Repro/GI wk 3
Terms
undefined, object
copy deck
- 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.