Sandbox 2

Lower GI bleeding is defined as any bleed that occurs distal to the ligament of Treitz.

Incidence

• In the United States the incidence of LGIB ranges from 20.5 to 27 per 100,000 persons per year.

Age

• There is a greater than 200 fold increase from the third to the ninth decade of life.

Classification

• Lower GI bleeding can be classified into 3 groups based on the severity of bleeding:
  • Occult lower GI bleeding
  • Moderate lower GI bleeding
  • Severe lower GI bleeding

	Severe lower GI bleeding	Moderate lower GI bleeding	Occult lower GI bleeding
Age	> 65 years	Occur at any age	Any age
Presenting symptoms	Hematochezia or bright red blood per rectum.	Hematochezia or melena.	Symptoms of anemia (fatigue, tirdness)
Hemodynamics	Unstable	Stable	Stable
Lab findings	hemoglobin equal to or less than 6 g/dl.	Microcytic anemia	Microcytic hypochromic anemia due to chronic blood loss.
Differential	Diverticulosis and angiodysplasias	Neoplastic disease Inflammatory, <br> infectious, benign anorectal, and congenital diseases.	Inflammatory, neoplastic and congenital.

Blood supply

• The SMA and IMA are connected by the marginal artery of Drummond.
• This vascular arcade runs in the mesentery close to the bowel.
• As patients age, there is increased incidence of occlusion of the IMA.
• The left colon stays perfused, primarily because of the marginal artery.

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)	Portal system.
Hindgut	Distal one-third of the transverse colon Splenic flexure Descending colon, Sigmoid colon Rectumhu	Inferior mesenteric artery (IMA)	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

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.
  • Diverticula are most common in the descending and sigmoid colon.
  • 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.
  • Most of the time bleeding from diverticulosis stops spontaneously, however, in about 5% of patients, the bleeding can be massive and life-threatening.

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 and anal fissures are the most common disease under anorectal disease responsible for GI bleeding.
• 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 symptoms 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.

• 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

• 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.
• 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.
• Ulcerative colitis generally begins at the rectum and is a continuous process confined exclusively to the colon.

• Neoplasia

• Colon carcinoma follows a distinct progression from polyp to cancer.
• 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.
• These tumors tend to bleed slowly, and patients present with hemocult positive stools and microcytic anemia.
• Although cancers of the small bowel are much less common than colorectal cancers, they should be ruled out in cases of lower GI bleeding in which no other source is identified.

• 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.
• Although 75% of angiodysplasia cases involve the right colon, they are a significant cause of obscure bleeding and the most common cause of bleeding from the small bowel in the elderly.

Epidemiology

Prevalence

• Approximately 20 patients/100,000 population in the U.S.

Incidence

• The estimated annual incidence of lower GI bleeding is approximately 0.03% in the adult population as a whole.

Demographics

Gender

• More common in men than women

Age

• Rare in children
• The incidence of lower GI bleeding increases with age with a 200-fold increase from the second to eighth decades of life la.
  • Largely due to the increase in the prevalence of diverticular disease and angiodysplasia with age.

Symptoms

• Occult LGIB may present with symptoms of iron deficiency anemia such as fatigue, palpitations, and dyspnea.
• Patients with intussusception may present with pallor and vomiting in addition to LGIB
• Associated symptoms, such as abdominal pain or change in bowel habits, may also aide in the diagnosis
• Bloody diarrhea associated with abdominal pain may suggest an infectious cause or IBD in a younger patient and ischemic colitis in an older patient with vascular disease
• Painless bleeding usually suggests angiodysplasia, diverticular disease, or internal hemorrhoids
• Perianal pain suggests a perianal fissure or fistula

History

• A detailed description of the nature of the blood loss can help in pinpointing the likely source of bleeding.

Past Medical History

• The clinical history should identify whether this is a recurrent bleed.
• Bleeding from angiodysplasia is usually recurrent and chronic, but severe bleeding resulting in hemodynamic instability can occur.
• Associated weight loss suggests malignancy.
• The presence of systemic diseases such as atherosclerotic disease, IBD, coagulopathies, and HIV, and a history of pelvic irradiation for malignancy should be considered

Past Surgical History

• A history of recent colonic polypectomy or biopsy indicates iatrogenic bleeding.
  • This is usually low grade and limited, although it can be severe if an underlying artery is involved or if there is an inadequate coagulation of the polypectomy stalk.
  • In 1.5% of polypectomies bleeding occurs immediately. However, delayed bleeding can occur several hours or days following the procedure
• It is essential to establish the presence of comorbid diseases, as these not only help in diagnosis but may also influence treatment.

Family history

• A family history of diseases such as IBD or colorectal malignancy is relevant.

Causes

Common causes

• Colonic diverticulosis
  • Colonic diverticulosisis the most common cause of acute LGIB in the western world, accounting for 15% to 55% of all LGIB
  • Diverticula can occur anywhere in the gastrointestinal tract, but are most common in the sigmoid colon. However, approximately 60% of diverticular bleeds arise from diverticula in the right colon, highlighting a tendency for right-sided diverticula to bleed
  • Hemorrhage results from rupture of the intramural branches (vasa recta) of the marginal artery at the dome of a diverticulum and can give rise to a massive, life-threatening LGIB
  • This is by far the most common cause of bleeding in the elderly, as the prevalence of diverticular disease increases with age, being as high as 85% by the age of 85 years

• Obesity has recently been recognized as a risk factor in the development of diverticular disease, and the risk of diverticular bleeding in this group of patients is higher than that in patients who are not obese
• Vascular ectasias (angiodysplasias/angioectasias):
  • Tortuous dilated submucosal vessels that account for approximately 10% of LGIB.
  • They appear endoscopically as small, flat lesions (5-10 mm) with ectatic capillaries radiating from a central vessel (Fig. 1)
  • The prevalence of angiodysplasia in the gastrointestinal tract is not well known, but a pooled analysis of three colonoscopic cancer screening studies detected angiodysplasia in 0.8% of the patients The prevalence of angiodysplasia is higher in older populations and, in the past, has been linked to certain conditions such as end-stage renal disease, Von Willebrand disease , and aortic stenosis In one series, 37% of colonic dysplasias were found in the cecum, 17% in the ascending colon, 7% in the transverse colon, 7% in the descending colon, and 32% in rectosigmoid area
  • Angiodysplasia can also be found throughout the small bowel and is responsible for up to 40% of small intestinal bleeding in patients older than 40 years.
  • Angiodysplasia of the stomach and duodenum is responsible for up to 7% of UGIB I
• Iatrogenic:
  • Bleeding is recognized as the most common complication of colonoscopy and polypectomy, occurring in 0.3% to 6.1% of polypectomies
  • Risk factors for bleeding include polyp size greater than 1 cm, patient age older than 65 years, presence of comorbid disease, and polypectomy using the cutting mode of current
  • The risk is also greater in patients taking anticoagulant or antiplatelet agents
• Ischemic colitis:
  • Ischemic colitis accounts for approximately 20% of LGIB
  • Ischemia results from a sudden reduction in blood flow to the mesenteric vessels as a result of hypotension, occlusion, or spasm of the mesenteric vessels
  • Nonocclusive disease typically affects the watershed areas of the bowels, such as the splenic flexure and adjacent transverse colon due to the poor blood supply from the marginal artery.
  • Occlusive disease is rarer but can occur as a result of thrombus formation or embolus.
  • It is a recognized complication of aortic surgery
  • Elderly patients with comorbid disease are at higher risk of developing ischemic colitis.
  • There may be a history of ischemic heart disease
  • The majority of patients with ischemic colitis improve following conservative management; however, approximately 20% will progress to develop colonic gangrene
  • Other complications include chronic colitis and stricture formation
  • Diagnosis requires a high index of suspicion
• Colorectal malignancy:
  • Colorectal cancer accounts for approximately 10% of bleeds, either as occult bleeding presenting with anemia or as frank blood loss per rectum
  • A family history of colorectal cancer is important to establish
• Anorectal abnormalities:
  • Hemorrhoids, fissures, fistulae, and polyps can all present with bright red rectal bleeding, which may be intermittent in nature
  • Hemorrhoids are the most common cause of rectal bleeding in adults younger than 50 years
  • The finding of hemorrhoids in older patients with LGIB should not preclude further investigation, as hemorrhoids are an extremely common finding and may not be the cause of bleeding
• Inflammatory bowel disease (IBD):
  • IBD refers to both Crohn disease and ulcerative colitis Accounts for 5% to 10% of bleeds.
  • It is by far the most common cause of LGIB in Asian populations in whom the prevalence of diverticular disease is much lower
  • A previous history of IBD in patients with LGIB is important, as these patients have a higher risk of developing colorectal malignancy than do the general population
• Infectious colitis:
  • The most common organisms in the U.S. are species ofSalmonella,Campylobacter,Shigella, andYersinia

Rare causes

• Colonic polyps:
  • These can occur in isolation or as part of an inherited polyposis syndrome
  • Can cause occult or overt LGIB

• Radiation proctitis:
  • This usually occurs a few months following ionizing radiation for pelvic malignancies (Fig. 2). In one study of patients with radiation proctitis following pelvic irradiation, 69% presented with bleeding within 1 year and 96% within 2 years

• Rectal varices:
  • Associated with portal hypertension; may result in massive bleeding
  • Stercoral ulceration:
  • Can cause significant fresh rectal bleeding in elderly constipated patients

• Meckel diverticulum:
  • These small bowel diverticula may contain ectopic gastric mucosa that can ulcerate and cause bleeding
  • They are the most common cause of massive LGIB in young children, and can be diagnosed with angiography, Meckel scans, and radionuclide imaging

• Intussusception :
  • More common in children, with the highest incidence between the ages of 6 months and 2 years
• Henoch-Schönlein purpura (HSP):
  • Most commonly affects children
  • Bleeding may be a direct result of vasculitis or secondary to intussusception, which is associated with HSP
• Aortoenteric fistula:

• Abdominal aortic aneurysms, especially those of the inflammatory type, may fistulate into the small bowel, giving rise to a massive, life-threatening hemorrhage

• Peutz-Jeghers syndrome:
  • Polyps may give rise to frank or occult bleeding
• Klippel-Trenaunay-Weber syndrome:
  • Hemangiomas in the colon can cause significant bleeding

• Hereditary hemorrhagic telangiectasia:
  • Blood loss from mucosal telangiectasia can be chronic or acute
• Neurofibromatosis :
  • Neurofibromas within the lumen of the bowel can ulcerate, causing bleeding
• Blue rubber bleb syndrome:
  • Bleeding can arise from hemangiomas in the bowel Usually occult in nature

Risk factors

Common risk factors in the development of lower GI bleeding include:

• Advancing age
• Previous history of gastrointestinal bleed
• Chronic constipation
• Hematologic disorders
• Anticoagulants medications
• Nonsteroidal anti-inflammatory drugs
• Human immunodeficiency virus

Chronic constipation	Results in colonic diverticula and predispose patients to anal fissures and hemorrhoid formation
Hematologic disorders	Deficiencies in clotting factors, such as factor VII and factor VIII, predispose persons to LGIB
Anticoagulants medications	Patients taking warfarin and heparin, aspirin, and platelet inhibitors are at increased risk of bleeding in general
Nonsteroidal anti-inflammatory drugs	NSAIDs cause ulceration in the terminal ileum and proximal colon, and can exacerbate IBD
Human immunodeficiency virus	In patients with HIV, bleeding is caused by opportunistic infections, cytomegalovirus colitis, Kaposi sarcoma, or lymphoma