DSA20 - Chronic Diarrhea and Malabsorption

Passage of loose or watery stools, typically at least 3 times in a 24-hour period (for 14 days or less)

Define ACUTE Diarrhea

Passage of loose or watery stools, typically at least 3 times in a 24-hour period (for > 2 wks)

Define CHRONIC Diarrhea

Stool volume > 14L/day (may cause severe dehydration and death)

Define Severe Diarrhea

Systemic symptoms (fever) + Bloody diarrhea

Define Dysentery

Usually when luminal ion channels are disrupted -> ↑ion secretion or ↓ion absorption -> ↑ions in GI tract -> water follows the ions -> watery diarrhea; occurs with and without food

Define Secretory Diarrhea

Stimulates Cl- secretion --> Body response w/ Na+ and H2O

How is Cholera a "Secretory Diarrhea"?

↑Osmole (sugar, salt, meds, etc) in the bowel lumen -> draws too much water into the bowels -> watery diarrhea; IMPROVES WITH FASTING

Define Osmotic Diarrhea

Body can't digest lactose --> that sugar stays in bowel lumen ==> water drawn out ==> DIARRHEA

How does a Lactase Deficiency cause Osmotic Diarrhea?

Results from inadequate nutrient absorption; associated with steatorrhea (Fatty Stool); IMPROVES WITH FASTING ​

Define Malabsorptive Diarrhea

Unable to create enzymes for fat breakdown --> Can't absorb nutrients properly ==> Lost in LOTS of stool

How does Pancreatic Insufficiency cause Malabsorptive Diarrhea?

D/t inflammatory disease causing purulent, bloody diarrhea - CONTINUES during fasting

Define Exudative Diarrhea

GI tract becomes irritated/inflamed --> Stool filled with blood or inflammatory cells

How does Ulcerative Colitis/IBD cause Exudative Diarrhea?

Intraluminal Digestion - b/c won't allow protein, carbs and fats to be broken down into absorbable forms

In what phase of Nutrient Absorption do CF and Chronic Pancreatitis create a problem and why?

Terminal Digestion - b/c won't allow carb and peptide hydrolysis to occur in SI brush border

In what phase of Nutrient Absorption do Celiac Disease and Lactose Intolerance create a problem and why?

Transepithelial transport - b/c doesn't allow certain nutrients to be transported across and processed in SI epithelium (affects transport of cholesterol components)

In what phase of Nutrient Absorption does Abetalipoproteinemia create a problem and why?

Lymphatic Transport - causes obstruction for lipids that need to be transported by the lymphatic system

In what phase of Nutrient Absorption do Whipple Disease and Mycobacteria create a problem and why?

Malabsorption

Define Condition:

When nutrients can't be absorbed in the GI tract d/t disruption of at least one of the 4 phases of nutrient absorption

-Sx:

> Diarrhea

> Wt Loss

> Weakness

-PE:

Vitamin or Mineral Deficiencies

> Anemia, Mucositis (B6, B9 or B12)

> Bleeding (Vit K)

> Osteopenia, Tetany (Ca, Mg, Vit D)

> Neuropathy (Vit A or B12)

Stool Qualities

> Steatorrhea (fatty stool)

>> Acholic Stool

>> Voluminous stools

>> Stool floating in water (fat isn't soluble in water)

> Watery Stool (Carb)

> Edema (Protein)

-Dx:

Fat

> Sudan Stain (Qualitative fecal fat test)

>> Micro detect of fat on special stain

>> Castor/Mineral Oil suppositories may cause false positives

> Quantitative Fecal Fat Test (CONFIRMATORY)

>> Measures amt of fat in stool over 1-3 days

Carb

> D-xylose

>> Test carb absorption in SI - used to test integrity of SI mucosa (Small Bowel Disease vs Pancreatic Disease)

>> Fasting --> pt ingests

>> Monosaccharide that should be absorbed in SI w/o enzymes

>> Measured in serum/urine

>> Normal = Pancreatic Disease (D-xylose in blood/urine); Abnormal = Bowel malabsorption (D-xylose NOT in blood/urine)

Cystic Fibrosis (CF)

Define Condition:

Primary intraluminal digestion defect caused by mutation in CTFR gene (encodes ATP gated Cl- channel that secretes Cl- in lungs AND GI Tract)

-Path: Defective CFTR --> Less Cl- (and H2O) secretion --> Compensatory Na+ reabsorption via ENaC ==> H2O reabsorption --> Abnormally thick mucus secreted into GI tract and Pancreas

-Sx/PE: (usually in Infancy)

> Meconium Ileus

> FTT

> Pancreatic Insufficiency --> Steatorrhea + Chronic Diarrhea + Fat Vitamin Deficiency (Night Blindness = A, Coagulopathy = K)

-Dx:

> (+) Sweat Chloride Test

> Normal D-xylose (Small bowel mucosa integrity maintained)

Bile Acid Malabsorption (BAM)

Define Condition:

Inability to reabsorb bile acids in the distal ileum

-Hx:

> Ileal Resection

> Crohn's Disease of Ileum

-Path: Bile acids are passed into the colon -> bile acids draw in water and salt AND Excess/Overproduction of bile acid ==> chronic diarrhea

-Sx/PE:

> Chronic Diarrhea

-Dx:

> Normal D-xylose Test (Small bowel mucosa integrity maintained)

Small Intestinal Bacterial Overgrowth (SIBO)

Define Condition:

Abnormal bacterial overgrowth within the small intestine​ (normal small bowel has low bacterial colony count)

-Hx:

> Surgery causing food to get caught in a "loop"

> Motility Disorders

-Path:

> Bacterial overgrowth -> excessive breakdown of bile salts -> fat malabsorption -> diarrhea and fat-soluble vitamin (ADEK) deficiency

> Excess bacteria metabolizes Vit B12 to inactive analogues --> compete w/ normal Vit B12 for binding/absorption ==> Vit B12 Deficiency

-Sx/PE:

> Diarrhea

> Fat Soluble Vitamin Deficiency (ADEK)

>> Night Blindness = A

>> Osteopenia = D

>> Coagulopathy = K

> Peripheral Neuropathy/Anemia = B12

-Dx:

> (+) Lactulose (Carb) Breath Test (Less Invasive)

> Endoscopy --> Small bowel cultures (INVASIVE)

-Tx:

> Abx

> Parenteral supplement of vitamins/proteins

Celiac Disease (aka Gluten-Sensitive Enteropathy, Celiac Sprue)

Define Condition:

Terminal digestion defect d/t chronic Autoimmune disorder causing immune-mediated damage to small bowel villi from GLUTEN EXPOSURE

-Hx: A/w...

> HLA-DQ2

> HLA-DQ8

> Type I Diabetes

> Autoimmune Thyroiditis

> Sjogren Syndrome

-Path:

> Usually d/t protein Gliadin in Gluten

> Gliadin absorbed by enterocytes -> gliadin is deamidated by tTG -> deamidated gliadin is presented by APCs via MHC class II -> CD4+ T cells to produce an immune response causing local inflammation via Cytokines (INF-gamma that damage epithelial cells, IL-15 that stimulate CD8+ T cells that kill epithelial cells w/ NKG2D receptor & MHC-1) that stimulate Ab production from B cells -> destroys small bowel villi

> Usually affects Duodenum

-Sx/PE:

> Children = FTT

> Adults

>> Steatorrhea + Diarrhea (destruction of villi)

>> Flatulence

>> Bloating

>> Recurrent Canker Sores

>> Anemia d/t Iron Deficiency, Folate deficiency, or Vit B12 deficiency

>> Dermatitis herpetiformis (Inflammatory skin disease seen in 10% pts)

>>> Itchy blistering

>>> Herpes-like lesion

>>> D/t IgA deposition in dermal papillae

-Dx:

> Antibody Screening

>> Most Sensitive = IgA tTG Ab

>> Most Specific - IgA endomysial Ab

>> If IgA Deficient, use anti-tTG IgG Abs instead

> Duodenal Biopsy (CONFIRMATORY/GOLD STANDARD)

>> Intestinal villous atrophy (blunting or flattening of villi)

>> More intraepithelial lymphocytes

>> Crypt hyperplasia (elongation of crypts)

> D-xylose ABNORMAL

-Tx: Gluten-Free Diet

-Prog:

> Risk of Enteropathy-Associated T-Cell Lymphoma (EATL)

> Risk of SI ACA

> Risk of Lymphocytic colitis & Lymphocytic gastritis

Environmental Enteric Dysfunction (EED) (aka Environmental Enteropathy)

Define Condition:

Acquired small intestine disorder among people living in conditions of poverty (defect in terminal digestion) --> enteric inflammation, villous blunting, decreased crypt-to-villus ratio

-Hx: A/w...

> Chronic malnutrition (stunted growth)

> Wasting

> Megaloblastic Anemia (Vit B12/B9 deficiency)

-Path: Enteric inflammation, villous blunting, decreased crypt-to-villus ratio ==> Less absorptive SA and impaired intestinal barrier function

-Sx/PE: Anemia d/t Iron Deficiency, Folate deficiency, or Vit B12 deficiency

-Tx: Abx

Lactose Deficiency (Intolerance)

Define Condition:

Terminal digestion defect d/t Disaccharidase deficiency

-Hx:

> Congenital = Rare autosomal recessive disorder

> Acquired = down-regulation of lactase gene expression

>> MC = Native Americans, African Americans, Asians

>> Late childhood

> Transient/Secondary = Follow Viral Gastroenteritis (Rotavirus or Norwalk virus) but pt recovers after 1-2 wks of illness

-Path: Deficiency of enzyme found in the brush border of enterocytes (tips of the villi) -> failure to break down lactose into glucose and galactose -> undigested lactose is osmotically active

-Sx/PE: (w/n 30 min to 2 hrs of consuming dairy)

> Osmotic Diarrhea & Flatulence/Bloating (Intestinal Bacteria)

> Abdominal Pain

> Nausea

-Dx:

> (+) Lactose Hydrogen Breath Test

>> Ingest lactose --> if undigested, bacteria ferment lactose ==> Release Hydrogen & Measure levels (elevated if intolerance)

> D-xylose = NORMAL

> Biopsy:

>> Acquired = Normal Villi on Biopsy

>> Transient = Virus --> sloughing of the tips of villi

Abetalipoproteinemia

Define Condition:

TRANSEPITHELIAL Transport defect d/t Autosomal recessive deficiency of apolipoprotein B-48 & B-100 (for synthesis and export of chylomicrons and VLDL, respectively)

-Path: Mutation in the microsomal triglyceride transfer protein in the small intestine -> failure to properly export lipids into blood -> build-up of lipids in enterocytes which appear as lipid-filled vacuoles and fat malabsorption

-Sx/PE: (presents in Infancy)

> FTV

> Diarrhea

> Steatorrhea

> Fat Soluble Vitamin Deficiency (ADEK)

>> Night Blindness = A

>> Osteopenia = D

>> Coagulopathy = K

-Dx:

> Biopsy:

>> Vacuoles of fat in villia

> Blood Smear:

>> Acanthocytes (50% or more red blood cells) in peripheral blood d/t lipid plasma membrane defects

Carcinoid Syndrome

Define Condition:

Group of Sx occuring when tumor secretes certain chemical (serotonin) into bloodstream --> Transepithelial transport defect

-Path: Tumor secretes serotonin -> ↑ intestinal motility and excessive secretion of the GI tract

-Sx/PE:

> Chronic & Watery Diarrhea

-Prog: Fasting doesn't reduce diarrhea (increased motility and secretion are independent of intake)

Whipple Disease

Define Condition:

Defect of lymphatic transport caused by Systemic infex d/t Tropheryma whipplei

-Hx:

> MC in Older Males (40-60 y/o) in Rural Areas

> NON-AIDS pt (AIDS = MAC)

-Path: Excess macrophages compressing lymph vessels in small bowel -> Bacteria damage the villi and cause malabsorption -> diarrhea and steatorrhea

-Sx/PE:

> Cardiac Isssues

> Arthralgias

> Neuro Sx

-Dx:

> Biopsy = PAS(+) Foamy (aka "STUFFED") Macrophages in intestinal lamina propria

Mycobacterium avium complex (MAC)

Define Condition:

Defect of lymphatic transport caused by Systemic infex d/t MAC (atypical mycobacterial infex/nonTB mycobacteria) made of M. avium and M. intracellulare

-Hx:

> Immunocompromised (HIV/AIDS)

-Path: MC Sites = Small Bowel & Large Bowel

-Sx/PE:

> Fever

> Diarrhea

> Malabsorption

> Loss of Appetitie

> Weight Loss

-Dx:

> Watery Diarrhea w/o fecal WBCs

> PAS (+) and diastase-resistant + (+) Ziehl Neelsen Acid Fast Stain

Microscopic Colitis

Define Condition:

Inflammatory disease of colon

-Hx: IDIOPATHIC

> Collagenous = Middle aged/Older Women

> Lymphocytic = A/w...

>> Celiac disease

>> Thyroiditis

>> Arthritis

>> Autoimmune Gastritis

-Sx/PE:

> Chronic Non-Blood Watery Diarrhea

> No Wt Loss

-Dx:

> Endoscopy = Normal Colonic Mucosa

Acute Graft vs Host Disease (GVHD)

Define Condition:

Immune-mediated disease due to cytokine induced damage by donor T-cells to recipient's epithelial cells after allogeneic hematopoietic stem cell transplantation

-Sx/PE: (w/n 100 days of allogenic HSC transplant) - involves upper & lower GI tract

> Watery diarrhea

> Abd Pain

> Nausea/Vomiting

> Anorexia

-Dx

> Biopsy (CONFIRM): Epithelial apoptosis