What are the 2 metabolic pathways for metabolizing ethanol?
- Major pathway = alcohol dehydrogenase in cytosol- Reaction reduces NAD to NADH + H+
- Alternate pathway = microsomal ethanol oxidizing system (MEOS) in smooth endoplasmic reticulum
- - Chronic alcoholics
- - Part of cytochrome P-450 enzyme system
How would ratio of NAD/NADH be affected by alcohol dehydrogenase pathway? (p.40)
Understand connection between alcohol intoxication and/or chronic alcoholism to following disturbances: fatty liver, hyperlipidemia, hypoglycemia, hyperlacticacidemia, and cirrhosis. (p.40)
- Fatty liver - oxidation of fatty acids --> increased cholesterol, fatty acids, TG formation --> accumulation of fat in liver
- Hyperlipidemia - because protein synthesis usually not involved, increased TG and cholesterol synthesis --> increased synthesis of VLDL --> hyperlipidemia
- Hypoglycemia - NAD+ necessary for gluconeogenesis; decreased NAD+ --> decreased gluconeogenesis --> decreased blood glucose
- Hyperlacticacidemia - Low NAD --> inhibition of TCA --> increased lactate --> lactic acidosis
- Cirrhosis - ETOH = fatty liver = hyperlipidemia = hypoglycemia = hyperlacticacidemia = cirrhosis
What is the relationship between protein breakdown and ammonia formation?
- Protein breakdown via deamination
- Ammonia released during deamination process
- Ammonia removed from bloodstream by liver --> urea – excreted by kidneys
How is ammonia normally detoxified by the body?
Liver turns ammonia into urea by combining ammonia with CO2.
What would be the potential consequence of toxic levels of ammonia on the brain?
- Term for chronic end-stage liver disease
- Chronic irreversible disease of liver in which normal architecture of entire liver destroyed by connective tissue and regenerative nodules
Clinical manifestations of cirrhosis.
- Decreased urea synthesis --> increased blood ammonia --> hepatic encephalopathy
- Decreased clotting factors (V, VII, IX, X), fibrinogen, and prothrombin --> hemorrhage
- Decreased albumin --> ascites
- Decreased hormone detoxification --> increased circulating estrogen --> gynecomastia, testicular atrophy, hair loss
- Altered liver structure --> decreased blood circulation through liver --> shunting --> undetoxified blood --> increased blood ammonia --> hepatic coma
- Portal hypertension --> varices, splenomegaly
- Impaired bile circulation --> jaundice
In hepatic cirrhosis, why is hypoalbuminemia associated with ascites? (p.42)
- Albumin = large protein produced in the liver
- One of main proteins involved in oncotic pressure of vascular system
- Oncotic pressure keeps water in vascular space
- No albumin --> decreased oncotic pressure
- Water shifts into interstitial spaces and cavities – peritoneal cavity
- Decreased albumin synthesis --> loss of vascular volume --> ascites