MALABSORPTION MALABSORPTION SYNDROMESYNDROME

Dr. SabirDr. Sabir

mechanismsmechanismsLuminal phase (processing defect)Luminal phase (processing defect)Digestive enzyme deficiency / inactivationDigestive enzyme deficiency / inactivationbile salt synthesis; bile salt synthesis; Excretion; Excretion; loss;loss; bile salt de-conjugation bile salt de-conjugationgastric acid; gastric acid; intrinsic factor (p. anemia)intrinsic factor (p. anemia)Bacterial consumption of nutrientsBacterial consumption of nutrientsProtein & fat malabsorptionProtein & fat malabsorption

Mucosal phaseMucosal phaseEpithelial transport defect – inflammationsEpithelial transport defect – inflammations infections infectionsBrush border enzyme defectBrush border enzyme defect congenital/acquired disacharidase deficiencycongenital/acquired disacharidase deficiency

Post-absorptive phasePost-absorptive phaseEnterocyte processing – AbetalipoproteinemiaEnterocyte processing – AbetalipoproteinemiaLymphatic obstruction – intestinalLymphatic obstruction – intestinal lymphangectasia lymphangectasia

causescausesExocrine pancreatic Exocrine pancreatic insufficiencyinsufficiency ch. Pancreatitisch. Pancreatitispancreatic CApancreatic CAcystic fibrosiscystic fibrosisInactivation of pancreatic Inactivation of pancreatic lipaselipase – Gastrinoma (ZES) – Gastrinoma (ZES) drugs (orlistat) drugs (orlistat)bile acid (impaired bile acid (impaired micelle formation) micelle formation)cholestatic liver discholestatic liver disBacterial overgrowthBacterial overgrowthAnatomic stasisAnatomic stasis(blind loop,stricture,fistula)(blind loop,stricture,fistula)Functional stasisFunctional stasis(DM, scleroderma)(DM, scleroderma)Interrupted enterohepatic Interrupted enterohepatic circulation of bile acidcirculation of bile acid(ileal resection, Crohn’s )(ileal resection, Crohn’s )Drugs (bind or precipitate b. Drugs (bind or precipitate b. salt)salt) neomycin, chlestyramine neomycin, chlestyramine

Impaired mucosal absorbtion/Impaired mucosal absorbtion/mucosal loss or defectmucosal loss or defectintestinal resection or bypassintestinal resection or bypassinflammation/infiltration/infecinflammation/infiltration/infect.t.(celiac, tropical sprue, (celiac, tropical sprue, lymphoma,lymphoma,scleroderma, Crohn’sscleroderma, Crohn’s Impaired nutrient transportImpaired nutrient transportlymphatic obstructionlymphatic obstruction(lymphoma, (lymphoma, lymphangectasia)lymphangectasia)CHFCHFGenetic disordersGenetic disorders disacharidase defficiency disacharidase defficiency Agamaglobulinemia AgamaglobulinemiaEndocrine/Metabolic disordersEndocrine/Metabolic disorders DM DM

HyperthyroidismHyperthyroidism adrenal insufficiency adrenal insufficiency

carcinoid syndromecarcinoid syndrome

Clinical featuresClinical featuresDepend on the cause and Depend on the cause and severityseverity

GlobalGlobalDiffuse mucosal-Diffuse mucosal- involvement involvementImpaired absorption Impaired absorption of all nutrientsof all nutrientsClassic manifestationClassic manifestationDiarrhea(steatorrhDiarrhea(steatorrhea)ea)weight lossweight lossMajority – sub clinicalMajority – sub clinicalE.g.. Celiac diseaseE.g.. Celiac disease

Partial (isolated)Partial (isolated)2°2° to diseases that to diseases that

interfere with interfere with absorption of absorption of specific nutrientsspecific nutrientsE.g. Pernicious E.g. Pernicious AnemiaAnemia Lactase Lactase deficiencydeficiency

Signs & symptomsSigns & symptomsCalorieCalorie Weight loss with normal appetiteWeight loss with normal appetite

FatFatPale, voluminous, greasy offensive diarrheaPale, voluminous, greasy offensive diarrhea

ProteinProteinEdema, muscle atrophy, amenorrheaEdema, muscle atrophy, amenorrhea

carbohydratecarbohydrateAbdominal bloating, flatus, w. diarrheaAbdominal bloating, flatus, w. diarrhea

B12B12Macrocytic anemiaMacrocytic anemia

Subacute combined degeneration of sp. cordSubacute combined degeneration of sp. cord

Folic acidFolic acidMacrocytic anemiaMacrocytic anemia

Vit B (general)Vit B (general)Cheilitis, glossitis, Angular stomatitisCheilitis, glossitis, Angular stomatitis

IronIronMicrocytic anemiaMicrocytic anemia

Ca & Vit DCa & Vit DOsteomalacia (bone pain, pathologicOsteomalacia (bone pain, pathologic#), Tetany#), Tetany

Vit AVit AFollicular hyperkeratosis, Night blindnessFollicular hyperkeratosis, Night blindness

VIt KVIt KBleeding diathesis, HematomaBleeding diathesis, Hematoma

Investigations:

General:

- CBC: microcytosis, macrocytosis, lymphopenia

- RFT: low urea & creatinine, hypokalemia

- hypocalcemia, low s. albumin

- prolonged PT

- low s. Fe, vit B12, folate

- low s. carotene, cholesterol

Investigations:

Specific:

Tests of fat absorption:

Quantitative fecal fat

Patient should be on daily diet containing 80-100 grams of fat.

Fecal fat estimated on 72 h collection.

6 grams or more of fat/day is abnormal.

May be due to: - Pancreatic dis

- Small intestinal dis

- Hepatobiliary disease

D-xylose testD-xylose test

A Pentose monosacharide absorbed A Pentose monosacharide absorbed exclusively at the proximal SB exclusively at the proximal SB

Used to asses proximal SB mucosal functionUsed to asses proximal SB mucosal function

The testThe testAfter overnight fast, 25gm D-xylose p.oAfter overnight fast, 25gm D-xylose p.o..

Urine collected for next 5 hrsUrine collected for next 5 hrs

Abnormal test - <4.5 gm excretionAbnormal test - <4.5 gm excretion show duodenal / jejunal mucosal disshow duodenal / jejunal mucosal dis..

Other tests for carbohydrate malabsorptionOther tests for carbohydrate malabsorptionLactose tolerance testLactose tolerance testP.o. 50gm lactoseP.o. 50gm lactoseBlood glucose at 0, 60, 120 minBlood glucose at 0, 60, 120 min..BG <20mg/l + development of S/S – diagnosticBG <20mg/l + development of S/S – diagnostic

Breath tests (hydrogenBreath tests (hydrogen,,13Co13Co22))Test for bacterial overgrowthTest for bacterial overgrowthQuantitative bacterial count from aspiratedQuantitative bacterial count from aspirated SB. Normal countSB. Normal count: < 10: < 10 /ml (jejunum)/ml (jejunum) > 10/ml (ileum) > 10/ml (ileum)

Tests for pancreatic insufficiencyTests for pancreatic insufficiencyStimulation of pancreas through adm. of a mealStimulation of pancreas through adm. of a mealor hormonal secretagogues , then analysis of duodenalor hormonal secretagogues , then analysis of duodenalfluidfluidTests for protein malabsorptionTests for protein malabsorption Enteral protein loss Enteral protein loss measuring alpha-1 antitirypsin clearance measuring alpha-1 antitirypsin clearance

Investigation….contInvestigation….cont

Radiographic techniques:

- Plain abdominal X-ray - U/S abdomen

- ERCP - CT abdomen

- endoscopy and biopsy - capsule endoscopy

1)1) Radiography of small intestine:Radiography of small intestine:

Barium swallow and follow-through – to Barium swallow and follow-through – to seesee

- Blind loops- Blind loops

- Strictures- Strictures

- Jejunal diverticuli- Jejunal diverticuli

2)2) Intestinal mucosal biopsy:Intestinal mucosal biopsy:

-by endoscopy and duodenal biopsy-by endoscopy and duodenal biopsy

e.g: Coeliac disease, tropical spruee.g: Coeliac disease, tropical sprue

Small Intestinal Bacterial Small Intestinal Bacterial OvergrowthOvergrowth ( SIBO ) ( SIBO )

Normal proximal small intestinal lumen harbors less Normal proximal small intestinal lumen harbors less than 100000 bacteria / ml of intestinal contents ( than 100000 bacteria / ml of intestinal contents ( relatively sterile) becrelatively sterile) bec: :

– Acidity of stomachAcidity of stomach– Intestinal peristalsis (major)Intestinal peristalsis (major)– ImmunoglobulinsImmunoglobulins

Cause of bacterial growth:Cause of bacterial growth:– Small intestinal diverticuliSmall intestinal diverticuli– Blind loopBlind loop– StricturesStrictures– DM/ SclerodermaDM/ Scleroderma

PathophysiologyPathophysiology

1)1) Bacteria : deconjugate bile salts resulting in: Bacteria : deconjugate bile salts resulting in: Bile SaltBile Salt Impaired intraluminal micelle formationImpaired intraluminal micelle formation Malabsorption of fat. Malabsorption of fat.

2)2) Intestinal mucosa is damaged by:Intestinal mucosa is damaged by: Bacterial invasionBacterial invasion ToxinToxin Metabolic productsMetabolic products Damage villi Damage villi may cause total villous atrophy. may cause total villous atrophy.

Clinically:Clinically: SteatorrheaSteatorrhea AnaemiaAnaemia B12 def.B12 def.Reverse of symptoms after antibiotic Reverse of symptoms after antibiotic

treatment.treatment. Diagnosis:Diagnosis: Breath testBreath test Culture of aspirate (definitive)Culture of aspirate (definitive)Treatment:Treatment: surgery for correctable surgery for correctable

abnormalities such as fistulae abnormalities such as fistulae Antibiotic for non-correctable abnormalities:Antibiotic for non-correctable abnormalities: Tetracycline, cipro, metroTetracycline, cipro, metro some pts may need single 2 wk course for some pts may need single 2 wk course for

prolonged remission , others may need prolonged remission , others may need frequent intermittent coursesfrequent intermittent courses

Postgastrectomy Postgastrectomy malabsorptionmalabsorption

the risk is greatest after total the risk is greatest after total gastrectomy and progressively gastrectomy and progressively decreases after partial decreases after partial gastrectomy and gastrojejunal gastrectomy and gastrojejunal anastomoses anastomoses ((Billroth IIBillroth II)), , antrectomy and gastric- duodenal antrectomy and gastric- duodenal anastomoses anastomoses ((Billroth I)Billroth I)

MechanismMechanism

Several mechanisms, the most Several mechanisms, the most common is the common is the ""poor mixing and poor mixing and poor timingpoor timing." ." Rapid gastric emptying Rapid gastric emptying coupled with decreased release of coupled with decreased release of secretin and cholecystokinin results secretin and cholecystokinin results in suboptimal exposure of the in suboptimal exposure of the nutrient bolus to both bile salts and nutrient bolus to both bile salts and pancreatic enzymes as it traverses pancreatic enzymes as it traverses the small intestinethe small intestine..

Intestinal lymphomaIntestinal lymphoma

Primary lymphoma usually not Primary lymphoma usually not associated with malabsorption.associated with malabsorption.

Enteropathy-associated T-cell Enteropathy-associated T-cell lymphoma (EATL) and Small lymphoma (EATL) and Small Intestinal Immuo-Proliferative Intestinal Immuo-Proliferative Disease (IPSID): both cause Disease (IPSID): both cause malabsorption.malabsorption.

IPSIDIPSID

IPSID is common in young in Middle East, cause IPSID is common in young in Middle East, cause diffuse infiltration of mucosa and submucosa diffuse infiltration of mucosa and submucosa with B lymphocytes and plasma cells:with B lymphocytes and plasma cells:

Abdominal pain, anorexia, diarrhea, wt loss, Abdominal pain, anorexia, diarrhea, wt loss, and as disease progresses: ascites and and as disease progresses: ascites and hepatosplenomegalyhepatosplenomegaly

Dx: serum protein electrophoresisDx: serum protein electrophoresisRx: prolonged course antibiotics(6 m): Rx: prolonged course antibiotics(6 m):

tetracycline, metro esp. in early disease, but tetracycline, metro esp. in early disease, but once frank lymphoma is established: once frank lymphoma is established: combination chemotherapycombination chemotherapy± radiotherapy± radiotherapy

Protein-losing Protein-losing enteropathyenteropathy

Several small intestinal diseases are Several small intestinal diseases are associated with loss of protein in stools associated with loss of protein in stools leading to malnutrition, edema and ascites. leading to malnutrition, edema and ascites. Causes include:Causes include:

- Mucosal erosion or ulcerationMucosal erosion or ulceration: IBD, TB, : IBD, TB, lymphoma, radiationlymphoma, radiation

- Other mucosal diseasesOther mucosal diseases: Tropical sprue, : Tropical sprue, celiac dis, bacterial overgrowth, Menetrier’s celiac dis, bacterial overgrowth, Menetrier’s disdis

- Lymphatic obstructionLymphatic obstruction: lymphoma, intestinal : lymphoma, intestinal lymphangiectasia, constrictive pericarditislymphangiectasia, constrictive pericarditis

Diagnosis by measurement of Diagnosis by measurement of fecal fecal αα1-1-antitrypsinantitrypsin. .

Intestinal tuberculosisIntestinal tuberculosisInfection with human or bovine strains of Infection with human or bovine strains of

Mycob. tuberculosisMycob. tuberculosis may cause chronic may cause chronic inflammation, ulceration and fibrosis of inflammation, ulceration and fibrosis of small intestinal mucosa. The terminal ileum small intestinal mucosa. The terminal ileum is the site of maximal pathology. is the site of maximal pathology. Malabsorption results from loss of protein Malabsorption results from loss of protein and blood from ulcers (protein-losing and blood from ulcers (protein-losing enteropathy), lymphatic obstruction, enteropathy), lymphatic obstruction, bacterial overgrowth due to strictures or bacterial overgrowth due to strictures or ileal disease or resection. The disease is ileal disease or resection. The disease is commoner in underdeveloped countries and commoner in underdeveloped countries and AIDS patients. Pulmonary disease is usually AIDS patients. Pulmonary disease is usually absent and tuberculin test is frequently absent and tuberculin test is frequently negative. Diagnosis by tissue biopsy and negative. Diagnosis by tissue biopsy and culture. The main DDx is Crohn’s disease. culture. The main DDx is Crohn’s disease.

Multiple tuberculous strictures small intestineBa. Meal follow-through

Small intestinal T.B.Ileoscopy

Extensive small bowel Extensive small bowel resection (short bowel resection (short bowel syndrome)syndrome) This is done for Crohn’s dis, This is done for Crohn’s dis,

extensive ischemia or tumours. extensive ischemia or tumours. Patients need total parenteral Patients need total parenteral nutrition (TPN) at first with risk of nutrition (TPN) at first with risk of dehydration. Adaptation of the dehydration. Adaptation of the remaining bowel occurs within remaining bowel occurs within several months. several months.