patho quiz 5.txt

  1. Definition of atelectasis
    Atelectasis, also known as collapse, is loss of lung volume caused by inadequate expansion of airspaces
  2. What are the three classes of atelectasis?
    • Resorption Atelectasis: Caused by aspiration of foreign bodies that prevent air from reaching distal airways
    • Compression Atelectasis: Caused by congestive heart failure associated with accumulations of fluid, blood, or air within the pleural cavity, such as pleural effusions
    • Contraction Atelectasis(Irreversible atelectasis): Caused by local or generalized fibrotic changes in the lung that hamper expansion and increase elastic recoil during expiration
  3. Pathogenesis of ARDS.
    • Step-1) Acid aspiration, trauma, or exposure to bacterial lipopolysaccharide�!They attack alveolar epithelium
    • Step-2) Pulmonary macrophage releases IL-8
    • Step-3) IL8-dependent chemotacsis of neutrophils into alveolus
    • Step-4) Neutrophil is activated by TNF and IL-1 released from macrophage
    • Step-5) Activated neutrophils produce: cellular protease, leukotrienes, and PAF (platelet activating factor)
    • Step-6) Lung tissue injury and inflammatory cascade are activated
  4. Definition of emphysema
    Refers to abnormal permanent enlargementof the air spaces distal to the terminal bronchioles accompanied by destruction of their walls without obvious fibrosis.
  5. 4. Definition of asthma
    Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning.
  6. Pathogenesis of emphysema
    • Step-1) Smoking increases the numbers of neutrophils and macrophages in alveoli
    • Step-2) Accumulated neutrophils release cellular protease (such as neutrophil elastase)which can be inhibited by serum a�1-anti-trypsin.
    • Step-3) In smokers, reactive oxygen (free-radicals) inactivate serum a�1- anti-trypsin, and thus, causes functional a�1-antitrypsin deficiency.
    • Step-4) Tissue proteolytic activity is gradually increased and consequently, emphysema results.
  7. Extrinsic asthma (atopic asthma): 70%
    • Serum IgE level usually elevated
    • Initiated by Type I hypersensitivity reaction
    • The most common type is atopic asthma
    • TH2 cells drive atopic asthma
  8. Intrinsic Asthma: 30%
    • Serum IgE level usually stable
    • Initiated by non immune mechanism
    • The cause of intrinsic asthma is not as clear as in patients with extrinsic asthma.
  9. Pathogenisis of asthma
    • Step-1) Inhalation (= Inspiration) of antigen.
    • Step-2) Type I Hypersensitivity Reaction (TH2 cells are sensitized)
    • Step-3) Sensitized TH2 cells release cytokines IL-4, IL-5, and IL-13.
    • Step-4) The released cytokines favor IgE synthesis, Mast cell proliferation, Eosinophils activation & growth. (3 major Key mediators of extrinsic asthma)
  10. Bronchitis
    persistent productive cough for at least 3 consecutive months and in at least 2 consecutive years.
  11. Pathogenesis of bronchitis
    • cigarette smoking
    • air pollutions (sulfur dioxide, nitrogen dioxide)
  12. bronchiestasis.
    Bronchiectasis is the permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic supporting tissue, resulting from or associated with chronic necrotizing infection.
  13. Pathogenesis of bronchiestasis:
    • Obstructions such as:tumor, foreign body
    • Chronic persistent infection: staphylococci, streptococci, pneumococci&
  14. Pathogenesis of pulmonary thromboembolism
    More than 95% of all pulmonary emboli arise from thrombi in the large deep veins of the lower legs.
  15. Risk Factors of pulmonary thromboembolism
    • prolonged bed rest (particularly with immobilization of the legs)
    • Surgery on the legs
    • Severe trauma (including burns or multiple fractures)
    • Congestive heart failure
    • Women in the period around parturition or who take birth control pills with high estrogen content
    • Disseminated cancer
  16. Pathogenesis of primary pulmonary hypertension.
    • Step-1) Vascular hyper-reactivitydue to endothelial dysfunction and autoimmune diseases
    • Endothelial dysfunction includes:
    • " reduced production of prostacyclin
    • " reduced nitric oxide
    • " increased generation of endothelin
    • Step-2) results in chronic vasoconstriction (= Vascular Sclerosis)
    • Step-3) Primary pulmonary hypertension
    • Also, studies from rare familial pulmonary hypertension indicates any acquired defects in the TGF-b�receptor (Transforming Growth Factor-beta receptor) signaling may be important in the pathogenesis of primary pulmonary hypertension.
  17. Pathogenesis of Secondary Tuberculosis
    Secondary TB is the pattern of disease that arises in a previously sensitized host. When host defenses are compromised, latent lesions are reactivated.
  18. 9. Pathogenesis of primary tuberculosis.
    • Primary TB is the form of disease that develops in a previously unexposed, and therefore unsensitized, person.
    • Caused by Mycobacterium Tuberculosis.
    • The most important risk factor for the development of tuberculosis is life style that weakens immune defense.
    • Major Steps of Progression
    • Step-1) Immunity to a Mycobacteria infection is primarily mediated by CD4/T cells.
    • Step-2) Primary TB induces hypersensitivity and increased resistance.
    • Step-3) The foci of scarring may harbor viable bacilli for years (or for life.)
    • Step-4) It will be reactivated at a later time when host defense are compromised (by immunosuppression).
    • Step-5) Uncommonly, the primary TB may develop without interruption into so-called progressive primary TB.
  19. Pneumothorax:
    the presence of air or gas in the pleural cavity
  20. 10. Pathogenesis of bronchogenic carcinoma.
    • Heavy smoker: 60-fold higher than nonsmoker Squamous and small cell carcinomas show the strongest association with tobacco exposure
    • Environmental factors: miners, Asbestos workers: 5-fold higher, Other exposures: arsenic, chromium, uranium, nickel, vinyl chloride, and mustard gas
    • Genetic changes: tumor suppressor genes, oncogenes (Table 139, p530)
    • oSCLC: >90% mutations in RB, p53;
    • oNSCLC: 20-30% mutations in K-Ras and EGFR
  21. Chylothorax:
    milky lymphatic fluid in the pleural cavity
  22. Hemothorax:
    the presence of blood in the pleural cavity
  23. Hydrothorax:
    serous fluid in pleural cavity
  24. Pathogenesis of nasopharyngeal carcinoma.
    EBV -associated tumor, especially in Chinese
  25. Definition of Hepatic Failure
    Hepatic failure is the most severe clinical consequence of liver diseases. The damage of hepatic functional capacity must exceed 80-90%
  26. Clinical Features of hepatic failure
    • Jaundice: build up of billirubin
    • hypoalbuminemia: leads to peripheral edema
    • hyperammonemia: due to defective hepatic urea cycle function
    • Life-threatening symptoms: Hepatic encephalopathy, Hepatorenal Syndrome
  27. Three Alterations that cause hepatic failure:
    • Massive hepatic necrosis: This is most often caused by Fulminant viral hepatitis, Drugs and chemicals: rifampin, isoniazid, carbon tetrachloride, mushroom poisoning
    • Chronic liver disease: most common route to hepatic failure
    • Hepatic dysfunction without overt necrosis: fatty liver of pregnancy, tetracycline toxicity.
  28. Cirrhosis
    Cirrhosis is a diffused process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Cirrhosis is among top 10 causes of death in the Western world.
  29. Pathogenesis of cirrhosis
    • Hepatocellular death
    • Regeneration
    • Progressive fibrosis
  30. Clinical Features of cirrhosis
    • Nonspecific manifestations: anorexia, weight loss, weakness..
    • Progressive liver failure
    • Development of portal hypertension
    • Development of hepatocellular carcinoma
  31. Definition of Jaundice:
    yellow discolorization of skin and sclerae (icterus) occurs when systemic retention of bilirubin leads to elevated serum levels above 2.0 mg/dL
  32. Causes of Jaundice:
    hemolytic anemias, hepatitis, and obstruction to the flow of bile.
  33. Common Clinical Course of hepatitis
    • Carrier state: without apparent disease, or with subclinical chronic hepatitis
    • Asymptomatic infection: serologic evidence only
    • Acute hepatitis: anicteric or icteric
    • Chronic hepatitis: with or without progression to cirrhosis
    • Fulminant hepatitis: submassive to massive hepatic necrosis
  34. Clinical Progression of Chronic Alcoholic:
    • (1) Hepatic steatosis: also known as fatty liver. Follow moderate consumption (8 beers/evening), small lipid droplets accumulate in hepatocytes. 99-100% heavy drinkers develop steatosis!
    • (2) Alcoholic hepatitis:Accumulation of lipid causes failure to export protein. This results in water intake and hepatocyte swelling, and necrosis. 15-20 yr of excessive drinking.
    • (3) Alcoholic cirrhosis: end stage
  35. Pathogenesis of alcoholic liver disease
    • " Increased lipid biosynthesis: due to generation of excess reduced nicotinamide-adenine dinucleotide by alcohol dehydrogenase and acetaldehyde dehydrogenase
    • " Impaired assembly and secretion of lipoproteins
    • " Increased peripheral catabolism of fat
    • " Increased induction of cytochrome P-450: leads to augmented transformation of other drugs to toxic metabolites
    • " Generation of free radicals
    • " Alcohol directly affects microtubular and mitochondrial function and membrane fluidity
    • " Neutrophil infiltration of the liver
    • " Antigenic alteration of hepatic proteins induced by alcohol and acetaldehyde
    • " Induced lipid peroxidation by acetaldehyde
  36. Pathogenesis of HCC: three major etiologic associations
    • (1)HBV and HCV infection
    • (2)Chronic liver disease (alcoholic liver cirrhosis)
    • (3)Hepatocarcinogens in food (primarily aflatoxins)
  37. How can HBV infection contribute to the pathogenesis of HCC?
    • " Repeated cycles of cell death and regeneration lead to increased cell proliferation
    • " Continuous cell divisions increase the accumulation of mutations
    • " HBV DNA integration may activate or inactivate certain genes contributing to cell proliferation
    • " HBV X-proteins disrupt normal growth control by activation of host cell protooncogenes and disruption of cell cycle control
    • " Certain HBV proteins bind to and inactivate the tumor suppressor p53
  38. Clinical features of HCC.
    • Most common liver tumors are metastatic carcinomas from colon, lung and breast.
    • Most primary carcinomas in the liver may present as silent hepatomegaly, they are often encountered in patients with cirrhosis of the liver who already have symptoms of the underlying disorder.
    • Rapid increase in liver size, sudden worsening of ascites, or the appearance of bloody ascites, fever, and pain call attention to the development of a tumor.
    • Laboratory studies are helpful but not diagnositc. Approximately 90% of patients have elevated serum levels of a�-fetoprotein. Unfortunately this is not a specific marker for HCC. However, very high levels (>1000 ng/ml) are rarely encountered except in HCC.
    • Median survival is 7 months.
    • Causes of death: profound cachexia, gastrointestinal or esophageal variceal bleeding, liver failure with hepatic coma, or rupture of the tumor with fatal hemorrhage.
    • Surgical resection of smaller tumors increases 5 years survival rate to 60% and immunization against HBV in high risk world population is the best hope for controlling this dismal disease.
  39. cholelithiasis.
    Gallstone refers to deposits of crystalline cholesterol monohydrate or bilirubin salts that occur within gall bladder.
  40. Pathogenesis of cholelithiasis
    • Four conditions must be met to permit the formation of cholesterol gallstones
    • (1) Supersaturation of the bile with cholesterol
    • (2) Establishment of nucleation sites by microprecipitates of calcium salts
    • (3) Hypomobility of the gallbaldder (stasis), which promotes nucleation
    • (4) Mucus hypersecretion to trap the crystals, enhancing their aggregation into stones
  41. Risk Factors of cholelithiasis:
    • (1) Age and gender: low in younger and high in older people, female is higher than male
    • (2) Ethnic and geographic: 75% in Native American-Pima, Hopi and Navajos (related to biliary cholesterol hypersecretion).
    • (3) Environment: estrogenic influences such as contraceptives, obesity, rapid weight loss. These factors likely increase cholesterol secretion.
    • (4) Acquired disorders: pregnancy, spinal cord injury  reduce gall bladder motility
    • (5) Heredity: variety of inborn errors of metabolism associated with impaired bile salt synthesis and secretion
  42. cholecystitis.
    Inflammation of the gallbladder and is almost always associated with gallstones. Cholecystitis is one of the most common indications for abdominal surgery in the US.
  43. Clinical Features of cholecystitis:
    • (1) Gallbaladder is usually enlarged (2-3 fold increase)
    • (2) Severe, steady upper abdominal pain often radiating to the right shoulder
    • (3) Fever, nausea, and others related to blockage of bile duct
    • (4) 25% patients require emergency surgery
    • (5) Severe complications could occur: bacterial superinfection with sepsis, gallbladder perforation, local abscess formation, diffuse peritonitis, and cardiac, pulmonary, renal or liver decompensation.
Card Set
patho quiz 5.txt
Pathophys quiz 5