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E.S.Prakash, MBBS, MD Division of Basic Medical Sciences

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1 GI Physiology Resource 1 Problem Solving Exercises - Discussion 9 am Jan 17, 2012
E.S.Prakash, MBBS, MD Division of Basic Medical Sciences Mercer University School of Medicine URLs last accessed Jan External links may be under access control. License: This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited. External links within the article are provided for convenience and may be under access control.

2 Question 1 How has the contribution of the cephalic phase to gastric acid output been investigated in experimental animals? See Figures in Wood J. Physiology,

3 Question 2 A 35 year old man C: Progressive difficulty in swallowing over the last 12 months. HPC: Initially he had difficulty swallowing solid food but since the last month the ability to swallow liquids had diminished as well, and swallowing was associated with chest pain.

4 Upper GI series: dilated esophagus with a bird beak like narrowing of the lower end of the esophagus. Upper GI endoscopy: no mucosal abnormality in the esophagus. Discuss the pathophysiologic mechanisms of the symptomatology. What are the available therapeutic strategies?

5 The basic efferent arm in the ENS that mediates peristalsis

6 Barium swallow: http://www. nature
Esophageal motility study: Radiograph in diffuse esophageal spasm: Related illustration (does not apply to the Case in Q 2 - Aspiration (secondary to a defect in pharyngeal phase of swallowing)

7 What is the defining abnormality in achalasia?
Absence of deglutitive inhibition of the LES And absence of propulsive peristalsis in the esophagus Therapeutic modalities: Calcium channel blockers Endoscopic dilation of LES Botulinum toxin injections into LES Surgical division of the LES

8 Question 3 By the end of the third trimester of pregnancy, 50-80% of pregnant women have had new or exacerbation of preexisting heartburn. What are the likely mechanisms contributing to this observation? See the Figure at this link below.

9 Crura of diaphragm; phreno-esophageal ligament
Intra-esophageal pressure; salivation; esophageal clearance Pressure in lumen of LES Intragastric pressure; gastric emptying Tone and competence of PS

10 Factors affecting LES tone and pressure
INCREASE LES PREESURE (AND DECREASE LIKELIHOOD OF GER) DECREASE LES PREESURE (AND INCREASE LIKELIHOOD OF GER) Muscarinic receptor agonist; Alpha-adrenergic agonist; Dopamine 2 receptor antagonist; Gastrin; Motilin; MMC Protein meal Botulinum toxin; Calcium channel blocker; Dopamine; Gastric distention; Secretin, CCK, Progesterone Fat meal, Chocolate, Smoking GER – Gastroesophageal Reflux

11 Normal LES pressure: 20 mm Hg
Transient relaxation of LES (TLESR) occurs at the frequency of MMC; i.e. LES relaxation unrelated to swallowing and esophageal peristalsis. Function of TLESR? What is the mechanism of belching? Stimulus – proximal gastric distention Response – TLESR Integrated in – medulla (blocked by cerv. Vagotomy) Also blocked by – NOS inhibitors

12 The sphincter effects of smooth muscle in LES is augmented by contraction of crural fibres of diaphragm GER cannot happen unless the LES is incompetent.

13 Question 4: Epidemiologic studies indicate a significant association between obesity and gastroesophageal reflux disease (GERD). What mechanistic evidence supports the possibility of a cause and effect relationship between obesity and GERD?

14 Theories proposed include:
Fat, chocolate reduce LES tone Slower gastric emptying with fat meal Hiatal hernia – in a study cited in the paper below, as many as 50% of morbidly obese patients selected for bariatric surgery had hiatal herniahttp:// Adipokines from adipose tissue may have an effect on the LES Gastric motor abnormalities have been documented to be more frequent in obesity (especially morbid obesity) abnormalities included especially diminished gastric compliance and raised intragastric pressure Ref: Obesity reviews (2002) 3, 9–15

15 Question 5 50 year old man with recurrent heartburn.
HPC: He has been taking antacids and H2 receptor blockers on and off with some improvement. He inquires about surgical options and indicates being willing to undergo surgery if the likelihood of permanent symptom control would be highly likely. How can one establish if his symptoms are indeed attributable due to gastroesophageal reflux? What other physiologic information would help decide if anti-reflux surgery would be helpful or not?

16 Why is the esophagus prone to injury by acid and pepsin?
What is the mechanism of water brash? Diagnosis of GERD in practice is almost always presumptive. What is the principle of management of GERD?

17 Establishing a diagnosis by ambulatory pH monitoring of the esophagus
Before anti-reflux surgery, check: Pathologic reflux is highly likely to be the cause of the symptomatology Defective salivation is not the cause of GERD Defective esophageal peristalsis is not the cause of GERD

18 Question 6 Do tests of gastric acid secretion have a role in establishing a diagnosis of peptic ulcer disease? Explain.

19 There is considerable interindividual variability in BAO and MAO.
Typically DU is characterized by an increase in BAO and MAO. Depending on location, GU may be associated with normal, low or elevated BAO.

20 Indications for gastric acid secretory testing:
Evaluation of hypergastrinemia (allows distinction between gastrinoma and pernicious anemia) Checking BAO for completeness of vagotomy such as in an individual with ulcers following vagotomy

21 Question 7 A 55 year old man with a history of recurrent episodes of heartburn, epigastric pain and duodenal ulcer was investigated and found to have a gastrin-secreting tumor in the pancreas. His basal acid output (BAO) was determined to be 20 mmol/hour (normally 2-3 mmol/hour). The patient also had a history of steatorrhea (fatty, bulky, malodorous stool; fat excretion > 6 g on a 24 hour stool collection). What is the most likely reason for the excretion of large amount of fat in stool? How would you manage this patient if he was not willing to undergo surgery?

22 Question 8 What would be the effect of resection of upper small intestine on meal stimulated gastric acid output?

23 Question 9 How does H. pylori infection of the antral mucosa perturb gastric acid secretion – does it result in hypochlorhydria or hyperchlorhydria? Explain. Acute infections – hypochlorhydria Chronic infections – hyper or hypochlorhydria Hyperchlorhydria occurs with ulcers limited to antrum and with gastric metaplasia of the duodenum Host response is an important factor.. N methyl histamine (a H3 receptor agonist) from H pylori postulated to inhibit somatostatin release from D cells and thereby increase gastrin release and cause hyperchlorhydria.

24 Hypochlorhydria with a chronic atrophic pangastritis
Large fraction of patients may develop this. Often asymptomatic Mechanisms: Molecular mimicry: H. pylori antigens and H-K ATPase The hypochlorhydria may reverse with successful eradication of H. pylori Hypochlorhydria suggested to offer some protection against development of GERD and Barrett’s esophagus. Details in Sleisenger and Fordtran’s Gastrointestinal Disease, pp. 830 (available via Mercer Med Library)

25 Question 10 The pain of an uncomplicated duodenal ulcer is frequently relieved by food. Why may this be so?

26 Question 11 Defecation following meals is the rule in children’. Why may this be so?

27 Question 12 Truncal vagotomy surgery for intractable peptic ulcer disease is typically accompanied by a gastrojejunostomy. What purpose does the gastrojejunostomy serve? What would be expected to happen to BAO and MAO following truncal vagotomy? What is the line of section of vagi in a truncal vagotomy? See Figure at

28 Question 13 A 50 year old man underwent truncal vagotomy, antrectomy and a gastrojejunostomy for chronic duodenal ulcer complicated by gastric outlet obstruction 4 months ago. He presented with complaints of nausea, vomiting and epigastric discomfort following a meal. These symptoms have been there since the last 2-3 months. He had also undergone cholecystectomy 10 years ago. On examination, he was in no apparent distress; vital signs – WNL. CVS, RS – WNL. Per abdomen: soft, nontender, no organomegaly, no free fluid, no abnormal masses.

29 Upper GI endoscopy revealed swelling, redness, erosions and bile staining of the gastric mucosa.
Discuss the mechanisms likely contributing to the symptomatology and the clinical signs.

30 Dumping Syndrome: Mechanisms postulated:
Early Phase symptoms (within min of a meal) Impairment of receptive relaxation Loss of the antral pump effect Loss of regulation of gastric emptying (pyloric sphincter gone) Rapid delivery of hyperosmolar chyme into the jejunum (this induces hypovolemia) Late Phase symptoms (2 hr after a meal): Rapid absorption of glucose into blood, insulin secretion and reactive hypoglycemia 2 hr following a meal

31 Question 14 A 60 year old male presented with a history of fatigability on exertion and weakness of the lower limbs since the past 4 months. He had undergone Roux-en-Y-bypass surgery 10 years ago for managing severe obesity.

32 OE: pale but in no distress.
BP: 140/90 mmHg; pulse: 94/min; respiration: 16/min. CVS, RS, abdomen and genitourinary exam – WNL. GIT: the tongue was smooth Neuro: a mild impairment in cognition was noted, Romberg’s sign was present ankle reflexes were absent on both sides. The plantar response was initially flexor and then extensor. No other abnormality was noted. Investigations: Blood [Hb]: 10 g/dL

33 We need to explain why this individual has developed:
Peripheral smear showed macrocytosis and vitamin B12 levels in serum were considerably diminished. Serum ferritin level was lower than normal. Could the surgery he underwent 10 years ago have predisposed him to the symptom complex now observed? Explain. We need to explain why this individual has developed: Vitamin B12 deficiency Iron deficiency

34 Question 15 A 50 year old man with a longstanding history of type I diabetes presented with complaints of vague discomfort in the epigastric region. Symptoms started 6 months ago and included mild nausea and vomiting within couple of hours of a meal. These symptoms first occurred 6 months ago. He also frequently experienced lightheadedness and shaking tremors about an hour after a meal. There was no history of chest pain, abdominal pain. Medications included insulin injections taken before meals.

35 He did not smoke or drink alcohol.
He had not undergone any surgeries in the past. The vomitus consisted of undigested, chewed food. OE: BP: 140/94 mmHg, HR – 82/min. CVS, RS – WNL. PA: The abdomen was soft, nontender, and there was no organomegaly, masses or free fluid. Serology for H. pylori was negative. Omeprazole 20 mg od for three weeks did not produce any improvement in symptoms.

36 Administration of a test meal with radioisotope indicated retention of greater than 40% of the meal in the stomach four hours following ingestion. He was prescribed metoclopramide but these had to be stopped within 2 months because of tardive dyskinesia. Dyspeptic symptoms showed significant improvement with erythromycin. Discuss the pathophysiologic basis of this presentation and the therapeutic strategy.

37 Gastroparesis – delayed emptying of a standard test meal.
Causes: Longstanding diabetes Following truncal vagotomy and other gastric surgeries Gastric outlet obstruction due to a chronic DU; rarely due to hypertrophic and hypertonic pyloric sphincter Chronic ischemia of the stomach

38 There is evidence that chronic hyperglycemia and end products of products of advanced glycosylation (AGE) lead to: Loss of interstitial cells of Cajal Antral hypomotility Isolated pyloric contractions Acute or chronic gastric dilation may occur in some instances. See

39 Therapeutic strategies depend on cause and severity of the gastroparesis
Metoclopramide (D2 receptor antagonist) Domperidone Erythromycine (motilin receptor agonist) Gastrostomy Corrective surgery (in the case of gastric outlet obstruction)

40 Question 16 Comment on this equilibrium phase diagram (URL below) of cholesterol – phospholipid and mixed bile salt system (37°C, 0.15M NaCl, pH 7, total lipid concentration 7.5 g/dL) and explain its relevance to the pathogenesis of gallstones

41 Risk Factors for Gallstones
Incidence increases with age More common in females Diets rich in fat Rapid weight loss Infection of the biliary tract Oral contraceptive use Total parenteral nutrition Prolonged fasting Terminal ileal resection Excessive hemolysis Excessive hemolysis (for Ca bilirubinate stones)

42 Pathophysiologic mechanisms:
Lithogenic bile: lower in bile salts and lecithin and richer in cholesterol. Defects in bile acid secretion in bile; decrease in bile salt pool due to any cause; E.coli secretes beta-glucuronidase that deconjugates bilirubin diglucuronide and bilirubin is insoluble and precipitates as calcium bilirubinate Stasis of Bile: Total parenteral nutrition; prolonged fasting, denervation of gall bladder; obstruction in the biliary tract. Excessive secretion of gall bladder mucins? Biliary sludge – a mix of cholesterol crystals, mucin, and calcium bilirubinate.

43 Question 17 A 32 year old pregnant woman in the third trimester of her pregnancy presents with a history of bothersome itching since the past 2 weeks. To begin with, itching was prominent in the palms and soles but it was now generalized. Past history is notable for cholecystectomy done 3 years ago. She is not on any medication. She is not jaundiced. Physical examination is unremarkable. Vital signs – WNL. She reported fetal movements and fetal heart rate was within normal limits. What is the likely pathophysiologic basis of this presentation?

44 Issue – Transport of bile acids and bile salts by the hepatocyte
Figure Link:

45 Question 18 Bilirubin is conjugated by liver cells to bilirubin mono-and diglucuronide and secreted in bile. In conjugated hyperbilirubinemia, there is a predominance of conjugated bilirubin in the blood stream. How does conjugated bilirubin enter the blood stream?

46 MRP2 (MOAT) extrudes conjugated bilirubin into the canaliculus; MRP3 is not normally expressed in the sinusoidal membrane but expressed in Dubin Johnson syndrome See Figure 1 at Advances in Physiol Educ 2007

47 Question 19 What acid-base abnormality would you expect vomiting from gastric outlet obstruction or pyloric stenosis to produce? What are the pathophysiologic considerations in the management of this acid-base abnormality?

48 Question 20 Describe the various mechanisms that contribute to the occurrence of ascites in an individual with cirrhosis of the liver. See this figure:

49 ↑ Resistance to blood flow through portal venules and hepatic sinusoids
Hepatic arteriolar dilation ↑ formation of lymph in the liver ↑ Portal vein pressure Retrograde transmission to splanchnic capillaries Ascites ↓ in effective arterial blood volume, cardiac output ↓ Renal blood flow Activation of renal renin-angiotensin-aldosterone axis and renal retention of Na, Cl and H2O (secondary hyperaldosteronism) Reflex ↑ renal sympathetic nerve activity Dilation of portosystemic collaterals Hypoalbuminemia

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