Small and Large Intestine Flashcards by Denisse Tiangco

Disrupted migration of neural crest cell from cecum to rectum
Distal intestinal segment lacks both Meissner’s submucosal and Auerbach’s myenteric plexus (aganglionosis)

Hirschprung’s

Congenital aganglionic megacolon

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Gene alteration in Hirschprung’s

Heterozygous loss of function mutations in receptor tyrosine kinase

RET accounting for majority of familial cases 15% sporadic

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Hirschprung involves the

Rectum
Sigmoid

Absence of ganglion in affected segment

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Weakess or defect in wall of peritoneal cavity permiting protrusion of serosa lined pouch of peritoneum

Hernia sac

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Hernia complications

Incarceration entraped

Strangulation infarcted

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Mucosal infarct

Hypoperfusion

No deeper than muscularis mucosa

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Mural infarct

Hypoperfusion

Mucosa to submucosa

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Transmural infarct is caused by

acute vascular obstruction

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Atherosclerosis is frequent in origin of

mesenteric vessel

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Intestinal ischemia pathogenesis (2)

1 initial hypoxic - resistant

2 reperfusion - greatest damage (free radical, neutrophil infiltration, inflamm mediator protein and cytokine)

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Variables that determine severity of ischemia

Severity of vascular compromise
Time frame which it develops
Vessels affected

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Watershed zones susceptible to ischemia

Splenic flexure (SM And IM termination)
Sigmoid
Rectum (IM, pudendal, iliac)

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epithelial atrophy and necrosis is a signature of ischemic intestinal disease bec of the anatomy:

intestinal capillary run alongside gland from crypt to surface before making hairpin turn at surface to empty into postcap venule
Allows oxygenated blood to supply
crypts but leaves the epithelium vulnerable to ischemic injury

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Transmural ischemia complication

coagulative necrosis of muscularis prop 1-4d with purulent serositis and perforation

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Involves splanchnic bed
Impaired venous movement impairs entry of oxygenated arterial blood
Less abrupt transition

Mesenteric venous thrombosis

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Atrophy or sloughing of surface epithelium
Neutrophilic inf if acute
Fibrous scarring of lamina propria if chronic
Stricture
Partially detached villous if acute
Hyperchromatic nuclei of crypt cell

Ischemia of intestinal vessel

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Ischemic bowel disease occurs in

Sudden severe abd pain, tenderness
nausea vomiting grossly melanotic stool

older with coexisting cardiac or vascular disease

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May masquerade as inflammatory bowel disease

Episodes of bloody diarrhea with periods of healing

Chronic ischemia

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Ischemic GI as consequence of viral tropism and infection of endothelial cell
Complication of immunosuppresive therapy

CMV infection

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GI irradiation
Vascular injury with radiation fibroblast within the stroma
Anorexia, cramps, malabsorptive diarrhea (acute)
Indolent often inflammatory (chronic)

Radiation enterocolitis

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Transmural necrosis

Most common acquired gastrointestinal emergency of neonates esp premature after initiation of oral feeding

NEC

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Malformed submucosal and mucosal blood vessel
Most often in the cecum or right colon after 6th decade
20% of major episodes of lower intestinal bleeding
hemorrhage may be chronic and intermittent or acute and massive

Angiodysplasia

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Vessels within inferior hemorrhoidal plexus below anorectal line

External hemorrhoids

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Dilation of superior hemorrhoidal plexus within distal rectum

internal hemorrhoids

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Chronic malabsorptive disorders (3) most common

Pancreatic insufficiency Celiac Crohn

Important cause of malab and diarrhea following allogeneic hematopoietic stem cell transplantation Small bowel and colon secondary to targeting antigen on recipient’s epithelial cells by donor T cell Epithelial apoptosis of crypt Watery diarrhea

graft-versus-host disease

Inc in stool mass freq fluidity volumes greater than 200ml

Diarrhea

Painful bloody small volume diarrhea

dysentery

Isotonic stool and persists during fasting

Secretory diarrhea

Lactase deficiency due to osmotic forces by unabsorbed luminal solute Fluid more than 50mOsm more concentrated than plasma Condition ABATES with fasting

Osmotic diarrhea

Inadequate nutrient absorption with steatorrhea and RELIEVED by fasting

Malabsorption

Inflammatory disease | Purulent bloody stool CONTINUES during fasting

Exudative diarrhea

Four phases of nutrient absorption

intraluminal digestion terminal digestion transepithelial transport lymphatic transport

proteins carbohydrates fats broken down into absorbable forms

Intraluminal digestion

Hydrolysis of carbohydrates and peptides by disaccharides and peptidase in brush border of small intestinal mucosa

terminal digestion

nutrient fluid and electrolytes are transported across and processed within small intestine

Transepithelial transport

Absence of CFTRc leading to defect in intestinal and pancreatic Cl ion secretion

Cystic fibrosis ``` Defective luminal hydration Meconium ileus Intraductal concretion in pancreas Exocrine pancreatic insufficiency 80% Failure in intraluminal phase ``` Tx oral enzyme supplement

Immune mediated (innate and immune) enteropathy triggered by ingestion of gluten-containing cereal

Celiac sprue | Gluten sensitive enteropathy

Gluten is digested into AA by brushborder enzymes and into a degradation resistant peptide called

gliadin presented to CD4 T cell and CD8 by alleles on APC

Celiac disease is assoc with allelles

HLA DQ2 HLA DQ8 Also assoc with type 1 DM, thyroiditis, Sjogren’s

Celiac dse dx

Second portion of duodenum and proximal jejunum biopsy with inc no of CD8 T

Intraepithelial lymphocytosis CD8 T crypt hyperplasia villous atrophy

Celiac disease

Sensitive nonivasive test for celiac disease

IgA antibodies to tissue transglutaminase IgA or IgG deaminated gliadin Highly specific: antiendomysial antibody

Most common celiac disease assoc cancer

Enteropathy assoc T cell lymphoma aggressive tumor Small intestinal adenocarcinoma

AR, mutation in gene encoding lactase Rare, explosive diarrhea watery frothy stool and abdominal distention after milk Abate when milk terminated

Congenital lactase deficiency

Downregulation of lactase gene expression | Assoc with viral or bacterial infection

Acquired lactase

AR, inability to secrete TAG rich lipoproteins Transepithelial transport defect Lipid defect in plasma resulting in acanthocytic red cell (spur)

Abetalipoproteinemia

Abetalipoproteinemia results from mutation in

microsomal triglyceride transfer protein

Chronic nonbloody watery diarrhea without weight loss Middle aged older women Dense subepithelial collagen layer Inc intraepithelium lymph with mixed inflamm infiltrate in lamina propria

Collagenous microscopic colitis

Chronic nonbloody watery diarrhea without weight loss Subepithelial collagen is of normal thickness, inc in epithelial lympho greater Assoc with celiac and autoimmune thyroiditis, arthritis, gastritis

Lymphocytic microscopic colitis

Loss of brushborder surface area and deficient enterocyte maruration as result of immune mediated epithelial damage

Celiac disease

Celiac disease and tropical sprue defect in malabsorption

Terminal digestion Terminal transport Autoimmune enteropathy

Chronic pancreatitis Cystic fibrosis Primary bile acid malabsorption

Intraluminal digestion Primary bile also transepithelial transport

Dissacharide def malabsorption

Terminal digestion

Whipple disease malabsorption

Lymphatic transport

Abetalipoproteinemia malabsorption

Transepithelial transport

Viral gastro Bacterial gastro Parasitic gastro

Terminal digestion | Transepithelial transport

Inflammatory bowel disease

Intraluminal digestion Terminal digestion Transepithelial transport

Cholera toxin enterotoxin delivered via retrograde transport causea secretory diarrhea by

``` stimulating adenylate cyclase inc cAMP opens CFTR releases Cl ions dec Na and bicarb absorption osmosis of water out to lumen ```

C jejuni virulence

``` motility - flagella adherence - colonization, invasion toxin production - cholera like enterotoxin invasion - dysentery Enteric fever - LN prolif ```

C jejuni can result with

reactive arthritis in HLA B27 Erythema nodosum GBS

Acute self-limited colitis Prominent lamina propria intraepithelial neutrophil infiltrate Cryptitis, crypt abscess Not distinguised by biopsy Dx

``` C jejuni Shigella Salmonella E coli Yersinia ``` Stool culture

Less resistant to acidic environment, infective at less than 100, Shigella is taken up by Modulating epithelial junctions to expose basolateral bacterial receptor Injected into host cytoplasm by type III secretion

M microfold cell

Inhibits eukaryotic protein synthesis and causes host cell death

Shiga toxin stx

Shigella infection is prominent in the Pseudomembrane, hemorrhagic ulcerated mucosa

left colon ileum (M cell in Peyer’s) Initially watery becoming dysenteric Antidiarrheal meds contraindicated

Shigella complication

Reactive arthritis Reiter’s (urethritis and conjunctivitis) HLAB27 + Also HUS

Principal cause of traveller’sc | Express heat labile toxin similar to cholera and heat stable toxin inc cGMP similar to increased cAMP

Enterotoxigenic E coli

Consumption of inadequately cooked ground beef, milk and vegetable Produce shiga like toxin causes dysentery HUS

Enterohemorrhagic E coli

Do not produce toxin but shigella like Invade gut epithelium Dysentery

Enteroinvasive E coli

Attach by fimbriae | Produce LT and shiga like toxin but min damage

Enteroaggregative E coli

Salmonella possess virulence genes that encode capable of transfering bacteria protein to M cell activating Rho GTPases Also releases eicosanoid drawing neutrophil

type III secretion system

Enteric fever course

Febrile phase 2 week sustained fever with abdominal tenderness mimicking AA, rose spots Extraintestinal complication: enceph meningitis pneumoniae carditis chole Sickle cell patients susceptible to osteomyelitis

Toxins of this organism cause ribosylation of small GTPases such as Rho leading to disruption of epithelial cytoskeleton and tight junction barrier loss Formation of pseudomembranous colitis

Clostridium difficile Rf: antibiotic Neutrophil emanating from crypt - volcanic eruption

C difficile dx

detection of C difficile toxin and histopath

Most common cause of severe childhood diarrhea and death Minimal effective inoculuM

Rotavirus 10 viral

Rotavirus selectively infects and destroys mature (absorptive) enterocyte in small intestine and villus surface is repopulated by

immature secretory cell

Eggs hatch in intestine larvae penetrate mucosa Migrate via splanchnic circ to liver creating hepatic abscess Then to lung as pneumonitis Larva also migrates to trachea and swallowed

Ascaris lumbricoides

Penetrate unbroken skin Migrate through lungs to trachea Autoinfection

Strongyloides

Hookworm Larval penetration into skin Lung development swallowed into duodenum suck blood and cause IDA

Necator | Ancylostoma

Most common pathogenic parasite in human

Giardia Ingestion of cyst

Diverticulosis pathogenesis

Elevated intraluminal pressure in sigmoid Nerves and vasa recta of penetrate muscularis propria creating discontinuities bec of taenia coli Spasmodic seq of bowel segments

Small flask like out pouching in between taenia coli of sigmoid Surrounded by fat containing epiploic appendices May infect into diverticulitis and perforate Low fiber, colonic spasm

Diverticulosis

Reduced freq of enteric infection due to improved hygiene resulted in inadequate dev of regulatory process limiting mucosal immune responses in early life in IBD

hygiene hypothesis

IBD results from combination of errant

host interaction with intestinal microbiota intestinal epithelial dysfunction aberrant mucosal immune response

Susceptibility gene in Crohn’s encoding protein that binds to intracellular bacterial peptidoglycan activating NF kappa B Rendering them less effective to recognize and combat bacteria and trigger inflammation

NOD2 nucleotide oligomerization binding domain 2 ATG16L1 IRGM Monozygotic concordance rate: 50%

Inflammatory bowel disease pathogenesis

1 genetics 2 mucosal immune response (THI, TH17, IL23, IL13) 3 epithelial defect 4 microbiota

Smoking inc risk of and dec that of

Crohn’s disease Ulcerative colitis

Most common sites of Crohn’s

terminal ileum ileocecal valve cecum

Multiple separate sharp delineated areas of skip lesions Earliest lesion: apthous ulcer becoming serpentine Sparing of interspersed mucosa become cobblestone Fissures between folds Transmural; Fat extending around serosal surface: creeping fat Distortion of mucosal architecture (ulceration) with crypt abscess (neutrophil)

Crohn’s Intermittent attacks of relatively mild diarrhea, fever, and abdominal pain RLQ pain 20% mimicking AA IDA in colonic disease

Pseudopyloric metaplasia (gastric antral appearing gland) Paneth cell metaplasia in left colon (normally absent) Hallmark: Noncaseating granuloma Granuloma in mesenteric LN Cutaneous granuloma nodules misleading: metastatic Crohn disease Absence of granuloma does not preclude a diagnosis of IDA may develop

Crohn’s disease ``` Fibrosis of ileum tx with surgery Recurrence at site of anastomosis Fistulas, perforation, abscess Extraintestinal manif: arthritis, sacroilitis, ankylosing spondylitis Risk of malignancy ```

Ulcerative colitis involves

rectum and extends proximally to involve part of the colon Skip lesions

Mild mucosal inflammation of distal ileum referred as

backwash ileitis

Slightly red, granular with broad based ulcers Regenerating islands bulging into lumen termed pseudopolyp Mucosal atrophy and flat smooth mucosal surface Absent mural thickening, serosal surface is normal and strictures do not occur

Ulcerative colitis

Toxic megacolon with risk of perforation Skip lesions absent and inflammation limited to mucosa and superficial submucosa Sparing of muscularis propria Granuloma not present

Ulcerative colitis

Bloody diarrhea with stringy mucoid material and lower abdominal pain and cramps relieved by defecation Tx: colectomy Infectious enteritis precedes onset

Ulcerative colitis

Clinical overlap of 2 IBD | Small intestine not involved

Ideterminate colitis

Feared long term complication of IBD Related to factors

Dysplasia 8-10 inc after initiation Pancolitis greater risk than with left sided disease Greater freq severity of active inflamm (neutrophil) Surveillance program 8 years after diagnosis of IBD

At time of dx px with this disease is subjected to surveillance bec of significant risk of neoplasia

Primary sclerosing cholangitis Regular extensive mucosal biopsy Dysplasia in flat areas

``` Ileum and colon with occasional rectal involvement Skip lesion Stricture Thick bowel wall Transmural inflamm Moderate pseudopolyp Deep knifelike ulcer Marked lymphoid rx Marked fibrosis Marked serositis Granuloma, fistula and sinus Perianal fistula in colonic dse Fat and vitamin malabsorption Malignant potential only with colonic involvement Recurrence after surgery No megacolon ```

Crohn’s disease

``` Colon only always with rectal involvement Diffuse distribution Rare strictures Thin bowel wall appearance Limited mucosa and submuc inflamm Marked pseudopolyp Superficial, broad based ulcer Moderate lymphoid Mild to no fibrosis No serositis, granuloma, fistula and sinus No perianal fistula No fat/vitamin malab With malignant potential No recurrence after surgery With toxic megacolon ```

Ulcerative colitis