Lower gastrointestinal bleeding pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Pathophysiology

Blood supply

• Superior mesentric artery and inferior mesentric artery are the two major blood vessels that supply lower gastrointestinal tract.
• The superior mesentric artery and inferior mesentric artery are interconnected through a branch of anatomizing branches which are collectively called as marginal artery of Drummond. 
• This vascular arcade runs in the mesentery close to the bowel.

Lower GI Tract		Arterial Supply	Venous Drainage
Midgut	Distal duodenum jejunum Ileum Appendix Cecum Ascending colon Hepatic flexure Proximal transverse colon.	Superior mesenteric artery (SMA) Ileocolic Right colic Middle colic branches	Superior mesenteric vein
Hindgut	Distal one-third of the transverse colon Splenic flexure Descending colon, Sigmoid colon Rectumhu	Inferior mesenteric artery (IMA) Left colic Sigmoid Superior rectal (hemorrhoidal) branches	Portal system ɸ
ɸ -Except lower rectum, which drains into the systemic circulation.

Blood supply to the intestines includes the celiac artery, superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and branches of the internal iliac artery (IIA).
Source: By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Pathogenesis

The pathogenesis of lower gastrointestinal bleeding can be discussed based on the etiology. Diverticulosis is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by anorectal disease, ischemia, inflammatory bowel disease (IBD), neoplasia and arteriovenous (AV) malformations.

• Diverticulosis
  • The colonic wall weakens with age and results in the formation of saclike protrusions known as diverticula.
  • These protrusions generally occur at the junction of blood vessel penetrating through the mucosa and circular muscle fibers of the colon resulting in painless bleeding
  • Despite the majority of diverticula being on the left side of the colon, diverticular bleeding originates from the right side of the colon in 50% to 90% of instances.

Diagram of sigmoid diverticulum
Source:By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

• Anorectal disease

• Hemorrhoids are engorged vessels in the normal anal cushions. When swollen, this tissue is very friable and susceptible to trauma, which leads to painless, bright red bleeding.
• Anal fissures are defined as a tear in the anal mucosa. With the passage of stool, the mucosa continues to tear and leads to bright red bleeding.

• Mesenteric Ischemia

• Mesenteric ischemia results when there is inadequate blood supply at the level of the small intestine.
• 2 or more vessels (celiac ,SMA, or IMA) must be involved for bleeding to occur.
• Non occlusive mesenetric ischemia affects critically ill patients who are vasopressor-dependent.
• Venous thrombosis of the visceral vessels can also precipitate an acute ischemic event.
• Decreased blood flow leads to transmural infarction with necrosis and perforation.
• Associated mucosal sloughing results in bleeding.

• Ischemic Colitis

• Ischemic colitis is caused by poor perfusion of the colon, which results in the inability of that area of the colon to meet its metabolic demands.
• It can be gangrenous or nongangrenous, acute, transient, or chronic.
• The left colon is predominantly affected, with the splenic flexure having increased susceptibility.
• Intraluminal hemorrhage occurs as the mucosa becomes necrotic, sloughs, and bleeds.
• Damage to the tissue is caused both with the ischemic insult as well as reperfusion injury.

• Inflammatory Bowel Disease
  • Crohn's diseas
    • In Crohn's disease T cell activation stimulates interleukin (IL)-12 and tumor necrosis factor (TNF)-a, which causes chronic inflammation and tissue injury.
    • Initially, inflammation starts focally around the crypts, followed by superficial ulceration of the mucosa.
    • The deep mucosal layers are then invaded in a noncontinuous fashion, and noncaseating granulomas form, which can invade through the entire thickness of the bowel and into the mesentery and surrounding structures resulting in bleeding

• Ulcerative colitis
  • In ulcerative colitis T cells cytotoxic to the colonic epithelium accumulate in the lamina propria, accompanied by B cells that secrete immunoglobulin G (IgG) and IgE.
  • This results in inflammation of the crypts of Lieberkuhn, with abscesses and pseudopolyps along with rupturing of minute blood vessels in mucosa resulting in bleeding.

• Neoplasia

• Mutations of multiple genes are required for the formation of adenocarcinoma, including the APC gene, Kras, DCC, and p53.
• Certain hereditary syndromes are also classified by defects in DNA mismatch repair genes and microsatellite instability.
• As tumor grows it invades the surrounding tissue disrupting the normal vasculature along with it
• Therefore tumors tend to bleed slowly, and patients present with hemocult positive stools and microcytic anemia.

• AV Malformation/Angiodysplasia

• In AV malformation direct connections between arteries and veins occur in the colonic submucosa.
• The lack of capillary buffers causes high pressure blood to enter directly into the venous system, making these vessels at high risk of rupture into the bowel lumen.
• In Angiodysplasia over time, previously healthy blood vessels of the cecum and ascending colon degenerate and become prone to bleeding.

Gross and Microscopic Pathology

Disease	Gross Pathology	Microscopic Pathology
Diverticulosis	Multiple, small, flask like invaginations Thick and corrugated circular muscle with prominent accordion-like mucosal folds.	Inflammatory cells Intramucosal ganglion cells Lymphoid infiltrate Lymphoglandular complexes Mucin depletion Mild cryptitis Achitectural distortion Paneth cell metaplasia Ulceration
Angiodysplasia	Tortuous dilation of multiple small submucosal and mucosal blood vessels	Dilated and thin-walled vessels in mucosa and submucosa often in clusters. Surrounding mucosa may be eroded
Hemorrhoids	Tortuous superficial dilations of multiple blood vessels.	Dilated, thick-walled, congested submucosal vessels Papillary endothelial hyperplasia Internal hemorrhoids are lined by rectal or transitional mucosa, External hemorrhoids have a squamous lining Superficial ulcerations Pagetoid dyskeratosis
Mesenteric ischemia	Hemorrhagic infarctions Ulcerations Mucosal plaque Strictures	Lamina propria hemorrhage Superficial epithelial necrosis, Deep crypts Minimal inflammation Strictures
Ischemic colitis	Discrete or serpiginous ulcerations (may be discrete or serpiginous) Cobblestone pattern resembling Crohn’s disease Pseudopolyps resembling ulcerative colitis Hemorrhagic infractions Frank blood or dark mucus in lumen Late fibrosis and stricture formation	Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation Necrosis Ulceration and granulation tissue extend into submucosa and surrounding smooth muscle fibers of muscularis mucosa
Crohn's disease	Dull and granular serosa Creeping fat Thick/rubbery intestinal wall (due to edema, inflammation, fibrosis, hypertrophy of muscularis propria) Strictures (string sign on barium enema) Skip areas Aphthous mucosal ulcers	Superficial or deep ulceration Adjacent granulation tissue extending into deep submucosa or below. Transmural inflammation with lymphoid aggregates Goblet cells Focal neutrophils in epithelium and overlying lymphoid aggregates and plasmacytosis Edematous mucosa and submucosa
Ulcerative colitis	Deep fissuring ulcerations Hemorrhagic mucosa Pseudopolyps	Diffuse mononuclear inflammatory infiltrate in lamina propria Crypt abscesses (neutrophils in glandular lumen) and cryptitis Granulation tissue and reepithelialization Submucosal fibrosis Schwann cell proliferation