describe the life cycle of giardia.
- human ingests water, food, or hands contaminated with infective cysts--swallow as few as 10!
- cysts have up to 4nuclei
- beavers = reservior
- each cyst gives rise to 2 pear-shaped trophozoites (2 nuclai/troph)
- trophs attach to intestinal wall, mainly proximal SI--NON-invasive
- their presence causes local inflammation and improper fluid reabsorption --> diarrhea (foul, watery, fatty), flatulence, nausea
what tests would you do for suspected giardiasis?
- #1 = stool antigen test -- sn/sp 100%
- if negative EDG for aspirate or biopsy to r/o other cuases
what is the management for giardiasis?
- tinidizole best option b/c take ONCE
- OR nitazonaxide 2x/d for 3d
- OR paromycin 3x/d for 5-10
- OR metronidazole, but take 3x/d for 5-7d (not FDA approved for giardia)
what if person with suspected AND confirmed giardiasis was not getting better?
You would suspect that they have hypoimmunoglobinemia (IgA deficiency), which means they are at risk for more difficult infection & relapse
describe what you see in the image:
nL villi with pear-shaped giardia
what is the ddx for someone presenting with dermatitis herpetiformis?
- only celiac dz (?)
- nocturnal diarrhea
- steatorrhea, wgt loss
- mm weakness
what are the diagnostic tests for someone w/loose watery stools, cramping after meals, with a "rash" and no recent travel hx or abx use?
- initial lab tests (CBC, serum electrolytes, TSH, LFTs)
- stool test
- stool electrolytes (osm>125=osmotic, <50=secretory)
- anti-tissue transglutaminase ab assay is most reliable BUT MUST BE confirmed by biopsy
- "diagnosis of celiac sprue is established by clinical, histologic, and immunologic response to a gluten-free diet"
- loss villi
- dense plasma cell infiltrates in lamina propria & T lymphocytes
- ??Endoscopy: *most pt's w/Celiac have small bowel that appears nL, however FIVE concurrent endoscopic images have been associated with high specificity for celiac: scallopig of small bowel folds, paucity in folds, mosaic pattern of mucosa ("cracked-mud"), prominence of submucosa bvs, nodular pattern of mucosa.
what is the mechanism of diarrhea in celiac dz?
- Diarrhea 2ndary to:
- steatorrhea due to changes in jejunal mucosal fn
- 2ndary lactase deficiency due to changes in jejunal brush border enzymatic fn
- bile acid malabsorption leading to bile acid-induced fluid secretion in the colon (for more extensive cases involving the ileum)
- endogenous fluid secretion from crypt hyperplasia
- *pt's w/more severe involvement w/celiac sprue may get temporary improvement with lactose & fat restriction while awaiting the full effects of total gluten restriction, which is the primary therapy
describe the cycling of bile acids.
Bile acids are primarily absorbed via a Na-dependent transport process that is located only in the ileum. A relatively small quantity of bile acids (~500 mg) is not absorbed in a 24-h period and is lost in stool. Fecal bile acid losses are matched by bile acid synthesis. The bile acid pool (the total amount of bile acids in the body) is ~4 g and is circulated twice during each meal or six to eight times in a 24-h period.
what phases of nutrient absorption contribute to malabsorption?
- disturbance1/4 phases of nutrient absorption:
- (1) intraluminaldigestion, in which proteins, CHO, and fats are broken downfor absorption;
- (2) terminal digestion--hydrolysis CHOs & peptides by disaccharidases and peptidases in brush border of the SI mucosa;
- (3) transepithelial transport nutrients, fluid, and electrolytes are transported across and processed within the SI epithelium
- (4) lymphatic transport of absorbed lipids.
what disease of malabsorption is the only one to be associated with lymphatic transport?
Whipple's...also unlike the others, it is not associated with disturbances in intraluminal & terminal digestion, & transepithelial transport.
what is the pathogenesis of celiac dz?
- innate & adaptive immune mechanisms:
- (1) gliadin gets taken in & deaminated by tissue transglutaminase
- APC presents it to Th1 or Th2 cells
- ----*APC's w/ HLA-DQ2 or 8 are at higher risk
- -->Bcells make ant-gliadin Abs -->inflammation
- (2)gliadin on villi surface activates MIC-A and IL-15
- MIC-A = stress protein plays role w/ T-cell, CD8+
- the CD8+ T-cell expresses NKG2D
- --> more damage
- all leading to morphological alterations:
- epithelial proliferation w/ crypt elongation
- loss of villi
- increased IntraEpithelial Lymphocytes
what are the 5 main lesions associated w/ gluten sensitivity?
- 3--destructive (total mucosal atrophy, complete loss of villi, enhanced epithelial apoptosis, & crypt hyperplasia)
- 4--hypoplastic (seein in T cell lymphoma)
what is the management of celiac sprue?
- Gluten-Free (no wheat, rye, barley)
- abx & folate admin.
how would you differentiate b/w celiac & tropical sprue?
- person usually has h/o travel to tropical or subtropical area
- they DON'T respond to gluten restriction
what are the early and late complications/associations of celiacl disease?
- nutritional deficiencies leading to:
- dental enamel defects & osteoporosis
- increased transaminases
- T-cell lymphoma
- dermatitis herptetiformis
- downs syndrome
- selective IgA deficiency
- type I DM
- thyroid dz
- liver dz
describe/dx the images provided:
- A: nL
- B: unTx celiac
- C: Txed celiac
- D: intestinal lympangiectasia
- E: Whipple's dz
- F: Lymphoma
- G: Giardiasis
in someone with celiac & good adherence to diet, but bad progress, what is the net step in managment?
- evaluate bacterial growth & pancreatic insufficiency
- upper GI endoscopy or colonoscopy & biopsy
- intraepithelial lymphocyte pheonotype on duodenal biopsy
- abd radiology (sm bowel study & CT)
- video-capsule endoscopy
what are the phenotypes for refractory celiac disease?
describe the image:
what are diagnostic tests indicated in suspected intestinal amoebiasis? what are the indications for endoscopy?
- Direct fecal
- Indications for endoscopy:
- Stool exam (–) and immediate diagnosis required
- Stool exam (–), serum anti-amebic antibody (–), acute presentation with high suspicion
- Stool exam (–), serum anti-amebic antibody (+)
what would biopsy for amebic colitis show?
- necrotic centers filled with mucoid material seen as flask-shaped ulcers with hemorrhagic centers, the surrounding mucosal folds can be nL
- the trophs have one central nucleus, but can often see ingested RBCs
- trophs are much larger vs cysts, only cysts (4nuclei) can survive to the stool
what is the life cycle of E. histolytica in amebiasis?
- cysts ingested --> intestine
- trophs emerge & invade colon & mesenteric vessels
- -->spread to liver (abscess), lungs, spleen, brain, kidney
describe the spectrum of disease caused by amebiasis.
- Intestinal, starts with, and progresses to:
- aSx infection
- Sx, non invasive
- acute dysentery
- fulminant colitis w/ perforation
- toxic megacolon
- chronic nondysenteric colitis
- perianal ulceration
- live abscess
- liver abscess complicated by:
- lung abscess
- brain abscess
- genitourinary dz
what is the management of amebic dysentery?
- metronidazole 750mgPO/8hr x 7-10d
- OR tinidazole 2g 1x/d x 5d
- THEN to Tx the cysts:
- iodoquinol /8hr x 20d (after meals)
- OR paromomycin 3/d x 7d (with meals)
in someone presenting with flu-liek illness, wgt loss, constant dull RUQ pain, and enlarged tender liver with guaiac (-) stool, no masses. what is next step?
- CT abd (shows abscess)
- CT guided aspiration of intra-hepatic collection (malodorous, creamy-brown fluid, numerous PMNs, no organisms seen on G-stain, culture grows as lactose-fermenting, G(-) rod)
- do serology of indirect hemagglutinin antibody (IgG) if suspecting amoebiasis
what is the ddx for the following:
in someone presenting with flu-liek illness, wgt loss, constant dull RUQ pain, and enlarged tender liver with guaiac (-) stool, no masses. CT shows liver abscess. culture of aspirate grows lactose-fermenting G- rod.
- can't r/o amoeba b/c are NOT found in liver aspirate!
- *liver abscess is most commnly due to ascending cholangitis
- subclinical appendicitis/diverticulitis
- 40% of cases are UKNOWN etiology
what is the management for pyogenic enteric liver abscess?
- metronidazole (good b/c covers amebic liver abscess too)
- if in ICU add imipenem, meropenem or combo amp+metro+ciprofloxacin
- AND pink tail catheter IF it's localized & >/=5cm and slow resonse to abx for drainage
what is the management for amebic liver abscess?
- to kill trophs:
- metronidazole 750mg/8hr x 5-10d
- OR tinidazole 2g 1/d x 5d
- AND to kill cysts:
- paromomycin 500mg/8hr