• digestion/absorption is very efficient with high capacity
• digestive enzymes work at low concentrations(i.e. pancreas is at 10% capacity)
• transport mechanisms can work against a concentration gradient (i.e. 97% of calories taken in are absorbed)
• deficiency is only clinically detectable if extensive loss of function occurs; most dysfunction is subclinical

• (1) Loss of Regulated Gastric Emptying
• (a) Subtotal Gastrectomy: removal of part of the stomach (usually antrum and pylorus) due to ulceration or cancer
• requires plumbing to be reconnected Þ gastroduodenostomy (Billroth I); gastrojejunostomy (Billroth II)
• (b) Truncal Vagotomy: remove vagus innervation of stomach Þ removes cephalic phase of acid secretion (ulcer treatment)
• truncal vagotomy also kills antral motility Þ gastric emptying requires pyloroplasty (destroy pylorus) or Billroth
• either way, normal gastric emptying is lost and maldigestion occurs to a certain extent
• food may enter the small intestine too quickly to properly mix with the digestive enzymes; especially after Billroth II where food may enter the jejunum directly and bypass the duodenum; this is usually not a problem unless compounded by pancreatic or biliary disease
• 10% of truncal vagotomy patients have ‘intestinal hurry’ Þ diarrhea within minutes of eating
• possible that patient had rapid peristalsis moderated by gastric emptying (which was then removed)
• iron deficient anemia: absorption of iron requires gastric acid
• osteomalacia: from decreased absorption of calcium; can lead to sudden fractures
• (c) Dumping Syndrome: may occur in response to large volume meal, especially hypertonic foods (milkshakes, ice cream)
• rapid gastric emptying causes entry of a hypertonic solution to the jejunum
• Þ decreased blood volume as fluid pulled into the intestine results in tachcardia, sweating, fainting
• Þ intestinal distention from water and food leads to pain and nausea
• Þ osmotic diarrhea within an hour
• Þ if a large carbo meal: insulin surge in response to CHO in duodenum exceeds actual intake Þ hypoglycemia
• (2) Insufficient Pancreatic Exocrine Function
• either dysfunction of more than 90% of acini, ductal obstruction, or some combination
• ß lipase Þ steatorrhea
• decreased absorption of lipid soluble vitamins
• ß amylase (lingual amylase insufficient) Þ Ý starch fermentation in gut Þ bulky, frothy stools
• ß protease Þ azotorrhea Þ meat fibers in stool
• possible decreased B12 absorption because undigested proteins compete for intrinsic factor
• can be treated with oral digestive enzymes taken with meals
• (3) Bile Salt Deficiency
• normal: bile salts activate enterokinase, pancreatic and mucosal esterases, form micelles for lipid absorption
• 1.5 moles of bile salts solubilizes 1.5 moles of lipid, 0.06 choloesterol, 0.15 phospholipids, 0.1 monoglycerides
• micelles in contact with mucosa allow lipid diffusion into the cells
• decreased bile salt concentrations (liver disease)
• result of either impaired synthesis (chronic liver disease) or impaired delivery (obstruction of biliary system)
• biliary cirrhosis results in impaired excretion and impaired synthesis
• drugs can bind bile salts either unintentionally as with antibiotic neomycin sulfate; or intentionally as with
• cholestyramine (used to treat bile salt induced diarrhea following ileal resection or to treat puritus of biliary obstruction)
• altered bile salt structure (bacterial overgrowth)
• Þ deconjugation of bile salts to free bile acids (less soluble, less efficient detergents)
• Þ dehydroxylation of bile salts (tri-hydroxy bile salts are much better than mono-hydroxy bile salts)
• dehydroxy bile acids Þ diarrhea
• impaired reabsorption of bile salts (ileal resection or disease)
• enterohepatic circulation involves reabsorption/recycling of bile salts to augment those produced by the liver because the liver cannot synthesize enough bile salts to meet the daily need
• bile acid pool: 2.5 - 4.0 g; 0.5 g/d in stool; 6-12 cycles of recycling per day
• reabsorption of bile salts for enterohepatic circulation occurs only in the distal ilium
• consequence of disruption of the distal ilium by resection or disease depends on the length of ilium affected
• < 100 cm Þ diarrhea from increased bile salts entering the colon; inhibited fluid and electrolyte absorption
• > 100 cm Þ depletion of bile salt pool; impaired fatty acid absorption
• cholecystectomy decreases the bile acid pool, but does not result in insufficient bile salts in the lumen
• (4) Mucosal Disease
• loss of terminal stages of digestion: loss of enterocyte brush border enzymes (maltase, lactase, sucrase)
• isolated lactose deficiency: lactase does not persist past weening in most Af. Am., Asian, Indonesian populations
• Þ lactose intolerance
• loss of peptidases, phosphatases have not been shown to cause any symptoms or deficiencies
• loss of endocrine function: damage to enterocytes can result in CCK deficiency
• Þ ß gall bladder contraction; ß pancreatic secretion; ß enzyme activation
• loss of exocrine function (ß secretion of enteropeptidase): enteropeptidase secreted into lumen is important to activate zymogens (i.e. trypsinogen)

• the majority of a meal is absorbed in the duodenum and early jejunum; vitamins and minerals like iron and calcium are abosrbed primarily in proximal and middle intestine
• B₁₂ and bile acids are only absorbed in the distal ilium (the only necessary function of the ilium)
• ileal resection leads to bile deficiency, B12 deficiency (Þ anemia)
• calcium oxalate nephrolithiasis: bile salt deficiency causes decreased FA absorption; FA displace oxalate from
• Ca in the gut and allow it to be absorbed (not normally absorbed); oxalate binds Ca in kidney Þ stones
• (1) Loss of Surface area – most common cause of malabsorption
• surgical resection: Short Bowel Syndrome
• up to 40% of small bowel can be removed safely (if distal ileum Þ B12, bile salt deficiency)
• hyperplasia and hypertrophy can compensate, Short Bowel Syndrome can be transient
• bypasses and short circuits
• gastrocolic, duodenocolic fistulas from ulcers, Crohn’s disease
• jejunal-ilial bypass in treatment of obesity (no longer done due to malabsorption side effects)
• diffuse mucosal damage
• i.e. gluten sensitive enteropathy (celiac disease or non-tropical sprue) – severe malabsorption with diarrhea
• idiosyncratic immune reaction to gluten protein in wheat, barley, oats, etc
• Þ immunologically-induced loss of intestinal villi (villous atrophy)
• elongated crypts, absent villi, inflammatory cells, smooth appearance on CT; enterocytes renew abnormally fast rate resulting in immature cells at top Þ lack of absorptive capacity and hydrolases!
• (2) Impaired Circulation or Lymphatic Damage
• acute blockage leads to rapid death, and malabsoption doesn’t have a chance to manifest
• chronic impaired venous drainage: thrombosis or heart failure
• impaired lymphatics: congenital lymphangiectasia (bad lymphatic hookups); tumor or infection blocking ducts or cisterna chyli; inflammation of regional lymph nodes
• Þ mucosal edema, dilation of lacteals Þ tissue fluids leak to lumen Þ protein loss (protein losing enteropathy) Þ hypoalbuminemia, secondary edema, serum proteins in feces
• (3) Mucosal Infiltration with Abnormal Cells
• leads to disruption of normal stromal and vascular architecture
• (a) invasion of bowel wall by neoplasm esp. lymphoma cells
• (b) Whipple’s disease: Trophyrema whippelii invades tissue without acute response Þ lamina propria becomes stuffed with macrophages
• (c) chronic inflammation and scarring from X-ray irradiation of abdominal tumors (radiation enteritis)
• (4) Genetic Mutations of Transport Proteins
• present shortly after birth as a specific malabsorption defect rather than generalized malabsorption
• can be very severe (i.e. glucose malabsorption)
• Hartnup disease: less severe; impaired absorption of neutral amino acids in gut and kidney Þ aminoaciduria
• tryptophan malabsorption could lead to niacin deficiency (pellagra)
• oligopeptides are still absobed Þ indicates a separate transporter
• Congenital beta-lipoprotein deficiency
• lack of plasma lipoprotein that forms chylomicrons
• Þ lipid accumulation in enterocytes Þ steatorrhea
• (5) Impaired Motility
• lack of motility means less mixing and less time in contact with the gut wall
• scleroderma: GI smooth muscle degenerates and fibroses
• diabetes complicated with autonomic neuropathy: intrinsic innervation of gut wall is impaired
• bacterial overgrowth is also a problem in reduced motility

Bacterial Overgowth Syndrome – more than 10⁵ / ml are indicative

• causes:
• obstruction (stricture, impaired peristalsis)
• gastrocolic or duodenocolic fistula
• blind loops or diverticula in the proximal gut (congenital diverticulitis, afferent loop of Billroth II)
• consequences:
• competition for nutrients:
• most important is B₁₂ (required by many enteric bacteria)
• bacterial use of carbohydrates leads to increased exhaled H₂
• molecular alterations:
• deconjugation and dehydroxylation of bile salts
• metabolism of amino acids
• many bacteria produce folic acid Þ increased in plasma with overgrowth
• hydroxylation of fatty acids Þ cathartics (inhibit colonic water absorption)
• diagnosis: aspiration of the gut
• treatments: remove anatomical defect, treat with antibiotics, administer B12

• non-invasive: mainly compete for nutrients
• Diphyllobothrium latum (fish tapeworm: competes for B₁₂) Þ megaloblastic anemia
• Giardia lamblia: multiplies, covers much surface area; compete for carbohydrates and vitamins; damages brush border and brush border enzymes
• invasive: damage mucosa, produce inflammatory response
• Strongyloides stercoralis (hookworm): inflammatory reaction in proximal small intestine
• Cryptosoridium: common in AIDS; affects water and electrolyte transport Þ diarrhea

• infection damages enterocytes Þ impaired absorption (Norwalk group and rhodaviruses)

• Clinical Presentation
• weight loss/failure to thrive
• edema due to malabsorption of amino acids
• anemia from Fe deficiency (microcytic); folic acid/B12 deficiency (macrocytic)
• peripheral neuropathy from thiamin/B12 deficiency
• easy bruising due to vit C (scurvy) and K deficiency (K is fat soluble, so often secondary to fat malabsorption)
• rickets, pathological fractures from malabsorption of vit D/Ca
• mental changes related to niacin/B12
• impaired night vision due to vit A
• Laboratory Tests
• (1) tests for fecal fat: most specific and sensitive test for maldigestion/malabsorption
• carbohydrates and amino acids are used by bacteria, fat is not Þ best estimate of absorption/digestion
• normal fat excretion is ~7% of intake; > 10% Þ steatorrhea
• part 1: Sudan III stain: numerous large droplets and skeletal muscle fibers Þ maldigestion Þ pancreatic insufficiency (tests for TG not FFA)
• part 2: detects dietary long chain fatty acids; acetic acid Þ saponified Þ converted to free fatty acids
• if part 1 is negative and part 2 is positive, diagnosis is steatorrhea due to intestinal malabsorption or impaired micelle formation; if part 1 is positive, cannot do part 2 since acetate has no effect on triglycerides
• (2) tests for pancreatic exocrine insufficiency (maldigestion)
• administer Lundh meal (standard meal) or CCK/secretin via IV Þ measure pancreatic secretions (most accurate)
• radiolabeled triolein: reduced uptake indicates lack of pancreatic lipase
• bentiramide test: bentiramide is a synthetic amino acid with PABA linked via a peptide bond; normal function is to cleave this bond and excrete PABA in the urine; abnormal: no PABA excretion Þ cannot accurately quantitate degree of pancreatic insufficiency
• (3) tests for intestinal malabsorption
• xylose tolerance test: D-xylose is absorbed, but 80% is excreted in the urine; subnormal excretion indicates either malabsorption or bacterial metabolism (D-xylose is a monomer, so it is not digested)
• radiolabeled oleic acid: reduced uptake indicates lack of bile salts or other intestinal malabsorption
• (4) breath tests:
• label triolein or oleic acid with ¹⁴C and test breath for ¹⁴CO₂
• H₂ in the breath indicates bacterial metabolism of carbohydrates
• (5) other lab tests
• x-ray, ERCP, CT studies can diagnose anatomic abnormalities, calcification seen in chronic pancreatitis
• biopsy mucosa for histologic evidence of damage
• serum tests for albumin, anemia (B₁₂, folate, Fe)
• prothrombin time (vit K)