1. MALABSORPTION SYNDROME
Dr. M.A. SOFI
MD; FRCP(London); FRCPEdin; FRCSEdin

2. Malabsorption Syndrome:
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality.
Clinical features
Malabsorption, from whatever cause, may be accompanied by:
Changes in weight and growth:
Inadequate absorption of calories will lead to loss of weight in adults or stunting of growth in children.
Adults will complain of unintended weight loss and perhaps tiredness, lethargy and fatigue.
Children may have similar symptoms accompanied by failure to thrive with growth failure (falling through the centile charts for height and weight).

3. Malabsorption Syndrome:
Diarrhea: Diarrhea frequently is watery, reflecting the osmotic load received by the intestine.
Bacterial action producing hydroxy fatty acids from undigested fat further worsening the diarrhea.
Steatorrhea: is the result of fat malabsorption.
The hallmark of steatorrhea is the passage of pale, bulky, and malodorous stools.
Such stools often float on top of the toilet water and are difficult to flush. Also, patients find floating oil droplets in the toilet following defecation.

4. Malabsorption Flatulence and abdominal distention
Bacterial fermentation of unabsorbed food releases gaseous products, such as hydrogen and methane, causing flatulence.
Flatulence often causes uncomfortable abdominal distention and cramps.
Weight loss and fatigue:
Weight loss is common and may be pronounced.
Weight loss increases in diseases involving the intestine, such as celiac disease and Whipple disease.

5. Malabsorption Edema Anemia
Anemia can be either microcytic or macrocytic
Iron deficiency anemia often is a manifestation of celiac disease.
Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency.
Edema
Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema.
Extensive obstruction of the lymphatics, can cause protein loss.
Severe protein depletion, ascites may develop.

6. Malabsorption Bleeding disorders:
Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia.
Ecchymosis usually manifests, although, occasionally, melena and hematuria occur.
Metabolic defects of bones:
Vitamin D deficiency can cause bone disorders, such as osteopenia or osteomalacia.
Bone pain and pathologic fractures may be observed.
Malabsorption of calcium can lead to secondary hyperparathyroidism.

7. Malabsorption Vitamin malabsorption can cause:
Generalized motor weakness (pantothenic acid, vitamin D)
Peripheral neuropathy (thiamine)
Loss for vibration and position (cobalamin),
Night blindness (vitamin A)
Seizures (biotin).
Neurologic manifestations:
Hypocalcemia & hypomagnesemia, can lead to tetany, manifesting as the Trousseau sign and the Chvostek sign.

8. Causes:
Malabsorption and mal-digestion are pathophysiologically different, the processes underlying digestion and absorption are interdependent.
In clinical practice the term malabsorption has come to denote derangements in both processes.
Three steps are required for normal nutrient absorption:
Luminal and brush border processing
Absorption into the intestinal mucosa
Transport into the circulation
Malabsorption can result from defects in each of these three phases . Furthermore, one or more mechanisms may exist concurrently. Thus, while the clinical sequelae may be similar for two causes of malabsorption, the underlying pathophysiology and treatment may be very different.

9. Malabsorption syndrome: Causes
Mucosal causes
Coeliac disease usually presents in childhood but can present later. It is due to allergy to gluten in the diet that results in subtotal villous atrophy.
Cows' milk intolerance.
Soya milk intolerance.
Fructose intolerance and malabsorption: simultaneous consumption of glucose reduces fructose malabsorption.

10. Infection: Malabsorption syndrome: Causes
Giardiasis
Whipple's disease
Intestinal tuberculosis
Tropical sprue
Traveller's diarrhoea
Diphyllobothriasis (tapeworm can cause vitamin B12 malabsorption)
Ancylostomiasis (hookworm)
Strongyloidiasis (nematode)
In patients with an inflammatory bowel disorder and malabsorption, an immune deficiency, including HIV enteropathy, should be considered.
Intestinal lymphangiectasia and other causes of lymphatic obstruction include lymphoma, tuberculosis and cardiac disease.

11. Malabsorption syndrome: Causes
Intraluminal causes
Pancreatic insufficiency:
Cystic fibrosis
Chronic pancreatitis
Carcinoma of pancreas
Zollinger-Ellison syndrome
Defective secretions of bile salts, due to cholestatic jaundice or disease of the terminal ileum.
Drugs.
Structural causes
Intestinal hurry:
Post-gastrectomy
Post-vagotomy
Gastrojejunostomy
The blind loop syndrome involves disturbance of normal gut flora with malabsorption.
Fistulae.
Diverticulae and strictures.
Crohn's disease.
Amyloidosis.
Short bowel syndrome.
Eosinophilic gastroenteropathy.
Mesenteric arterial insufficiency.
Radiation enteritis.

12. Phase and nature of malabsorptive defect Example
Luminal phase
A. Substrate hydrolysis
1. Digestive enzyme deficiency
Chronic pancreatitis
2. Digestive enzyme inactivation
Zollinger-Ellison syndrome
3. Dysynchrony of enzyme release, inadequate mixing
Post Billroth II procedure
B. Fat Solubilization
1. Diminished bile salt synthesis
Cirrhosis
2. Impaired bile secretion
Chronic cholestasis
3. Bile salt de-conjugation
Bacterial overgrowth
4. Increased bile salt loss
Ileal disease or resection
C. Luminal availability of specific nutrients
1. Diminished gastric acid
Atrophic gastritis - vitamin B12
2. Diminished intrinsic factor
Pernicious anemia - vitamin B12
3. Bacterial consumption of nutrients
Bacterial overgrowth - vitamin B12

13. Phase and nature of malabsorptive defect Example
Mucosal (absorptive) phase
A. Brush border hydrolysis*
1. Congenital disaccharidase defect
Sucrase-isomaltase deficiency
2. Acquired disaccharidase defect
Lactase deficiency
B. Epithelial transport
1. Nutrient-specific defects in transport
Hartnup's disease
2. Global defects in transport
Celiac sprue
Postabsorptive, processing phase
A. Enterocyte processing
Abetalipoproteinemia
B. Lymphatic
Intestinal lymphangiectasia
* This process is sometimes considered as part of the luminal phase.

14. Weight loss with normal appetite
Malabsorption
Clinical features
Laboratory findings
Calories
Weight loss with normal appetite
Fat
Pale and voluminous stool, diarrhea without flatulence, steatorrhea
Stool fat >6 g/day
Protein
Edema, muscle atrophy, amenorrhea
Hypoalbuminemia, hypoproteinemia
Carbohydrates
Watery diarrhea, flatulence, acidic stool pH, milk intolerance, stool osmotic gap
Increased breath hydrogen
Vitamin B12
Anemia, subacute combined degeneration of the spinal cord (early symptoms are paresthesias and ataxia associated with loss of vibration and position sense)
Macrocytic anemia, vitamin B12 decreased, abnormal Schilling test, serum methylmalonic acid and homocysteine increased
Folic acid
Anemia
Macrocytic anemia, serum and RBC folate decreased, serum homocysteine increased

15. Malabsorption Clinical features Laboratory findings Folic acid Anemia
Macrocytic anemia, serum and RBC folate decreased, serum homocysteine increased
Vitamin B, general
Cheilosis, painless glossitis, acrodermatitis, angular stomatitis
Iron
Microcytic anemia, glossitis, pagophagia
Serum iron and ferritin decreased, total iron binding capacity increased
Calcium and vitamin D
Paresthesia, tetany, pathologic fractures due to osteomalacia, positive Chvostek and Trousseau signs
Hypocalcemia, serum alkaline phosphatase increased, abnormal bone densitometry
Vitamin A
Follicular hyperkeratosis, night blindness
Serum retinol decreased
Vitamin K
Hematoma, bleeding disorders
Prolonged prothrombin time, vitamin K-dependent coagulation factors decreased

16. Acrodermatitis enteropathica
Cheilosis
Glossitis
Follicular Keratosis

17. Physical signs General physical examination Abdominal examination
Patients may have orthostatic hypotension.
Patients may complain of fatigue.
Signs of weight loss, muscle wasting, or both may be present.
Patients may have signs of loss of subcutaneous fat.
Abdominal examination
The abdomen may be distended, and bowel sounds may be hyperactive.
Ascites may be present in severe hypoproteinemia.

18. Physical signs Dermatologic manifestations
Pale skin may reveal anemia.
Ecchymoses due to vitamin K deficiency may be present.
Dermatitis herpetiformis, erythema nodosum, and pyoderma gangrenosum may be present.
Pellagra, alopecia, or seborrheic dermatitis may be present.
Neurologic examination
Motor weakness, peripheral neuropathy, or ataxia may be present.
The Chvostek sign or the Trousseau sign may be evident
Cheilosis, glossitis, or aphthous ulcers of the mouth

19. Differential diagnosis:
Laboratory studies:
Hematologic tests:
A CBC count may reveal microcytic anemia due to iron deficiency or macrocytic anemia due to vitamin B-12 or folate malabsorption.
Serum iron, vitamin B-12, and folate concentrations may help establish a diagnosis.
Prothrombin time may be prolonged because of malabsorption of vitamin K, a fat-soluble vitamin.
Acrodermatitis Enteropathica
Cystic Fibrosis
Hartnup Disease
Intestinal Lymphangiectasia
Whipple Disease
Zollinger-Ellison Syndrome

20. Laboratory Studies:
Fat malabsorption can lead to low serum levels of triglycerides, cholesterol, and alpha- and beta-carotene.
Westergren sedimentation rate is elevated in Crohn disease and Whipple disease.
Electrolytes and chemistries:
Malabsorption can involve electrolyte imbalances, such as hypokalemia, hypocalcemia, hypomagnesemia, and metabolic acidosis.
Protein malabsorption may cause hypoproteinemia and hypoalbuminemia.

21. Laboratory Studies: Serology:
No serologic tests are specific for malabsorption.
Serum antigliadin and antiendomysial antibodies can be used to help diagnose celiac sprue.
Serum IgA can be used to rule out IgA deficiency.
Determination of fecal elastase and chymotrypsin (2 proteases produced by the pancreas) can be used to try to distinguish between pancreatic causes and intestinal causes of malabsorption.

22. Laboratory Studies:
Flocculation of the barium occurs in the gut lumen.
Small bowel dilatation and diverticulosis in scleroderma.
Regional enteritis of the small intestine can lead to stricture, ulceration, and fistula formation.
Imaging Studies:
Small bowel barium studies
An abnormal small bowel pattern from barium studies may reveal the nature of malabsorption.
The mucosa pattern in celiac disease often becomes obliterated or coarsened.

23. ERCP in chronic pancreatitis
Celiac disease
Severe pancreatic duct changes with dilation of the main pancreatic duct and of the primary and secondary branches.
Scalloped duodenal folds seen on endoscopy in a patient with celiac disease

24. Other Tests Tests of fat malabsorption
Many disease processes result in fat malabsorption.
Quantitative measurement of fat absorption, a 72-hour fecal fat collection is often performed.
Patients will consume a normal amount ( g/d) of fat before and during the collection.
Based on this intake, fecal fat excretion in healthy person should be less than 7 g/d.
Serum retinyl palmitate to identify severe cases of fat malabsorption may be useful relative to the 72-hour fecal fat test.
Qualitative tests include the acid steatocrit test and Sudan III stain of stool, but these tests are less reliable

25. Laboratory Studies D-xylose test
D-xylose test is used to document the integrity of the intestinal mucosa.
Facilitated diffusion in the proximal intestine primarily absorbs D-xylose.
In normal individuals, a 25 g oral dose of D-xylose will be absorbed and excreted in the urine 4.5 g in 5 hours.
If the absorption of D-xylose is impaired due to either a luminal factor (e.g., bacterial overgrowth) or a reduced or damaged mucosal surface area (e.g., surgical resection, celiac disease), urinary excretion is lower than normal.
Cases of pancreatic insufficiency usually result in normal urinary excretion because the absorption of D-xylose is still intact.

26. Other tests: Tests of carbohydrate absorption:
A simple sensitive test for carbohydrate malabsorption is the hydrogen breath test, in which patients are given an oral solution of lactose.
In cases of lactase deficiency, colonic flora digest the unabsorbed lactose, resulting in an elevated hydrogen content in the expired air.
Bacterial overgrowth or rapid transit also can cause an early rise in breath hydrogen, necessitating the use of glucose instead of lactose to make a diagnosis. However, 18% of patients are hydrogen nonexcretors, causing a false-negative test result.

27. Other tests: Test of bile salt absorption:
Bile salt breath test can determine the integrity of bile salt metabolism.
The patient is given oral conjugated bile salt, such as glycine cholic acid with the glycine radiolabeled in the carbon position.
The bile salt is deconjugated and subsequently metabolized by bacteria, leading to a radioactively labeled elevated breath carbon dioxide level if interrupted enterohepatic circulation, such as bacterial overgrowth, ileal resection, or disease, is present.

28. Other tests: Wireless capsule endoscopy :
 Wireless capsule endoscopy allows for visualization of the entire small bowel and allows for much more detailed evaluation of small bowel mucosal disease than barium studies. Thus, it may have a role in evaluating suspected small bowel disease (such as Crohn's disease) associated with malabsorption.
Because of the risk of retention, wireless capsule endoscopy should generally be avoided in patients with known or suspected small bowel strictures

29. Other tests: Upper endoscopy with small bowel mucosal biopsy
Establishing a definitive diagnosis of malabsorption of the mucosal phase often can be achieved by histologic examination of biopsied mucosal specimens obtained during routine upper endoscopy
Examples of conditions that can be diagnosed this way include celiac sprue, giardiasis, Crohn disease, Whipple disease, amyloidosis, abetalipoproteinemia, and lymphoma.

30. Laboratory features of malabsorption
Decreased
Increased
Hemoglobin
Oxalate in urine
Serum or RBC folate
Prothrombin time
Serum
Serum total iron binding capacity
Iron
Ferritin
Vitamin B12
Calcium
Magnesium
Cholesterol
Carotene
Albumin
25-hydroxyvitamin D

31. Principles of management:
Identification and treatment of the underlying disease
Treatment of the diarrhea that often accompanies these disorders
Identification and correction of nutritional deficits.
There are three major principles underlying the management of patients with malabsorption and maldigestion, and appropriate care of such patients in the majority of cases necessitates that each of these three are addressed:

32. Principles of management:
Because symptoms may be absent or mimic other diseases, a routine battery of blood tests is often helpful as an initial step
Several invasive and noninvasive tests are available to establish the cause of malabsorption. Further testing may not be necessary in patients who have gross steatorrhea.
Summary and recommendations:
Malabsorption depend upon the cause and severity of the disease
The etiology can often be obtained from a detailed patient history, which can also exclude other causes of symptoms.
Deficiencies of specific nutrients and vitamins may also identify the underlying cause and its duration

33. Practical advice in diagnosis of Malabsorption
1. Stools may appear normal even when laden with excess fat.
2. Patients with carbohydrate malabsorption may have watery diarrhea and complain of
excess flatus and abdominal distension. Symptoms typically occur within 90 minutes of
carbohydrate ingestion.
3. Abdominal pain is unusual in malabsorption except in the case of chronic pancreatitis,
Crohn disease, or intestinal pseudo-obstruction (eg, scleroderma).
4. Patients with celiac disease often have a childhood history of ill health and a positive
family history of gluten sensitivity or Crohn disease. Anemia or mildly elevated liver
enzymes, is commonly the sole initial indication of disease.
5. The prevalence of celiac disease in patients with type 1 diabetes mellitus is higher than
the general population.
6. Always ask about previous surgery.
7. Always ask about a history of recurrent peptic ulcer disease.
8. Do a careful physical examination looking for signs of nutrient malabsorption.
9. Do not forget to ask about alcohol consumption. It usually takes 10 to 20 years for
pancreatic insufficiency to develop in alcoholics.
10. A history of oil drops separated from the main stool mass, becoming whitish and firm
after cooling (non-hydrolyzed triglycerides), strongly points toward pancreatic
insufficiency as the cause.

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