PathoPhys Test 2

  1. What is the anatomical disorder of achalasia? (p.9)
    • Incomplete relaxation of LES (lower esophageal sphincter) when swallowing and decrease in distal esophagus peristalsis
    • Esophagus enlarges over time
    • Stasis of food leads to putrefaction, infections, and ulcerations of mucosa
  2. What is esophageal reflux? (p.10)
    • Regurgitation of gastric juices into the esophagus that can lead to ulceration and erosion of mucosal lining
    • GERD commonly associated with transient relaxation of LES
    • NOT associated with swallowing
  3. When is GERD (esophageal reflux) most likely to occur?
    • After meals
    • When gastric emptying slowed due to digestion of fatty substances
    • Other causes include gastric intubation, radiation, alcohol intake, cigarette smoking, CNS-depressant drugs (morphine, valium), hiatal hernias, pregnancy
  4. What factors contribute to mucosal damage in GERD?
    • Length of time flux in contact with mucosa
    • Amount of HCl and pepsin in gastric juice (+ bile salts increases damage)
    • Ability of esophageal mucosa to repair itself
  5. What common measures are indicated for management of reflux? (p.12)
    • Elevate HOB
    • Avoid bedtime snacks and fatty foods
    • Stop smoking
    • Decrease alcohol intake
    • Medications: H2-receptor blockers; proton-pump inhibitors
    • Fundoplication
  6. How would you describe Barrett's Epithelium and its significance? (p.11)
    • Metaplastic cellular changes in esophagus secondary to GERD or other chemical or mechanical offenders
    • Pre-cancerous cells - must be watched closely
    • Outcome of long-standing esophageal reflux
    • Normal squamous mucosa replaced by columnar epithelium
    • Metaplasia --> dysplasia --> cancer
  7. A linear tear in the gastroesophageal wall associated with episodes of retching is referred to as what syndrome?
    • Mallory-Weiss syndrome
    • Characterized by linear tear in gastroesophageal junction
    • NOT disease
    • Mechanical tear
    • At risk: hiatal hernia, alcoholism, cigar smoking, tobacco chewing
  8. Acetylcholine effect on parietal cell:
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    • Sight of smell of food --> secretion of ACh by vagus nerve
    • Bind M3 receptors on parietal cell
    • Activates Ca2+ channels
    • Movement of Ca2+ into parietal cells
    • Augments H+ - K+ ATPase pump (proton pump)
    • Reabsorbs K+ and secretes H+ ions; Cl- passively diffuses --> HCl secretion
  9. ECL cells effect on parietal cells
    • *Most significant*
    • ACh cells bind M1 receptors on ECL cells --> Histamine secretion
    • Histamine binds H2 receptors on parietal cells
    • Histamine H2 receptor binding activates enzyme adenylate cyclase
    • Activates ATP-driven H+-K+ pump
    • Secretes H+ and reabsorbs K+; Cl- diffuses passively into lumen combined with H+ forms HCl
  10. Gastrin effect on parietal cells
    • Food in stomach increases antral pH (pH >4)
    • Stimulates gastrin secretion
    • Circulates in bloodstream then acts on gastrin receptors (G receptors) on parietal cells and ECL cells
    • In parietal cells, gastrin mobilizes intracellular Ca2+, which like ACh, augments proton pump
    • On ECL cells, gastrin stimulates release of histamine --> increases HCl output
  11. At what pH will pepsin have maximal proteolytic activity? (p.15-16)
    pH < 3
  12. What is the goal for PPIs on gastric pH for healing of ulcers?
    • Increase gastric pH > 4
    • Inhibit proton-pump directly
  13. What are the most effective drugs for decreasing the secretion of HCl?
    Proton-pump inhibitors = 95% effective
  14. What are the potential adverse effects of proton-pump inhibitors?
    • Adverse effects have to do with increased pH >4.
    • Once pH>4, iron salts and B12 not well absorbed
    • Bacterial and viral infections also increase
  15. Factors associated with pathogenesis of acute gastritis. (p.17)
    • Erosive gastritis
    • Involves focal necrosis of mucosa
    • Leads to erosion into deeper tissues
    • Then acute ulcer, inflammation, and hemorrhage
  16. Mechanism of injury of acute gastritis. (p.17)
    • Chemical irritants - ASA, NSAIDs, ETOH
    • Severe illness - trauma, sepsis, surgery, burns, hypothermia, bile reflux, drugs given during course of illness
  17. Cushing's Ulcer (p.18)
    • Response to traumatic/surgical injury to CNS or rapidly progressing ICH
    • Brain injury --> increased vagal tone & increased acid secretion in stomach
  18. Curling's Ulcer (p.18)
    • Occurs in severely burned patients, in shock, sepsis, and other forms of trauma
    • Probably due to autonomic response to shock
    • Shunts blood from GI tract to more critical areas --> ischemia --> inhibits PG synthesis --> impairs mucus-bicarb layer
  19. Autoimmune gastritis
    (chronic gastritis)
    • Antibodies attack parietal cells --> destruction of gastric glands
    • Causes parietal cell malfunction and eventual absence of HCl secretion (achlorydia) and intrinsic factor secretion (needed for B12 absorption)
    • Lack of B12 causes impaired folic acid metabolism, needed for DNA synthesis of new cells.
    • Ultimately leads to atrophy of gastric epithelium.
  20. Infectious gastritis
    (chronic gastritis)
    • Primarily Helicobacter pylori (H. pylori), gram-negative bacteria
    • Causes chronic gastritis of antrum and body of stomach
    • H. pylori burrows through mucus layers, attaches to epithelial cells, and colonizes
    • H. pylori damages cells by producing urease, which increases ammonia levels in stomach, increasing pH
    • H. pylori disrupts bicarb layer with mucolytic enzymes
  21. What is the gold standard for diagnosing peptic ulcers and H. pylori? (p.21)
    Biopsy and rapid urease test (CLO test - campylobacter-like organism)
  22. What is the least invasive test to document H. pylori and document bacterial eradication
    after treatment?
    Urea breath test
  23. Describe Zollinger-Ellison syndrome. How is it related to peptic ulcer disease? (p.20)
    • Endocrine syndrome affecting islet cells of pancreas (pancreatic tumor)
    • Produces gastrin, which increases secretion of acid by the stomach

    • Leads to chronic inflammation and eventual ulceration of mucosal lining
    • Further ulceration can occur as submucosa exposed to acid and gastrin
  24. Enterotoxigenic E. coli
    Secretes toxins
  25. Enteropathogenic E. coli
    • Adheres to mucosal cells
    • Destroys microvilli
    • Leads to absorption problems
  26. Enteroinvasive E. coli
    Invades and injures mucosa
  27. Enterohemorrhagic E. coli (EHEC)
    • Adheres to and damages epithelial cells
    • Does not invade mucosa
    • Serotyped 0157:H7
    • Found in intestines of cattle
  28. Most worrisome complication of EHEC
    • Bloody diarrhea --> decreased volume --> renal failure
    • Hemolytic uremic syndrome (HUS)
  29. HUS - Hemolytic Uremic Syndrome
    • Hemolytic anemia
    • Thrombocytopenia
    • Acute renal failure
  30. Connection between E. coli and HUS
    • E. coli in bloodstream releases shiga-like toxins that bind to glomerular capillaries
    • Inactivates protein synthesis and ribosomal activity
    • Injury to cells
    • Platelet aggregation and fibrin replacement in glomerular capillaries --> Acute Renal Failure
    • Also causes RBC hemolysis
  31. If you patient had history of diverticular disease but at present there was not an acute inflammatory condition, what dietary recommendations would you make and why? (p.27)
    • High fiber diet - increase transit through GI tract
    • Wheat bran, fruits, vegetables, legumes
    • Women = 25g/day, Men = 38g/day
  32. Clinical manifestations of Appendicitis (p.31)
    • Epigastric, periumbilical, cramping pain
    • - may be diffuse
    • - initially RLQ
    • Nausea and vomiting
    • Low-grade fever
    • Pain shifting to RLQ with point tenderness
  33. Inflammatory Bowel Diseases (p.27)
    • Term used for Crohn's disease and ulcerative colitis.
    • Common features:
    • - inflammation of bowel
    • - no proven causal agent
    • - pattern of familial occurrence
    • - systemic manifestation
  34. How does Crohn’s contribute to malabsorption, malnutrition, and weight loss? (p.27-28)
    • Any portion of GI tract may be affected - most often small intestine and colon
    • Transmural - all 3 layers of bowel involved
    • Segments of inflamed tissue separated by normal tissue - cobblestone and patchy - interferes with absorption leading to malnutrition and weight loss
  35. What is distinction between Crohn's disease and ulcerative colitis based on anatomic localization and histologic appearance? (p.29)
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  36. Identify symptoms and theories of Irritable Bowel Syndrome (IBS). (p.29)
    • Symptoms:
    • - chronic abdominal pain - crampy sensations with periodic exacerbations
    • - associated with episodes of diarrhea and constipation
    • Theories:
    • - visceral hypersensitivity
    • - abnormal GI motility (esp. colon)
    • - emotional stress
    • - cholecystectomy (perpetual drip of bile into duodenum)
  37. What are the risk factors, sign/symptoms of Celiac disease? (p.34)
    • Risk factors - genetic predisposition – HLA-DQ2 and HLA-DQ8 gene alleles
    • Signs and symptoms:
    • - Chronic diarrhea
    • - Abdominal distention
    • - Painful stomach bloating
    • - Foul-smelling stools
    • - Fatigue, extreme lethargy
    • - Weight loss
    • - Muscle wasting
    • - Vomiting
    • - Irritability
    • - Children – not grow normally, not absorbing nutrients
  38. What is the pathogenic process considered to initiate intestinal damage in Celiac disease?
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  39. If you suspected celiac disease in your patient, what initial test would be most appropriate to perform?
    • Serologic screening for IgA transglutaminase antibody test (IgATTG)
    • Followed by endoscopic biopsy of duodenal mucosa
  40. Once confirmed, what is the treatment for celiac disease?
    • Lifetime gluten-free diet
    • CAN eat: fish, chicken, milk, veggies, corn, rice, eggs, fresh meats, unprocessed cheeses, dry beans, fruits
  41. What are functions of bile salts?
    • Conjugated bile acids
    • Necessary for micelle formation
    • Facilitates emulsification and absorption of fat and fat-soluble vitamins
    • Decreased bile salts = Decreased fat absorption
  42. In what conditions/disorders would you expect deficiency of bile salt secretion?
    • Liver disease
    • Gallstones
    • Bypass of distal ileum
    • Bacterial overgrowth - decreased motility --> stasis of bacterial --> deconjugates bile salts --> ineffective micelle formation and fat absorption
  43. How is unconjugated bilirubin excreted from the body?
    • Heme portion of RBC oxidized into biliverdin, which is then reduced to bilirubin
    • Bilirubin then binds to protein and enters vascular system [Bilirubin-Albumin Complex]
    • This type of bilirubin CANNOT be excreted
    • Has potential to build up in lipid parts of membranes, such as the brain
    • Lipid soluble
    • Measured as indirect bilirubin
  44. How is conjugated bilirubin excreted from the body?
    • UN-conjugated bilirubin transported to liver and passed from one protein to another.
    • Once in smooth endoplasmic reticulum of liver, exposed to glucuronyl transferase
    • Conjugates bilirubin into bilirubin glucuronides = DIRECT bilirubin
    • Now water-soluble
    • Can be excreted by kidneys
    • Can go through biliary system and small intestine and be excreted in feces as well
  45. Between conjugated and unconjugated bilirubin, which is most toxic to body and why?
    • Unconjugated = most toxic
    • Builds up in lipid membranes (i.e., brain)
    • Can cause necrosis of neurons and glia (connective tissue)
    • KERNICTERUS or Bilirubin Encephalopathy
  46. What would urine positive for bilirubin and negative for urobilinogen suggest? (p.38)
    Intrahepatic or extrahepatic biliary obstruction
  47. Would bilirubin in urine reflect conjugated or unconjugated form?
    Conjugated – water soluble; can be excreted by kidneys in urine
  48. 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
  49. How would ratio of NAD/NADH be affected by alcohol dehydrogenase pathway? (p.40)
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  50. 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
Card Set
PathoPhys Test 2
Gastrointestinal system