Gi Pathophysiology Lecture 5: Intestinal Malabsorption

Front 1

Role of the stomach in digestion and absorption.

The main contributions of the stomach to digestion and absorption are:

Name 5

Back 1

1. Gastric lipase production. Importance: Neonates, pancreatic insufficiency, (CF patients 3-4x inc)

2. Mechanical disruption of the meal and the efficient emulsification of gastric contents.

3. Regulated delivery of nutrients to the small bowel.

4. Intrinsic factor (Parietal cells) production, which is essential for the absorption of vitamin B12.

5. Digestion of cobalamin (vitamin B12) complexes and binding to R-proteins occurs in stomach.

Front 2

1. 80% macronutrient uptake is normally complete in area of intestine.....

Back 2

.... proximal to Ligament of Treitz.

Front 3

The __________ alone absorbs iron, folate, and calcium.

Back 3

duodenum

Front 4

The _________ alone absorbs conjugated bile salts and vitamin B12 complexed with intrinsic factor.

Back 4

ileum

(ileum is specialized for uptake of 1) conjugated bile acids and 2) Vit B12

Front 5

Redundancy exists in the ________, which is the portion whose loss is most easily accommodated.

Back 5

jejunum

Front 6

Key Clinical Points

Selective malabsorption of iron and folate, resulting in anemia, may occur in _________ affecting the duodenum and proximal jejunum, because the ileum cannot compensate for these functions, although it can compensate for proximal malabsorption of fats and carbohydrates.

Back 6

mild celiac sprue

Front 7

Key Clinical Points

Selective malabsorption of bile salts and vitamin B12 may be observed in _______ affecting only the distal ileum.

Back 7

Crohn's disease

Front 8

Processes that affect the rate of exfoliation from the tip of the villus (e.g., ____________) or that affect cell proliferation and consequently replacement of extruded cells (e.g., _______________) will result in a reduced capacity for nutrient absorption in association with a "flattened" mucosa devoid of villi, termed ____________

Back 8

1st blank = bacterial infection

2nd blank = chemotherapy/radiation injury

3rd blank = villous atrophy.

Front 9

Small Intestinal Motility.

The fed pattern results in:

Back 9

food being squished around to maximize mixing and contact of lumenal contents with the mucosa as it gradually proceeds caudally.

Front 10

Small Intestinal Motility.

The fasting pattern consists of:

Back 10

long periods of inactivity followed by a burst of peristaltic activity occurring approximately every 1-2 hrs.

This serves to sweep the intestine of debris and prevents bacterial overgrowth.

Front 11

Small Intestinal Motility.

Control of SI motor activity involves:

Back 11

extrinsic innervation plus intrinsic myogenic properties of SI smooth muscle, hormonal factors. Vagal independent.

Front 12

Small Intestinal Motility.

Normal transit time of an intestinal bolus in the human smallintestine is

Back 12

30 minutes to 3 hours.

Front 13

INTESTINAL HYPOMOTILITY

Symptoms relate to:

Back 13

1) intestinal obstruction (nausea and vomiting)

2) bacterial overgrowth. (major concern)

Front 14

INTESTINAL HYPOMOTILITY

Neuropathic process:

Back 14

1) It is characterized as a dysfunction of the enteric plexus.

Pharmacological interventions are possible

Prototype: Diabetes Mellitus

Front 15

INTESTINAL HYPOMOTILITY

Myopathic process:

Back 15

1) It is characterized as a dysfunction of the end organ (smooth muscle).

No known effective therapy treatment. Manage bacterial overgrowth.

Prototype: Scleroderma.

Front 16

Role of Pancreas in digestion and absorption

Pancreas secretes 4 major enzyme groups:

Back 16

Amylolytic,Proteolytic, Lipolytic and Nucleolytic.

Front 17

Role of Pancreas in digestion and absorption

__________ responsible for alkalinization of pancreatic fluid. _______(channel) involved.

Back 17

Bicarbonate secretion

CFTR

Front 18

ROLE OF THE COLON IN DIGESTION AND ABSORPTION

Back 18

1. Reabsorb fluid and electrolytes

2. Temporary storage of luminal waste products

3. Enteric flora

4. Short chain fatty acids:energy source for colonocytes
(diversion colitis)

Front 19

ROLE OF THE COLON IN DIGESTION AND ABSORPTION

3. Enteric flora

Back 19

- bacterial metabolism of intraluminal substances

- symptoms of malabsorption from bacterial metabolites ie bloating, diarrhea, gas (H2,CO2)

- protection from potential pathogens

Front 20

Bacterial Metabolism of Intraluminal Substances

Hydrolysis of carbohydrates to component monosaccharides. →

Back 20

OSMOTIC DIARRHEA

Front 21

Bacterial Metabolism of Intraluminal Substances

Fermentation of monosaccharides to form absorbable shorter chain fatty acids (acetic, propionic and butyric acid), H2, CO2.

Back 21

GAS, BLOATING, FLOATING STOOL

Front 22

Bacterial Metabolism of Intraluminal Substances

Metabolism of protein and urea to form ammonia. →

Back 22

HEPATIC ENCEPHALOPATHY

Front 23

Bacterial Metabolism of Intraluminal Substances

Hydrolysis of unabsorbed triglycerides to free fatty acids. →

Hydroxylation of unabsorbed fatty acids →

Deconjugation of bile salts and sterols. →

Back 23

SECRETORY DIARRHEA

Front 24

Bacterial Metabolism of Intraluminal Substances

Consumption of vitamin B12 complexed with intrinsic factor. →

Back 24

MACROCYTIC ANEMIA

Front 25

Carbohydrate Malabsorption

Normal Carbohydrate Absorption.

Monosaccharides glucose and galactose ________ absorbed via _________, which is a coupled ____________

Back 25

actively
SGLT-1
Na+ cotransporter

Front 26

CARBOHYDRATE ABSORPTION

Fructose absorption is ________mediated by ________ (carrier)

Back 26

passively
GLUT-5

Front 27

CARBOHYDRATE ABSORPTION

__________is the rate limiting step in the absorption of lactose

(EXAM Q - LECTURE)

Back 27

Lactase activity

In general, transport of monosaccharides across the brush border as opposed to hydrolysis by disaccharidases, is the rate-limiting step in carbohydrate absorption. However, lactase represents the rate-limiting process in the processing of lactose.

Front 28

Lactase deficiency- Key clinical points

Lactose hydrolyzed by flora in large intestine produce glucose and galactose plus fermentation products (H2, CO2). Result is:

Back 28

bloating and gas

Front 29

Lactase deficiency- Key clinical points

Unabsorbed lactose, glucose, galactose _________ osmotic load; may cause _________

Back 29

increase
diarrhea.

Front 30

Lactase deficiency- Key clinical points

Lactase expression in BBM _______ with injury and inflammation/infection (examples of diseases =___________)

Back 30

decreased

sprue, gastroenteritis

Front 31

Other Causes of Carbohydrate Malabsorption.

(In course packet but not in presented lecture)

Back 31

- high fructose corn syrup -->absorptive capacity of the intestine for fructose may be overwhelmed by doses of this sugar encountered in a normal diet.

- Sorbitol is a polyalcohol sugar that is widely used as a sweetener in dietetic foods and "sugar-free" products --> it is poorly absorbed by the intestine, excessive ingestion of this sugar (by chewing packs of "sugar-free" gum) can lead to symptoms (bloating, diarrhea).

Front 32

Protein absorption

T/F Luminal (pancreas) phase is more important than mucosal phase

Back 32

False:

Both luminal (pancreas) and mucosal phases are important

Front 33

Protein absorption

Normally proprtion of protein absorbed in the jejunum _____ than that in the ileum

Back 33

greater (80% vs. 10%)

Front 34

Protein absorption

The colonic bacteria will metabolize some of the protein entering the colon, releasing ______.

Impairment of the liver will result in poor clearance of _______ produced in the colon, and is clinically manifested by alterations in mental status (____________)

Back 34

ammonia

The ammonia reaches the liver via the portal system and is incorporated into urea and amino acids.

ammonia; hepatic encephalopathy

Front 35

Protein malabsorption- Key clinical points

Most frequent causes of protein malabsorption:

Back 35

- loss of normal jejunal mucosal surface

- pancreatic insufficiency (loss of secretions: proteases and bicarbonate to neutralize the pH)

Front 36

Protein malabsorption- Key clinical points

Diffuse loss of jejunal surface: (examples that might cause this)

Back 36

Celiac sprue, surgical resection

Protein loss from intestinal mucosal damage (sprue) leads to protein losing enteropathy

surgery: loss of the small bowel (i.e., resection of infarcted bowel resulting in short bowel syndrome)

Front 37

Protein malabsorption- Key clinical points


Pancreatic insufficiency: (examples that might cause this)

Back 37

CF, chronic pancreatitis

Front 38

Diagnosis of Protein Malabsorption.

The conditions that lead to protein malabsorption are often associated with conditions that lead to ___________.

The clinical picture is therefore often dominated by symptoms relating to __________.

Back 38

fat malabsorption,
fat malabsorption

**There is no readily available clinical test to document the fecal loss of ingested proteins.

Front 39

Fat absorption: Review of pathways

1. Fat represents 40% caloric intake

2. Dietary fat mostly long chain triglyceride.

Absorption requires:

Back 39

- physical dispersion
- hydrolysis by lipases
- micellar solubilization
- transport and uptake at BBM

Front 40

Fat absorption: Review of pathways

T/F Bile acids not required.

Bile acids are synthesized in liver from __________.

Back 40

False

cholesterol

Bile acids are conjugated with glycine and taurine.

Bile acid pool circulates 3-5X each meal, total of 15-20 times daily.

Highly efficient enterohepatic
circulation.

Front 41

Fat absorption: Review of pathways

Some more points to be aware of:

Back 41

Pancreatic lipase-colipase act at emulsion interface, producing MG and FFA

Hydrolysis products form mixed micelles facilitating delivery to BBM.

Within enterocyte, FFA, MG re-esterified to complex lipids and secreted in chylomicrons

Front 42

Fat malabsorption: Key clinical considerations

Causes of fat malabsorption include:

Back 42

Intraluminal maldigestion
Mucosal disorders
Postmucosal obstruction

Front 43

Fat malabsorption: Key clinical considerations

A. Intraluminal maldigestion:

1. Pancreatic insufficiency
(Examples of diseases)

Back 43

Exocrine pancreatic insufficiency:
-CF,
- Chronic pancreatitis

Functional enzymatic insufficiency
- Zollinger-Ellison syndrome (inactivation of lipase at pH <4)

Front 44

Fat malabsorption: Key clinical considerations

A. Intraluminal maldigestion:

2. Intraluminal bile salt deficiency

Back 44

* Ileal dysfunction
* Bacterial overgrowth.
* Biliary obstruction

Front 45

Fat malabsorption: Key clinical considerations

A. Intraluminal maldigestion:

2. Intraluminal bile salt deficiency

* Ileal dysfunction

Back 45

(Crohn's disease, radiation therapy, ileal resection >100 cm). This affects the enterohepatic circulation of bile acids, and depending on the extent of dysfunction, can result in intraluminal bile salt deficiency.

Front 46

Fat malabsorption: Key clinical considerations

A. Intraluminal maldigestion:

2. Intraluminal bile salt deficiency

* Bacterial overgrowth.

Back 46

Premature bacterial deconjugation of bile acids can result in functional intraluminal bile salt deficiency, even though the bile salt pool size is relatively normal. This is because of the altered physical properties (e.g., pKa) of unconjugated bile acids compared with conjugated bile acids. This results in precipitation of the unconjugated bile salts as well as premature jejunal uptake of bile salts via passive nonionic diffusion.

Front 47

Fat malabsorption: Key clinical considerations

A. Intraluminal maldigestion:

2. Intraluminal bile salt deficiency

* Biliary obstruction

Back 47

(Biliary strictures, tumors, cholestatic liver diseases). These disorders are usually manifested by jaundice.

Front 48

Fat Malabsorption.

A. Intraluminal Maldigestion.

3. Poor mixing of biliary and pancreatic secretions with the meal. This is usually observed after

4. Rapid Transit. This is observed in ____________

Back 48

3. This is usually observed after gastric surgery involving bypass of the duodenum, such as a Billroth II anastomosis or bypass for bariatric surgery.

4. This is observed in hyperthyroidism. 25% of hyperthyroid patients have evidence of (mild) steatorrhea.

Front 49

Fat Malabsorption.

B. Mucosal Disorders. (In Course Packet but not in Lecture)

Back 49

1. Injury or reduction of intestinal mucosal surface. Diseases that produce extensive diffuse lesions of the small intestinal mucosa result in generalized malabsorption of nutrients including fats and fat soluble vitamins. Examples include celiac sprue, post-infectious enteropathy, tropical sprue, radiation or chemotherapy induced injury.

2. Specific defects in intracellular lipid metabolism (rare) such as abetalipoproteinemia, a defect in apolipoprotein B packaging into chylomicrons.

Front 50

Fat Malabsorption.

C. Postmucosal Obstruction.

Back 50

Lymphatic obstruction or lymphangiectasia may be primary (due to congenital malformation of intestinal or more proximal vessels) or secondary (neoplasms such as lymphoma, retroperitoneal fibrosis, tuberculosis, Whipple's, trauma).

Front 51

Intestinal resection and diarrhea: Key clinical points. (POSSIBLE EXAM Q)

1. There are differing sites and mechanisms of fat and bile salt absorption.

Fat absorption occurs almost exclusively in the __________

Bile salt absorption occurs __________ in the __________ and ______________, but _________ only in the ileum.


In the colon, _________ absorption of __________bile salts also occurs

Back 51

Fat absorption occurs almost exclusively in the PROXIMAL INTESTINE.

Bile salt absorption occurs PASSIVELY in the DUODENUM and JEJUNUM, (mostly dihyrdoxy conjugates)

but ACTIVELY only in the ileum.(all bile salts)


In the colon, PASSIVE absorption of UNCONJUGATED bile salts also occurs

Front 52

Intestinal resection and diarrhea: Key clinical points.

2. The characteristics of diarrhea following ileal resection or disease depends critically on the:

Back 52

length of functional ileum remaining.

Front 53

Intestinal resection and diarrhea: Key clinical points.

T/F Increased incidence Ca oxalate kidney stones

Back 53

True

Oxalate absorption increased in patients with fat malabsorption. Increased incidence Ca oxalate kidney stones

Calcium is found in fat soaps (when too much fat in colon) and frees up oxalate for absorption --> kidney stones

Front 54

2. Consequences of deficiencies of the fat soluble Vitamins

Vitamin A:
Vitamin D:
Vitamin K:
Vitamin E:

Back 54

Vitamin A: (night blindness),
Vitamin D: (osteopenia and in extreme cases tetany)
Vitamin K (easy bruising).
Vitamin E: deficiency rarely causes clinical symptoms, but areflexia and ophthalmoplegia can occur in severe bile salt deficiencies.

Front 55

Clinical Features of Intestinal Malabsorption.

Presenting Features:
Diarrhea

Describe the cause:

Back 55

Nutrient malabsorption; small intestinal secretion of fluid and electrolytes; action of unabsorbed bile acids, hydroxy fatty acids, and organic acids on the colonic mucosa

Front 56

Clinical Features of Intestinal Malabsorption.

Presenting Features:
Weight loss

Describe the cause:

Back 56

Nutrient malabsorption

Front 57

Clinical Features of Intestinal Malabsorption.

Presenting Features:
Flatus

Describe the cause:

Back 57

Bacterial fermentation of unabsorbed dietary carbohydrates

Front 58

Clinical Features of Intestinal Malabsorption.

Presenting Features:
Abdominal pain

Describe the cause:

Back 58

Distention of bowel, muscle spasm, serosal and peritoneal involvement by disease process

Front 59

Clinical Features of Intestinal Malabsorption.

Presenting Features:
Glossitis, Stomatitis, Cheilosis

Describe the cause:

Back 59

Iron, riboflavin, niacin deficiency

Front 60

Algorithm for malabsorption workup

1. Malabsorption suspected by history, physical findings, with our without biochemical and hematologic findings

What is the first test?

Back 60

Test for steatorrhea: Sudan stain for fat globules; 72h fecal fat collection

The stools of patients with steatorrhea are pale and yellow and have a rancid odor. The feces are often described as sticky and difficult to flush. Because patients' descriptions of their stools are notoriously inaccurate, there is no substitute for visual inspection of the stool.

Sudan Stain: This test has the advantage of simplicity, speed, and low cost. However, it is not sensitive and is positive only if the steatorrhea is of major proportions. A negative test therefore does not exclude the presence of steatorrhea. Ingestion of mineral oil can yield false positives.

72 hour fecal test: "gold standard". The amount of fat excreted in stool collected for 24-72 h, while the patient is on a defined intake of fat (100g/day). The normal value for fat excreted is 5-6 g while the patient is on a 100 g fat diet. (Actually 99% of the ingested fat is absorbed and the 5% observed reflects endogenous losses due to normal turnover of the epithelium, etc.) The advantages of the test are its reliability, sensitivity, and low false negative rate. A major disadvantage is the time involved, the high cost due to the length of hospitalization required for the test, and the long turn-around time for results

If neg: yay!

If pos:
1) Workup small bowel disease
2) Workup pancreatic/biliary disease

Front 61

Algorithm for malabsorption workup

If Steatorrhea positive:

what is the next test?

Back 61

d-xylose absorption test

d-xylose - is passively absorbed - if you absorb these, that means these transports are present and normal and now you're looking at pancreatic insufficiency - if they are not normal youre looking at small bowel series

Front 62

Algorithm for malabsorption workup

If Normal d-xylose excretion, what do you do next?

Back 62

Rule out pancreatic insufficiency (imaging or Bentiromide or secretin testing)

Front 63

Algorithm for malabsorption workup

Abnormal d-xylose excretion, what do you do next?

Back 63

Obtain small bowel series

Front 64

Algorithm for malabsorption workup

Abnormal small bowel series, what does this suggest?

Back 64

Suggestive of specific disorder: Crohn’s disease, fistula, diverticulosis etc

Front 65

Algorithm for malabsorption workup

Nonspecific findings on small bowel series --> followed up with a small bowel biopsy to confirm --> abnormal biopsy - this suggest?

if normal biopsy - this suggest?

Back 65

Treat specific condition (e.g. Celiac sprue)

If normal:
Symptoms may be due to predisposing factor for bacterial overgrowth: Treat with metronidazole

If no predisposing factor for bacterial overgrowth: order a lactulose breath test/SB culture if available

Front 66

TESTS ON PROXIMAL INTESTINE

Back 66

- D-xylose absorption test
- Barium studies (help guide obtaining biopsies)
- Peroral biopsy of the small intestine
- Diffuse or patchy
- Diagnostic vs abnormal but not diagnostic
- Special stains

Front 67

Blood Tests for Malabsorption

Back 67

Anemia,

Decreased serum calcium,
- Low serum calcium levels may result from longstanding calcium malabsorption and vitamin D deficiency or binding of calcium to unabsorbed fatty acids.

Decreased serum albumin,

Decreased cholesterol.

Serum iron studies, folate, and vitamin B12 may be abnormal.

Magnesium deficiency (manifested as tetany)

Zinc deficiency (manifested as dermatitis and poor wound healing)

Front 68

Hepatobiliary disorders are often manifested by ________________ due to impaired excretion of _______.

Back 68

jaundice (yellow tinting of the skin, sclera and mucous membranes)

bilirubin

Front 69

T/F:

The level of steatorrhea associated with pancreatic insufficiency tends to be higher than the level observed for intestinal disease.

Back 69

True

(~50 g) vs. (~20 g)

Front 70

A. D-xylose absorption test.

Back 70

Used to assess the absorptive capacity of the proximal small intestine.

D-xylose is absorbed primarily by a passive mechanism at the luminal concentrations achieved after ingestion of a 25 g dose, and therefore reflects mucosal absorptive surface area rather than specific carbohydrate transport (in contrast to the lactose tolerance test)

Test: Administer 25g d-Xylose in water, collect blood sample @ 0,2h, Urine collection @5h. Should contain ≥5g d-xylose.

In diseases affecting the mucosa < 5 g will be excreted in the urine over 5 h

Caveats: Delayed gastric emptying (d-xylose might not get to intestine); Abn Renal function (not going to excrete d-xylose normally); Ascites (d-xylose might be sequestered in large fluid volume --> inc Volume of distribution); NSAIDs (reduce intestinal permeability ; Bact overgrowth (may consume/convert d-xylose in intestine altering results)

Front 71

B. Barium studies.

The small bowel radiologic series (UGI/SBFT or enteroclysis) is useful for:

Back 71

(1) detecting and localizing mucosal abnormalities, which will help guide the strategy for obtaining mucosal biopsies (i.e., distinguishing between proximal intestinal disease, which is observed in celiac sprue or distal ileal disease, which is often observed in Crohn's disease) and

(2) detecting conditions that predispose to bacterial overgrowth.

Caveats: Important to note that a normal study does not rule out the presence of mucosal lesions and should not necessarily deter one from obtaining mucosal biopsies.

It is important to obtain samples for stool cultures and for ova and parasites prior to obtaining barium studies, since the barium will reduce detection of organisms by inhibiting growth.

Front 72

Case 1

36 y/o white man who presents with iron deficiency anemia that has not responded to oral iron supplementation. The patient denies seeing blood in his stool or black stools. • His exam is normal and the stool was guaiac negative. • Anti tissue transglutaminase (tTG IgA) positive.

Diagnosis:

Back 72

Celiac Sprue:

Rule of thumb: denial of blood in stools young man with iron deficiency anemia excluding GI bleeding; blood test positive for
Tissue Trans Glutaminase
= TTG+ = diagnostic for celiac disease

+ small intestinal biopsy confirms LACK of villi = DIAGNOSTIC = villi atrophy = Celiac Sprue

• The mucosal lesions are diffuse--- ie villous atrophy, but are not specific. • Biopsy required for diagnosis. • Reversion to normal morphology on a gluten free diet may take months. • Mechanism of injury secondary to gliadin fragments in gluten. • Blood tests- antiendomysial (EMA IgA) or anti-tissue-transglutaminase (tTG-IgA) are highly sensitive (90%) and specific (>95%). If serologic studies negative, consider measuring serum IgA levels since up to 3% celiac sprue patients IgA deficient (10-15X higher than general population).

Loss of normal haustral fold pattern = celiac sprue

Front 73

Celiac Sprue

The mucosal lesions occur in the ___________ and then extend _________.

Back 73

proximal small intestine

distally

Front 74

Case 1: Celiac Sprue

Why did the patient only present with iron deficiency and no diarrhea or fat malabsorption?

Back 74

Because his disease only involved the most proximal intestine.

Front 75

Case 1: Celiac Sprue

Treatment is lifelong: Describe it.

Back 75

Requires removal of gluten from the diet: No wheat, barley or rye. Can eat rice, soybeans and corn. Some can tolerate oats.

Front 76

Celiac Sprue

Mechanism:

Back 76

The mechanism of injury is felt to be due to an immune response to gliadin, a complex mixture of proteins that is obtained by alcohol extraction of gluten.

Front 77

Celiac Sprue

Diagnosis:

Back 77

The pathological findings, which include shortening or absence of villi, crypt hyperplasia, and inflammation of the lamina propria, can also be observed in other diseases such as tropical sprue, viral gastroenteritis, and intestinal lymphoma. Consequently the diagnosis cannot be made unless one observes a prompt clinical improvement as well as resolution of the mucosal lesions following withdrawal of gluten-containing cereal grains from the diet.

Front 78

DIAGNOSIS OF LACTOSE INTOLERANCE

Back 78

Empiric: Eliminate or reduce lactose intake to < 3 g (2 oz milk or cheese)

Abnormal H2 breath test: Challenge with ingestion of 25-50 g lactose. Colonic bacteria do not normally see lactose. If you do malabsorb, the bacteria will generate H2 from the lactose spilling into the colon, which is then excreted by the lungs. (Will be negative if you are not colonized by hydrogen producing bacteria).

Other caveats: Diabetes (delayed gastric emptying); Antibiotic use.

Front 79

H2 breath test

Back 79

Only bacteria can produce H2

End-expiratory hydrogen is measured by gas chromatography at baseline and at 30-min intervals after the test meal.

Problem is ~15% patients do not harbor H2 producing bacteria.

Glucose is attractive because 100% is absorbed before reaching the colon.

Often patients have elevated fasting levels (>20 ppm). (Average normal fasting is 7 ppm).

Front 80

CASE 2

56 y/o white woman was admitted to the neurology service for evaluation of weakness and decreased sensation in her lower extremities. “ I can’t tell when I’m pressing down on the brakes when I drive the car”. She also complained of diarrhea and abdominal cramps.

PMH: Cervical cancer diagnosed 10 years ago which had been treated with pelvic radiation. Labs: Megaloblastic anemia; serum vitamin B12 low. Upper GI series with a small bowel follow through showed multiple intestinal strictures.

Diagnosis:

Back 80

Diagnosis: Small bowel bacterial overgrowth

This patient developed intestinal strictures as a complication of her radiation treatment. The strictures led to stasis and bacterial overgrowth.

The bacteria in the small intestine competed for vitamin B12 and prevented her from absorbing vitamin B12 as subsequently demonstrated by the Schilling test.

Her vitamin B12 deficiency manifested as megaloblastic anemia and neurological symptoms (position and vibration, neuropsychiatric changes).

Front 81

Algorithm for Workup of Suspected Small Bowel Overgrowth

Small bowel bacterial overgrowth suspected by: History, physical examination, biochemical and hematologic profile

What do you do first?

Back 81

Specific screen: Schilling test with Intrinsic factor, Qualitative fecal fat with or without 72-hour quantitative fecal fat collection

Front 82

2. Schilling test.

What is it and how does it work?

Back 82

The Schilling test evaluates the absorption of B12 by the use of cobalt57 labeled vitamin B12. A priming dose of cold vitamin B12 is given intramuscularly to correct the deficiency and to saturate all internal B12 binding sites, and then an oral dose of Co57 B12 is given orally. The excretion of Co57 in the urine is measured to assess mucosal absorption. (The normal lower limit is 8% of the administered dose.)

Front 83

Schilling test results & interpretation for case 1

Back 83

In this patient there was abnormally low secretion of radioactive vitamin B12 in the urine. She then underwent Stage II. In Stage II, patients receive radioactive B12 along with intrinsic factor. In this patient the Stage II test was abnormal. This could be due to either ileal dysfunction or bacterial overgrowth. She had the test repeated after taking antibiotics for two Weeks, (Stage IV). This time she had normal excretion of radioactive vitamin B12 in the urine.

Front 84

Algorithm for Workup of Suspected Small Bowel Overgrowth

Schilling Test positive and no known predisposing factor: do what?


Schilling Test positive + predisposing factor: do what?

Back 84

Schilling Test positive and no known bacterial predisposing factor: Barium Study, upper GI tract

If test neg: consider alternative diagnosis

Schilling Test positive + bacterial predisposing factor = Trial antibiotics and nutrient replacement

Front 85

Algorithm for Workup of Suspected Small Bowel Overgrowth

Barium Study upper GI tract

Back 85

- If Anatomic cause demonstrated --> Treat or investigate underlying cause as appropriate --> Trial of antibiotics and replace nutrients

- If no cause identified
Duodenal intubation with biopsy and bacterial culture and quantification --> Trial of antibiotics if positive; consider alternative diagnosis if negative

Front 86

Schilling Test:

Describe:

Stage 1
Stage 2
Stage 3
Stage 4

Back 86

Stage 1: Co57-labeled B12
Stage 2: Co57-labeled B12 + IF
Stage 3: Co57-labeled B12 + Pancreatic Enzymes
Stage 4: Co57-labeled B12 + Metronidazole (antibiotic)

Front 87

Management of malabsorption

Back 87

• Reduction of fat intake (50%) • Medium chain triglycerides • Dietary supplementation of fat soluble vitamins
• Parenteral supplementation of vitamin B12 • Antidiarrheal agents (cholestyramine may exacerbate fat malabsorption)

Front 88

Proton pump inhibitors:

Back 88

Proton Pump Inhibitor can induce decreased B12 absorption due to lower gastric phs less efficient degradation of Cobalamin/R protein complexes - less efficient action in duodenum

associated with calcium malabsorption - risk of hip fracture goes UP - PPIs associated with hip fracture and osteopenic bone disease

Front 89

PPIs and hip fractures?

Back 89

• Role of calcium malabsorption – Acid facilitates release of ionized calcium from insoluble calcium salts – In rats, gastrectomy or omeprazole therapy lead to Ca2+ malabsorption and decrease BMD

– In humans, gastrectomy and pernicious anemia are associated with increased osteopenia and fracture

Front 90

PPI in long term use- conclusions :

Back 90

• Limited data on long-term use of PPIs

• Most studies only suggest an association with potential adverse effects (B12 deficiency, pneumonia, C. difficile, fractures), but more study needed

• Mechanisms underlying susceptibility and modifiers for these associations have yet to be delineated.

• Consider re-evaluation for PPI prescription at regular intervals, especially in elderly population.