Sandbox:Aditya

HAS-BLED score

Components	Points
Hypertension	1
Abnormal renal/liver functions Dialysis, Kidney transplantation, Creatinine >2.6 mg/dl Cirrhosis, total bilirubanc>2X, AST/ALT >3e	1
Stroke	1
Bleeding history	1
Liable INR	1
Elderly( >65 years)	1
Drugs	1
INTERPRETATION OF HAS-BLED score
1	3%
2	4%
3	5%
4	8%
5	9%

Causes

Common causes

• Peptic ulcer disease
  • Responsible for around 33%-50% of upper GI bleeding
  • Peptic ulcer disease is most commonly due to H.pylori or nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Upper GI bleeding is the most common complication of peptic ulcer disease and may be the initial presentation.
• Esophageal varices
  • Responsible for around 14% of upper GI bleeding
  • These dilated veins within the esophagus are usually secondary to portal hypertension from cirrhosis.
  • Massive variceal hemorrhage is responsible for acute life-threatening upper GI bleeding which is an medical emergency .
• Mallory-Weiss syndrome :
  • Responsible for around 5% of upper GI bleeding
  • A longitudinal mucosal laceration in the distal esophagus and/or proximal stomach that usually results from forceful retching

Less common causes

• Neoplasms
  • gastric cancer
  • esophageal tumors
• Esophagitis (complications due to erosive or necrotizing infectious esophagitis )
• Gastric erosions/gastropathy
  • Acute erosive gastritis caused by drugs, radiation, infection, or direct trauma.
  • Reactive gastropathy may be due to bile reflux, particularly after partial gastrectomy.
  • Portal hypertensive gastropathy, which results in increased friability of gastric mucosa in patients with cirrhosis.
• Dieulafoy lesions
  • Dilated aberrant submucosal vessels that erode the overlying epithelium in the absence of an ulcer
• Gastric varices
• Gastric antral vascular ectasia
  • Dilated gastric vessels of unknown etiology that cause chronic UGIB and iron-deficiency anemia

Rare causes

• Bleeding from the hepatobiliary tract
  • Most commonly secondary to a liver or biliary tract injury, from trauma or following procedures or surgery.
  • Diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) and treated with arteriography
• Aortoenteric fistulas,
  • Most commonly involves the lower duodenum.
  • Common causes include aortic aneurysms or prosthetic vascular grafts, syphilis and tuberculosis
  • Presents with frank UGIB along with a pulsatile mass and abdominal pain radiating to the back.
  • Diagnosed by endoscopy.
• Crohn disease involving the upper gastrointestinal tract
• Metastatic malignancy involving the upper gastrointestinal tract, such as melanoma or renal cell carcinoma
• Hemosuccus pancreaticus
  • Pancreatic inflammation or cancer may result in bleeding into the pancreatic duct, which connects to the duodenum

Risk factors

• Advancing age
• Previous history of gastrointestinal bleed
• Chronic kidney disease
• Underlying cardiovascular disease
• Cirrhosis and portal hypertension
• Presence of H.pylori
• NSAID or aspirin use in patients with a history of ulcer disease
  • Those on dual antiplatelet therapy; those on anticoagulant therapy; or those with two or more of the following risk factors
    • Age 60 years or older
    • Glucocorticoid use
    • Dyspepsia
    • Gastroesophageal reflux disease
• Critical illness
  • Nosocomial stress ulcers due the to the use of mechanical ventilation for more than 48 hours, and coagulopathy
  • Other risk factors for nosocomial stress ulcerations in critically ill patients include a history of gastrointestinal ulceration or bleeding within the past year; or two or more of the following risk factors: presence of sepsis, ICU admission lasting longer than 1 week, occult gastrointestinal bleeding lasting 6 days or longer, and administration of more than 250 mg of hydrocortisone or equivalent glucocorticoid therapy
• Rare conditions associated with gastric acid hypersecretion, such as Zollinger-Ellison syndrome, mastocytosis, or a retained antrum following partial gastrectomy.

Causes of Acute Upper GI bleeding
Esophagus	Esophagitis Mallory–Weiss tear Esophageal varices Esophageal ulcers Esophageal cancer
Gastric	Gastric ulcer Gastric cancer Gastritis Gastric varices Portal hypertensive gastropathy Gastric antral vascular ectasia Dielafuoy lesions
Duodenal	Duodenal ulcer Vascular malformations, including aorto-enteric Fistulae Bleeding from the bile duct due to Liver biopsy Trauma Arteriovenous malformations Liver tumors

Associated Conditions

• Heyde syndrome, aortic valve stenosis with associated gastrointestinal bleeding thought to be due to acquired reduction of von Willebrand factor.

History

Obtaining the history is the most important aspect of making a diagnosis of upper GI bleed. It provides insight into the cause, precipitating factors and associated comorbid conditions and also helps in determining the severity of the bleed as well as in identifying the potential source of bleed:

• History of any liver disease
• History of NSAID use
• A thorough review of prescription and nonprescription medications
• History of previous aortic repair
• History ulcer disease
• History of binge drinking

Symptoms

• Hematemesis
• Melena
• Hematochezia
• Syncope
• Presyncope
• Dyspepsia
• Epigastric pain
• Heartburn
• Diffuse abdominal pain
• Dysphagia
• Weight loss
• Jaundice

Primary Prevention

Effective measures for the primary prevention of upper GI bleeding include administration of PPI in patients with an increased risk due to critical illness or use of NSAIDs or aspirin. In patients with cirrhosis and suspected portal hypertension, who found to have esophageal varices patients are given prophylactic treatment with a nonselective β-blocker or undergo endoscopic variceal ligation (EVL) with surveillance endoscopy.

Patients with stress ulcers

• The American Society of Health-System Pharmacists developed clinical practice guidelines that recommend prophylaxis with a PPI or with a histamine-2 receptor antagonist (H2RA) for ICU patients at high risk for UGIB.

Patients on NSAID, aspirin, or antiplatelet therapy

• Joint gastroenterology and cardiology society practice guidelines recommend gastroprotective therapy with a PPI for patients considered to be at increased risk of bleeding from chronic NSAID and aspirin therapy.

Patients with cirrhosis and varices

• EGD is used to screen for the presence of varices in patients with cirrhosis complicated by portal hypertension.
• In patients with cirrhosis who do not have varices, no prophylaxis is indicated.
• In patients with cirrhosis and varices that have not bled, prophylactic treatment with nonselective β-blockers, such as nadolol or propranolol, may decrease portal blood flow and thus decrease the risk of variceal bleed.
• In patients with cirrhosis who have medium or large varices that have not bled, EVL is an alternative prophylactic treatment.
• EVL is repeated every several weeks until obliteration of varices is seen.
• Surveillance EGD should then be performed 1 to 3 months after obliteration and then every 6 to 12 months to check for variceal recurrence.

Secondary Prevention

Effective measures for the secondary prevention of UGIB include discouraging the use of NSAIDS in all patients with a history of UGIB.

Seondary Prevention

• NSAID use in all patients with a history of UGIB should be discouraged.

UGIB from peptic ulcer disease

• Avoid NSAIDs.
• For patients who are at high risk for rebleeding (elderly patients; those taking anticoagulant and antiplatelet medications), indefinite use of a PPI may be recommended.
• H pylori status should be determined, and patients should be treated if positive.
• Eradication is confirmed with stool sample or repeat endoscopy with biopsy.

UGIB from varices

• A combination of nonselective β-blockers plus EVL is the best option for secondary prophylaxis of UGIB from varices.
• The nonselective β-blocker should be titrated up as tolerated.
• Variceal banding should be repeated every 2 to 3 weeks until the varices are obliterated.
  • EGD must be performed 1 to 3 months after initial obliteration then every 6 to 12 months to check for variceal recurrence.

Prognosis

• Prognosis is generally good with appropriate treatment, and the 1-year mortality rate of patients with nonvariceal UGIB is approximately 10%.
• In UGIB, the prognosis doesn't depend on the severity of bleeding but depends upon patients age and comorbid conditions.
• The majority of patients with UGIB will stop bleeding spontaneously.
• A clean ulcer base has less than a 3% chance of rebleeding; therefore, these lesions are not usually treated or scoped again.
• In otherwise stable patients, patients with a clean ulcer base has less than a 3% chance of rebleeding and are good candidates for early discharge.
• Treatment includes management of underlying liver disease and prevention of complications of cirrhosis.
• Despite advances in gastric acid suppression as well as improved endoscopic diagnostic and therapeutic techniques, the mortality rate from UGIB has remained stable.

Complications

Complications of UGIB include:

• End-organ damage
  • Cardiac ischemia
  • Renal failure
  • Ischemic hepatitis
  • Anoxic brain injury
• Iron-deficiency anemia

Epidemiology and Demographics

Incidence

The incidence of acute UGIB is approximately 50 to 100 per 100,000 individuals worldwide.

Gender

Males are more commonly affected by UGIB than females. The males to female ratio is approximately 2 to 1.

Pathophysiology

Blood supply of Foregut

The digestive system is supplied by the celiac artery. The celiac artery is the first major branch from the abdominal aorta, and is the only major artery that nourishes the digestive organs.

Foregut		Blood supply
Esophagus	Upper esophageal sphincter Cervical esophagus	Inferior thyroid artery
	Thoracic esophagus	Aortic esophageal arteries or branches of the bronchial arteries
	Distal esophagus Lower esophageal sphincter	Left gastric artery and left phrenic artery
Stomach	Lesser curvature	Right and left gastric arteries
	Greater curvature	Right and left gastroepiploic arteries
	Gastric fundus	Short gastric arteries
Duodenum	First and second parts	Gastroduodenal artery (GDA) and Superior pancreaticoduodenal artery
	Third and fourth parts	Inferior pancreaticoduodenal artery

Blood supply of stomach
Source: By Mikael Häggström.https://commons.wikimedia.org/w/index.php?curid=3416062

Pathogenesis

Peptic Ulcer Disease

• Gastric and duodenal ulcers are the most common cause of upper GI bleeding.
• Ninety percent of duodenal ulcers and 70% of gastric ulcers are associated with Helicobacter pylori.
• Another common cause of peptic ulcer disease is nonsteroidal anti-inflammatory drugs (NSAIDs).
• Helicobacter pylori disrupts the mucosal barrier and causes inflammation of the mucosa of the stomach and duodenum.
• NSAIDs inhibit cyclooxygenase, leading to impaired mucosal defenses by decreasing mucosal prostaglandin synthesis.
• NSAIDs have a more pronounced effect on the stomach than on the duodenum, with a 40-fold increase in gastric ulcers and an 8-fold increase in duodenal ulcers.
• Regardless of etiology, as the ulcer progresses beyond the mucosa to the submucosa the inflammation causes weakening and necrosis of arterial walls, leading to pseudoaneurysm formation followed by rupture and hemorrhage.
• The severity of the bleed is directly related to the size of the involved vessels.

Mallory-Weiss Tear

• Mallory-Weiss is responsible for up to 15% of upper GI bleeds.
• Mallory-Weiss tears consists of longitudinal lacerations in the cardia of the stomach or gastroesophageal (GE) junction.
• Most commonly associated with vomiting following an alcoholic binge drinking and is due to a sudden increase in intragastric pressure.

Gastritis

• The mucosa of the stomach is protected from the acidic environment by mucus, bicarbonate, prostaglandins, and blood flow.
• If the balance of gastric acid secretion and mucosal defenses is disrupted, acid interacts with the epithelium to cause damage.
• During stress, there is acid hypersecretion; therefore, the breakdown of mucosal defenses leads to injury of the mucosa and subsequent bleeding.

Dieulafoy Lesion=

• Dieulafoy lesions are large, tortuous, histologically normal vessels located in the submucosa.
• These tortuous vessels often protrude through mucosal defects, rendering them at risk for rupture because of necrosis of the arterial wall from exposure to gastric acid.
• Dieulafoy lesions are most commonly found often within 6 cm of the GE junction on the lesser curve of the stomach.

Gastroesophageal Varices

• Gastroesophageal varices occur as a result of portal hypertension or secondary to the decompression of the portal venous system into the systemic circulation.
• GE varices begin to occur at a pressure gradient of 8 to 10 mm Hg, with bleeding risk increased at a gradient of 12 mm Hg.
• Esophageal varices are due to dilation of the coronary vein, whereas gastric varices are secondary to backflow through the short gastric veins.
• The most common location of bleeding is at the GE junction, as it is where the varices are most superficial and have the thinnest wall.
• Acute variceal bleeding occurs in 25% to 40% of cirrhotic patients and carries a mortality of 25% to 30%, making it one of the most dreaded complications of portal hypertension.
• In addition to controlling the bleeding by the mechanisms outlined in the next section, prophylactic antibiotics should be administered to this patient population because this intervention decreases mortality.