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81 Cards in this Set

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213
213
Definition of alcoholic
80g alcohol or more/day
Three routes of alcohol metabolism (1st step)
(all result in acetaldehyde) 1. ADH – most used 2. Microsomal cytochrome p450 (resp. for toxicity of tylenol w/ alcohol) 3. Catalase, H2O2
Degradation of Acetaldehyde
ALDH1, ALDH2 --> Acetate
ADH differences in asian
Everyone – ADH 1-5. Asians – ADH 2 metabolizes alcohol faster. Results in more acetaldehyde
2 main classes of ALDH
Cytosolic (ALDH1) vs mitochondrial(ALDH2 – mutated in asians)
Disulfiram
Antabuse. Blocks ALDH
Which pathway of alcohol degradation generates ROS's
Microsomal
Hepatotoxicity of acetaldehyde
1. Inc lipid peroxidation 2. Bind plasma membranes 3. Block ETC 4. Inhib Nuclear Repair 5. Block microtubule 6. Inc collagen
3 morphologies of Alc Liver Disease
Fatty liver, Alcoholic Hepatitis, Cirrhosis
Mech – Fatty liver
Increased FA synthesis, uptake, and triglyceride synth w/ decreased secretion and oxidation
Which type of fatty liver is in alcholics?
Usually macrovesicular
Mech – Alcohol hepatitis
Necrosis of liver cells (pericentrally) b/c of: Hyaline dep., Acetaldehyde, Drug enzymes, PMN's
Mallory bodies
Hyaline deposits in the liver in alcoholic hepatitis.
Megamitochondria
Large (LM visible) Mitochondria in liver disease
Clinical features of Alc Hep
1.Malaise, anorexia, fever. 2. RUQ pain, 3. Jaundice, leukocytosis Can progress to Fulminant Hepatic Failure.
Perivnular fibrosis
Fibrosis around central veinds.
Pericellular fibrosis
Fibrosis circling single groups of liver cells
Perisinusoidal Fibrosis
W/in sinusoids and space of Disse.
Iron is stored as:
Ferritin, hemosiderin
How much iron is required to overload the liver
40 -80 gms
3 common places for iron deposition
Liver, Heart, Endocrine organs
Hemochromatosis gene
HFE
Symptoms of hemochromatosis
1. Bronze skin 2. Pigmentary micronodula cirrhosis 3. Diabetes 4. CHF 5. Endocrine organ symptoms
Bantu Siderosis
African iron overload.
Diff b/t primary and secondary hemochromatosis
Prim: iron in cytoplasm Sec: Iron in kupffer cells.
Gene mutations (4) in a-antitrypsin deficiency
PiF (fast) PiM (med) PiS (slow) PiZ (very slow)
PiZZ
Common mutation in children needing liver transplantation.
Function of alpha1-antitrypsin
Inhibit elastase activity of leukocytes
Primary problem in a-1-antitrypsin def
Elastace degrades alveolar elastic tissue of lung. Also shows globules of buildup in liver.
Ceruloplasm
Copper transport protein – binds free ionic copper
Total body content of copper
180 mg
Wilson's disease
Genetic defect in copper transporting ATPase. Copper builds up in hepatic cytoplasm, lysosomes
Therapy of wilson's
Chelation
Common problems in wilson's
<10: Liver 10-18 Liver& neuro >18: Neuro
Kayser fleischer ring
Ring around the outside of iris from >> copper.
209
209
Neoplasms of the hepatocyte: (2)
Liver cell adenoma, Hepatocellular carcinoma
Neoplasms of the bile duct cell: (2)
Bile-duct adenoma, cholangiocarcinoma
Neoplasms of the hepatoic endothelial cell: (2)
Hemangioma, Hemangiosarcoma
Liver cell adenoma
Large, well circumscribed liver lesion. Sheets and cords resemble normal liver.
Diff in relationship of HCV & HBV to HCC
HBV is stronger rel. and encorporates into genome causing HCC. HCV is via oxidative/inflammatory stress.
Two most common gene mutations for HCC
P53 (via aflatoxin) , P16
Common mutations for HCC mets
Rb, P21
4 common features in HCC
Hyperchromatosis, Nuclear pleomorphism, Apoptotic bodies, Necrosis (also multiple cell thick cords.)
Two serum markers for HCG
Alpha-fetoprotein & Gamma-carboxy-prothrombin
Alpha-fetoprotein tolerances
<10 good. 10-500 grey >500 HCC
Systemmic symptoms of HCC
Hypoglycemia, Erythrocytosis, Hypercalcemia
Cholangiocarcinoma: Causes
Flukes – cause chronic inflammation.
Cholangiocarcinoma: Morphology
Excess proliferation of glandualar structures.
208
208
Start & end of intrahepatic biliary system
Start: Bile canaliculus. End: Hepatic ducts
Start & end of extrahepatic
Fissure of the hepatic ducts to Duodenum
Sphincter of Oddi
Sphincter at the common bile duct and the duodenum
Ampulla of vater
Also at the common bile duct and the duodenum
What biliary diseases are pathologic at the canaliculus?
1. Drugs 2. Cholestasis of pregnancy 3. Benign Postoperative cholestasis 4. Benign recurrant cholestasis 5. Cholestasis of Hodgkins
Where does primary biliary cirrhosis affect?
Interlobular bile duct
Where does sclerosing cholangitis affect?
Large intrahepatic duct.
What effect does bile obstruction have on the canaliculi?
Villi become shorter & smaller (and dilation)
4 main effects of cholestasis
1. Pruritis (via bile & nuerogenic) 2. Jaundice/Xanthomas 3. Fat & fat vitamin malabsorption 4. Liver damage
4 effects of fat malabsorption w/ cholestasis
1. Steatorrhea 2. Bone disease 3. Coagulopathy 4. Night Blindness
Primary biliary cirrhosis - Cause
Idiopathic. Theory is antimitochondrial antibodies.
Primary biliary cirrhosis – clinical
Cholestasis, portal hypertension. Way more common in women (40-60)
4 Histological stages of PBC
Stage 1: Florid duct lesions Stage 2: Ductular proliferation Stage 3: Fibrosis Stage 4. Cirrhosis
Which stage of PBC shows granulomas?
Stage 1.
PBC associated symptoms
Dry eyes, dry mouth. Sometimes rheum. Arth., thyroiditis, raynaud's
PBC lab findings
Inc. Alk phosphotase, Inc bilirubin, Inc immunoglobins
Primary sclerosing cholangitis Def
Nonspecific inflammatory fibrosis of wall of biliary tree (--> stenosis, ectasia)
Primary scleroising cholangitis – Clinical
Fatigue, UQ pain, jaundice, prog liver failure. Typically over 50 yrs
PSC – associated disorders
Ulcerative colitis, Crohns, Retroperitoneal fibrosis, Reidels thyroiditis, Orbital pseudotumor
Causes of PSC
1. Infection (portal endotoxemia w/ UC) 2. Genetic 3. Immune – PANCA, hypergammaglobulinemia, or Tcell
PSC Lab findings
Inc alk phosphatase, Inc ANCA, beaded appearance of biliary tract on ERCP
Cholelithiasis – Def
Gall stones. More common in women, often asymptomatic (if symptoms: colic pain, cholecystitis)
What falls out of solution in gall stones?
Bilirubin & cholesterol
What naturally prevents gall stones?
Lecithin & bile
3 steps in gallstones.
1. Supersaturate bile. 2. Nucleation, 3. Growth.
Risk factors for gall stones
Obesity, High fat diet, Hyperlipidemia, Drugs, Genetic.
3 types of gall stones
1. Cholesterol 2. Pigment 3. Mixed
Calculous cholecystitis
Acute cholecystitis b/c of bacterial infection.
Adenocarcinoma of the galladder – def
Adenocarcinoma, typically in 6th/7th decade women.
Courvoisier's Law
Palpable gallbladder due to biliary obstruction, often w/ pancreatic cancer.