Malabsorption Syndromes

Prepared by

Tarek ShetaLecturer of internal medicine

Pathophysiology

Digestion and Absorption of Nutrients

Digestion of food Absorption of digestedfood

Presence of digestiveenzymes and bile in the

intestinal lumen

Availability of absorptivemucosal surface

Pathophysiology

Defects in digestion offood

Defects in absorption ofdigested food

Presence of digestiveenzymes and bile in the

intestinal lumenAvailability of absorptive

mucosal surface

Digestion and Absorption of Nutrients

Maldigestion Malabsorption

Defects in digestion offood

Defects in absorption ofdigested food

Clinically, both are described as “Malabsorption”

Clinical Presentation

Malabsorption may involve:– a broad range of nutrients i.e. panmalabsorption.– only a single nutrient or a class of nutrients i.e.

specific malabsorption.

Symptoms and signs of the disease dependon the deficiency of the nutrient(s) that ismalabsorbed.

Malabsorption may involve:– a broad range of nutrients i.e. panmalabsorption.– only a single nutrient or a class of nutrients i.e.

specific malabsorption.

Symptoms and signs of the disease dependon the deficiency of the nutrient(s) that ismalabsorbed.

Steatorrhea: bulky,floating, malodorousstool-difficult to flush.

Weight loss. Flatulence. Weakness and

fatigue. Paresthesias. Tetany. Diffuse abdominal

pain.

Symptoms of anemia. Bone aches. Abnormal bruising. Milk intolerance. Night blindness. Amenorrhea &

infertility.

Symptoms

Steatorrhea: bulky,floating, malodorousstool-difficult to flush.

Weight loss. Flatulence. Weakness and

fatigue. Paresthesias. Tetany. Diffuse abdominal

pain.

Symptoms of anemia. Bone aches. Abnormal bruising. Milk intolerance. Night blindness. Amenorrhea &

infertility.

Signs

Pallor.

Glossitis, stomatitis, cheilosis.

Clubbing.

Ecchymosis and purpura.

Dermatitis.

Dehydration and hypotension.

Edema.

Peripheral neuropathy.

Pallor.

Glossitis, stomatitis, cheilosis.

Clubbing.

Ecchymosis and purpura.

Dermatitis.

Dehydration and hypotension.

Edema.

Peripheral neuropathy.

Blood Screening Tests– Hemoglobin: low.– Serum levels of calcium, albumin, iron, vitamin

B12, folate, carotene, cholesterol:low.– Prothrombin time (PT): prolonged.

Quantitative fecal fat:- Patient should be on daily diet containing 80-100

gms of fat.- Fecal fat estimated on 72 H collection.- 6 grams or more of fat/day is abnormal.- May be due to: - Pancreatic

- Small intestinal- Hepatobiliary disease

Investigations

Blood Screening Tests– Hemoglobin: low.– Serum levels of calcium, albumin, iron, vitamin

B12, folate, carotene, cholesterol:low.– Prothrombin time (PT): prolonged.

Quantitative fecal fat:- Patient should be on daily diet containing 80-100

gms of fat.- Fecal fat estimated on 72 H collection.- 6 grams or more of fat/day is abnormal.- May be due to: - Pancreatic

- Small intestinal- Hepatobiliary disease

D-xylose Absorption Test:- Normally, afer oral digestion of 25 gm.Xylose, at least 1/5 the amount (5 gm.)passes in urine.

- If > 5gm. passes in urine: Maldigestion.- If < 5gm. passes in urine: Malabsorption.

Small bowel biopsy Tests for pancreatic structure and

function

Investigations

D-xylose Absorption Test:- Normally, afer oral digestion of 25 gm.Xylose, at least 1/5 the amount (5 gm.)passes in urine.

- If > 5gm. passes in urine: Maldigestion.- If < 5gm. passes in urine: Malabsorption.

Small bowel biopsy Tests for pancreatic structure and

function

Barium follow throughInvestigations

Malabsorption Disorders - Investigations

Malabsorption suspected clinically

Quantitative Fecal Fat

D-Xylose absorption test

Disorders of theintestinal mucosa

Positive Negative

Disorders ofdigestion

Disorders of transport in the intestinal mucosa Generalized mucosal abnormalities:

– Celiac disease– Tropical sprue– Whipple’s disease– Crohn’s disease– Lymphoma– Radiation enteritis

Malabsorption Disorders - Classification

Disorders of transport in the intestinal mucosa Generalized mucosal abnormalities:

– Celiac disease– Tropical sprue– Whipple’s disease– Crohn’s disease– Lymphoma– Radiation enteritis

Family history positive in about 25% cases.

Characterized by an abnormal mucosa in the small intestine.

Induced by a component of the gluten protein (i.e. gliadin) ofwheat, barley, and some oats.

Local immune responses to the gluten component damage themucosa causing partial or subtotal villous atrophy.

Antibodies to gliadin are found in the peripheral blood.

Celiac Disease

Family history positive in about 25% cases.

Characterized by an abnormal mucosa in the small intestine.

Induced by a component of the gluten protein (i.e. gliadin) ofwheat, barley, and some oats.

Local immune responses to the gluten component damage themucosa causing partial or subtotal villous atrophy.

Antibodies to gliadin are found in the peripheral blood.

The disease usually presents in children under 2years of age and within 6 months of starting cereals.The child ceases to thrive and becomes irritable.

Less commonly the disorder manifests in adult lifeand occasionally even in the elderly.

There is often association with other auto-immunediseases like type 1 diabetes, auto-immune thyroiddisease, vitiligo, etc.

Celiac Disease – Clinical Presentation

The disease usually presents in children under 2years of age and within 6 months of starting cereals.The child ceases to thrive and becomes irritable.

Less commonly the disorder manifests in adult lifeand occasionally even in the elderly.

There is often association with other auto-immunediseases like type 1 diabetes, auto-immune thyroiddisease, vitiligo, etc.

Symptoms range frommild anemia andfatigue to floridmalabsorptive statedeveloping rapidlyover a period ofweeks.

Diarrhea/steatorrhea. Weight loss. Anemia. Peripheral neuropathy. Vitamin deficiency. Edema. Bone pain. Tetany. Clubbing. Glossitis & stomatitis. Amenorrhea & infertility.

Celiac Disease – Clinical Presentation

Symptoms range frommild anemia andfatigue to floridmalabsorptive statedeveloping rapidlyover a period ofweeks.

Diarrhea/steatorrhea. Weight loss. Anemia. Peripheral neuropathy. Vitamin deficiency. Edema. Bone pain. Tetany. Clubbing. Glossitis & stomatitis. Amenorrhea & infertility.

An abnormal small bowel biopsy and agood clinical response to gluten free dietare sufficient for the diagnosis.

Biopsy of the small bowel shows areduced height of the epithelial cells,increased number of plasma cells in thelamina propria and intraepitheliallymphocytes.

Celiac Disease - Investigations

An abnormal small bowel biopsy and agood clinical response to gluten free dietare sufficient for the diagnosis.

Biopsy of the small bowel shows areduced height of the epithelial cells,increased number of plasma cells in thelamina propria and intraepitheliallymphocytes.

Celiac Disease - Investigations

Normal small bowel Celiac Disease

Endomysial (EMA) and Tissue transglutaminase (t-TG)antibodies (IgA for both) are highly sensitivite and specific forthe diagnosis of untreated celiac disease.

These antibodies can also be used as screening tests.

In the presence of a typical clinical picture and the presence ofthese antibodies, a confirmatory small bowel biopsy may notalways be required.

Anti-reticulin antibodies (ARA) are also very sensitive but notso specific, as they are seen in other gastrointestinalconditions (e.g. Crohn's disease).

Anti-gliadin antibodies (AGA) are less sensitive.

Celiac Disease - Investigations

Endomysial (EMA) and Tissue transglutaminase (t-TG)antibodies (IgA for both) are highly sensitivite and specific forthe diagnosis of untreated celiac disease.

These antibodies can also be used as screening tests.

In the presence of a typical clinical picture and the presence ofthese antibodies, a confirmatory small bowel biopsy may notalways be required.

Anti-reticulin antibodies (ARA) are also very sensitive but notso specific, as they are seen in other gastrointestinalconditions (e.g. Crohn's disease).

Anti-gliadin antibodies (AGA) are less sensitive.

Dermatitis herpetiform: itchy red papules on the extensorsurface of the body.

Celiac Disease - Complications

Lymphoma and carcinoma:

– T cell Lymphoma of the small intestine is arecognized complication of celiac disease.

– There is also a higher risk of small bowelcarcinoma.

Ulcerative jejuno-ileitis:

– Patients develop multiple ulcers in the intestinewhich may bleed or perforate.

Celiac Disease - Complications

Lymphoma and carcinoma:

– T cell Lymphoma of the small intestine is arecognized complication of celiac disease.

– There is also a higher risk of small bowelcarcinoma.

Ulcerative jejuno-ileitis:

– Patients develop multiple ulcers in the intestinewhich may bleed or perforate.

A gluten free diet must be taken indefinitely (this requires exclusion ofwheat, barley and oats and imposes severe restrictions which must befully explained to the patient).

Rice and corn based diets are allowed.

Mineral and vitamin supplements may berequired, especially in the beginning.

The skin lesions of dermatitis herpetiformisimprove with gluten free diet, but sometimesdapsone may be needed.

Dietary adherence can be monitored by serialtests for EMA.

A repeat intestinal biopsy should be performedif clinical progress is suboptimal.

Celiac Disease - Management A gluten free diet must be taken indefinitely (this requires exclusion of

wheat, barley and oats and imposes severe restrictions which must befully explained to the patient).

Rice and corn based diets are allowed.

Mineral and vitamin supplements may berequired, especially in the beginning.

The skin lesions of dermatitis herpetiformisimprove with gluten free diet, but sometimesdapsone may be needed.

Dietary adherence can be monitored by serialtests for EMA.

A repeat intestinal biopsy should be performedif clinical progress is suboptimal.

Malabsorption due to small intestinal disease in apatient in or from the tropics.

There has to be an absence of other intestinaldisease or parasites.

Its manifestations resemble those of celiac disease.

Tropical Sprue

Malabsorption due to small intestinal disease in apatient in or from the tropics.

There has to be an absence of other intestinaldisease or parasites.

Its manifestations resemble those of celiac disease.

The prevalence of tropical sprue is in certain welldefined tropical countries and localities such as WestIndies, Asia, Southern India, Sri Lanka, Malaysia andIndonesia.

Its epidemiological pattern, including occasionalepidemics, suggests that an infective agent or agentsmay be involved.

It is thought that this agent may be toxigenic E. coli The small bowel histological changes closely

resemble Celiac disease, although partial villousatrophy rather than subtotal villous is the usuallesion.

Tropical Sprue

The prevalence of tropical sprue is in certain welldefined tropical countries and localities such as WestIndies, Asia, Southern India, Sri Lanka, Malaysia andIndonesia.

Its epidemiological pattern, including occasionalepidemics, suggests that an infective agent or agentsmay be involved.

It is thought that this agent may be toxigenic E. coli The small bowel histological changes closely

resemble Celiac disease, although partial villousatrophy rather than subtotal villous is the usuallesion.

Tropical Sprue – Clinical Features

Diarrhea Abdominal distention Anorexia Fatigue Weight loss Edema Glossitis & stomatitis Anemia

In visitors to the tropics,the onset of diarrheamay be sudden andaccompanied by fever.

Remissions andrelapses may occur.

Diarrhea Abdominal distention Anorexia Fatigue Weight loss Edema Glossitis & stomatitis Anemia

In visitors to the tropics,the onset of diarrheamay be sudden andaccompanied by fever.

Remissions andrelapses may occur.

Dehydration and electrolyte deficiencies must becorrected in severe diarrhea.

Tetracycline 1 g daily in divided doses for 28 days.

Folic acid and Vitamin B12 supplementation are givenas this relieves folate deficiency and improvesabsorption.

The small bowel mucosa soon returns to normal.

Tropical Sprue – Management

Dehydration and electrolyte deficiencies must becorrected in severe diarrhea.

Tetracycline 1 g daily in divided doses for 28 days.

Folic acid and Vitamin B12 supplementation are givenas this relieves folate deficiency and improvesabsorption.

The small bowel mucosa soon returns to normal.

Tropical Sprue – Management

Before treatment After treatment

Tropical Sprue: Small Bowel biopsy before and after antibiotic treatment

Due to exocrine pancreatic insufficiency. Common causes are:

– Chronic pancreatitis.– Cystic fibrosis.– Carcinoma of pancreas.

Steatorrhea with Fecal fat > 7 g/ 24 hrs. Management is with exogenous pancreatic enzyme

supplementation.

Pancreatic Insufficiency

Due to exocrine pancreatic insufficiency. Common causes are:

– Chronic pancreatitis.– Cystic fibrosis.– Carcinoma of pancreas.

Steatorrhea with Fecal fat > 7 g/ 24 hrs. Management is with exogenous pancreatic enzyme

supplementation.

Deficiency of enzyme Lactase in the brush border.

Lactose cannot be hydrolyzed and passes into thecolon where it is converted to short chain fatty acids,H2 and CO2 which cause discomfort and diarrhea.

Patients complain of colic, abdominal distention,increased flatus and sometimes diarrhea afteringesting milk or milk products.

Lactose Intolerance

Deficiency of enzyme Lactase in the brush border.

Lactose cannot be hydrolyzed and passes into thecolon where it is converted to short chain fatty acids,H2 and CO2 which cause discomfort and diarrhea.

Patients complain of colic, abdominal distention,increased flatus and sometimes diarrhea afteringesting milk or milk products.

In primary lactase deficiency, the small bowel biopsyis normal.

Secondary lactase deficiency can occur in smallbowel diseases like celiac disease, tropical sprue andCrohn’s disease.

A lactose free or lactose restricted diet isrecommended depending on the severity ofsymptoms.

Lactose Intolerance

In primary lactase deficiency, the small bowel biopsyis normal.

Secondary lactase deficiency can occur in smallbowel diseases like celiac disease, tropical sprue andCrohn’s disease.

A lactose free or lactose restricted diet isrecommended depending on the severity ofsymptoms.

Also known as:– Contaminated bowel syndrome.– Blind loop syndrome.– Small intestine stasis syndrome.

It is an intestinal abnormality associated withbacterial overgrowth in the small intestine andcausing steatorrhea and Vitamin B12 malabsorption.

These abnormalities improve with administration oforal broad spectrum antibiotics.

Bacterial Overgrowth Syndrome

Also known as:– Contaminated bowel syndrome.– Blind loop syndrome.– Small intestine stasis syndrome.

It is an intestinal abnormality associated withbacterial overgrowth in the small intestine andcausing steatorrhea and Vitamin B12 malabsorption.

These abnormalities improve with administration oforal broad spectrum antibiotics.

The bacterial overgrowth syndrome is caused by:

– Conditions that impair normal physiologicalmechanisms controlling bacterial proliferation in theintestine such as gastric acidity, intestinal motility andantibodies to the bacteria in the intestinal juice.

– Structural abnormalities which deliver colonic bacteriato the small intestine (fistulas), or which provide asecluded haven away from the main peristaltic stream(blind loops, diverticula etc).

Bacterial Overgrowth Syndrome

The bacterial overgrowth syndrome is caused by:

– Conditions that impair normal physiologicalmechanisms controlling bacterial proliferation in theintestine such as gastric acidity, intestinal motility andantibodies to the bacteria in the intestinal juice.

– Structural abnormalities which deliver colonic bacteriato the small intestine (fistulas), or which provide asecluded haven away from the main peristaltic stream(blind loops, diverticula etc).

Bacterial deconjugation of bile acids limiting micelleformation and fat malabsorption.

Mucosal damage from bacterial toxins and toxineffects of free bile acids leads to malabsorption offats, carbohydrates and proteins.

The bacteria also compete for nutrients like VitaminB12 leading to malabsorption.

Bacterial Overgrowth Syndrome - Mechanism

Bacterial deconjugation of bile acids limiting micelleformation and fat malabsorption.

Mucosal damage from bacterial toxins and toxineffects of free bile acids leads to malabsorption offats, carbohydrates and proteins.

The bacteria also compete for nutrients like VitaminB12 leading to malabsorption.

Diarrhea and steatorrhea

Anemia because of Vitamin B12 deficiency

Weight loss

Muscle loss

Symptoms from the underlying intestinal lesions

Bacterial Overgrowth Syndrome - Clinical Features

Diarrhea and steatorrhea

Anemia because of Vitamin B12 deficiency

Weight loss

Muscle loss

Symptoms from the underlying intestinal lesions

Specific Causes Jejunal Diverticula Intestinal obstruction Strictures Gastrocolic or enterocolic fistulas Afferent loop syndrome Diabetes Progressive systemic sclerosis Acquired hypogammaglobulinemia

Bacterial Overgrowth Syndrome

Specific Causes Jejunal Diverticula Intestinal obstruction Strictures Gastrocolic or enterocolic fistulas Afferent loop syndrome Diabetes Progressive systemic sclerosis Acquired hypogammaglobulinemia

Duodenal Diverticulum

Bacterial Overgrowth Syndrome

Duodenal Diverticulum

Antibiotic therapy for 1 – 2 weeks:– Tetracycline– Amoxicillin/clavulinic acid– Cephalosporins– Metronidazole– Ciprofloxacin

Patients may have to be retreated if symptoms recur

Correct any anatomical abnormality if possible

Bacterial Overgrowth Syndrome - Treatment

Antibiotic therapy for 1 – 2 weeks:– Tetracycline– Amoxicillin/clavulinic acid– Cephalosporins– Metronidazole– Ciprofloxacin

Patients may have to be retreated if symptoms recur

Correct any anatomical abnormality if possible

Malabsorption is multifactorial:– Loss of stomach reservoir.– Food reaches jejunum before bile is mixed with it.– Stasis and bacterial overgrowth 2ry to vagotomy.

Billroth II surgery causes significantmalabsorption of Ca++ and Fe++.

There is diarrhea but usually steatorrhea is mild. Treatment consists of antibiotics, antidiarrheals

and antiperistaltic agent.

Malabsorption after gastric surgery

Malabsorption is multifactorial:– Loss of stomach reservoir.– Food reaches jejunum before bile is mixed with it.– Stasis and bacterial overgrowth 2ry to vagotomy.

Billroth II surgery causes significantmalabsorption of Ca++ and Fe++.

There is diarrhea but usually steatorrhea is mild. Treatment consists of antibiotics, antidiarrheals

and antiperistaltic agent.

Malabsorption after gastric surgery

Malabsorption occurs because of: Extensive direct mucosal involvement.

Stricture formation and bacterial

overgrowth.

Fistula formation leading to bacterial

overgrowth.

Surgical resection of the small bowel.

Crohn’s Disease

Malabsorption occurs because of: Extensive direct mucosal involvement.

Stricture formation and bacterial

overgrowth.

Fistula formation leading to bacterial

overgrowth.

Surgical resection of the small bowel.

Radiation can cause damage to:– Small bowel :- Radiation enteritis– Colon :- Radiation colitis– Rectum :- Radiation proctitis

Radiation injury can be divided into:– Acute phase – within days

• Mucosal injury – resolves as mucosa regenerates

– Chronic phase – after years• Extensive direct mucosal involvement

• Stricture formation and bacterial overgrowth

• Fistula formation leading to bacterial overgrowth

Radiation Enteritis

Radiation can cause damage to:– Small bowel :- Radiation enteritis– Colon :- Radiation colitis– Rectum :- Radiation proctitis

Radiation injury can be divided into:– Acute phase – within days

• Mucosal injury – resolves as mucosa regenerates

– Chronic phase – after years• Extensive direct mucosal involvement

• Stricture formation and bacterial overgrowth

• Fistula formation leading to bacterial overgrowth

Diagnosis– Depends on careful history and typical radiological findings.

Management– There is no specific treatment.

– Diarrhea in the acute phase is treated with antidiarrheals.

– Antibiotics may help if there is bacterial overgrowth.

– Dietary manipulations may improve nutrition.

Radiation Enteritis

Diagnosis– Depends on careful history and typical radiological findings.

Management– There is no specific treatment.

– Diarrhea in the acute phase is treated with antidiarrheals.

– Antibiotics may help if there is bacterial overgrowth.

– Dietary manipulations may improve nutrition.

Several types of lymphomas involve thesmall bowel.

The most common are diffuse large celllymphoma and small non-cleaved lymphoma.

Malabsorption occurs because of bacterialovergrowth and terminal ileal involvement.

Small Bowel Lymphoma

Several types of lymphomas involve thesmall bowel.

The most common are diffuse large celllymphoma and small non-cleaved lymphoma.

Malabsorption occurs because of bacterialovergrowth and terminal ileal involvement.

Resection of the small bowel, sometimesextensive, may be necessary in Crohn’sdisease and bowel gangrene from vascularinsufficiency.

Ileal resection is associated with significantconsequences than jejunal resection.

There is severe diarrhea with fluid andelectrolyte loss.

Small Bowel Resection

Resection of the small bowel, sometimesextensive, may be necessary in Crohn’sdisease and bowel gangrene from vascularinsufficiency.

Ileal resection is associated with significantconsequences than jejunal resection.

There is severe diarrhea with fluid andelectrolyte loss.

Management Parenteral fluids and nutrition may be necessary

initially.

Antidiarrheal medications as loperamide anddiphenoxylate are sometimes helpful.

Antisecretory medications (H2 Blockers and PPI) mayreduce gastric secretions.

Cholestyramine may help bind bile salts and preventtheir cathartic effects in the colon.

Some patients may require life long parenteralnutrition.

Small Bowel Resection

Management Parenteral fluids and nutrition may be necessary

initially.

Antidiarrheal medications as loperamide anddiphenoxylate are sometimes helpful.

Antisecretory medications (H2 Blockers and PPI) mayreduce gastric secretions.

Cholestyramine may help bind bile salts and preventtheir cathartic effects in the colon.

Some patients may require life long parenteralnutrition.

An uncommon chronic bacterial infection withmultisystem involvement caused by a grampositive organism Trophyrema whippelli.

There is infiltration of the intestinal mucosawith foamy macrophages containing periodicacid-Schiff (PAS) positive material.

Electron microscopy shows numerousintracellular bacilliform bodies.

Whipple’s Disease

An uncommon chronic bacterial infection withmultisystem involvement caused by a grampositive organism Trophyrema whippelli.

There is infiltration of the intestinal mucosawith foamy macrophages containing periodicacid-Schiff (PAS) positive material.

Electron microscopy shows numerousintracellular bacilliform bodies.

Whipple’s Disease

Low magnification view (2x) of the small bowel mucosa.The lamina propria is expanded by aggregates and sheets

of foamy histiocytes.

High power view (40x)of the small bowelmucosa demonstrated

sheets of foamy histiocytes in the lamina propria

Low magnification view (2x) of the small bowel mucosa.The lamina propria is expanded by aggregates and sheets

of foamy histiocytes.

High power view (40x)of the small bowelmucosa demonstrated

sheets of foamy histiocytes in the lamina propria

PAS stain of the small bowel mucosa demonstrates numerousround sickle shaped bacilli within histiocytes. Theappearance is characteristic of Whipples disease.

Antibiotic therapy provides an excellentresponse in most patients:- Penicillin - Ampicillin- Tetracycline - Erythromycin- TMP-SMX - Chloramphenicol

Therapy must be taken for a long time(months to years).

Relapses are common.

Whipple’s Disease – Management

Antibiotic therapy provides an excellentresponse in most patients:- Penicillin - Ampicillin- Tetracycline - Erythromycin- TMP-SMX - Chloramphenicol

Therapy must be taken for a long time(months to years).

Relapses are common.

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