hepatic
encephalop
athy
• Coma
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Hepatopulmonary
syndrome (HPS)
• Chronic liver disease
• Hypoxemia
• Intra-pulmonary vascular
dilations
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Cirrhosis
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Increased resistance to flow in the
portal venous system and
sustained portal vein pressure
above 12mm Hg
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Ascites
The fluid amount in the
peritoneal cavity is
increased
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The mechanisms of
ascites
• Increase in capillary pressure
due to portal hypertension
• Obstruction of venous flow
through the liver
• Salt and water retention by the
kidney
• Decreased colloidal osmotic
pressure due to impaired
synthesis of albumin by the
liver
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Spontaneous bacterial
peritonitis
• Fever
• Abdominal pain
• Worsening of hepatic
encephalopathy
• Diarrhea
• Hypothermia
• Shock
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Spleno megaly
Hyper splenism-a decrease
in the life span of all the
formed elements of the blood
and a subsequent decrease
in their numbers, leading to
anemia, thrombocytopenia,
and leukopenia
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Porto systemic Shunts
• Gradual obstruction of
venous blood flow in the
liver
• The pressure in the
portal vein increases
• Large collateral
channels develop
between portal and
systemic veins that
supply the lower rectum
and esophagus and the
umbilical veins of the
falciform ligament
•
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Thank you for your
atention