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==Historical Perspective==
Lower GI bleeding is defined as any bleed that occurs distal to the ligament of Treitz.
*The term "metabolic syndrome" dates back to at least the late 1950s, but came into common usage in the late 1970s to describe various associations of risk factors with diabetes.<ref>Joslin EP. The prevention of diabetes mellitus. ''JAMA'' 1921;76:79–84.</ref><ref>Kylin E. [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome] (German). ''Zentralbl Inn Med'' 1923;44: 105-27.</ref>
==Incidence==
*In 1947, Dr. Jean Vague proposed a theory that upper body obesity predisposed to [[diabetes]], [[atherosclerosis]], [[gout]], and [[calculi]].<ref>Vague J. La diffférenciacion sexuelle, facteur déterminant des formes de l'obésité. Presse Med 1947;30:339-40.</ref>
*In the United States the incidence of LGIB ranges from 20.5 to 27 per 100,000 persons per year.
*In 1967, Avogaro, Crepaldi and co-workers discovered obese patients with diabetes, [[hypercholesterolemia]], and marked [[hypertriglyceridemia]] improved when they were put on a hypocaloric, low carbohydrate diet.<ref>Avogaro P, Crepaldi G, Enzi G, Tiengo A. Associazione di iperlipidemia, diabete mellito e obesità di medio grado. ''Acta Diabetol Lat'' 1967;4:572-590.</ref>
==Age==
*In 1977, Haller coined the term "metabolic syndrome" for the first time when describing the additive effects of risk factors on atherosclerosis.<ref>Haller H. [Epidemiology and associated risk factors of hyperlipoproteinemia] (German). ''Z Gesamte Inn Med'' 1977;32(8):124-8. PMID 883354.</ref>
*There is a greater than 200 fold increase from the third to the ninth decade of life.
*In 1977, Singer coined the term hyperlipoproteinemia to describe the associations of obesity, gout, diabetes mellitus, and hypertension with metabolic syndrome.<ref>Singer P. [Diagnosis of primary hyperlipoproteinemias] (German). ''Z Gesamte Inn Med'' 1977;32(9):129-33. PMID 906591.</ref>
==Classification==
*In 1977 and 1978, Gerald B. Phillips developed the concept that risk factors for myocardial infarction are not only associated with heart disease, but also with [[aging]], obesity and other clinical states.<ref>Phillips GB. Sex hormones, risk factors and cardiovascular disease. ''Am J Med'' 1978;65:7-11. PMID 356599.</ref><ref>Phillips GB. Relationship between serum sex hormones and glucose, insulin, and lipid abnormalities in men with myocardial infarction. ''Proc Natl Acad Sci U S A'' 1977;74:1729-1733. PMID 193114.</ref>
*Lower GI bleeding can be classified into 3 groups based on the severity of bleeding:
*In 1988, Gerald M. Reaven proposed [[insulin resistance]] as the underlying factor and named the constellation of abnormalities as Syndrome X.<ref>Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607. PMID 3056758.</ref>
**Occult lower GI bleeding
==Screening==
**Moderate lower GI bleeding
According to the Endocrine Society clinical guidelines, screening for metabolic syndrome is recommended every 3 years among patients with one or more risk factors (type 2 DM or with a family history of dyslipidemia, CVD, or hereditary conditions associated with cardiovascular mortality such as polycystic ovary syndrome, and in cases of childhood obesity). Screening assessment includes measurement of:<ref name="pmid18664543">{{cite journal |vauthors=Rosenzweig JL, Ferrannini E, Grundy SM, Haffner SM, Heine RJ, Horton ES, Kawamori R |title=Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline |journal=J. Clin. Endocrinol. Metab. |volume=93 |issue=10 |pages=3671–89 |year=2008 |pmid=18664543 |doi=10.1210/jc.2008-0222 |url=}}</ref>
**Severe lower GI bleeding
*Blood pressure
*Waist circumference
*Fasting lipid profile, and fasting glucose.
==Natural History==
*If left untreated, consistently high levels of insulin in metabolic syndrome usually leads to type 2 diabetes. Insulin resistance is also associated with many changes in the body prior to its manifesting as disease including chronic inflammation and damage to arterial walls, decreased excretion by the kidneys, and coagulopathies.
==Complications==
Common complications of metabolic syndrome include:
*Cardiovascular disease
*Type 2 DM
*Nonalcoholic fatty liver disease
*Infertility
*Osteoarthritis
*Gout
*Cancer
==Prognosis==
Prognosis is generally good with appropriate treatment and life style modifications.
==Pathophysiology==
Adipose tissue and inflammatory process play an important role in the pathogenesis of metabolic syndrome.
===Role of adipose tissue===
*Adipose tissue has two major functions
**Storage and release of energy-rich fatty acids
**Secretion of proteins required for endocrine and autocrine regulation of energy metabolism.
*Adipocytes exert their metabolic effects by the release of free fatty acids, enhanced by the secretion of
**Catecholamines
**Glucocorticoids
**Increased β-receptor agonist activity
**Reduction of lipid storage mediated by insulin
*Visceral adipose tissue has been identified as an important source of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as anti-inflammatory cytokines such as adiponectin.
*Increased levels of proinflammatory cytokines likely contribute to the etiology of insulin resistance primarily by obstructing insulin signaling and contributing to down-regulation of peroxisomal proliferator-activated receptor-γ, processes that are fundamentally important regulators of adipocyte differentiation and control.
*Additionally, insulin resistance may promote inflammation through the diminution of insulin’s anti-inflammatory effects.
*Finally, oxidative stress is increased in obesity, primarily as a result of excessive intake of macronutrients and a concomitant increase in metabolic rate. These factors also contribute to the inflammatory response.
*Proteins such as leptin and adiponectin, are produced primarily by adipocytes, are classified as adipokines. Although leptin is primarily involved in appetite control, its immunologic effects include protection of T lymphocytes from apoptosis and regulation of T-cell activation and proliferation.
*Other cytokines (primarily IL-6 and TNF-α) and adipokines (leptin, adiponectin, and adipose-derived resistin) are two additional major groups of inflammatory proteins produced and released by adipose and adipose-associated tissue.
*Reduced leptin levels may increase appetite and slow metabolism, but they may also increase susceptibility to the toxicity of proinflammatory stimuli, such as endotoxin and TNF-α.
*Elevated leptin levels are proinflammatory, and this feature likely plays an important role in the progression of heart disease and diabetes, especially in obese patients. *Serum levels of adiponectin correlate with insulin sensitivity and do not rise in obesity. Significantly reduced adiponectin levels are found in patients with type 2 diabetes.
*Adiponectin reduces both TNF-α production and activity. It also inhibits IL-6 production.
*Resistin, an adipokine that induces insulin resistance, is induced by endotoxin and cytokines.
===Immune response===
*Native immune responses act aberrantly in obese individuals.
*Natural killer (NK) cell cytotoxic activity is depressed in obesity, as well as plasma levels of cytokines such as IL-12, IL-18 and interferon-γ known to regulate NK cell function.
*Resistin, an adipokine that induces insulin resistance, is induced by endotoxin and cytokines.
*Resistin acts at the cellular level to up-regulate production of proinflammatory cytokines, most likely through the nuclear factor κB (NFκB) pathway. 
*Resistin appears to present a molecular link among metabolic signaling, inflammatory processes, and the development of cardiovascular disease.
*Resistin levels have been associated with inflammatory markers apparently independently of BMI in humans. 
*Both free fatty acids and TNF-α act through intracellular inflammatory cascade pathways to arrest insulin signaling. This process is mediated by activation of transcription factors present within the cell cytoplasm, which, following their translocation to the nucleus, eventually bind to transcription factors regulating the inflammatory process. *The cytoplasm also contains NFκB, another transcription factor whose activation is implicated in a number of diseases, including diabetes.
*NFκB is also induced by hypoxia, and it increases production of proinflammatory cytokines TNF-α and IL-6, both of which are frequently increased in patients with OSA syndrome.  Therefore, inflammation provides the common linkage underlying the association of obesity, metabolic syndrome, and OSA.


==Associated Conditions==
The metabolic syndrome has been associated with several obesity-related disorders including:
*Fatty liver disease with steatosis, fibrosis, and cirrhosis
*Hepatocellular and intrahepatic cholangiocarcinoma
*Chronic kidney disease (CKD)
*Polycystic ovary syndrome
*Obstructive sleep apnea
*Hyperuricemia and gout
==Pathophysiology==
{{familytree/start}}
{{familytree | | | | | | | | | | | | A01 | | | | | |A01=Physical inactivity <br> Smoking <br> Energy dense food <br>Stress}}
{{familytree | | | | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | | | | B01 | | | | | |B01=Positive energy balance resulting in <br> Adipose tissue hyperplasia and hypertrophy}}
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{{familytree | | | | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|.| }}
{{familytree | | | | | C01 | | | | | | | | | | | | C02 |C01=Altered FFA metabolism|C02=Altered release of adipokines}}
{{familytree | | | | | |!| | | | | | | | | | | | | |!| |}}
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{{familytree | |!| | | | | | | |!| | | | | |!| | | | | | | |!| |}}
{{familytree | E01 | | | | | | E02 | | | | E03 | | | | | | E04 |E01=↑ Portal FFA|E02=Insulin resistance hyperinsulinemia|E03=↑Leptin<br>↑AT-II<br>↑Aldosterone|E04=↑ Factor VII<br>↑ Factor V<br>↑ PAI-I}}
{{familytree | |!| | | | | | | |!| | | | | |!| | | | | | | |!| | }}
{{familytree | F01 | | | | | | F02 | | | | F03 | | | | | | F04 |F01=↑ Lipoprotein synthesis<br>↑ Gluconeogenesis|F02=Impairs 𝛽-cell function<br> of pancreas|F03=Activate RAAS and SNS|F04=Oxidative stress<br>endothelial dysfunction}}
{{familytree | |!| | | | | | | |!| | | | | |!| | | | | | | |!| | }}
{{familytree | G01 | | | | | | G02 | | | | G03 | | | | | | G04 |G01=Dyslipidemia|G02=Hyperglycemia|G03=↑ Sodium reabsorption<br> Vasoconstriction|G04=Proinflammatory state<br>prothrombotic state}}
{{familytree | |!| | | | | | | |!| | | | | |!| | | | | | | |!| | }}
{{familytree | |!| | | | | | | |!| | | | | H01 | | | | | | H02 | H01=Hypertension|H02=Hypercoagulable state}}
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{{familytree | | | | | | | | | | | | |!| | | | | | | | | | | | | }}
{{familytree | | | | | | | | | | | | I01 | | | | | | | | | | | |I01=Metabolic syndrome}}
{{familytree/end}}
===Insulin resistance===
*Insulin resistance is defined as a condition in which the peripheral target tissues such as adipose, muscle, and liver fail to respond to normal levels of insulin levels in response normal blood glucose.
*Free fatty acids inhibit insulin-mediated glucose uptake in the muscles by downregulating signaling pathways.
*As a result, pancreatic beta cells of pancreas secretes more insulin (i.e., hyperinsulinemia) to overcome the hyperglycemia among insulin-resistant individuals.
*These responses by pancreas may cause an overexpression of insulin activity in some normal tissues.
*Imbalance between normal and resistant tissue responses to insulin is believed to be responsible for the clinical manifestations of metabolic syndrome.
*Binding of insulin results in a tyrosine phosphorylation of downstream substrates and activation of two parallel pathways
** The phosphoinositide 3-kinase (PI3K) pathway
** The mitogen-activated protein (MAP) kinase pathway.
{| class="wikitable"
{| class="wikitable"
!
!
!PI3K pathway
!Severe lower GI bleeding
!(MAP) kinase pathway
!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, <nowiki><br></nowiki> 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.
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Lower GI Tract
! align="center" style="background:#4479BA; color: #FFFFFF;" | Arterial Supply
! align="center" style="background:#4479BA; color: #FFFFFF;" |Venous Drainage
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |Midgut
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Distal duodenum jejunum
* Ileum
* Appendix
* Cecum
* Ascending colon
* Hepatic flexure
* Proximal transverse colon.
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Superior mesenteric artery (SMA)
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Portal system.
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |Hindgut
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Distal one-third of the transverse colon
* Splenic flexure
* Descending colon,
* Sigmoid colon
* Rectumhu
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Inferior mesenteric artery (IMA)
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Portal system '''<sup>ɸ</sup>'''
|-
| colspan="4" style="padding: 5px 5px; background: #F5F5F5;" align="center" |ɸ -Except lower rectum, which drains into the systemic circulation.
|}
 
[[Image: Colonic blood supply1.gif|thumb|center|300px|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). <br>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.
*'''<u>Diverticulosis</u>'''
**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.
[[Image:Sigmoid diverticulum (diagram).jpg|thumb|center|400px|Diagram of sigmoid diverticulum<br>Source:By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons]]
*'''<u>Anorectal disease</u>'''
:*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.
*'''<u>Mesenteric Ischemia</u>'''
:*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.
*'''<u>Ischemic Colitis</u>'''
:*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.
*'''<u>Inflammatory Bowel Disease</u>'''
:*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.
*'''<u>Neoplasia</u>'''
:*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.
*'''<u>AV Malformation/Angiodysplasia</u>'''
:*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.
==Symptoms==
*The clinical presentation of LGIB varies with the anatomic source of the bleeding.
*Commonly, LGIB from the right side of the colon can manifest as maroon stools, whereas a left-sided bleeding source may be evidenced by bright red blood per rectum.
*The presentation of LGIB can also vary depending on the etiology.
**A young patient may present with fever, dehydration, abdominal cramps, and hematochezia caused by infectious or noninfectious (idiopathic) colitis.
**An older patient may present with painless bleeding and minimal symptoms caused by diverticular bleeding or angiodysplasia.
**LGIB can be mild and intermittent, as often is the case with angiodysplasia, or it may be moderate or severe, as may be the situation in diverticula-related bleeding.
**Young patients may present with abdominal pain, rectal bleeding, diarrhea, and mucous discharge that may be associated with IBD.
** Elderly patients presenting with abdominal pain, rectal bleeding, and diarrhea may have ischemic colitis.
** Elderly patients with atherosclerotic heart disease may present with intermittent LGIB and syncope that may be due to angiodysplastic lesions.
** Stools streaked with blood, perianal pain, and blood drops on the toilet paper or in the toilet bowl may be associated with perianal pathology, such as anal fissure or hemorrhoidal bleeding.
** The passage of maroon stools or bright red blood from the rectum is usually indicative of massive lower GI hemorrhage.
* Massive LGIB is a life-threatening condition in which patients present with a systolic blood pressure (SBP) of below 90 mm Hg and a hemoglobin (Hb) level of 6 g/dL or less.
{| class="wikitable"
! colspan="2" |Disease
!Symptoms
|-
| colspan="2" |Diverticular bleeding
|Painless bleeding
Mild abdominal cramping
 
If the bleeding is brisk and voluminous, patients may be hypotensive and display signs of shock
|-
| colspan="2" |Angiodysplasia
|Painless, hematochezia or melena (slow but repeated bleeding episodes)
Syncope
|-
| rowspan="4" |Colitis
|Ischemic colitis
| rowspan="4" |Fever
Abdominal pain
 
Bloody diarrhea
 
Dehydration
 
Hypotension in severe cases
 
Weight loss
|-
|Infectious colitis
|-
|Radiation-induced colitis
|-
|Ulcerative colitis
|-
| colspan="2" |Colon cancer
|Right-sided bleeding (Maroon stools or melena)
Insidious
 
Patients presents with iron-deficiency anemia and syncope
 
Whereas left-sided colonic neoplasms can present as bright red blood per rectum
|-
| colspan="2" |Hemorrhoids
|Painless, whereas bleeding secondary to fissures tends to be painful.
Can also present with strangulation, hematochezia, and pruritus.
|}
===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:<ref name="pmid23997409">{{cite journal |vauthors=Navuluri R, Kang L, Patel J, Van Ha T |title=Acute lower gastrointestinal bleeding |journal=Semin Intervent Radiol |volume=29 |issue=3 |pages=178–86 |year=2012 |pmid=23997409 |pmc=3577586 |doi=10.1055/s-0032-1326926 |url=}}</ref><ref name="pmid16303575">{{cite journal |vauthors=Strate LL |title=Lower GI bleeding: epidemiology and diagnosis |journal=Gastroenterol. Clin. North Am. |volume=34 |issue=4 |pages=643–64 |year=2005 |pmid=16303575 |doi=10.1016/j.gtc.2005.08.007 |url=}}</ref><ref name="pmid17131153">{{cite journal |vauthors=Ríos A, Montoya MJ, Rodríguez JM, Serrano A, Molina J, Ramírez P, Parrilla P |title=Severe acute lower gastrointestinal bleeding: risk factors for morbidity and mortality |journal=Langenbecks Arch Surg |volume=392 |issue=2 |pages=165–71 |year=2007 |pmid=17131153 |doi=10.1007/s00423-006-0117-6 |url=}}</ref><ref name="pmid12695275">{{cite journal |vauthors=Strate LL, Orav EJ, Syngal S |title=Early predictors of severity in acute lower intestinal tract bleeding |journal=Arch. Intern. Med. |volume=163 |issue=7 |pages=838–43 |year=2003 |pmid=12695275 |doi=10.1001/archinte.163.7.838 |url=}}</ref>
* Advancing age
* Previous history of gastrointestinal bleed
* Chronic constipation
* Hematologic disorders
* Anticoagulants medications
* Nonsteroidal anti-inflammatory drugs
* Human immunodeficiency virus
{| class="wikitable"
|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
|}
==Management==
===Initial Evaluation===
*In patients with acute lower gastrointestinal bleeding who are unstable rapid assessment and resuscitation should be initiated even before diagnostic evaluation.
*The initial steps in the management of a patient with lower gastrointestinal bleeding are to assess the severity of bleeding, and then institute fluid and blood resuscitation as needed.
*Once hemodynamic stability is achieved, nasogastric lavage should be performed to rule of upper GI source.
*Equilibration between the intravascular and extravascular volumes cannot be achieved until 24 to 72 hours after bleeding has occurred.
 
===Role of Nasogastric tube (NGT)===
*Nasogastric tube (NGT) lavage is recommended in all patients with lower gastrointestinal bleeding once the patient is stabilized.
*A carefully placed nasogastric tube (NGT) with irrigation and aspiration of bile is necessary to ensure sampling of duodenal contents.
*If there is a bloody NGT aspirate then an esophagogastroduodenoscopy (EGD) is warranted (11 to 15% of patients despite “negative” NGT aspirates are due to upper GI bleeding).
*Obtaining clear fluid favors a lower GI source of bleeding.
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="2" style="background:#efefef;" | Workup and Initial Management
|-
|I'''nitial Evaluation'''
|
* Airway Breathing, Circulation
|-
|'''Supportive Therapy'''
|
* Ensure patent and protected airway
 
* [[Intubation|Intubate]] if needed
* Consider [[mechanical ventilation]]
 
* 2 large-bore, peripheral intravenous lines
 
* Can consider [[Central venous catheter|large-bore central venous catheter]] or intraosseous line if rapid transfuser will be needed
|-
|'''Blood transfusion'''
|
* Resuscitate with 1:1:1 of packed red blood cells (PRBCs) to fresh frozen plasma (FFP) to platelets.
 
* Consider massive transfusion protocol
 
* Res:Low riskto a target hemoglobin of 7 mg/dL.
 
* Consider Sengstaken-Blakemore tube for control of immediately life-threatening upper GI bleeding
|}
===Assessment of severity of bleeding===
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="1" style="background:#efefef;" | Bleeding severity
! colspan="1" style="background:#efefef;" | Vital signs
! colspan="1" style="background:#efefef;" | Blood loss
|-
|Minor
|Normal
|<10%
|-
|Moderate
|Postural hypotension
|10-20%
|-
|Severe
|Shock
|>25%
|}
===Fluid resuscitation===
*Two large caliber (16-gauge) peripheral catheters or a [[Central venous catheter|central venous line]] should be inserted in patients who are [[hemodynamically unstable]].
*The rate of fluid resuscitation is proportional to the severity of [[bleeding]] with the goal of restoring and maintaining the patient’s [[blood pressure]].
*Infusion of 500 mL of [[normal saline]] or lactated [[Ringer's lactate|Ringer's solution]] over 30 minutes is preferred treatment for patients with [[Bleeding|active bleeding]] before [[Blood type|blood type matching]] and blood [[transfusion]].
*Intensive monitoring with a [[pulmonary artery catheter]] is recommended to monitor the response of initial resuscitation efforts and any complications of fluid overload.
*If the blood pressure fails to respond to initial resuscitation, the rate of fluid administration should be increased and urgent intervention (eg, angiography) considered.
 
===Blood transfusion===
*Patients with severe [[bleeding]] need to be transfused.<ref name="pmid24063362">{{cite journal |vauthors=Al-Jaghbeer M, Yende S |title=Blood transfusion for upper gastrointestinal bleeding: is less more again? |journal=Crit Care |volume=17 |issue=5 |pages=325 |year=2013 |pmid=24063362 |pmc=4056793 |doi=10.1186/cc13020 |url=}}</ref><ref name="pmid23281973">{{cite journal |vauthors=Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, Santaló M, Muñiz E, Guarner C |title=Transfusion strategies for acute upper gastrointestinal bleeding |journal=N. Engl. J. Med. |volume=368 |issue=1 |pages=11–21 |year=2013 |pmid=23281973 |doi=10.1056/NEJMoa1211801 |url=}}</ref>
*[[Fresh frozen plasma|Fresh frozen plasma,]] [[platelets]], or both should be given to patients with [[coagulopathy]] who are actively bleeding and to those who have received more than 10 units of packed [[erythrocytes]].
 
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="2" style="background:#efefef;" |Indications for transfusion
|-
! colspan="1" style="background:#efefef;" |Age
! colspan="1" style="background:#efefef;" |Target Hematocrit
|-
|Elderly patient ( >45)
|30%
|-
|Younger patient (<45)
|25%
|-
|Patients with portal hypertension
|28%
|}
 
===Triage and consultations ===
*All patients with visible rectal bleeding warrants an immediate evaluation in all cases. The timing and setting of the evaluation depends upon the severity of bleeding and the patient's comorbid illnesses.
*A gastroenterology consultation should be obtained early in the hospital course of patients with acute lower GI bleeding.
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="1" style="background:#efefef;" |Evaluation setting
! colspan="1" style="background:#efefef;" |Patient catagories
|-
|ICU
|Patients with high-risk features.
|-
|Outpatient
|Patients with low-risk features.<sup>†</sup> 
|-
|Regular Ward
|Most other patients can be admitted to a regular medical ward.<sup>♦</sup>
 
|-
| colspan="2" style="background:#efefef;" |
* '''†''': Low-risk features include a young, otherwise healthy patient with minor, self-limited rectal bleeding suspected to be from an anal source)
 
* ♦: Requires continuous electrocardiogram monitoring and pulse oximetry.
|}
 
===Risk stratification===
Clinical features can predict the risk of complications in patients with presumed acute lower GI bleeding. These features can also be used to categorize patients as either low or high risk. The number of high-risk features present correlates with the likelihood of a poor outcome.
High-risk features include:
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="1" style="background:#efefef;" |High-risk features
|-
|
*Hemodynamic instability (hypotension, tachycardia, orthostasis, syncope)
*Persistent bleeding
*Significant comorbid illnesses
*Advanced age
*Bleeding that occurs in a patient who is hospitalized for another reason
*A prior history of bleeding from diverticulosis or angiodysplasia
*Current aspirin use
*Prolonged prothrombin time
*A non-tender abdomen
*Anemia
*An elevated blood urea nitrogen level
*An abnormal white blood cell count
|}
==Pharmacotherapy==
Epinephrine is used alone or in conjunction with other surgical techniques to treat a variety of causes of LGIB. Local injection of epinephrine stops bleeding by both pressure tamponade and the vasoconstrictor effect.  In patients with rebleeding, surgery should be considered. Pharmacotherapy is only used as an adjuvant therapy for all patients with LGIB.
:*Preferred regimen (1): Local injection of 1:10,000 to 20,000 solution (Intra-arterial vasopressin infusions begin at a rate of 0.2 U/min. If the bleeding persists, the rate of the infusion is increased to 0.4-0.6 U/min).
:*Note:- The bleeding stops in about 91% of patients receiving intra-arterial vasopressin but recurs in up to 50% of patients when the infusion is stopped.
===Major contraindications===
*Closed-angle glaucoma
*Labor
*Shock
*Sulfite hypersensitivity
*CAD, PAD
===Complications===
During vasopressin infusion, monitor patients for:
*Recurrent hemorrhage
*Myocardial ischemia (Nitroglycerine drip can be used to overcome cardiac complications).
*Arrhythmias
*Hypertension
*Volume overload with hyponatremia.
==Colonoscopy==
*Colonoscopy is considered as the initial diagnostic modality of choice in patients presenting with lower GI bleeding. Colonoscopy can identify the origin of severe LGI bleeding in 74% to 82% of patients.
*As long as patients remain stable during the bowel preparation and sedation, colonoscopy has the advantage of not only localizing the source of bleeding, but also allowing intervention via clips, epinephrine injection, thermoregulation, or laser photocoagulation.
*In patients with massive lower GI bleeding, colonoscopic hemostasis is an effective means of controlling bleeding from a diverticular source when appropriately skilled providers are available.
*In cases in which no source of bleeding is seen on colonoscopy, esophagogastroduodenoscopy should be undertaken, as occasionally, brisk UGIB increases transit time and presents as blood per rectum.
*If a patient has pain associated with bleeding, ischemic bowel disease should be considered. CTA may be a more appropriate first-line investigation in patients with abdominal pain or suspected peritonitis.
===Timing of colonoscopy===
*In patients with ongoing bleeding or high-risk clinical features, a colonoscopy should be performed within 24 hours of presentation after adequate colon preparation to potentially improve diagnostic and therapeutic yield.
===Bowel preparation===
*In a patient who is not actively bleeding, rapid bowel preparation can be administered with 3 to 4 L of polyethylene glycol.
*This can be administered orally or via a nasogastric tube to avoid nausea and reduce the potential risk of aspiration.
*However, there is the potential risk of fluid overload in the acutely ill patient receiving rapid bowel preparation this way.
*Metoclopramide, 10 to 20 mg, can be administered with the bowel preparation as a prokinetic agent to facilitate gastric emptying and reduce the risk of vomiting.
*Some have advocated colonoscopy following limited bowel preparation using polyethylene glycol purges supplemented with rectal enemas.
*Blood is cathartic to the colon and tends to facilitate the emptying of colonic residue.
===Complications===
*Perforation of the luminal wall, resulting in peritonitis and sepsis.
*Poor visualization in an unprepared colon.
 
===Non surgical options===
*Once the bleeding site is localized, therapeutic options include coagulation and injection with vasoconstrictors or sclerosing agents.
*In cases of diverticular bleeding, bipolar probe coagulation, epinephrine injection, and metallic clips may be used.
*If recurrent bleeding is present, the affected bowel segment can be resected.
*In cases of angiodysplasia, thermal therapy, such as electrocoagulation or argon plasma coagulation, is generally successful.
*Angiodysplastic lesions may be missed at colonoscopy if the lesions are small or covered with blood clots.
*Endoscopic hemostasis therapy is a safe and effective method to control high-risk indications of hemorrhage: active bleeding, nonbleeding visible vessel, or adherent clot.
*It is also effective for diverticular bleeding, angioectasia bleeding, and post-polypectomy bleeding.
*In patients with brisk, active lower gastrointestinal bleeding, obtain a surgical consultation.
 
{| class="wikitable"
!
!
!
!
!
|-
|-
|Effected by
|Diverticulosis
Insulin resistance
|
|
|
* Yes
|No
|
|
|-
|-
|Results in
|Angiodysplasia
|
|
*Reduction in endothelial NO production resulting
in an endothelial dysfunction
*Reduction in GLUT4 translocation
|
|
* Continued endothelin-1 (ET-1) production
* Mitogenic stimulus to vascular smooth muscle cells
|
|
|-
|-
|Decreased glucose intake
|Hemmrohoids
by
|
|
|
|-
|
|
|
|
|-
|
|
|
* Decreased skeletal muscle and fat glucose uptake
|
|
|
|
|}
|}
 
===CXXX===
====PI3K-Akt pathway====
*Diverticula are most common in the descending and sigmoid colon.  
*The PI3K-Akt pathway is affected, while, the MAP kinase pathway functions normally in insulin resistance.
*Most of the time bleeding from diverticulosis stops spontaneously, however, in about 5% of patients, the bleeding can be massive and life-threatening.
*This leads to a change in the balance between these two parallel pathways.
 
 
*In these ways, an insulin resistance leads to the vascular abnormalities that predispose to atherosclerosis. Although insulin-resistant individuals need not be clinically obese, they nevertheless commonly have an abnormal fat distribution that is characterized by a predominantly upper body fat.
*Regardless of the relative contributions of visceral fat and abdominal subcutaneous fat to insulin resistance, a pattern of abdominal (or upper body) obesity correlates
more strongly with the insulin resistance and the MetS than does lower body obesity.


==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 19:13, 13 December 2017

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.

Symptoms

  • The clinical presentation of LGIB varies with the anatomic source of the bleeding.
  • Commonly, LGIB from the right side of the colon can manifest as maroon stools, whereas a left-sided bleeding source may be evidenced by bright red blood per rectum.
  • The presentation of LGIB can also vary depending on the etiology.
    • A young patient may present with fever, dehydration, abdominal cramps, and hematochezia caused by infectious or noninfectious (idiopathic) colitis.
    • An older patient may present with painless bleeding and minimal symptoms caused by diverticular bleeding or angiodysplasia.
    • LGIB can be mild and intermittent, as often is the case with angiodysplasia, or it may be moderate or severe, as may be the situation in diverticula-related bleeding.
    • Young patients may present with abdominal pain, rectal bleeding, diarrhea, and mucous discharge that may be associated with IBD.
    • Elderly patients presenting with abdominal pain, rectal bleeding, and diarrhea may have ischemic colitis.
    • Elderly patients with atherosclerotic heart disease may present with intermittent LGIB and syncope that may be due to angiodysplastic lesions.
    • Stools streaked with blood, perianal pain, and blood drops on the toilet paper or in the toilet bowl may be associated with perianal pathology, such as anal fissure or hemorrhoidal bleeding.
    • The passage of maroon stools or bright red blood from the rectum is usually indicative of massive lower GI hemorrhage.
  • Massive LGIB is a life-threatening condition in which patients present with a systolic blood pressure (SBP) of below 90 mm Hg and a hemoglobin (Hb) level of 6 g/dL or less.
Disease Symptoms
Diverticular bleeding Painless bleeding

Mild abdominal cramping

If the bleeding is brisk and voluminous, patients may be hypotensive and display signs of shock

Angiodysplasia Painless, hematochezia or melena (slow but repeated bleeding episodes)

Syncope

Colitis Ischemic colitis Fever

Abdominal pain

Bloody diarrhea

Dehydration

Hypotension in severe cases

Weight loss

Infectious colitis
Radiation-induced colitis
Ulcerative colitis
Colon cancer Right-sided bleeding (Maroon stools or melena)

Insidious

Patients presents with iron-deficiency anemia and syncope

Whereas left-sided colonic neoplasms can present as bright red blood per rectum

Hemorrhoids Painless, whereas bleeding secondary to fissures tends to be painful.

Can also present with strangulation, hematochezia, and pruritus.

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:[1][2][3][4]

  • 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

Management

Initial Evaluation

  • In patients with acute lower gastrointestinal bleeding who are unstable rapid assessment and resuscitation should be initiated even before diagnostic evaluation.
  • The initial steps in the management of a patient with lower gastrointestinal bleeding are to assess the severity of bleeding, and then institute fluid and blood resuscitation as needed.
  • Once hemodynamic stability is achieved, nasogastric lavage should be performed to rule of upper GI source.
  • Equilibration between the intravascular and extravascular volumes cannot be achieved until 24 to 72 hours after bleeding has occurred.

Role of Nasogastric tube (NGT)

  • Nasogastric tube (NGT) lavage is recommended in all patients with lower gastrointestinal bleeding once the patient is stabilized.
  • A carefully placed nasogastric tube (NGT) with irrigation and aspiration of bile is necessary to ensure sampling of duodenal contents.
  • If there is a bloody NGT aspirate then an esophagogastroduodenoscopy (EGD) is warranted (11 to 15% of patients despite “negative” NGT aspirates are due to upper GI bleeding).
  • Obtaining clear fluid favors a lower GI source of bleeding.
Workup and Initial Management
Initial Evaluation
  • Airway Breathing, Circulation
Supportive Therapy
  • Ensure patent and protected airway
  • 2 large-bore, peripheral intravenous lines
Blood transfusion
  • Resuscitate with 1:1:1 of packed red blood cells (PRBCs) to fresh frozen plasma (FFP) to platelets.
  • Consider massive transfusion protocol
  • Res:Low riskto a target hemoglobin of 7 mg/dL.
  • Consider Sengstaken-Blakemore tube for control of immediately life-threatening upper GI bleeding

Assessment of severity of bleeding

Bleeding severity Vital signs Blood loss
Minor Normal <10%
Moderate Postural hypotension 10-20%
Severe Shock >25%

Fluid resuscitation

Blood transfusion

Indications for transfusion
Age Target Hematocrit
Elderly patient ( >45) 30%
Younger patient (<45) 25%
Patients with portal hypertension 28%

Triage and consultations

  • All patients with visible rectal bleeding warrants an immediate evaluation in all cases. The timing and setting of the evaluation depends upon the severity of bleeding and the patient's comorbid illnesses.
  • A gastroenterology consultation should be obtained early in the hospital course of patients with acute lower GI bleeding.
Evaluation setting Patient catagories
ICU Patients with high-risk features.
Outpatient Patients with low-risk features.
Regular Ward Most other patients can be admitted to a regular medical ward.
  • : Low-risk features include a young, otherwise healthy patient with minor, self-limited rectal bleeding suspected to be from an anal source)
  • ♦: Requires continuous electrocardiogram monitoring and pulse oximetry.

Risk stratification

Clinical features can predict the risk of complications in patients with presumed acute lower GI bleeding. These features can also be used to categorize patients as either low or high risk. The number of high-risk features present correlates with the likelihood of a poor outcome. High-risk features include:

High-risk features
  • Hemodynamic instability (hypotension, tachycardia, orthostasis, syncope)
  • Persistent bleeding
  • Significant comorbid illnesses
  • Advanced age
  • Bleeding that occurs in a patient who is hospitalized for another reason
  • A prior history of bleeding from diverticulosis or angiodysplasia
  • Current aspirin use
  • Prolonged prothrombin time
  • A non-tender abdomen
  • Anemia
  • An elevated blood urea nitrogen level
  • An abnormal white blood cell count

Pharmacotherapy

Epinephrine is used alone or in conjunction with other surgical techniques to treat a variety of causes of LGIB. Local injection of epinephrine stops bleeding by both pressure tamponade and the vasoconstrictor effect. In patients with rebleeding, surgery should be considered. Pharmacotherapy is only used as an adjuvant therapy for all patients with LGIB.

  • Preferred regimen (1): Local injection of 1:10,000 to 20,000 solution (Intra-arterial vasopressin infusions begin at a rate of 0.2 U/min. If the bleeding persists, the rate of the infusion is increased to 0.4-0.6 U/min).
  • Note:- The bleeding stops in about 91% of patients receiving intra-arterial vasopressin but recurs in up to 50% of patients when the infusion is stopped.

Major contraindications

  • Closed-angle glaucoma
  • Labor
  • Shock
  • Sulfite hypersensitivity
  • CAD, PAD

Complications

During vasopressin infusion, monitor patients for:

  • Recurrent hemorrhage
  • Myocardial ischemia (Nitroglycerine drip can be used to overcome cardiac complications).
  • Arrhythmias
  • Hypertension
  • Volume overload with hyponatremia.

Colonoscopy

  • Colonoscopy is considered as the initial diagnostic modality of choice in patients presenting with lower GI bleeding. Colonoscopy can identify the origin of severe LGI bleeding in 74% to 82% of patients.
  • As long as patients remain stable during the bowel preparation and sedation, colonoscopy has the advantage of not only localizing the source of bleeding, but also allowing intervention via clips, epinephrine injection, thermoregulation, or laser photocoagulation.
  • In patients with massive lower GI bleeding, colonoscopic hemostasis is an effective means of controlling bleeding from a diverticular source when appropriately skilled providers are available.
  • In cases in which no source of bleeding is seen on colonoscopy, esophagogastroduodenoscopy should be undertaken, as occasionally, brisk UGIB increases transit time and presents as blood per rectum.
  • If a patient has pain associated with bleeding, ischemic bowel disease should be considered. CTA may be a more appropriate first-line investigation in patients with abdominal pain or suspected peritonitis.

Timing of colonoscopy

  • In patients with ongoing bleeding or high-risk clinical features, a colonoscopy should be performed within 24 hours of presentation after adequate colon preparation to potentially improve diagnostic and therapeutic yield.

Bowel preparation

  • In a patient who is not actively bleeding, rapid bowel preparation can be administered with 3 to 4 L of polyethylene glycol.
  • This can be administered orally or via a nasogastric tube to avoid nausea and reduce the potential risk of aspiration.
  • However, there is the potential risk of fluid overload in the acutely ill patient receiving rapid bowel preparation this way.
  • Metoclopramide, 10 to 20 mg, can be administered with the bowel preparation as a prokinetic agent to facilitate gastric emptying and reduce the risk of vomiting.
  • Some have advocated colonoscopy following limited bowel preparation using polyethylene glycol purges supplemented with rectal enemas.
  • Blood is cathartic to the colon and tends to facilitate the emptying of colonic residue.

Complications

  • Perforation of the luminal wall, resulting in peritonitis and sepsis.
  • Poor visualization in an unprepared colon.

Non surgical options

  • Once the bleeding site is localized, therapeutic options include coagulation and injection with vasoconstrictors or sclerosing agents.
  • In cases of diverticular bleeding, bipolar probe coagulation, epinephrine injection, and metallic clips may be used.
  • If recurrent bleeding is present, the affected bowel segment can be resected.
  • In cases of angiodysplasia, thermal therapy, such as electrocoagulation or argon plasma coagulation, is generally successful.
  • Angiodysplastic lesions may be missed at colonoscopy if the lesions are small or covered with blood clots.
  • Endoscopic hemostasis therapy is a safe and effective method to control high-risk indications of hemorrhage: active bleeding, nonbleeding visible vessel, or adherent clot.
  • It is also effective for diverticular bleeding, angioectasia bleeding, and post-polypectomy bleeding.
  • In patients with brisk, active lower gastrointestinal bleeding, obtain a surgical consultation.
Diverticulosis
Angiodysplasia
Hemmrohoids

CXXX

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

References

  1. Navuluri R, Kang L, Patel J, Van Ha T (2012). "Acute lower gastrointestinal bleeding". Semin Intervent Radiol. 29 (3): 178–86. doi:10.1055/s-0032-1326926. PMC 3577586. PMID 23997409.
  2. Strate LL (2005). "Lower GI bleeding: epidemiology and diagnosis". Gastroenterol. Clin. North Am. 34 (4): 643–64. doi:10.1016/j.gtc.2005.08.007. PMID 16303575.
  3. Ríos A, Montoya MJ, Rodríguez JM, Serrano A, Molina J, Ramírez P, Parrilla P (2007). "Severe acute lower gastrointestinal bleeding: risk factors for morbidity and mortality". Langenbecks Arch Surg. 392 (2): 165–71. doi:10.1007/s00423-006-0117-6. PMID 17131153.
  4. Strate LL, Orav EJ, Syngal S (2003). "Early predictors of severity in acute lower intestinal tract bleeding". Arch. Intern. Med. 163 (7): 838–43. doi:10.1001/archinte.163.7.838. PMID 12695275.
  5. Al-Jaghbeer M, Yende S (2013). "Blood transfusion for upper gastrointestinal bleeding: is less more again?". Crit Care. 17 (5): 325. doi:10.1186/cc13020. PMC 4056793. PMID 24063362.
  6. Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, Santaló M, Muñiz E, Guarner C (2013). "Transfusion strategies for acute upper gastrointestinal bleeding". N. Engl. J. Med. 368 (1): 11–21. doi:10.1056/NEJMoa1211801. PMID 23281973.