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

Overview

Disease	Symptoms							Other features	Diagnosis
	Abdominal pain	Rectal pain	Weightloss	Fever	Type of GI bleeding	Diarrhea	Constipation		Laboratory findings	Radio-Imaging findings
Meckel's diverticulum	-	-	-	-	Frank blood	-	-	Painless bleeding May present with complications such as: Bowel obstruction Intussusception Diverticulitis Perforation	Signs of iron deficiency anemia may be present such as: Decreased Hematocrit Decreased Hemoglobin Positive stool guaiac test	Technetium-99m pertechnetate scanning helps in the detection of a symptomatic bleeding Meckel’s diverticulum. Upper GI series with small-bowel follow-through may help in the detection of a diverticulum. Appearance of Meckel's diverticulum on upper GI series: Smooth Globular White Location: Arising from the antimesenteric border of the ileum 50cm proximal to the ileocecal valve
Diverticulosis	-	-	-	-	Red or maroon-colored blood	-	+	Self limiting Seen in elderly	Normal	Globular outpouchings on CT scan
Angiodysplasia	-	-	-	-	Frank blood	-	-	Painless bleeding Iron deficiency anemia	Normal	Normal
Hemorrhoids	-	+	-	-	Blood on tissues	-	+	Pain during defecation Anemia	-	Tortuous dilated vessels on anoscopy
Anal fissures	-	+	-	-	Blood on tissues	-	+	Pain during defecation Pain recurs with every bowel movement	Normal except mild leucocytosis	Anoscopy
Mesenteric Ischemia	+	-	+	+	Frank blood	+	-	Pain alters with eating habits Associated with other comorbid conditions	Leukocytosis Increased hematocrit High anion gap metabolic acidosis Lactic acidosis High phosphate levels	Mesenteric edema Bowel dilatation Bowel wall thickening Intramural gas Mesenteric stranding
Ischemic colitis	+	-	-	+	Frank blood	+	-	3 phases Hyperactive phase Paralytic phase (absent bowel sounds) Shock phase	Elevated white blood cell count more than 15,000/mm3 in 20 patients (27%) The serum bicarbonate level was less than 24 mmol/L in 26 patients (36%)	Mild moderate diffuse bowel wall thickening Marked hyperenhancement of the mucosa
Crohn's disease	+	-	+	+	Blood mixed with stools	+	+	Extra intestinal manifestations Uveitis Sacroiliitis Anemia Peripheral neuropathy	Anemia Leukocytosis Thrombocytosis Anti-Saccharomyces cerevisiae antibodies	Skip lesions Bowel wall thickening Surrounding inflammation, abscess, and fistulae
Ulcerative colitis	+	+	+	+	Blood mixed with stools	+	+	Joint swelling Joint pain Inflammation of the eye Skin involvement Fatty liver Thromboembolism Parenchymal lung disease	Anemia Thrombocytosis A high platelet count	Loss of the vascular appearance of the colon Erythema (or redness of the mucosa) and friability of the mucosa Superficial ulceration, which may be confluent Pseudopolyps
Colon carcinoma	+	-†	+	+	Occult bleeding	+	+†		+ FOBT (fecal occult blood test) ↑ CEA( and CA 19-9 Hypercalcemia	Biopsy

The following table differentiates all the diseases presenting with abdominal pain and lower gastrointestinal bleeding.

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments Symptoms Signs Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Acute diverticulitis LLQ or RLQ (in case of Meckel's diverticulitis) + ± + − + ± − + Positive in perforated diverticulitis + + Hypoactive Leukocytosis CT scan Ultrasound History of constipation History of painless lower GI bleed (in case of Meckel's diverticulitis) Inflammatory bowel disease Diffuse ± − − ± − + + + − − − Normal or hyperactive Anti-neutrophil cytoplasmic antibody (P-ANCA) in Ulcerative colitis Anti saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease String sign on abdominal x-ray in Crohn's disease Extra intestinal findings: Uveitis Arthritis Infective colitis Diffuse + − ± − − + − + Positive in fulminant colitis ± ± Hyperactive Stool culture and studies Shiga toxin in bloody diarrhea PCR CT scan Bowel wall thickening Edema Colon carcinoma Diffuse/localized − − − − ± ± + + ± − − Normal or hyperactive if obstruction present CBC Carcinoembryonic antigen (CEA) Colonoscopy Flexible sigmoidoscopy Barium enema CT colonography  PILLCAM 2: A colon capsule for CRC screening may be used in patients with an incomplete colonoscopy who lacks obstruction Hemochromatosis RUQ − − − − − − − Positive in cirrhotic patients − − − N >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: Hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Mesenteric ischemia Periumbilical Positive if bowel becomes gangrenous − + − − + + + Positive if bowel becomes gangrenous Positive if bowel becomes gangrenous − Hyperactive to absent Leukocytosis and lactic acidosis Amylase levels D-dimer CT angiography SMA or SMV thrombosis Also known as abdominal angina that worsens with eating Acute ischemic colitis Diffuse + ± + − − + + + + + + Hyperactive then absent Leukocytosis Abdominal x-ray Distension and pneumatosis CT scan Double halo appearance, thumbprinting Thickening of bowel May lead to shock Ruptured abdominal aortic aneurysm Diffuse ± − + − − − + + + − − N Fibrinogen D-dimer Focused Assessment with Sonography in Trauma (FAST)  Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage Diffuse ± − ± − − − − + + − − N ↓ Hb ↓ Hct CT scan History of trauma

Cirrhosis occurs due to long term liver injury which causes an imbalance between matrix production and degradation. Early disruption of the normal hepatic matrix results in its replacement by scar tissue, which in turn has deleterious effects on cell function.

Surgery Incidentally discovered Meckel diverticulum When a Meckel diverticulum is incidentally discovered at laparoscopy or laparotomy, the surgeon must decide whether to resect. Most surgeons generally do not resect a diverticulum with a wide mouth. However, a diverticulum with a narrow neck, which may obstruct or twist, can be easily resected at the neck without the need for segmental resection. A diverticulum deemed abnormal because of inflammation, thickening, or intramural pathology should be resected, with the decision for local or segmental resection based on the pathology. [5]

In 1976, Soltero and Bill reported that the lifetime risk of complications from Meckel diverticulum was 4.2% and that the risk decreased with age. [9] Their data indicated that 800 asymptomatic diverticula would have to be removed to save the life of one patient. On that basis, they opposed surgical excision.

Miltiadis et al stated that resection of incidentally found Meckel diverticulum protected patients from future surgery caused by complications of Meckel diverticulum. This strategy could help reduce morbidity and mortality, especially in elderly patients.

Cullen et al reported that prophylactic diverticulectomy is warranted to eliminate the possibility of future deaths. [3] As a result, they advocated diverticulectomy for asymptomatic disease even in the older age group.

Overall, selected cases of incidentally discovered diverticula in adults and most asymptomatic diverticula found in children [10] may be removed. Resection is recommended in the following cases:

Patients younger than 40 years Diverticula longer than 2 cm Diverticula with narrow necks Diverticula with fibrous bands Suspected ectopic gastric tissue Inflamed, thickened diverticula Removal of a healthy diverticulum in the presence of peritonitis, Crohn disease, ulcerative colitis, or any other complication that would militate against resection is not advised.

Meckel

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References

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Portal HTN results from the combination of the following:

• Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
•  Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.

Pathogenesis of Cirrhosis due to Alcohol:

• More than 66 percent of all American adults consume alcohol.
• Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
• Mechanisms of alcohol-induced damage include:
  • Impaired protein synthesis, secretion, glycosylation
• Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
  • Lipoprotein secretion
  • Decreased fatty acid oxidation
  • Increased fatty acid uptake
• Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
• Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
  • Trafficking of hepatic proteins
  • Interrupting microtubule formation
  • Interfering with enzyme activities
• Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.
• Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
• Stellate cell activation leads to the production of extracellular matrix and collagen.
• Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
• Shrinkage of the liver occurs over years due to repeated insults that lead to:
  • Loss of hepatocytes
  • Increased production and deposition of collagen

Pathology

• There are four stages of Cirrhosis as it progresses:
  • Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
  • Development of biliary stasis and fibrosis
• Periportal fibrosis progresses to bridging fibrosis
• Increased proliferation of smaller bile ductules leading to regenerative nodule formation.

Causes

Drugs and Toxins	Infections	Autoimmune	Metabolic	Biliary obstruction(Secondary bilary cirrhosis)	Vascular	Miscellaneous
Alcohol	Hepatitis B	Primary Biliary Cirrhosis	Wilson's disease	Cystic fibrosis	Chronic RHF	Sarcoidosis
Methotrexate	Hepatitis C	Autoimmune hepatitis	Hemochromatosis	Biliary atresia	Budd-Chiari syndrome	Intestinal bypass operations for obesity
Isoniazid	Schistosoma japonicum	Primary Sclerosing Cholangitis	Alpha-1 antitrypsin deficiency	Bile duct strictures	Veno-occlusive disease	Cryptogenic: unknown
Methyldopa			Porphyria	Gallstones
			Glycogen storage diseases (such as Galactosaemia, Abetalipoproteinaemia)

Cirrhosis

Pathophysiology

• When an injured issue is replaced by a collagenous scar, it is termed as fibrosis.
• When fibrosis of the liver reaches an advanced stage where distortion of the hepatic vasculature also occurs, it is termed as cirrhosis of the liver.
• The cellular mechanisms responsible for cirrhosis are similar regardless of the type of initial insult and site of injury within the liver lobule.
• Viral hepatitis involves the periportal region, whereas involvement in alcoholic liver disease is largely pericentral.
• If the damage progresses, panlobular cirrhosis may result.
• Cirrhosis involves the following steps:
  • Inflammation
  • Hepatic stellate cell activation
  • Angiogenesis
  • Fibrogenesis
• Kupffer cells are hepatic macrophages responsible for Hepatic Stellate cell activation during injury.
• The hepatic stellate cell (also known as the perisinusoidal cell or Ito cell) plays a key role in the pathogenesis of liver fibrosis/cirrhosis.
• Hepatic stellate cells(HSC) are usually located in the subendothelial space of Disse and become activated to a myofibroblast-like phenotype in areas of liver injury.
• Collagen and non collagenous matrix proteins responsible for fibrosis are produced by the activated Hepatic Stellate Cells(HSC).
• Hepatocyte damage causes the release of lipid peroxidases from injured cell membranes leading to necrosis of parenchymal cells.
• Activated HSC produce numerous cytokines and their receptors, such as PDGF and TGF-f31 which are responsible for fibrogenesis.
• The matrix formed due to HSC activation is deposited in the space of Disse and leads to loss of fenestrations of endothelial cells, which is a process called capillarization.
• Cirrhosis leads to hepatic microvascular changes characterised by
  •  formation of intra hepatic shunts (due to angiogenesis and loss of parenchymal cells) 
  • hepatic endothelial dysfunction
• The endothelial dysfunction is characterised by
  • insufficient release of vasodilators, such as nitric oxide due to oxidative stress
  • increased production of vasoconstrictors (mainly adrenergic stimulation and activation of endothelins and RAAS)
• Fibrosis eventually leads to formation of septae that grossly distort the liver architecture which includes both the liver parenchyma and the vasculature. A cirrhotic liver compromises hepatic sinusoidal exchange by shunting arterial and portal blood directly into the central veins (hepatic outflow). Vascularized fibrous septa connect central veins with portal tracts leading to islands of hepatocytes surrounded by fibrous bands without central veins.
• The formation of fibrotic bands is accompanied by regenerative nodule formation in the hepatic parenchyma.
• Advancement of cirrhosis may lead to parenchymal dysfunction and development of portal hypertension.
• Portal HTN results from the combination of the following:
  • Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
  •  Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.

Pathogenesis of Cirrhosis due to Alcohol:

• More than 66 percent of all American adults consume alcohol.
• Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
• Mechanisms of alcohol-induced damage include:
  • Impaired protein synthesis, secretion, glycosylation
• Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
  • Lipoprotein secretion
  • Decreased fatty acid oxidation
  • Increased fatty acid uptake
• Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
• Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
  • Trafficking of hepatic proteins
  • Interrupting microtubule formation
  • Interfering with enzyme activities
• Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.
• Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
• Stellate cell activation leads to the production of extracellular matrix and collagen.
• Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
• Shrinkage of the liver occurs over years due to repeated insults that lead to:
  • Loss of hepatocytes
  • Increased production and deposition of collagen

Pathology

• There are four stages of Cirrhosis as it progresses:
  • Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
  • Development of biliary stasis and fibrosis
• Periportal fibrosis progresses to bridging fibrosis
• Increased proliferation of smaller bile ductules leading to regenerative nodule formation.

Video codes

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Floating video

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Redirect

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synonym website

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Image

Normal versus Abnormal Barium study of esophagus with varices

Image to the right

C. burnetii, the Q fever causing agent

Image and text to the right

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Gallery

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  Histopathology of a pancreatic endocrine tumor (insulinoma). Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

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  Histopathology of a pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

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  Histopathology of a pancreatic endocrine tumor (insulinoma). Insulin immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

References

REFERENCES