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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
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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
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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
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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
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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
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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
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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
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Acetylcholine effect on parietal cell:
- 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
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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
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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
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At what pH will pepsin have maximal proteolytic activity? (p.15-16)
pH < 3
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What is the goal for PPIs on gastric pH for healing of ulcers?
- Increase gastric pH > 4
- Inhibit proton-pump directly
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What are the most effective drugs for decreasing the secretion of HCl?
Proton-pump inhibitors = 95% effective
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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
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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
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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
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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
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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
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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.
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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
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What is the gold standard for diagnosing peptic ulcers and H. pylori? (p.21)
Biopsy and rapid urease test (CLO test - campylobacter-like organism)
-
What is the least invasive test to document H. pylori and document bacterial eradication
after treatment?
Urea breath test
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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
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Enterotoxigenic E. coli
Secretes toxins
-
Enteropathogenic E. coli
- Adheres to mucosal cells
- Destroys microvilli
- Leads to absorption problems
-
Enteroinvasive E. coli
Invades and injures mucosa
-
Enterohemorrhagic E. coli (EHEC)
- Adheres to and damages epithelial cells
- Does not invade mucosa
- Serotyped 0157:H7
- Found in intestines of cattle
-
Most worrisome complication of EHEC
- Bloody diarrhea --> decreased volume --> renal failure
- Hemolytic uremic syndrome (HUS)
-
HUS - Hemolytic Uremic Syndrome
- Hemolytic anemia
- Thrombocytopenia
- Acute renal failure
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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
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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
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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
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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
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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
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What is distinction between Crohn's disease and ulcerative colitis based on anatomic localization and histologic appearance? (p.29)
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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)
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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
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What is the pathogenic process considered to initiate intestinal damage in Celiac disease?
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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
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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
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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
-
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
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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
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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
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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
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What would urine positive for bilirubin and negative for urobilinogen suggest? (p.38)
Intrahepatic or extrahepatic biliary obstruction
-
Would bilirubin in urine reflect conjugated or unconjugated form?
Conjugated – water soluble; can be excreted by kidneys in urine
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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
-
How would ratio of NAD/NADH be affected by alcohol dehydrogenase pathway? (p.40)
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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
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