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=== Sporadic colorectal cancers ===
=== Sporadic colorectal cancers ===
The picture below depicts the molecular pathogenesis of sporadic colon cancer:
The picture below depicts the molecular pathogenesis of sporadic colon cancer:
[[Image:Sporadic Colon Cancer3.jpg|center|1000x1000px|frame|Molecular pathogenesis of sporadic colon cancer, (ɔ) Image courtesy of WikiDoc.org]]  
[[Image:Sporadic Colon Cancer3.jpg|center|1000x1000px|frame|Molecular pathogenesis of sporadic colon cancer]]  


*'''APC gene'''
*'''APC gene'''

Revision as of 12:23, 30 May 2020


Gastrointestinal Bleeding

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Muhammad Waleed Haider, M.D.[2]

Synonyms and Keywords: Blood loss from GI tract; bloody stool; blood in feces; PR bleeding; gastrointestinal hemorrhage; gastrointestinal hemorrhage; GI bleeding; bright red blood per rectum; BRBPR.

Overview

Gastrointestinal (GI) bleeding is defined as bleeding from any part of GI tract starting from mouth to anus. It can also be called as gastrointestinal hemorrhage. Based on the origin of bleeding it can be classified into upper gastrointestinal bleeding and lower gastrointestinal bleeding. Upper gastrointestinal bleeding (UGIB) is defined as bleeding from the gastrointestinal tract that originates proximal to the ligament of Treitz. Lower gastrointestinal bleeding is defined as blood loss originating distal to the ligament of Treitz. The most common causes of UGIB are peptic ulcer disease and esophageal varices while diverticulosis is the most commonly responsible for lower gastrointestinal bleeding. Clinical presentation includes overt bleeding from the gastrointestinal tract, rapid or slow, either manifested by hematemesis of fresh (blood-streaked to frankly bloody), old ('coffee ground') vomitus, melena and or as frank blood per rectum.

Common risk factors in the development of GI bleeding include advancing age, previous history of gastrointestinal bleeding, chronic constipation, hematologic disorders, anticoagulants medications, NSAIDs. It is essential to distinguish between lower gastrointestinal bleeding and brisk upper gastrointestinal bleeding as they can present with similar symptoms. Patients with severe bleeding or hemodynamic disturbance require hospitalization and urgent investigation. Treatment depends on the cause and the severity of the bleeding.

Types of bleeding

Bleeding from the gastrointestinal tract can be of the following types:

  • Hematemesis: Vomiting fresh red blood.
  • Coffee ground emesis: Vomiting of altered black blood.
  • Melena: Passage of black tarry stools.
  • Hematochezia: Passage of red blood per rectum (usually due to bleeding from the lower gastrointestinal tract but occasionally can be due to massive upper gastrointestinal bleeding).
  • Rebleeding: Defined as fresh hematochezia and/or melena associated with the development of shock (pulse greater than 100 beats/min, systolic pressure less than 100 mm Hg), a fall in CVP greater than 5 mm Hg, or a reduction in hemoglobin concentration greater than 20 g/l over 24 hours. Rebleeding should always be confirmed by endoscopy.

Causes

Gastrointestinal Bleeding Lethal Causes Common causes Less Common causes
Upper gastrointestinal bleeding
  • Anthrax
  • Ebola virus
  • Duodenal ulcer
  • Esophagitis
  • Esophageal varices
  • Gastric tumors
  • Gastric ulcer
  • Gastritis
  • Mallory-Weiss Syndrome
  • Peptic ulcer
  • Gastric cancer
  • Esophageal Tumors
  • Esophagitis
  • Gastric erosions/gastropathy
  • Dieulafoy lesions
  • Gastric antral vascular ectasia
Lower gastrointestinal bleeding
  • Diverticulosis
  • Vascular ectasias
  • Ischemic colitis
  • Colorectal malignancy
  • Hemorrhoids
  • Anal fissures
  • Crohn's disease
  • Ulcerative colitis
  • Infectious colitis
  • Colonic polyps
  • Radiation proctitis
  • Rectal varices
  • Stercoral ulceration
  • Meckel diverticulum
  • Intussusception
  • Henoch-Scholein Purpura (HSP)

Classification

The following flow chart elobarates the classification of gastrointestinal bleeding:

Gastointestinal
bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper GI bleedingLower GI bleeding
 
 
 
 
Based on blood lossBased on severity of blood loss
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
OvertOccultObscureSevereModerateOccult
 
 
 
 
 
 
 
 
 
 
 
 
Hematemesis Coffee-ground emesis MelenaMicroscopic Hemorrhage Heme-Occult positive stoolsSource is not identifiedHematocheziaHematocheziaMicroscopic Hemorrhage Heme-Occult positive stools


Syndrome of Inappropriate antidiuretic hormone classification

SIADH may be classified into several sub-types based on the pattern of arginine vasopressin (AVP) secretion in response to a range of plasma osmolalities into type A, type B, type C, and type D.

Classification Features
Type A
  • Accounts for about 60-70% of SIADH
  • Excessive secretion of arginine vasopressin (AVP) is noted
  • Associated with lung cancer and nasopharyngeal tumors
  • Patients are more susceptible to development of severe hyponatremia
Type B
  • Accounts for (20–40%) of the cases
  • Secretion of AVP occurs at lower than normal plasma osmolalities
Type C
  • Failure to suppress AVP secretion at plasma osmolalities below the osmotic threshold
  • Occurs due to dysfunction of inhibitory neurons in the hypothalamus, leading to persistent low-grade basal AVP secretion
Type D
  • Low or undetectable AVP levels and circulating AVP response is not defective
  • Nephrogenic SIADH (NSIAD) may be attributed to this condition
  • Associated with gain-of-function mutations in the vasopressin-2 (V2 receptor) receptor leading to a clinical picture of SIADH, with undetectable AVP levels
  • The condition is inherited in an X-linked manner, although heterozygous females may have inappropriate anti-diuresis of varying degrees.

Classification of Constipation

Constipation may be classified according to etiology into five subtypes:

  • Gastrointestinal
  • Neurologic
  • Metabolic
  • Endocrine
  • Psychiatric


Contipation
Classification
 
 
Etiology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NeurologicMetabolicEndocrineGastrointestinalPsychiatricDrugsIdiopathic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ObstructionAgangliosisIdiopathic megacolon
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hirschprung diseaseChagas disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multiple sclerosis Parkinson's disease Spinal cord InjuryHypercalcemia Hypermagnesemia Porphyria HypokalemiaHypothroidism Diabetes mellitus PanhypopituitarismDepression Eating disorderAnalgesics Anticholinergics Cation containing agents Neuron targeting agentsNormal colonic transit Sloww colonic transit Dyssynergic defecation


Colorectal cancer pathophysiology

The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC. Sporadic instability originates from the epithelial cells that line the colon or rectum. Colitis-associated CRC includes genetic instability, epigenetic alteration, chronic inflammation, oxidative stress, and intestinal microbiota. According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas.

Sporadic colorectal cancers

The picture below depicts the molecular pathogenesis of sporadic colon cancer:

Molecular pathogenesis of sporadic colon cancer
  • APC gene
  • Produces the APC protein, which prevents the accumulation of β-catenin protein (responsible for stem cell renewal)
  • Mutation of the APC protein leads to the accumulation of β-catenin protein and causes inappropriately high levels of stem cell renewal.
  • TP53|TP53 gene
  • Produces the P53 (protein)|p53 protein, which monitors cell division and promotes apoptosis if there are cell defects
  • mutation|Mutation mutation|s result in loss of control over cell division or apoptosis
  • TGF beta|TGF-β and DCC (Deleted in Colorectal Cancer)
  • Usually responsible for apoptosis, but deactivated in colorectal cancer
  • Oncogenes
  • Stimulate cellular division
  • Mutations lead to over-activation of cell proliferation