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Gastrointestinal Tract
BACKGROUND READING:
Saliva & salivary glands
Salivary gland function tests
Stomach Gastric secretion Gastro-intestinal
peptides
Digestion of carbohydrates, proteins & lipids
Gastrectomy and post-gastrectomy syndromes
Pancreas Pancreatitis
Gastrointestinal Tract
TREATED TOPICS Gastric function
and tests Zollinger-Ellison
syndrome Peptic ulcer Pancreatitis &
pancreatic function
Absorptive function of the gut
Gastro-intestinal peptides
Gastrin see later Secretin see later Cholecystokinin (CCK) see later Glucose-dependent insulinotrophic
peptide (GIP) found in duodenum and jejunum and involved in the post-prandial release of insulin
Gastro-intestinal peptides
Motilin: Found in duodenum and jejunum and responsible for intestinal motor activity
Pancreatic polypeptide: Found in the pancreas; relaxes gall bladder and inhibits enzyme secretion from the pancreas
Gastro-intestinal peptides
Gut glucagon-like immunoreactivity; Found in the ileum and colon; increases small intestinal mucosal growth and slows transit
Vasoactive intestinal peptide (VIP): Found in all areas; secretomotor, vasodilation and relaxation of smooth muscle.
Intestinal absorptive surface
.
Digestion and absorption: Absorptive surface of the gut
Digestion of carbohydrates Digestion of starch occurs mainly in the
intestinal lumen. Pancreatic amylase acts on starch producing maltose, maltotriose and α-limit dextrins by acting on 1– 4 glucosidic linkages.
Further metabolism of these products at the brush border which has isomaltase (-limit dextrinase) and disaccharidases (for maltose, sucrose, lactose) produce monosaccharides.
Digestion of carbohydrates
Carbohydrate malabsorption can result from:
Generalised intestinal disease affecting absorption.
Pancreatic disease causing amylase deficiency.
Intestinal disaccharidase deficiency Defects of monosaccharide
transport.
Digestion and absorption of proteins….1
Pepsin acts within the stomach. Trypsin and chymotrypsin act in
the intestinal lumen. These are all endopeptidases.
Pancreatic exopeptidases split off terminal amino acids from proteins and peptides.
Digestion and absorption of proteins….2
Proteins are digested to oligopeptides (2-6 amino acids long) and free amino acids.
Oligopeptides are digested at the brush border or within the luminal cell cytoplasm to amino acids.
Absorption of amino-acids
There are active transport mechanisms for transport of amino acids across mucosal cells into circulation.
There are active transport mechanisms for basic (cystine, lysine ornithine, arginine) acidic, neutral and -imino acids (proline, hydroxyproline).
Malabsorption of proteins can result from:
Generalised intestinal disease affecting absorption
Pancreatic disease causing deficiency of pancreatic peptidases
Specific transport defects e.g. cystinuria, Hartnup disease.
Digestion and absorption of lipids….1 Emulsification of lipids for digestion is
achieved by intestinal motility and the detergent-like action of bile acids.
Lipids are digested, solubilised and then absorbed.
Dietary triglycerides (TGs) are partially hydrolysed to free fatty acids (FFA) and mono and diacylglycerides
Digestion and absorption of lipids....2
The diacylglycerides, monoacylglycerides, FFA, cholesterol, phospho-lipids and fat soluble vitamins are organised into micelles (solubilisation) for absorption mainly in the jejunum.
Digestion and absorption of lipids....3 Within the mucosal cells triglycerides
are resynthesized and together with cholesterol, phospholipid and protein are organised into chylomicrons
Chylomicrons pass into the intestinal lymphatics and then into the thoracic duct.
Some TGs and other lipids are organised into VLDL within intestinal mucosal cells (exogenous VLDL).
Digestion and absorption of lipids....4
Some FFAs escape into the portal blood and get bound to albumin and are then taken to the liver.
Digestion and absorption of Triglycerides
.
Digestion and absorption of triglycerides
.
FA+ MGs
Abnormalities of lipid absorption can result from: Generalised intestinal disease
affecting absorption. Pancreatic disease causing lipase
deficiency Decreased lipase activity due to
high intestinal [H+] Deficiency of bile acids Abeta lipoproteinaemia
The stomach
.
GASTRIC FUNCTION
Histamine Cell and Parietal Cell
.
Ranitidine
Gastric acid inhibition of gastrin release
.
“H” cells
Histamine
H2R
Gastric acid secretion (Flow of
information )
Cephalic phase of gastric acid secretionVagus parietal cells (direct)Vagus nerve gastrin producing cells gastrin histamine producing cells histamine H2 R-parietal cells
Gastric acid secretion (Flow of
information )
Gastric phase of gastric acid secretion Secretagogues (protein, products of protein
digestion) parietal cells (direct) Distension of stomach Low gastric acid G-cells H-cells pareital cells gastrin histamine
Histamine Cell and Parietal Cell
.
Ranitidine
The proton pump
.
Omeprazole:
Proton pump inhibitor
Cimetidine:
Ranitidine:
H2R antagonists
The pentagastrin test Patient fasting Pass radio-opaque naso-gastric tubeAspirate: Resting juice Basal juice (60 min)Inject sub-cutan pentagastrin 6 g/kg
bdy wtAspirate: Post-pentagastrin secretion (4 x15
min)
Pentagastrin Test: Reference ranges
Resting juice: <50ml
Basal juice: <5 mmol/h (HCl)
Post-pentagastrin secretion (MAO/PAO)
♂: < 45mmol/h ♀: <35 mmol/h
Achlorhydria
Inability to secrete gastric acid so that the pH of gastric juice produced in response to the pentagastrin test ≥ 7
May be found in : Pernicious anaemia Gastric carcinoma
Acid output
: duodenal ulcer Zollinger-Ellison syndrome
: gastric ulcer gastric carcinoma
The above observations are not sufficiently constant
Peptic ulcer An ulcer in or adjacent to an acid
producing area of the gutCauses: mucosal resistance (Cells +
mucus) Acid + pepsin NB: effective management of PU
leads to 50% reduction in acid output (pre: intra-treatment)
The insulin-hypoglycaemia test (Hollander’s test) Patient fasting Pass radio-opaque naso-gastric tubeAspirate: Resting juice Basal juice (60 min)Inject sub-cutan insulin 0.2 u/kg bdy wtAspirate: Post-insulin secretion (8 x 15 min)
Blood glucose during Hollander’s test
Fasting blood glucose measured before injection of insulin
Blood glucose measured at 15, 30, 45 and 60 minutes after the injection of insulin
The insulin-hypoglycaemia test: Reference ranges
Hypoglycaemia: plasma glucose< 2.2 mmol/L in at least one of the blood specimens
[H+] > 20 mmol/L above basal⇒ Incomplete vagotomy
Output in any 4 consecutive 15 min specimens≥ 10 mmol⇒ Incomplete vagotomy
Plasma gastrin
Reflects the rate of gastrin production by the pyloric antrum
[Plasma gastrin] in the fasting state when gastric acidity is high
[Plasma gastrin] after meals when gastric acidity is low
Plasma gastrin In diseases causing hyperacidity (e.g.
DU) [plasma gastrin] except in Zollinger-Ellison syndrome
In hypochlorhydria or achlorhydria (e.g. pernicious anaemia) [plasma gastrin] except in a situation where atrophic gastritis has destroyed gastrin producing cells
Zollinger-Ellison syndrome 0.1% of all patients with PUD Severe, multiple recurrent peptic
ulcers Autonomous gastrin production ♂: 60-65%, ♀: 30-35% Excessive production of acid by the stomach Non- islet cell tumour of the pancreas May occur as part of the MEN syndromes
(20%)
Zollinger-Ellison syndrome
60% of the gastrinomas are malignant with metastasis in local lymph nodes and liver
Symptoms / signs: Abdominal pain & dyspepsia Chronic diarrhoea & malabsorption
as a result of inactivation of pancreatic enzymes by H+
Zollinger-Ellison syndrome: Diagnosis:
resting and basal juice in the pentagastrin test
Overnight aspiration (resting juice)> 1Lcontaining ≥ 100 mmol/L HCl
Diagnosis confirmed by finding [plasma gastrin] in the fasting patient
(100->1000 pg/ml) BAO/MAO> 0.6
.
.
Acid SecretinNutrients CCK-PZ
.
.
The stomach, duodenum and pancreas
.
Pancreatic enzymes:
Proteases: trypsin, chymotrypsin, carboxypeptidases
Amylase Lipolytic enzymes: lipase and co-
lipase
Acute pancreatitis
Acute inflammation of the pancreasTwo forms: Oedematous: (mortality: 5-10%)
Haemorrhagic /(Necrotizing) with severe tissue necrosis: (mortality: 20-50%)
Causes: (GET SMASHED) Gallstones Ethanol Trauma Steroids Mumps Auto-immune Scorpion venom
Hyperlipidaemia hypothermia,
hypercalcaemia ERCP and Emboli Drugs
Acute pancreatitis
Associations: 50+ years Biliary tract disease (e.g.
cholelithiasis) Alcoholism On elimination of the causative
factor, normal exocrine and endocrine functions are restored
Acute pancreatitis
Gall stones present in about 50% of all cases
About 5% of patients with gall stones develop acute pancreatitis
Vascular and infective causes also known
25% of all cases are not secondary to any known cause (idiopathic)
Complications of acute pancreatitis (early)
Shock Acute respiratory distress
syndrome (ARDS) Renal failure Sepsis Disseminated intravascular
coagulation (DIC)
Complications of acute pancreatitis (early)
Hypocalcaemia (lipolysis with release of FFAs, followed by saponification reactions with calcium salts)
Please read about late complications
.
.
Plasma -amylase Activity usually in acute pancreatitis Values > 5x the upper reference value
(180 Somorgyi u) found in > 50% of cases and usually occurs on the 1st or 2nd day of illness
Smaller increases in most acute abdominal conditions
In acute pancreatitis plasma -amylase activity returns to normal within 3-5 days
Urine -amylase Rises with plasma -amylase but offers
no advantage over measurement of plasma - amylase
Limitations: Renal decompensation in the elderly Macroamylasaemia (presence of
aggregates of -amylase with immunoglobulins in plasma which are unable to pass through the kidney filter)
Lipase and trypsin activities: Levels of lipase and trypsin are increased in
acute pancreatitis and in other conditions where plasma - amylase activity is increased
They are more difficult to measure than - amylase
Serum lipase is more sensitive and specific for pancreatitis and may eventually replace amylase measurements
Lipase is only slowly cleared from plasma so remains elevated for a longer period than plasma amylase
Methaem-albuminaemia:Index of severity of acute pancreatitis
Develops sometimes in acute pancreatitis: Proteolytic breakdown of haemoglobin Haem /methaem formed Haem metabolized to bilirubin Methaem combines with plasma albumin
to form methaem-albumin Usually only a trace of methaem-albumin
is detectable in the plasma of healthy individuals
Chronic pancreatitis
Persistence of pain or symptoms after acute episode
Structural and functional impairment: Impairment of pancreatic exocrine
function (e.g. release of lipase) Impairment of pancreatic endocrine
function (e.g. release of insulin)
Pancreatic function: Secretin, Cholecystokinin-Pancreozymin (Secretin-CCK-PZ) test (tubular test)
Patient fasting Passage of double calibre tubeAspiration of duodenal samples: 10 min preliminary sample 10min 10min basal/controls
Secretin Cholecystokinin-Pancreozymin (Secretin-CCK-PZ) test
Injection of secretin 1U/kg bdy wt slow I.V.
10 min 10 min 20 min 20 min duodenal aspirations
CCK-PZ I.V. or Caeruleindecapeptide
10min 10min
Results of the Secretin, CCK-PZ test
Volume pH bicarbonate Enzymes
Basal 10 ml 7.5 25 mmo/l +
Secretin >2ml/kg
bdy wt
8 75-90 mmol/l +
CCK-PZ >2ml/kg
bdy wt
8 75-90 mmol/l ++
Chr pancreat
≤60 mmol/l
Ca pancreas
Pancreatic function:
BT-PABA /14 C-PABA testResearch test (tubeless test)
BT-PABA Oral 14 C-PABA Urine Urine PABA 14 C-PABA
Chymotrypsin14C-PABAu = PABAu14C-PABAo BT-PABAo
Benzoyl tyrosyl paraamino benzoic acid test
Pancreatic function: Triglyceride breath test (also radioactive and tubeless)
This is one example of tests that have been devised so as to overcome the difficulties and unpleasantness of collecting faeces over several days (read about faecal fat).
Following digestion and absorption of an oral dose of 14C-triglyceride the (marker being in the fatty acid component) part of the fatty acid is metabolised to 14CO2 which is then excreted in the expired air.
Triglyceride breath test
A high 14CO2 excretion is associated with normal fat absorption whereas
14CO2 excretion is low in patients with fat malabsorption.
This test is convenient and rapid but because it is technically difficult it has not gained wide acceptance.
Xylose absorption test…1Screening test for carbohydrate malabsorption 550052
D-xylose, a pentose is normally absorbed rapidly from the small intestine and excreted in the urine. It is partly metabolised in the body but can be used satisfactorily to test the intestine’s ability to absorb monosaccharides (remember that all carbohydrates are absorbed as monosaccharides)
Xylose absorption test…2 D-xylose (5g) is given to the patient
after an overnight fast. The bladder is immediately emptied and this first specimen of urine discarded.
Urine is collected for the next 5h. At least 500 ml water is given during the early part of the test.
Normally in healthy individuals, more than 2g xylose is excreted in 5h.
Xylose absorption test…3
Impaired absorption and excretion of xylose is often observed in patients with disease of the small intestine (read on Crohn’s, Whipples, Tropical sprue, Gluten/gliadin enteropathy)
Bacterial colonisation of the small intestine may lead to low values because the bacteria metabolise xylose.
Xylose absorption test…4 In renal disease there may be impaired
excretion of xylose. Blood xylose measurements may be made for individuals with impaired renal function.
In patients over 50 yrs, due to progressive loss of renal function with age, xylose excretion may be low in the absence of intestinal malabsorption.
Xylose absorption test…5
The test can be used to monitor the response to therapy e.g. coeliac disease (gluten/gliadin enteropathy), tropical sprue syndrome.
Oral glucose tolerance test as a test of intestinal absorption
This test may help to differentiate pancreatic from other causes of malabsorption. Malabsorption caused by chronic pancreatitis is often found to have a “diabetic” type response whereas a “flat” response is more common in other forms of malabsorption
Glucose Tolerance Test
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Disaccharide tolerance
Disaccharidase deficiency manifests as intolerance to one or more of the disaccharides; lactose, maltose or sucrose. Commonest: lactase def
It may be congenital or acquired. NB: intestinal lactase activity
declines with age
Disaccharide tolerance tests…1
Determine whether there is an impairment of absorption of ingested disaccharides
Help define whether any impairment is due to intestinal disaccharidase deficiency.
Disaccharide tolerance tests…2
There is an overnight fast. A blood specimen for [glucose] is
taken 50g disaccharide (lactose, sucrose
or maltose) is given orally. Plasma glucose is measured at 30 minute intervals for the next 2 hours.
Disaccharide tolerance tests…3
In healthy individuals plasma [glucose] should increase by as much as 1.1mmol/L (in at least one of the specimens).
In disaccharidase deficiency / impairment of absorption the rise is usually less than 1.1mmol/L.
Disaccharide tolerance tests…4
To eliminate the possibility that generalised mucosal disease is present, the test should be repeated using a mixture containing 25g of each of the monosaccharides that together make up the dissacharide.
Disaccharide tolerance tests…5
Bacterial metabolism of unabsorbed disaccharide may lead to a faecal pH of less than 5.5.
The most direct way of specifically diagnosing small intestinal disaccharidase deficiency is by peroral biopsy of intestinal mucosa and the measurement of disaccharidase activity.
Protein losing enteropathy….1
Intestinal protein loss is usually detected by the parenteral administration of radio-isotopically labelled macromolecules such as 125I, or 131I-labelled proteins or labelled polyvinyl pyrrolidone.
Protein losing enteropathy….2
Faecal radioactive iodine is then measured. Alternatively, faecal radioactivity can be measured following in vivo labelling of plasma proteins with 51Cr