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                                                         Dz that involves epithelium or mucosa itself.
                                                         D-xylose is a water soluble, non-metabolized pentose
        MALABSORPTION                                       that is absorbed mainly in the duodenum and
Intestinal tract optimized for absorption of nutrients.     jejunum. No intraluminal handling. No pancreatic
   Have high surface area. Cylinder  folds  villi        enzymes needed. Will normally absorb across
   microvilli. Large surface area. Problems if              epithelium. Assimilation of this sugar does not
   compromise that surface area. If have decrease will      require the intraluminal pancreatic stage of digestion.
   take longer to absorb that nutrient. Mostly Ca and Fe    Abnormal test: SI mucosal disease  histological
Jejunum: Absorbed most nutrients.                             examination of the mucosa by biopsy. Also with
Ileum: bile acid and Vit B-12. Restricted to ileum. Can       the small intestinal bacterial overgrowth.
   be passively absorbed. Active reabsorption is in         Normal test: deficiency of intraluminal (pancreatic)
   ileum. If malabsorb bile bile acids in colon             digestive enzymes or bile acid deficiency.
   diarrhea. Vit B-12 anemic.
                                                            PABA Test to Evaluate Pancreatic function
General Mechanisms
                                                            Test is done w/PABA and an attached tripeptide. If
Arise from disorders of intraluminal events (e.g.                have exocrine function then will cleave off
   deficiency of pancreatic digestive enzymes or bile            tripeptide.
   acids), disorders of events at the cell surface (e.g.    Normal function: Ingest PAPA-tripeptide  tripeptides
   lack of specific cell-surface enzymes,                        cleaved  liberating PAPB which is absorbed 
   oligosaccharide deficiencies, specific transport              excreted in urine.
   defects, glucose-galactose malabsorption and amino       Abnormal: no cleavage of tripeptide. Is absorbed, but
   acid transport defects), abnormally of cellular events        PABA is not excreted in urine.
   (e.g. mucosal injury in celiac sprue, defects in         Causes of pancreatic exocrine sufficiency:
   intracellular chylomicron synthesis in                   Chronic or hereditary pancreatitis
   Abetalipoproteinemia) or abnormalities in post-          Pancreatic cancer
   cellular events (e.g. intestinal lymphangiectasia).      Operative resection
Pancreas: enzymes that breakdown fat. End up with           Ductal stricture or fistula
   number of proteolytic enzymes. Also amylase to           CF
   breakdown carbohydrate.                                  Protein-calorie malnutrition
Bile Acids: Cannot absorb fat without bile acids. What      Isolated enzyme deficiency.
   can go wrong. Most easily is fat absorption. Needs
   this extra stage. May not make if liver is dz, bile      Small intestinal x-ray
   duct obstruction, breakdown of bile acids before         may reveal typical changes of mucosal pathology,
   secreted.                                                  internal fistulae, blind loops, diverticulae or motility
Brush border in jejunum: enzyme dysfunction                  disorders which might be associated with bacterial
   dysfunction of lactase. Also inherited defects            overgrowth. It may also reveal ileal inflammatory
   glucose, galactose malabsorption.                          disease (e.g. regional enteritis) responsible for bile
Transport monosaccarides. Fat taken up by                     acid and/or vitamin B12 malabsorption.
   lymphatics. If have dz that affects lymphatics           Chronic pancreatitis: Output below normal. Low lipase
   (radiation, TB with blocked LN.) Do not deliver to         --. Low absorption of
                                                            Small bowel (jejunal) biopsy
A- lipoproteinemia: fat will hang up within epithelial
   cell.                                                    Diagnosis of intestinal mucosal dz. Specific diagnostic
                                                               features include:
Clinical Presentation                                       1. changes in the architecture of villi and crypts: normal
1. Diarrhea or steatorrhea                                     ratio of 4 to 1 Physiologic inflamed (normal). See
2. Weight loss                                                 some intraepithelial lymphocytes and plasma cells
3. Evidence of Vit deficiency                                  with occasional eosinophil and mast cell. Should see
    D: Osteomalacia, psuedofractures, tetany                 some CD4 cells. Celiac Dz.
    K: Bleeding tendency                                  2. cellular changes in the epithelium
    B: Cheliosis, glossitis                               3. specific types of cellular infiltration in the lamina
    Folate B-12: anemia, neuropathy.                         propria
                                                            4. as well as inclusions of bacteria or abnormalities of
         Tests of Malabsorption                                the lymphatics.
Several tests are available to pinpoint the specific        B12 absorption test (Schilling test)
   defects responsible for malabsorption. Since fat         Oral dose of radioactive cobalt-labeled B12 w/or w/out
   absorption is vulnerable to defects in either               IF. Measures the % or orally ingested isotope
   intraluminal digestive enzymes or defects at the            excreted in the urine.
   mucosal absorptive surface, the demonstration of         1. Abnormal B12 absorption alone: IF deficiency
   steatorrhea by qualitative or ultimately quantitative       (classical pernicious anemia). Gastric atrophy
   (72 hours) fecal fat measurement is the major            2. Abnormal vitamin B12 and IF: bacterial overgrowth
   criterion for establishing the presence of fat              or with disease of the ileum. If bacterial overgrowth
   malabsorption. From there, a logical sequence of            of the small intestine is. responsible for the abnormal
   tests should lead to the establishment of a specific        test, antibiotic therapy will return the test to normal.
                                                            Other Tests for Malabsorption
Quantitative Fecal Fat Excretion                           Pancreatic Function Tests. The secretin test is used to
Anything that causes malabsorption will cause problems        measure secretory capacity of the exocrine pancreas.
   w/fat absorption first.                                    After administration of secretin, bicarbonate
Sudan staining: look for fat globules                         concentration is measured in the juice aspirated from
Quantitative Fecal Fat excretion:                             the duodenum.
Pt placed on 100 gram/day fat diet for 3 total days. Nl    Measurements of serum iron, calcium, cholesterol,
    excrete ~ 3-5 grams fat/day. > 15 grams excretion        folate and vitamin B12 often are used as screening
   over the 3 days is (+) result  2 SD > normal mean.        tests for malabsorption, but are not specific.
Can easily get false positive: Poor food intake,           Prothrombin Time. If prolonged, may reflect
   constipation, forgot to collect stool. Eating nuts that    malabsorption or liver disease. These possibilities
   cause fat in stool.                                        can be distinguished by measuring the response to
D-Xylose Absorption-Excretion Test                            parenterally administered vitamin K.
Serum Carotene. Carotene is a fat-soluble substance                   the macrophages may, in fact, represent
   present in yellow vegetables and fruits, eggs, etc.                degenerating bacilli.
   Serum carotene levels tend to be depressed in                    EM: rod-shaped bacilli can be demonstrated in
   patients with fat malabsorption, but can be decreased              the lamina propria beneath the absorptive cells.
   also if the intake of dietary carotene is low.               Treatment: antibiotics.
          Differential Diagnosis                                1. Rare disease which begins in childhood, often before
                                                                   the age of one.
                                                                2. Characterized:
Celiac sprue
Crohn’s dz                                                          fat malabsorption
Eosinophilic gastroenteritis                                        hypolipidemia
Infection: Cryptosporidium, Isospora, Girardia, MAC.                acanthocytosis of the red blood cells
Lymphangiectasia                                                    cerebellar ataxia
Lymphoma                                                            "atypical" retinitis pigmentosa.
Mastocytosis                                                    3. Patients have an inability to make the protein-
Whipple’s disease.                                                 phospholipid-cholesterol coating of chylomicrons so
                                                                   the epithelial cells become laden with triglycerides.
Celiac Disease (Gluten-Sensitive                                4. On histology
Enteropathy)                                                        the villi are normal in shape
1. Precipitated by the ingestion of wheat, rye, and                 abundance of lipid droplets in the mucosal cells at
   barley. Activated by alcohol soluble proteins in                    the tips of the villi.
   wheat, rye, and barley which are termed gliadins,                No fat is found in the intracellular spaces and
   secalins, and hordeins, respectively. Rich in                       lacteals of the submucosa and lamina propria.
   glutamine and proline. Results in malabsorption.             5. Malabsorption usually is confined to fat. The liver
2. Wide spectrum of dz manifestations.                             biopsy can also show infiltration of triglycerides.
3. HA associated dz: Dz susceptibility is associated
   with the presence of HLA class II DQ sub-region
                                                                Intestinal Lymphangiectasia
   alleles DQA1 *0501, DQB 1*0201. These alleles can            Intestinal Lymphatic Obstruction
   be present in cis or trans and encode an HLA DQ2             1. Obstruction to the flow of lymph from SI  dilation
   molecule which appears to be necessary, but not                 of the intestinal lymphatic vessels in the villi,
   sufficient, for the phenotype expression of this                submucosa, serosa, and mesentery. The intestinal
   disease (i.e., these alleles are also present in                lymph that may leak from ruptured lacteals contains
   approximately 20% of healthy Caucasians). Peptide               plasma proteins, chylomicrons and small
   binding of specific HLA. Peptide from glydins that              lymphocytes. Cells look normal.
   bind to MHC II and activation of pathogenic T cells.         2. This disorder causes abnormalities in the delivery
4. Intestinal Histology: villous atrophy: loss of villi.           phase of absorption.
   Will only see entrance to crypts. Increased crypt                 Acquired: 2 to retroperitoneal disease,
   depth: only crypt. Actively proliferating. Abnormal                 lymphoma, radiation enteritis, abdominal
   surface epithelial cells. Lymphocyte and plasma cell                tuberculosis, etc.
   infiltrate of the lamina propria and an increased                 Congenital
   density of T lymphocytes in the intraepithelial                   congenital and acquired forms cannot be
   region.                                                             distinguished by small intestinal biopsy alone.
5) The lesion is most severe in the duodenum and                3. Findings:
   jejunum. Although the histological lesion is                      low albumin
   characteristic of this disease, it is not totally specific        low Ig level due to gastrointestinal protein loss
   since similar lesions can be seen in other diseases               low lymphocyte levels due to lymphocyte loss in
   such as tropical sprue, small intestinal lymphoma,                  the gut.
   Zollinger-Ellison syndrome and, in some instances,                Individuals do not absorb chylomicrons due to the
   common variable immunodeficiency syndromes.                         lymphatic obstruction.
6) Diagnosis: Can see similar picture in soy allergy.
   Gut can only respond in a few number ways to insult.         Common Variable Immunodeficiency
    Demonstrating malabsorption                               (Hypogammaglobinemia)
    Documenting the presence of the typical mucosal           1. As many as 60% of patients with common variable
       lesion                                                      immunodeficiency have diarrhea, and 20- 30% have
    Observing a prompt clinical response and                     mild to moderate malabsorption.
       improvement in mucosal histology upon                    2. The biopsy can vary from normal to having partial
       withdrawal of the offending proteins from the               villous atrophy, similar to that of celiac disease,
       diet.                                                       except for a lack of plasma cells in the lamina
Whipple's Disease                                               3. Girardia Lamblia, often is found in the small
Occurs in 4th and 5th decades, w/ incidence in (:,             intestinal aspirates of patients with this disorder.
   approximately 9:1).                                             Treatment of Girardia infection usually reverses the
Cause: Bacterial: Tropheryma Whippelii                             malabsorption and villous abnormalities.
Clinical Presentation:                                          4. Biopsy: lacks normal numbers of plasma cells.
    malabsorption                                             5. Nodular lymphoid hyperplasia of the small intestine
    fever, increased skin pigmentation, anemia,                  occurs in as many as 60% of patients, but does not
      lymphadenopathy, arthralgias and arthritis, as               correlate with the presence of diarrhea or
      well as occasional central nervous system                    malabsorption.
      symptoms.                                          Intestinal Lymphoma
                                                         1. May be 1* or 2* to lymphoma arising elsewhere. 1*
    Villi are broad and flat
                                                            lymphoma can be localized to a short segment of the
    Lamina propria contains dilated lymphatics: Do
                                                            bowel, it can be multifocal or diffuse, and can cause
      not look quite right.
                                                            a disease in the delivery phase of absorption.
    Foamy macrophages which stain (+) with PAS         2. The ileum and jejunum are among the most frequent
      stain. Not much staining in normal pt.                sites of involvement, the duodenum being less
      Glycoprotein in macrophages lights up. Want to        involved.
      do this SI not colon. The PAS-positive material in
3. 1* diffuse lymphoma involving the proximal small
   intestine is found in individuals in the Middle East,
   particularly Arabs and non-European Sephardic
   Jews. They can present with malabsorption, but also
   have abdominal pain, anorexia and fever. Early in the
   disease, there may be partial villous atrophy and the
   cellular infiltrate in the lamina propria consists of
   benign appearing plasma cells. Later malignant
   changes ensue with atypical plasma cells and
   reticulum cells. A number of these individuals have
   "-heavy chain" disease in which their serum and
   intestinal secretions contain an excess quantity of
   free-chains of the IgA molecule that frequently have
   a deletion in the normal amino acid sequence