An introduction to alcoholic liver disease part1
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An introduction to alcoholic liver disease
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An introduction to alcoholic liver disease part1
- 1. Alcoholic Liver disease: an introduction Pratap Sagar Tiwari, Lecturer, NGMC
- 2. Our Journey Alcohol & Liver Clinical Features Making a diagnosis Complications Portal Hypertension Hepatic encephalopathy Management
- 3. Causes of liver Dysfunction Infection Drugs Alcohol WilsonD Hemochromatosis Toxin Metabolic Liver Dysfn Infection Viral Bacterial Protozoal Malignancy Hepatoma Ischemic Obstructive Sepsis Autoimmune COngestive Others
- 4. Causes of liver Dysfunction Infection Drugs Alcohol WilsonD Hemochromatosis Toxin Metabolic Liver Dysfn Infection Viral Bacterial Protozoal Malignancy Hepatoma Ischemic Obstructive Sepsis Autoimmune COngestive Others
- 5. Alcoholic liver disease liver dysfunction because of Alcohol Liver Dysfunction What then ? Because of Alcohol How ?
- 6. Liver Dysfunction • What happens then ????? Dysfunction of liver Clinical/Pathological features
- 7. Functions that are affected.. • Detoxification • Bilirubin metabolism • Clotting factors Synthesis of • Thrombopoietin • Albumin • Angiotensinogen CHO /protein/ lipid metabolism Storage of Vitamins
- 8. Manifestations… Jaundice • Bilirubin metabolism • Clotting factors • Detoxification Coagulopathy Encephalopathy
- 9. ALD: Spectrum • The pathology of alcoholic liver disease consists of three major lesions, with the injury rarely existing in a pure form: (1) fatty liver, (2) alcoholic hepatitis, (3) cirrhosis.
- 10. Definition • Any pathological conditions of liver as a result of chronic and excessive alcohol consumption leading to a spectrum of conditions from ranging from asymptomatic fatty liver to alcoholic hepatitis to end-stage liver failure with jaundice, coagulopathy, and encephalopathy.
- 11. Etiology • Quantity and duration of alcohol intake are the most important risk factors involved in the development of ALD. • Women exhibit increased susceptibility to ALD at amounts >20 g/d. • Chronic infection with hepatitis C (HCV)) is an important comorbidity in the progression of ALD to cirrhosis in chronic and excessive drinkers. Quantity: • In men, 40–80 g/d of ethanol produces fatty liver; • 160 g/d for 10–20 yrs causes hepatitis/ cirrhosis. • Only 15% of alcoholics develop alcoholic liver disease.
- 12. Metabolism of Alcohol Ethanol Citric Acid cycle Oxidized Acetaldehyde alcohol dehydrogenase IB (ADH) CYP2E1 Catalase Tetrahydroisoquinolines CO2/ATP (TIQs) Acetaldehyde dehydrogenase enters Acetyl-coenzyme A synthetase acetyl-CoA Acetic acid Note: Disulfiram inhibits Acetaldehyde dehydrogenase
- 13. Alcohol & Acetaldehyde If not metabolized,releases free radicals Damage to embryonic neural crest cells = birth defects Alcohol forms “Adducts” that activate immune system cell injury Cytochrome CYP2E1 metabolizes ethanol to Acetate, releasing oxygen free radical radical induced injury Alcohol ↑ gut permeability ↑ endotoxin Kupffer cells activation THF a, IL6 Inflamation Alcoholic liver Disease Free Radicals:eg superoxide ( O2- ),hydrogen peroxide (H2O2), peroxynitrite Antioxidants are Vit A,C,E, Superoxide dismutase, beta carotene, glutathione
- 15. • End of Part one………….
Hinweis der Redaktion
- ethanol is oxidized to acetaldehyde mainly via the hepatic enzyme alcohol dehydrogenase IB (class I), beta polypeptide (ADH1B).Alcohol dehydrogenase: The name "alcohol dehydrogenase" sounds like quite a mouthful, but it is quite self-explanatory if we break it down into its component parts. "de-" is a prefix which means "to remove". We find it in such words as "dethrone" which means "to remove from the throne". "-ase" is a suffix which means "enzyme". Any time you see a chemical term which ends in the suffix "-ase" you know that you are dealing with an enzyme. "hydrogen" means "hydrogen" of course. So "de-hydrogen-ase" means "an enzyme which removes hydrogen atoms", and "alcohol dehydrogenase" means "an enzyme which removes hydrogen atoms from the alcohol molecule". The name alcohol dehydrogenase is sometimes abbreviated to ADH.The acetaldehyde released into the brain by the metabolism of alcohol by catalase has the potential to combine with neurotransmitters to form new compounds known as THIQs (tetrahydroisoquinolines, also sometimes called TIQs). Some researchers believe that THIQs are the cause of alcohol addiction and that the presence of THIQs distinguishes addicted drinkers from social drinkers.Acetaldehyde is a highly unstable compound and quickly forms free radical structures which are highly toxic if not quenched by antioxidants such as ascorbic acid (Vitamin C) and Vitamin B1 (thiamine). These free radicals can result in damage to embryonic neural crest cells and can lead to severe birth defects. Prolonged exposure of the kidney and liver to these compounds in chronic alcoholics can lead to severe damage.Acetaldehyde dehydrogenase does its work in the mitochondria of cells and removes a hydrogen atom from acetaldehyde to produce an acetic acid radical. This hydrogen atom combines with NAD+ to form NADH. This excess of NADH can lead to acidosis from lactic acid build-up and hypoglycemia from lack of glucose synthesis.The [NAD+]/[NADH] ratio in the cytosol of cells is a major regulatory mechanism. As the [NADH] increases, the ratio decreases.The citric acid cycle itself was finally identified in 1937 by Hans Adolf Krebs while at the University of Sheffield, for which he received the Nobel Prize for Physiology or Medicine in 1953