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How does ethanol contribute to the patho of alcoholic cirrhosis?
Ethanol metabolism results in oxygen radicals, DNA damage, and acetaldehyde
Ethanol causes fat to be deposited (fatty liver)
Ethanol also stims inflammatory response, leading to large accumulations of collagen
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How does acetaldehyde contribute to the patho of alcoholic cirrhosis?
Acetaldehyde stims hepatic fibrosis
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Cirrhosis is an ___-stage liver disease.
End-stage
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Will you still see lobules in a liver with cirrhosis?
Cirrhosis results in masses of scar tissue, nodules (islands of hepatocytes), and disruption of the architecture of the entire liver so no more lobules.
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What are the 2 most common causes of cirrhosis of the liver?
Alcoholic liver disease
Chronic hepatitic (usually HBV or HCV)
Less common causes: episode of liver necrosis, drug/chemical effects, genetic disease, chronic bile duct obstruction
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Cirrhosis is progressive firbosis of the liver which results in:
Sever disruption of blood flow (portal blood flow)
Hepatocytes don't properly filter the blood (impaired diffusion)
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What are the 2 major functional disturbances that occur with cirrhosis of the liver?
Impaired liver function (including changes from excess estrogen)
Portal hypertension
(may also lead to liver cancer)
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What is portal hypertension?
Increased pressure in the portal system due to increased portal blood flow or increased resistance to hepatic perfusion.
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What causes pre hepatic portal hypertension?
Thrombi and narrowing of a vein
splenomegaly shunting excessive blood
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What is responsible for hepatic portal hypertension?
Cirrhosis
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What is responsible for post hepatic hypertension?
Severe r. heart failure
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What are the major clinical consquences for portal hypertension?
Ascites
Shunting of blood into portal collaterals
Hepatic encephalopathy
Congestive splenomegaly
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What is ascites? What does it result in?
High portal v. pressure causes leakage out of capillaries.
Results in hypoalbuminemia
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Where is albumin produced?
Liver
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What is shunting of the blood in the liver? What are some common pathways?
Portal v. collateral circulation (anastomoses) develop to bypass the obstructed liver.
Stomach and spleen, esophageal v. (esophageal varices which freq rupture), rectal area
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What are 3 mophologic categories of liver failure?
Massive hepatic necrosis: direct toxic damage to hepatocytes
Chronic liver disease: ending in cirrhosis
Hepatic dysfunction: without overt necrosis
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What results in liver failure decomopenation?
Systemic infections
Electrolyte imbalance
Severe stress
GI bleeding
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What are the clinical signs of liver failure?
Jaundice (liver isn't processing bilirubin)
Hypoalbuminemia (ascites)
Hyperammonemia (hepatic encephalopathy)
Hyperestrogenemia
Coagulopathy
Susceptiple to failure of other organ systems
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What is hepatic encephalopathy?
A spectrum of disturbances in consciousness ranging from subte changes in behavior to confusion, stupor, coma, or death.
Due to shunting of blood around diseased liver, exposes brain to ammonia which would've normally been filtered through liver
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What is cholelithiasis?
Formation of cholesterol stones within gallbladder that occurs to 20% of the population
Due to deficient amount of bile salts in relationship to amount of cholesterol
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Describe the incidence rate of cholelithiasis
Higher in women, women with alotta kids, women on the pill, and fat women
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What comoplications do gallstones cause?
If a stone becomes lodged in the cystic duct:
Biliary colic (severe abd. pain w. smooth m. spasm)
Cholecystitis
Obstructive jaundice (bile back-up in liver)
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What are the 2 types of biliary cirrhosis?
Primary: slowly progressive chornic inflammation and destruciton of bile ducts, autoimmune disease against bile duct epithelium, jaundice
Secondary (obstructive): longstanding blockage of bile ducts, results in cholestasis, followed by portal tract inflammation/scarring
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What is cholestasis?
Retention of bile resulting from hepatic dysfunction or biliary obstruction
Back up in the bile ducts, icnreased pressure indces edema and inflammation
Elevated serum alkaline phosphatase (indication of liver cell death)
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When does intrahepatic cholestasis occur?
With cirrhosis of the liver or with a tumor
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What are primary carcinomas of the liver more common in Asian and African countries?
Increased incridence of chronic HBV carriers
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Why is the liver a common site of metastatic carcinoma?
Dual blood supply and its highly vascular
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What are the 3 hormones produced by the pancreas?
Alpha: glucagon
Beta: insulin
Delta: Somatostatin
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What causes acute pancreatitis?
Escape of pancreatic juice from its ducts into the pancreas (harmful digestive enzymes)
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What are the clinical signs of acute pancreatitis?
Severe abd pain
Vomiting
Has a high mortality rate
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What are 2 risk factors for acute pancreatitis?
Gallbladder disease
Exc. alcohol comsumption
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What is cystic fibrosis of the pancreas?
Abnormal cholide transport across cell membranes causes mucos to become abnormally thick and tends to precipitate and obstruct pancreatic ducts.
Causes pancreatic juice to accumulate and the cystically dilated ducts become surrounded by fibrous tissue
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What is maldigestion?
failure of chemical process to digestion
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What is malabsoption?
Failure of intestinal mucosa to absorb/transport digested nutrients
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What is pancreatic insufficiency?
Deficient production of pancreatic digestive enzymes leading to poor digestion (esp of fats)
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What is lactase deficiency?
Undigested lactose; gas formation and osmotic diarrhea
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What is bile salt deficiency? What vitamins are affected?
Poor absoptionof fats and fat-soluble vitamins
A: night blindness
D: decreased calcium absorption, b. deminerilization
K: blood clotting deficiency
E: testicular atrophy and neurologic defects in children
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What causes bile salt deficiency?
Advanced liver disease
Obstruction of common bile duct
Disease of ileum
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Where do carcinomas occur in the pancreas?
In the head of the pancreas
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What can tumors of the pancreas cause?
Obstruction of the bile duct resulting in obstructive jaundice
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What is a insulinoma?
Benign tumor of islet cells may cause episodes of severe hypoglycemia, can result in seizures
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What can cause of hyperglycemia?
Diabetes mellitus
Chronic pancreatic disease
Endocrine disease
Various drugs
Rare hereditary disease
All result in hyperglycemia, ketoacidosis
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What can cause hypoglycemia in diabetics?
Reduced intake of flood
Increased physical activity
Insulin overdose
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What results from hypoglycemia?
Confusion, loss of consciousness, convulsions, coma, death
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What is common with both diabetes insipidus and mellitus?
Polyuria and polydipsia
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What causes diabetes insipidus?
Pituitary dificiency of ADH
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What is diabetes mellitus?
Chronic disorders of carb, fat, and protein metabolism
Defective insulin secretory response causes imparied carb use which results in hyperlycemia
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What is common feature of both types of diabetes mellitus?
Hyperglycemia
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What is primary diabetes mellitus?
Type I and II
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What is secondary diabetes mellitus?
Caused by chronic pancreatitis. hormonal tumors, coticosteroid drugs, many many other different types of diabetes
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What do beta cells of the pancreatic islets do?
Syntehsize and store insulin in granules
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Glucose is a strong trigger for ____ release.
Insulin
A rise in blood glucose causes immediate insulin release, is the stimulus persists, so down the active synthesis of insulin
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_____ enables transport of glucose to amino acids across cell membranes.
Insulin
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How does sinulin affect the level of serum glucose?
Insulin decreases the level of serum glucose by promoting its influx into the liver and skeletal m. where it is used as glycogen
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What are 3 things insulin directly stimulates?
Influx of glucose into skeletal and cardiac m. cells
Conversion of gluxos to triglycerides in fat cells
Syntehsis of proteins from amino acids
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What does insulin binding to its receptor site on target cells stimulate?
GLUTs (glucos transport units) to move from the golgi apparatus to the plasma membrane
Facilitates glucose uptake by the cell
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Relate the differences of Type I and Type II diabetes
Type I:
<20 yrs, decreased blood insulin, ketoacidosis, autoimmune, 10-205
Type 2:
>40 yrs, obesity, insulin resistance, 80-80%
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What 3 mechanisms are responsibile for the destruction of islet cells?
Genetic susceptibility
Autoimmunity
Environmental insult
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Describe the automimmune effects of type I diabetes
Chronic automimmune attack against beta cell may exist for years before disease presents itself (even if it seems abrupt)
Signs don't show until 90% of beta cells have been destroyed
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What are some theories for the environmental factors that contribute to type I diabetes
Could be immune response against virus that shares amino acid sequence with a beta cell
or automimmunity could be triggered by damage to beta cell
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What is the main pathogenic factor for type II diabetes?
Genetic factors play a large role
Metabolic defects such as derangement of beta cell secretion of insulin or inability of peripheral tissue to respond to insulin
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