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BIOCHEMICAL EVALUATION OF GASTROINTESTINAL DYSFUNCTIONS

BIOCHEMICAL EVALUATION OF GASTROINTESTINAL DYSFUNCTIONS. Prof.Dr.Arzu SEVEN. GI tract is both a major endocrine organ and a major t a rget for many hormones. GI hormones influence motility, secretion, digestion and absorption in the gut. GASTRIN

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BIOCHEMICAL EVALUATION OF GASTROINTESTINAL DYSFUNCTIONS

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  1. BIOCHEMICAL EVALUATION OF GASTROINTESTINAL DYSFUNCTIONS Prof.Dr.Arzu SEVEN

  2. GI tract is both a major endocrine organ and a major target for many hormones. • GI hormones influence motility, secretion, digestion and absorption in the gut.

  3. GASTRIN • Originates from the cleavage of the precursor, preprogastrin • Clinical Significance: • Zollinger Ellison Syndrome(Z-E): • Fulminant peptic ulcer+massive gastric hypersecretion +non-B-islet cell tumors of pancreas.

  4. 12 hr. overnight HCI>100 mmol/L, basal HCI>20 mmol/L • Hypergastrinemia + diarrhea +steatorrhea + endocrinopathies • diagnosed by secretin challenge provocative test :

  5. 2 µg/kg body weight secretin is infused IV ,gastrin is measured 10 min and 1 min before the infusion and at 2,5, 10,15,20 and 30 min. following the infusion. • A positive test, consistent with the diagnosis of gastrinoma, is indicated by an increas in gastrin concentration of 200ng/L or more over the basal level →A standard test meal (Lundh meal ) has been found to produce a postprandial rise in serum gastrin of >%50.

  6. Hypergastrinemi: • Gastric ulcer disease • Infections with Helicobacter pylori • Pernicious anemia • Parietal cell antibody (+) chronic atrophic gastritis • Pyloric obstruction • Chronic renal failure

  7. Surgical resection or diseases of kidney/small intestine • Stomach carcinoma

  8. Cholecytokinin(CCK)_Pancreozymin (PZ) • Circulating levels of CCK are increased after a mixed meal. • CCK is rapidly cleared from plasma by the kidney.

  9. CCK secretion is completely inhibited after somatostatin infusion. • Clinical Significance: • Pancreatic exocrine insufficiency and celiac disease ( up to 8500 ng/L) • Fatty food intolerance, gastric ulcer, postgastrectomy state ,irritable bowel syndrome

  10. Secretin • Structural similarities to glucagon, • VIP, GIP, GHRH • Secretin is not released until pH is lowered to at least 4.5 • It is released primarily on contact of S cells with gastric HCI.

  11. Alcohol appears to increase secretin release by stimulation of gastric acid secretion with subsequent lowering of duodenal pH. • Kidney is the major site of degradation. • The only known physiological inhibitor of secretin release is somatostatin.

  12. Clinical Significance: • Transient decreases of secretin along with prolonged rises after meals, with highest levels occurring during night, make the normal diurnal patterns of secretion. • Fasting and severe physical stress cause increased secretion levels that can be reversed by glucose ingestion.

  13. Increased secretin secretion is seen in gastric acid hypersecretion (gastrinoma) • prolonged starvation • DM • Decreased secretin secretion in celiac disease.

  14. Vasoactive Intestinal Polypeptide (VIP) • Structural similarity to secretin, GIP and glucagon • Unlike other GI hormones, VIP is not found in the mucosal endocrine cells of GI tract. • Neurotransmitter limited to peripheral and central nervous tissue.

  15. ClinicalSignificance • Verner-MorrisonSyndrome (Pancreaticcholera) • Increased VIP concentration • Waterydiarrhea • Hypokalemia • Achlorhydria • hypotension

  16. Cutaneous flashing (vasodilation) (usually associated with a pancreatic tumor) • Overproduction of VIP by tumor is responsible for these symptoms =VIP omas • Medullary thyroid carcinoma • ganglioneuroblastoma

  17. A very useful screaning test for the diagnosis of VIP-secreting tms • An effective tm. marker for detecting occult metastases • hepatic cirrhosis • Crohn’s disease VIP

  18. Gastric Inhibitory Polypeptide (GIP) • Insulinotropic action of GIP glucose-dependent insulinotropic peptide

  19. Clinical Significance: • Starvation • prolonged fasting • type IV hyperlipoproteinemia GIP • renal failure • untreated ketotic juvenile DM

  20. Patients with cystic fibrosis or pancreatitis show an increased response of GIP to glucose and a lower response to TG (duo to lipase deficiency) • In duodenal ulcer disease, GIP shows an increased response to glucose (rapid gastric emptying)

  21. Somatostatin • Tissue: • antrum of stomach • upper small intestine • pancreas • Hypothalamus • Most potent inhibitor of endocrine secretion • Somatostatin inhibits GH, TSH, insulin, glucagon, gastrin, CCK, secretin, VIP, GIP, motilin, pancreatic polypeptide, neurotensin, substance P secretion

  22. Function:Inhibitor of pepsin secretion, gastric emptying,inhibition of gallbladder contraction, secretion of bile and pancreatic enzymes. • Long -acting somatostatin analogues inhibit hormone secretion and reduce clinical symptoms in gastrinoma, glucagonoma, VIP oma.

  23. Motilin • Widelydistributed in GI tract, fromtheesophagustocolon, includingthegallbladderandbiliarytract • Function • A strongstimulantforcontraction of smoothmuscles of upper GI tract, it increasesthemotility of thefundus, antrumandduodenumandcontractions of loweresophagealsphincter.

  24. Motilin is unique in that its actions are generally restricted to fasting state. • Motilin increases in : • Crohn’s disease • acute intestinal infection • Irritable bowel syndrome • tropical sprue • ulcerative colitis

  25. Pancreatic polypeptide(PP) • Tissue:pancreas • Biphasic effect:it initially increases and then inhibits secretion of pancreatic enzymes , water and electrolytes thus opposing the stimulatory effectors of secretin and CCK ,increases gut motility and gastric emptying ,relaxation of pyloric and ileocecal sphincters, colon and gallbladder.

  26. VIP oma PP • glucagonoma (biochemical marker • gastrinoma for pancreatic • insulinoma endocrine tm) • duodenal ulcer • Juvenile onset DM PP of long duration

  27. Enzymes of GI tract • Pepsin and Pepsinogen • 7 different fractions of pepsinogen • 5 fractions that migrate toward the anode most rapidly are identical immunologically (pepsinogen I=pepsinogen A)

  28. 2 other fractions migrate behind group I pepsinogens (pepsinogen II) • Pepsinogen I is the major proteinase in normal tissue. • Both group pepsinogens are detected in blood, only group I is present in urine, group II is present in semen.

  29. Pepsinogensecretion, likegastriclipase,is stimulatedbyvagusnerveand GI hormones (gastrin,secretin,CCK,VIP) • Pepsinogen I increasedgastricoutputand increasedparietalmass Z-E syndrome, gastrinoma, duodenalulcer (%30-50) acuteandchronicsuperficial gastritis

  30. H.pylori sero(+) patients have higher serum pepsinogen I levels screening test for H.pylori infection ( + ), marker of H.pylori eradication • Pepsinogen I is decreased in decreased cell mass ,atrophic gastritis,gastric carcinoma,myxedema,Addison’s disease and hypopituitarism .

  31. In pernicious anemia pepsinogen II levels are normal but pepsinogen I is low/undetectable. • PGI/PGII Ulcer in gastric body • PGI/PGII Duodenal ulcer

  32. The most sensitive test for fundic atrophic gastritis is PGI/PGII • PGI/PGII<3.3 moderate/ severe atrophic gastritis and aftere total gastrectomy • Normal ratio: • (PGI/PGII = 5-6)

  33. Enzymes Derived From Pancreas: • Amylase • Lipase • Proteolytic Enzymes

  34. Amylase • After an acute pancreatitis attack, amylase activity is increased after 2-12 hr ,reaches a peak at 12-72 hr • Relatively nonspecific

  35. Lipase • For the diagnosis of acute pancreatitis • Elevations are more pronounced, more prolonged and more specific. • Lipase and amylase (P-type izoenzyme) elevations complement pancreatitis diagnosis.

  36. Trypsinogen • Trypsin • Trypsin α1-proteinase inhibitor (α1-antitrypsin) Collectively Measured by İmmunological assays

  37. Very high trypsin levels in acute pancreatitis contrast sharply with low/normal levels in chronic pancreatitis • Normal in hepatic jaundice • High in renal disease

  38. Elastase Elastase 1 anionic, free or in complex with α-1 proteinase inhibitor in serum • Elastase 2 catonic, exists in serum mainly in bound form • Elastase I is increased in acute and relapsing chronic pancreatitis greater than serum amylase activity. • Elevations persist for a longer time and reflect a better clinical course than amylase. • Increase in carcinoma of pancreas head.

  39. GASTRİC FUNCTIONis evaluated by : • Helicobacter pylori test • Analysis of gastric residue • Secretion rate in basal state and after • stimulation • Intrinsic factor analysis • Pepsinojens analysis

  40. Gastric residue: • Content of the stomach after 12 hr fast is • 20-100 ml • Colorless • Odor is sharply sour • Total acidity includes hydrogen ions accurring as (1) free HCI (2) mucoprotein (3) acid salts (4) organic acids(Lactic and butyric acid)

  41. The concentration free acid in gastric residue is 0-40 mmol/L • Absence of free HCI is abnormal only if the condition persists after maximal stimulation with pentagastrin • Before the diagnosis of achlorhydria, gastric stimulation should be made.

  42. Stimulators of gastric secretion: • Test meals (Ewald meal ) • Caffeine sodium benzoate • Alcohol • Gastrin • Pentagastrin • İnsulin • Sham feeding

  43. Gastrin is the naturel and most powerful stimulus for gastric HCI secretion • (2 µg gastrin for key of body weight subcutaneously or 1µg gastrin/kg (IM) • Pentagastrin:synthetic product, 6 µg subcutaneously/kg body weight for maximal stimulation.

  44. Insulin • Hypoglycemia (0.1-0.2 u insulin/kg body weight IV) stimulates acid secretion by vagal and nonvagal mech.

  45. PANCREAS • Productionandsecretion of pancreaticjuice • Colorless • ph 8.0-8.3 • As high as 3000 ml/24 hr.

  46. Invasive tests • Nonsive tests Invasive tests: • those that stimulate intraluminally pancreatic secretion (by Lundhtmeal : %5 protein %6 fat %15 CH %74non-nutrientfibersor by duodenal infusion of essential AA) • those that stimulate pancreatic secretion by IV hormonal injection (secretin, CCK, secretin +CCK)

  47. Noninvasive tests: • 1-Measurement of unabsorbed food or fecal pancreatic enzymes: trypsin chymotrypsin elastase in stool (fecal lipids, steatorrhea by microscopic stool examinaton/fat absorption test • 2-measurement of products of food digestion or synthetic compounds hydrolysed by intraluminal pancreatic enzymes, absorbed by the gut ,detected in breath (CO2 Test ) in blood or urine) Serum carotene, vitamin A ,schilling test

  48. 3-measurements of plasma concentration of hormones, AA or enzymes. • These tests measure pancreatic function, do not diagnose a specific disorder • Pancreatic insufficiency can’t be demonstrated until at least %50 of acinar cells are destroyed. • Clinical symptoms don’t appear until %90 of acinar tissue is lost.

  49. No reference intervals for enzymes after stimulation with either secretin or CCK standardized techniques. • The chronic pancreatitis, the earliest change in secretin test is a decrease of bicarbonate <90 mmol/L • Sweat Test: • Chloride concentration of sweat is considered the most reliable single test in the diagnosis of cystic fibrosis

  50. Test becomes (+) between 3-5 wk. of age • Symptoms: • Unexplained chronic pulmonary disease + chronic hepatobiliary disease + hypoproteinemia + edema + failure to thrive

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