Lipid Malabsorption Clinical Concepts

Question 1

Intestinal permeability test

Answer 1

• D-xylose
• small-bowel follow-through

Question 2

Malabsorption refers to:

It can result from:

Answer 2

impaired absorption of nutrients

• It can result from
  
  • congenital defects in the membrane transport systems of the small intestinal epithelium (primary malabsorption)
  • acquired defects in the epithelial absorptive surface (secondary malabsorption).
  • maldigestion, impaired digestion of nutrients within the intestinal lumen
• Although malabsorption and maldigestion are pathophysiologically different, the term malabsorption has come to denote derangements in both processes.

Question 3

Digestion and absorption of fat involve a complex mechanism.

It requires:

Answer 3

• bile acids
• digestive enzymes
• a normally functioning small intestinal mucosa

Question 4

Dietary lipids, mostly as triacylglycerols, are initially _________and then __________into free fatty acids and monoglycerides

Answer 4

emulsified by bile acids; hydrolyzed by the pancreatic lipases and colipases

Question 5

In the proximal small bowel, hydrolyzed lipids form ______by the action of bile acids

which are then absorbed across the _________ and transported as ______ via the _________

Answer 5

• micelles
• intestinal villi; chylomicrons; intestinal lymphatics

Question 6

The causes of steatorrhea are numerous and subclassify under three broad categories:

Answer 6

1. conditions leading to Exocrine Pancreatic insufficiency (EPI)
2. bile acid deficiency states, and
3. diseases affecting the small intestine.

Question 7

EPI due to:

Answer 7

• chronic pancreatitis,
• cystic fibrosis (CF),
• and conditions resulting in pancreatic duct obstruction or resection of the pancreas (e.g., pancreatic tumors)

Question 8

Bile acid deficiency either due to:

Answer 8

• cholestasis (e.g. primary biliary cholangitis (PBC),
• primary sclerosing cholangitis (PSC))
• ileal resection or Crohn disease of the ileum
• deconjugation of bile acids (e.g., small intestinal bacterial overgrowth (SIBO))

Question 9

Diseases affecting proximal small intestines such as:

Answer 9

• celiac disease
• tropical sprue
• giardiasis
• Whipple disease
• lymphoma
• amyloidosis
• SIBO
• and HIV enteropathy

Question 10

Steatorrhea is one of the clinical features of fat malabsorption and noted in many conditions such as

Answer 10

• exocrine pancreatic insufficiency (EPI)
• celiac disease
• tropical sprue.

Question 11

An increase in the fat content of stools results in the production of

Answer 11

pale, large volume, malodorous, loose stools

Question 12

Screening for steatorrhea may be carried out by

Answer 12

examining stool samples for the presence of fat by Sudan III staining

quantitative fecal fat estimation is required to confirm the diagnosis

Question 13

Fat malabsorption causes symptoms therefore the history often allows you to diagnose this problem

Answer 13

• Foul smelling stools
• Oil in stool (oil droplets)
• Mild to moderate diarrhea
• history of intestinal resection
• History of pancreatitis

•OIL IS NOT WHITE (MUCUS)

Question 14

Answer 14

Question 16

Test for Fat Malabsorption

Stool Fat

Qualatative test:

Quantitative test:

Answer 16

• Qualitative test
  
  • Sudan stain
• Quantitative test
  
  • measure > 6 grams of fat per day in a stool specimen from a patient eating 100 grams of fat per day (72 hour collection)

Question 17

Pancreatic Insufficiency Tests

Answer 17

• The secretin stimulation test
  
  • secretin causes the secretion of bicarbonate-rich fluid from the pancreas.
• Fecal elastase
  
  • overall sensitivity and specificity of 93 percent for pancreatic insufficiency
  • Among pancreatic function tests, fecal elastase measurement is the most sensitive and specific in the early phases of pancreatic insufficiency.
• Fecal chymotrypsin is easy to measure and levels are stable in stool samples for days.
  
  • levels are usually elevated only in advanced pancreatic disease. As a result, the overall sensitivity for pancreatic insufficiency is only approximately 50 to 60 percent.

Question 18

Intestinal permeability tests

Answer 18

• D-xylose
• small-bowel follow-through

are neither specific nor sensitive and are not recommended for CD diagnosis.

Question 19

Jejunal Resection vs Ileal Resection

Absorption:

Vitamin and Bile salts absorption:

Adaptation:

Transit:

Answer 19

• Jejunal
  
  • adequate absorption unless >75% resected
  • Preserved absorption of B₁₂ and bile salts
  • Good ileal adaptation
  • Normal transit
• Ileal
  
  • Adequate calorie and fluid absorption
  • Malabsorption of
    
    • bile salts
    • vitamin B₁₂
  • Poor jejunal adaptation
  • Rapid intestinal transit

Question 20

Bile acids are absorbed only in the terminal ileum. Resection of ______ of ileum loses some bile salts to the colon where they act as laxatives. The liver increases the synthesis to maintain a normal bile salt pool size. It cannot compensate for a greater resection. Less bile salt leads to ________.

Answer 20

<100cm

maldigestion and steatorrhea

Question 21

Treatment

Malabsorption:

Maldigestion:

Answer 21

• Malabsorption
  
  • Treat the underlying intestinal disease
• Maldigestion
  
  • Supplemental enzymes that contain lipases

Question 22

Small Intestinal Diseases

Answer 22

• Celiac Disease
• Tropical Sprue
• Whipple’s Disease
• Bacterial Overgrowth

Question 23

A lifelong intolerance to gluten occurring in genetically predisposed individuals who mount an immunological response to an environmental factor, gliadin, a component of gluten

Answer 23

Celiac Disease

Dermatitis herpetiformis is closely related and should be considered an extra-intestinal, autoimmune, manifestation of celiac disease.

Question 24

Increased mortality compared to the general population due to an increase in the incidence of malignant disease

Answer 24

• Adenocarcinoma and T-cell lymphoma of the small intestine
• Squamous carcinoma of the esophagus and pharynx
• Non-Hodgkin’s lymphoma

Question 25

Epidemiology

• There has been a substantial increase in the prevalence of celiac disease over the last______ years and an increase in the rate of diagnosis in the last______ years.
• Celiac disease is considered common in _____where serological screening studies have demonstrated the prevalence to be _______of the general population.
• In the US the disease is considered rare (________) even though a large percentage of the population are of European origin

Answer 25

• 50; 10
• Europe; 1 in 250 to 300
• 1 in 4,800

Question 26

Genetic Factors

• The high concordance for the disease suggests a ________ predisposion
• The strong association with HLA phenotypes _______.a

Answer 26

• genetic
  
  • in identical twins (70%) and
  • rate among first degree relatives (10%) suggests a genetic predisposition.
• DQ2 and DQ8

Question 27

Environmental Factors

Answer 27

Gluten

• the alcohol soluble protein of wheat (gliadin) and similar proteins found in barley (hordeins) and rye (secalines) are considered toxic.
• Oats (avidins), formerly considered toxic, have recently been demonstrated to be tolerated.
• Rice is well tolerated

However oats should be avoided because of contamination with other grains at all stages of production and processing

Question 28

Celiac disease is one of the most common causes of chronic malabsorption

This results from:

Answer 28

• injury to the small intestine with loss of absorptive surface area,
• reduction of digestive enzymes, and
• consequential impaired absorption of micronutrients such as fat-soluble vitamins, iron, and potentially B12 and folic acid.
• In addition, the inflammation exacerbates symptoms of malabsorption by causing net secretion of fluid that can result in diarrhea.

Question 29

Celiac disease can present with many symptoms, including:

Answer 29

• typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also
• non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations

Many individuals with celiac disease may have no symptoms at all

Question 30

Celiac disease is usually detected by:

The diagnosis is confirmed by:

Answer 30

• serologic testing of celiac-specific antibodies
• duodenal mucosal biopsies

Both serology and biopsy should be performed on a gluten-containing diet

Question 31

Serology (Celiac disease)

Answer 31

• Serum immunoglobulin A (IgA) endomysial antibodies and IgA tissue transglutaminase (tTG) antibodies. Sensitivity and specificity > 95%.
• Testing for gliadin antibodies is no longer recommended because of the low sensitivity and specificity for celiac disease.
• The tTG antibody test is less costly because it uses an enzyme-linked immunosorbent assay; it is the recommended single serologic test for celiac disease screening in the primary care setting.

Question 32

In the diagnosis of celiac disease _______ defiencieny can give false negative

Answer 32

IgA deficiency

Confirmatory testing, including small bowel biopsy, is advised.

Question 33

Diagnosis of celiac disease

Gold standard of diagnosis:

Normal range:

Answer 33

• Intestinal biopsy
• Normally the crypt to villous ratio is 1:4. As villous atrophy increases in severity the villi shorten and crypts elongate.
• Partial villous atrophy is seen when the crypt: villous ratio ranges from 1:3 to 1:1.

Question 34

Label

Answer 34

Question 35

Label

Answer 35

Question 36

Answer 36

Jejunal mucosal biopsy from patient with celiac sprue (A)

Celiac sprue is characterized by small intestinal mucosal damage in susceptible patients after ingesting gluten, the water-insoluble protein component of grains. Note the flat mucosa, absence of villi, deep crypts, severe inflammation in the lamina propria

Question 37

Clinical Symptoms (Celiac disease)

• Chronic Diarrhea associated with Malabsorption
• Asymptomatic presentation

Answer 37

• Chronic Diarrhea associated with Malabsorption
  
  • Steatorrhea
  • Hypoproteinemia
  • Hypocalcemia
• Asymptomatic presentation
  
  • iron deficiency anemia
  • metabolic bone disease
  • vague gastrointestinal symptoms
    
    • labeled as an irritable bowel syndrome

Question 38

The diagnosis of celiac disease should be sought in those groups known to have an increased incidence of celiac disease

Answer 38

• insulin dependent diabetics
• autoimmune thyroid disease
• Sjogren’s syndrome
• Down’s syndrome
• primary biliary cirrhosis
• Irritable Bowel Syndrome

Question 39

Management of Celiac Disease

Answer 39

Strict adherence to a gluten-free diet is advised for life.

• Knowledge of the presence of hidden gluten in food additives, communion wafers, and as fillers in medications is important.
• Treat for iron, folate, and fat soluble vitamin deficiency
• Bone mineral density should be determined because of the great frequency of osteoporosis and osteopenia.
• Vitamin D deficiency and secondary hyperparathyroidism need to be excluded in those with reduced bone density.

Question 40

Management of Celiac Disease continued

Answer 40

• Pneumococcal vaccine should be administered on diagnosis because of hyposplenism which is very common at diagnosis and may resolve.
• A follow up biopsy is obtained at about a year.
• Annual testing for EMA is advised because of inadvertent gluten ingestion. Earlier antibody measurement and biopsy may be necessary if the course of the illness is atypical

Question 41

Answer 41

Jejunal mucosal biopsy from a patient with celiac sprue before (panel A), and 3 months after (panel B) treatment with a gluten-free diet. Celiac sprue is characterized by small intestinal mucosal damage and nutrient malabsorption in susceptible persons after ingesting gluten, the water-insoluble protein component of certain grains. Panel A illustrates the flat mucosal surface, absence of villi, hyperplastic crypts, and increased lamina propria cellularity that are characteristic of the disease. After 3 months of treatment (panel B) the mucosa is markedly improved and recognizable villi are present. However, the villi are short, and crypt hyperplasia and lamina propria hypercellularity persist. The severity of malabsorption and clinical symptoms can vary markedly in patients with celiac sprue, and are directly correlated with the length of the intestinal lesion. Usually, the proximal intestine is most involved and disease severity decreases distally along the length of small bowel. Patients with severe disease have flatulence, progressive weight loss, and multiple nutrient deficiencies. The diarrhea is often voluminous and may float on water because of increased gas and fat content. However, some patients have increased fecal mass without loose stools and complain of constipation. Removal of dietary gluten, present in wheat, rye, barely, oats, food additives, emulsifiers, and stabilizers, is essential for successful management. Patients who do not respond to a strict gluten-free diet may have refractory sprue or lymphoma.

Question 42

Answer 42

Question 43

Non Celiac Gluten Intolerance

Answer 43

• 17 times more common than Celiac Disease
• Does not have the HLA phenotype associations that Celiac Disease has, DQ2 and DQ8
• No villus atrophy on small intestine biopsy
• Negative serological tests for tTG
• Less GI symptoms, more constitutional ones, no autoimmune comorbidities
• Symptoms alleviated by a gluten free diet

Question 44

a malabsorption condition frequently characterized by megaloblastic anemia due to deficiency of either vitamin B12 and/or folic acid in a patient who was resident in an endemic tropical country and in whom a small intestinal biopsy shows villous atrophy (partial or total).

Answer 44

Tropical Sprue

A therapeutic response to folic acid and/or antibiotics is necessary in order to establish the diagnosis

Question 45

Tropical Sprue is endemic in

Answer 45

Asia, Africa, Central America, and several islands in the Caribbean and can be identified in current residents, in travelers from endemic areas and expatriates.

Question 46

Clinical Presentation and Diagnosis (Tropical Sprue)

Answer 46

• Diarrhea is frequent though not necessary.
• Other symptoms may be related to the associated vitamin deficiency states.
• The diagnosis is made after exclusion of parasitic and other enteric infections, and exclusion of celiac disease.
• The endoscopic and biopsy appearance can however mimic celiac disease, though celiac serologies are negative.
• The small bowel biopsy is often milder than that of celiac disease and partial villous atrophy is often patchy.
• Symptomatic presentation can occur many years after an expatriate leaves the endemic area.

Question 47

Treatment for Tropical Sprue

Answer 47

• The most frequently prescribed antibiotic is tetracycline.
• Folic acid 5 mg a day
• Vitamin B12 if the serum levels are low.

Question 48

Whipple’s Disease Signs and Symptoms

Answer 48

• Presents with diarrhea, weight loss, and abdominal pain.
• Arthropathy and hyperpigmentation are common.
• Neurological and cardiac involvement may occur indicating the systemic nature of the infection.
• The small intestinal biopsy appearance is one of villus atrophy and infiltration of the lamina propria with PAS-positive macrophages.
• Bacilli can be identified within the macrophages.
• Lymphangectasia secondary to enlarged lymph nodes is also seen.

Question 49

The causative organism for Whipple’s Disease has been identified as

Answer 49

the actinomyces, Tropheryma whippeli

Question 50

Answer 50

Figure 5-22. Jejunal biopsy from a patient with Whipple’s disease. The histologic appearance of biopsies obtained from involved small intestine is diagnostic for Whipple’s disease. In this patient, the villi are flat and widened. There is also extensive infiltration of the lamina propria with large periodic acid-Schiff-positive macrophages. Whipple’s disease is caused by a bacterial infection with a gram-positive bacillus. The gastrointestinal tract, musculoskeletal system, cardiovascular system, central nervous system, pulmonary system, skin, and lymph nodes may be involved, causing a broad range of symptoms. Treatment with appropriate antibiotics usually results in dramatic clinical improvement within 2 weeks. Antibiotic therapy should be continued for 1 year to decrease the risk of relapse. Short-term nutritional therapy to correct protein-calorie malnutrition and specific nutrient deficiencies, such as vitamin C deficiency, is often necessary until absorptive function improves.

Question 51

Treatment for Whipple’s disease

Answer 51

• The antibiotics of choice
  
  • parenteral penicillin and streptomycin
  • oral trimethoprin-sulphamethoxazole
    
    • for 1-2 years.
• A PCR is recommended to confirm eradication after therapy.

Question 52

(also called the blind loop syndrome) defined as contamination of the small bowel by multiple bacterial species that are usually inhabitants of the colon

The normal flora of the upper small intestine (gram positive aerobic bacteria) are replaced by massive amounts of gram negative bacteria and strict anaerobes such as Clostridium and Bacteroides species.

Answer 52

Bacterial overgrowth

Question 53

Predisposing factors include those that allow breakdown of the usual defenses that protect the small intestine from contamination.

Answer 53

• loss of gastric acid, stasis due to intestinal strictures or motility disorders (scleroderma, pseudo-obstruction, and diabetic autonomic neuropathy)
• jejunal diverticulosis,
• gastrocolic or jejunocolic fistulae
• postoperative states (gastrectomy, blind loops, loss of the ileocecal valve).

Question 54

the classical features of the blind loop syndrome

Answer 54

• Diarrhea and malabsorption of nutrients, especially vitamin B12
  
  • Steatorrhea is the usual cause of diarrrhea.
    
    • This is the result of deconjugation and dehydroxylation of bile salts by anaerobic bacteria causing impaired lipolysis and micelle formation.

Question 55

Bacterial Overgrowth continued

Answer 55

• Mucosal abnormalities are also seen (villous atrophy) and these are associated with reduced disaccharides levels and lactose malabsorption, contributing to the diarrhea.
• Impaired micellar formation results in fat soluble vitamin malabsorption.
• Vitamin B12 deficiency results from bacterial uptake of the vitamin B12-intrinsic factor complex.
• In contrast, folic acid, produced by luminal bacteria, is absorbed resulting in elevated serum levels.
• Bacterial overgrowth may be prominent due to reduced acid output and stasis in the afferent limb of the gastroenterostomy.

Question 56

Treatment for Bacterial Overgrowth

Answer 56

• Surgical correction of discrete structural abnormalities is the treatment of choice, but rarely feasible.
• Intermittent antibiotic therapy is the usual treatment.
  
  • Amoxicillin-clavulanic acid is the antibiotic of choice.
  • Other antibiotics are norfloxacin, ciprofloxacin, tetracycline, cefoxitin, chloramphenicol, and metronidazole.
  • These are typically given intermittently. Different regimes include use on an as needed basis, or one week a month each month, using the same antibiotic or rotating antibiotics.
• Bacterial overgrowth in scleroderma has responded to octreotide, given to increase intestinal motility.