Delta Sem (6) - GIT Lecture (9) - Malabsorption

• Interruption of normal digestion, nutrient absorption, and transport results in malnutrition, diarrhea, steatorrhea, and weight loss.

Causes of Malabsorption

• Celiac sprue
• Ileal resection
• Short bowel syndrome
• Radiation enteritis
• Small bowel lymphoma
• Bacterial Overgrowth
• Crohn's disease
• Tropical sprue
• Whipple disease
• Acquired immunodeficiency syndrome
• Diabetes mellitus
• Abetalipoproteinemia
• Amyloidosis
• Chronic pancreatitis
• Cystic fibrosis
• Pancreatic cancer
• Extrahepatic biliary obstruction
• Intrahepatic biliary obstruction
• Cirrhosis

Presentation of Malabsorption

• Weight loss can occur despite a good appetite and adequate oral intake
• Steatorrhea presents as an increased number of foul-smelling stools with an oily character.
• Vitamin A deficiency leads to night blindness
• Vitamin D deficiency leads to osteopenia
• Vitamin E deficiency leads to neurologic symptoms
• Vitamin K deficiency leads to bleeding tendency
• Vitamin B12 & Folic Acid deficiency causes megaloblastic anemia
• Iron deficiency causes anemia since the duodenum is the primary site for iron absorption
• Bile salts deficiency causes fat malabsorption and steatorrhea
• Carbohydrate malabsorption causes abdominal distention, flatulence, and abdominal cramps
• Other symptoms include fatigue, muscle wasting, edema, amenorrhea, and orthostatic hypotension

Evaluation of Malabsorption

• Qualitative fecal fat analysis utilizes Sudan III staining, where fat stains orange
• Quantitative fecal fat analysis measures fecal fat content for 48-72 hours while the patient is on a 100 g per 24-hour fat diet
• Normal fat absorption should be >95% efficient, and thus >5 g/day of fecal fat is abnormal and suggests abnormal fat absorption
• Fecal fat analysis cannot differentiate intestinal mucosal causes of malabsorption from hepatobiliary and pancreatic causes
• D-xylose absorption test is useful to confirm small bowel disorder
• D-xylose is a 5-carbon sugar absorbed in the small intestine without requiring digestion
• Patients are given 25 g of xylose orally, and urinary excretion, or serum concentration of xylose is measured
• Normally, a 5-hour urine collection should contain at least 5 g of D-xylose (25% of ingested D-xylose)
• In small intestinal mucosal disease, absorption is decreased, and less than 5 g of D-xylose is present in urine.
• In hepatobiliary and pancreatic disease, absorption is normal, and greater than 5 g of D-xylose is present in urine

Small Intestinal Imaging

• Barium small-bowel follow-through examinations
• Single- or Double-contrast intubated enteroclysis
• Computed tomography (CT)
• MR enterography
• Capsule endoscopy
• Push enteroscopy, and Double-balloon enteroscopy

Abetalipoproteinemia

• Abetalipoproteinemia is characterized by abnormal absorption of fat and fat-soluble vitamins and total absence of B-lipoprotein (LDL) in plasma.
• It is a rare autosomal recessive disorder caused by mutation in microsomal triglyceride transfer protein, leading to deficiencies in apolipoproteins B-48 and B-100
• Triglycerides accumulate in the liver and intestine but are not found in plasma
• Serum cholesterol level is low.

Tropical Sprue

• The exact cause is unknown, though it may be persistent bacterial, viral, amoebal, or parasitic infections
• Folic acid deficiency and the effects of malabsorbed fat on intestinal motility can cause persistent small intestinal bacterial overgrowth
• Link between small intestinal bacterial overgrowth and tropical sprue has been proposed
• Largely limited to within about 30 degrees north and south of the equator, so recent travel is a key factor in diagnosis
• Treatment is antibiotics and folate

Whipple's Disease

• Symptoms of Whipple's disease are Weight loss, Hyperpigmentation, Infection with tropherma whippelli, PAS-Positive granules in macrophages, Polyarthritis, Lymphadenopathy, and Steatorrhea
• Diagnosis can be made by biopsy, usually by duodenal endoscopy, which reveals PAS-positive macrophages in lamina propria containing nonacid-fast, Gram-positive bacilli
• Immunohistochemical staining for antibodies against T. whipplei has been used to detect the organism
• PCR of saliva, gastric or intestinal fluid, and stool specimens is highly sensitive, but not specific enough
• Treatment is penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years, or doxycycline with hydroxychloroquine for 12 to 18 months
• Hydroxychloroquine increases antibiotic and bactericides activity against bacterial replication in acidic vacuoles of macrophages

Small Intestinal Bacterial Overgrowth (SIBO)

• SIBO is a disorder of excessive bacterial growth in the small intestine
• Risk factors include dysmotility, anatomical disturbances in the bowel, and certain medications (proton pump inhibitors)
• The gold standard for diagnosis is an aspirate from the jejunum that grows in excess of 105 bacteria per ml
• Breath tests are based on bacterial metabolism of carbohydrates, measuring hydrogen, methane, or hydrogen sulfide, or by-products of digestion
• The hydrogen breath test involves fasting for a minimum of 12 hours then having the patient drink a substrate, and measuring expired hydrogen and methane concentrations over several hours
• Carbon-13 (13C) and carbon-14 (14C) based tests have also been developed based on the bacterial metabolism of D-xylose and bile acids
• Increased bacterial deconjugation of bile acids can occur
• Glycocholic acid breath test measures 14CO2, which would be elevated in bacterial overgrowth
• An empiric diagnosis of bacterial overgrowth can be made if treatment improves symptoms
• Elemental diet or antibiotics, followed by prokinetic drugs given to prevent recurrence

Lactose Intolerance

• Lactose intolerance is characterized by a lessened ability or complete inability to digest lactose due to a lack of the enzyme lactase
• The reduction of lactase production typically starts in late childhood or early adulthood, with prevalence increasing with age
• Primary lactose intolerance occurs as the amount of lactase declines over time
• Secondary lactose intolerance occurs due to injury to the small intestine from infection, celiac disease, inflammatory bowel disease, or other diseases
• Developmental lactose intolerance may occur in premature babies and usually improves over a short period of time
• Congenital lactose intolerance is an extremely rare genetic disorder in which little or no lactase is made from
• Symptoms resolving after eliminating lactose from the diet may be confirmatory, with other supporting tests being the lactose hydrogen breath test and stool acidity test
• Treatment includes decreasing lactose intake, taking lactase supplements, or treating the underlying disease

Coeliac Disease

• Occurs due to intestinal atrophy and inflammation as a result of T cell-mediated hypersensitivity to gluten
• Prevalence through Europe is 1:100, and is very rare in Black populations
• Females are affected slightly more commonly than males, with 10-15% of first degree relatives affected
• Concordance rates for identical twins are 70-100%
• There is a strong association with HLA-DQ2 and HLA-DQ8, and absence of these genes excludes Coeliac disease

Clinical Features of Coeliac Disease

• Children: Classically occurs after weaning, with failure to thrive, pallor, apathy, anorexia, and abdominal distension
• Adults: Presents most commonly in the 20s-30s
• Males: Low sperm counts and low plasma testosterone (loss of libido)
• Females: Infertility, 30% of childbearing age have amenorrhea
• Diarrhea: 3-4 loose, pale, often offensive stools, depending on gluten intake
• Constitutional symptoms: lassitude, weight loss, glossitis, angular stomatitis, and anemia
• Vitamin D deficiency or osteoporosis
• May also present as depression and unexplained mild macrocytic anemia with low serum folic acid

Other Coeliac Disease Facts

• 10-15% of Coeliac patients have abnormal LFTs, with a high incidence of autoimmune hepatitis and primary biliary cholangitis
• Includes associations with inflammatory bowel disease, Microscopic colitis, Ulcerative jejunitis, non-Hodgkin's lymphoma, gluten ataxia, and juvenile Rheumatoid Arthritis, and IgA deficiency
• Adult patients may present with typical or atypical manifestations (short stature, refractory anemia, metabolic bone disease and infertility)
• Screening of 'at-risk individuals' for chronic anemia, short stature, metabolic bone diseases, and type 1 diabetes

Investigations

• CBC may show anemia due to iron or folate deficiency and thrombocytosis
• Biochemistry may show low calcium, vitamin D, zinc, and albumin
• Serological tests include IgG and IgA anti-gliadin Ab, IgA anti-reticulin Ab, IgA anti-endomysial Ab, and IgA anti-tissue transglutaminase Ab
• IgA anti-tissue transglutaminase Ab is the most sensitive and specific
• 0.5-1% of general population are IgA deficient, so cause false-negative serological testing, indicating IgG isotype autoantibodies be tested
• Endoscopy (upper GI, Push enteroscopy, or Double-balloon) should be performed
• Endoscopy includes small bowel biopsy or four biopsies from 2nd part of duodenum
• The Modified Marsh classification evaluates crypt/villous architecture
• Barium follow-through can be abnormal, with loss of fine feathery mucosal pattern due to villous atrophy
• Abdominal CT may show splenic atrophy and lymph-adenopathy
• HLA DQ association test identifies HLA DQ2 and HLA DQ8, and negative results essentially rule out Celiac disease

The Modified Marsh Classification

• Type 0: ˂30 IEL/100 enterocytes in duodenum, normal crypt hyperplasia and villi
• Type 1: ˃30 IEL/100 enterocytes in duodenum, normal crypt hyperplasia and villi
• Type 2: ˃30 IEL/100 enterocytes in duodenum, increased crypt hyperplasia, normal villi
• Type 3A: ˃30 IEL/100 enterocytes in duodenum, increased crypt hyperplasia, mild atrophy of villi
• Type 3B: ˃30 IEL/100 enterocytes in duodenum, increased crypt hyperplasia, marked atrophy of villi
• Type 3C: ˃30 IEL/100 enterocytes in duodenum, increased crypt hyperplasia, complete atrophy of villi

Treatment

• Avoid wheat, rye, and barley, alongside fiber supplementation
• Repeat biopsy at 6 months is necessary to assess diet response
• Refractory celiac disease (RCD) is a persistent malabsorption and villous atrophy despite strict adherence to a gluten free diet for at least 6-12 months
• Corticosteroids reduce diarrhea and facilitate weight gain, though effects do not persist after stopping drugs
• Azathioprine used as a steroid sparing therapy
• Supplement with vitamins A, E, D, K, B12, Folic acid, iron and calcium

Presenting Problem Questions and Answers

• Intestinal causes of chronic diarrhea can be divided into small bowel and large bowel disorders
• Small bowel disorders: Coeliac disease, Tropical sprue, Parasitic infections, Immunodeficiency syndromes, Crohn's disease, Whipple's disease, A beta-lipoproteinemia
• Large bowel disorders: Irritable bowel syndrome, Ulcerative colitis, Microscopic colitis
• Questions that must be asked include inquiring whether the diarrhea is due to a functional disease like IBS, or an organic one related to weight loss, fever, or short duration
• Determine whether the diarrhea is of small-bowel type (large volume, frothy, greasy, foul-smelling stool with undigested food), or large-bowel type (more than six stools a day with blood, mucus and/or pus)
• Inquire about the presence of malabsorption (bulky, frothy, greasy stool with undigested food) or a systemic inflammatory response (fever, sweating or joint pains)
• The provided case is chronic and of small-bowel type, with features suggestive of malabsorption.

Examinations and Investigations

• Physical examination should note height, weight, and BMI, as well as signs of pallor, lack of secondary sexual characteristics, angular cheilitis, and stomatitis
• The physical examination indicates that the patient has short stature and nutritional deficiencies, indicating the site of disease is the small intestine

Tests to perform

• Hematological and biochemical tests to determine type of anemia and other effects of malabsorption
• Stool examination for fat, measurement of 72-h stool fat excretion, and D-xylose test
• Stool examination for ova and cysts of parasites
• Serological tests for Coeliac disease and serum immunoglobulin profile
• Lipid profile and apolipoprotein levels, Lactose and glucose hydrogen breath tests
• Endoscopic examination of upper part of intestine & mucosal biopsies