Upper GI Bleeding

• Mucosal barrier disruption and acid-mediated injury: The gastric and duodenal mucosa normally resists acid damage through multiple protective mechanisms including a mucus-bicarbonate layer (maintained by prostaglandins), mucosal blood flow delivering bicarbonate and oxygen, and rapid epithelial restitution. Gastric acid (HCl) and pepsin create a hostile environment with a pH gradient across the mucus layer, with intraluminal pH near 1-2 but submucosal pH maintained near 7. NSAIDs inhibit cyclooxygenase (COX-1 and COX-2), reducing prostaglandin E2 and prostacyclin synthesis, which decreases mucus production, bicarbonate secretion, and mucosal blood flow—directly increasing ulcer risk. Helicobacter pylori infection triggers chronic inflammation via bacterial urease producing ammonia (allowing bacterial survival in acid), flagellar proteins stimulating Toll-like receptors, and virulence factors (CagA, VacA) directly damaging epithelial cells and promoting IL-8 secretion and neutrophil recruitment. Acid hypersecretion (as in Zollinger-Ellison syndrome) overwhelms normal protective mechanisms through sheer volume of acid production and continuous epithelial damage.

• Vascular erosion and hemorrhage mechanisms: As mucosal ulceration deepens through the mucosa and submucosa, it eventually penetrates the muscularis propria and reaches submucosal and muscular blood vessels. Peptic ulcers most commonly erode the left gastric artery (anterior wall gastric ulcers), right gastroduodenal artery (posterior wall duodenal ulcers), splenic artery (greater curve gastric ulcers), or left hepatic artery (lesser curve ulcers). When vessel walls are exposed to acid and pepsin, enzymatic digestion of collagen and elastin occurs, vessel wall integrity fails, and frank hemorrhage ensues. Variceal bleeding occurs through a different mechanism: portal hypertension (elevated portal venous pressure >12 mmHg) creates portosystemic collaterals in the esophagus and gastric fundus where thin-walled vessels become engorged; mechanical rupture occurs due to wall tension (LaPlace's law: T = Pr, where increased pressure and vessel radius directly increase wall tension) and mucosal erosion overlying varices.

• Hemodynamic response and blood loss physiology: Upon bleeding, decreased intravascular volume triggers sympathetic nervous system activation, releasing norepinephrine and epinephrine, causing peripheral vasoconstriction (maintaining central perfusion), increased heart rate, and increased myocardial contractility. The baroreceptor reflex maintains blood pressure through these mechanisms until approximately 15-30% blood volume loss; beyond this (Class III hemorrhage), compensatory mechanisms fail and hypotension occurs. Decreased renal perfusion activates the renin-angiotensin-aldosterone system (RAAS), increasing angiotensin II (causing further vasoconstriction) and aldosterone (promoting sodium and water retention). Simultaneously, bleeding activates the coagulation cascade: tissue factor (released from damaged vessels) binds Factor VII, initiating the extrinsic pathway; thrombin (Factor IIa) converts fibrinogen to fibrin and activates platelets and factors V, VIII, and XIII to stabilize the clot. Endothelial damage and platelet exposure to collagen and tissue factor trigger primary hemostasis through platelet adhesion (via von Willebrand factor), activation, and aggregation. In acute bleeding, these mechanisms achieve temporary hemostasis in 5-10 minutes in normal hemostasis, but ongoing hemorrhage overwhelms platelet and clotting factor reserves.

• Variceal pathophysiology and portal hypertension mechanisms: Portal hypertension develops from elevated resistance to portal blood flow (prehepatic, intrahepatic, or posthepatic obstruction) or increased portal blood flow. Cirrhosis causes intrahepatic obstruction through architectural distortion (fibrosis and regenerative nodules), sinusoidal endothelial dysfunction (loss of fenestrations), activation of hepatic stellate cells producing collagen, and capillarization of sinusoids. Increased portal pressure triggers shear stress on endothelial cells, promoting angiogenesis and formation of portosystemic collaterals; nitric oxide (NO) produced by endothelial nitric oxide synthase is decreased in cirrhotic livers, reducing vasodilation and allowing unopposed vasoconstriction. These collaterals develop in the distal esophagus (esophageal varices from left gastric vein), gastric fundus (gastric varices from short gastric and left gastric veins), and rectum (rectal varices from superior and middle rectal veins). Variceal rupture risk correlates with variceal size, wall tension (proportional to vessel radius and transmural pressure), and overlying red signs (cherry-red spots indicating friable mucosa or endothelial erosions).

• Mallory-Weiss tear mechanism: These partial-thickness longitudinal tears in the gastroesophageal junction occur due to rapid esophageal distention followed by forceful vomiting or retching. The increased intraesophageal pressure during forceful vomiting (can exceed 100 mmHg) combined with violent longitudinal esophageal muscle contraction causes mechanical laceration of the mucosa and submucosa, typically in the right posterior wall of the distal esophagus near the gastroesophageal junction (where the esophageal mucosa transitions to the more distensible gastric mucosa). This mechanism explains the classic association with alcohol use (causing gastritis and vomiting) and hyperemesis; alcohol additionally impairs platelet function and may cause acute changes in esophageal and gastric mucosa.

• Hematemesis (vomiting of blood) is the most common presenting symptom, occurring in 80-90% of patients with UGIB. Bright red (frank) hematemesis indicates ongoing or recent bleeding, while coffee-ground emesis (dark, granular-appearing vomitus) results from oxidized blood (hemoglobin converted to methemoglobin by gastric acid) from older bleeding that has been exposed to gastric acid for several hours, indicating slower or resolved bleeding. The presence of hematemesis directly confirms UGIB and localizes the source proximal to the pylorus.

• Melena (black, tarry, foul-smelling stool) results from bacterial degradation of hemoglobin to hemosiderin in the colon; the characteristic appearance reflects blood transit time through the small intestine and colon (typically 2-4 hours for melena to develop). Melena indicates UGIB proximal to the ligament of Treitz or, less commonly, bleeding from the proximal small bowel; conversely, melena is uncommon in fast GI transit (as in diarrhea or severe bleeding with rapid passage).

• Hematochezia (bright red or maroon blood per rectum) typically indicates lower GI bleeding but can occur with massive UGIB (>1000 mL) with rapid small bowel and colon transit, bypassing the time needed for blood oxidation; in this setting, hemodynamic instability and other evidence of UGIB will be prominent. Hematochezia presenting with hemodynamic stability suggests lower GI bleeding.

• Syncope or presyncope reflects acute blood loss exceeding compensatory mechanisms (typically >20% of blood volume acutely) or abrupt decrease in cerebral perfusion pressure; represents Class III hemorrhage and is a sign of severe ongoing bleeding requiring urgent intervention.

• Dyspnea occurs in severe anemia (hemoglobin <7 g/dL) due to decreased oxygen-carrying capacity, or in patients with underlying cardiopulmonary disease when cardiac output is compromised by volume loss; dyspnea may also reflect pulmonary aspiration of blood or gastric contents.

• Abdominal pain is variably present depending on etiology: peptic ulcer bleeding often presents with epigastric pain that may temporarily improve with the bleeding event (as acid is diluted by blood), variceal bleeding typically occurs without preceding abdominal pain, and Mallory-Weiss tears are associated with preceding severe vomiting and retching with chest/epigastric discomfort.

• Tachycardia (heart rate >100 bpm) represents a sympathetic response to intravascular volume depletion; the degree of tachycardia correlates with blood loss severity, though elderly patients and those on beta-blockers may have blunted heart rate responses. Absence of expected tachycardia in the setting of significant bleeding suggests either slower chronic bleeding (as in gastric cancer), beta-blocker use, or severe shock (where cardiogenic mechanisms predominate).

• Hypotension (systolic <90 mmHg or mean arterial pressure <65 mmHg) indicates blood loss exceeding compensatory mechanisms; orthostatic changes (drop in systolic BP >20 mmHg or rise in heart rate >20 bpm with position change) suggest 10-20% blood volume loss and are sensitive markers of significant bleeding. Orthostasis can be elicited in ambulatory patients before frank hypotension develops.

• Pale or diaphoretic appearance reflects sympathetic activation causing peripheral vasoconstriction and sweating; cool, clammy skin with weak peripheral pulses indicates hypoperfusion and shock physiology.

• Altered mental status or confusion represents an ominous sign of severe shock with inadequate cerebral perfusion; in elderly or diabetic patients, hypotension may cause acute coronary syndrome or stroke before frank mental status changes occur.

• Classic presentations by etiology: Variceal bleeding typically presents with hematemesis and melena, often without preceding abdominal pain, frequently with signs of chronic liver disease (jaundice, ascites, spider angiomas, gynecomastia, palmar erythema); Mallory-Weiss tears classically follow forceful vomiting (often alcohol-related) with initial hematemesis that is usually self-limited; peptic ulcer bleeding may be preceded by epigastric pain, nocturnal pain, or food-related symptoms, and can present with perforation and acute peritonitis if the ulcer erodes through the anterior wall; Dieulafoy lesions present with sudden, brisk hematemesis in a patient with minimal prior GI symptoms; aortoenteric fistulas present with herald bleeding (minor bleeding episode) 1-4 weeks before massive hemorrhage.

• Bedside assessment and hemodynamic evaluation: Immediately determine orthostatic vital signs (lying and standing blood pressures and heart rates); a drop in systolic BP >20 mmHg or rise in heart rate >20 bpm with standing indicates significant intravascular volume depletion (typically 10-20% blood volume loss). Assess for signs of shock (cool extremities, weak pulse, altered mental status). Establish two large-bore IV lines (18-gauge or larger) before phlebotomy. Rapidly determine if bleeding is ongoing or recent by the presence of hematemesis and character (bright red vs. coffee-ground); a history of forceful vomiting preceding hematemesis suggests Mallory-Weiss tear, while absence of preceding vomiting suggests peptic ulcer or variceal bleeding.

• Laboratory assessment: Hemoglobin and hematocrit reflect red blood cell mass but may not accurately reflect acute blood loss in the first few hours (as plasma loss equilibrates with extravascular fluid); serial hemoglobin measurements (every 2-4 hours during acute bleeding) track ongoing bleeding. Platelet count, prothrombin time (PT)/INR,

Immediate stabilisation (before any endoscopy)

• Volume resuscitation and airway: two large-bore IVs, crystalloid, and intubation for ongoing massive hematemesis or altered mental status to prevent aspiration.
• Restrictive transfusion: the ACG 2021 upper GI/ulcer bleeding guideline endorses a hemoglobin threshold near 7 g/dL for most patients (higher in acute coronary syndrome). Over-transfusion raises portal pressure and worsens variceal rebleeding.
• Reverse coagulopathy selectively: hold and reverse anticoagulants per bleeding severity; do not delay endoscopy for a modestly elevated INR in cirrhosis, where INR does not reflect bleeding risk.

Pharmacologic therapy before source is known

• Proton pump inhibitors (e.g., pantoprazole IV): raise intragastric pH, stabilising clot by preventing pepsin-mediated fibrinolysis. IV PPI is commonly given before endoscopy in US practice, but the 2021 ACG guideline makes no recommendation for or against pre-endoscopic PPI, because it may downstage endoscopic lesions yet does not reduce rebleeding, surgery, or mortality; ACG does recommend high-dose PPI (continuous infusion or intermittent) for 3 days after endoscopic therapy of high-risk ulcer stigmata.
• Somatostatin analogue (octreotide): splanchnic vasoconstriction lowers portal pressure; give when variceal bleeding is suspected, per AASLD portal hypertensive bleeding guidance.
• Antibiotic prophylaxis: short-course prophylaxis is indicated in every cirrhotic with GI bleeding (AASLD, Baveno consensus); ceftriaxone 1 g IV daily is preferred in advanced (Child-Pugh B/C) disease, in patients already on quinolone prophylaxis, or where quinolone resistance is prevalent, while an oral fluoroquinolone remains an option in lower-risk patients. It reduces infection, rebleeding, and mortality.
• Erythromycin IV as a prokinetic before endoscopy to clear the stomach and improve visualisation.

Definitive therapy

• EGD within 24 hours of presentation (ACG): epinephrine injection must be combined with a second modality — thermal coagulation, hemoclips, or hemostatic powder — for Forrest Ia/Ib/IIa lesions.
• Variceal bleeding: endoscopic band ligation for esophageal varices; cyanoacrylate injection or BRTO for gastric varices.
• Escalation: repeat endoscopy for rebleeding; then transcatheter arterial embolization (preferred over surgery for ulcer bleeding); balloon tamponade (Sengstaken–Blakemore) or covered esophageal stent as a bridge to TIPS, with early/preemptive TIPS in high-risk Child-Pugh B/C bleeders. Surgery (oversewing the gastroduodenal artery) is last resort.

Contraindicated / avoid

• Tranexamic acid: ACG recommends against it in acute UGIB (no mortality benefit, thromboembolic harm).
• Nonselective beta blockers: not started during active hemorrhage — begin only after hemostasis for secondary prophylaxis.
• Routine NG lavage and NSAIDs/aspirin continuation without indication.

Emergencies of the bleed itself

• Hemorrhagic shock and multiorgan failure: loss beyond ~30% of blood volume overwhelms baroreflex and RAAS compensation; signalled by hypotension despite tachycardia, lactate elevation, and oliguria. Immediate transfusion and source control.
• Rebleeding: clot lysis over a high-risk vessel; heralded by recurrent hematemesis, fresh melena, tachycardia, or a hemoglobin drop after apparent stabilisation. Highest with Forrest Ia/Ib and IIa stigmata and with varices in the first 5 days. Repeat endoscopy is the next step.
• Aspiration pneumonia: blood and gastric contents enter the airway during hematemesis or endoscopy; new hypoxia, infiltrate, and fever. Prophylactic intubation in the actively vomiting or encephalopathic patient.
• Demand-mediated myocardial ischemia (type 2 MI): anemia plus tachycardia raises myocardial oxygen demand while lowering supply; look for chest pain, new ST depression, troponin rise in older patients.
• Perforation: an ulcer eroding the anterior wall rather than a posterior vessel produces free air under the diaphragm, rigid abdomen — surgical emergency.

Complications specific to cirrhosis and variceal bleeding

• Hepatic encephalopathy: intraluminal blood is a nitrogen load metabolised to ammonia; new asterixis and confusion. Treat with lactulose.
• Spontaneous bacterial peritonitis and other infection: bacterial translocation after hemorrhage — the reason AASLD mandates ceftriaxone prophylaxis.
• Hepatorenal syndrome / acute kidney injury: splanchnic vasodilation plus hypovolemia collapses renal perfusion; rising creatinine with bland sediment.

Treatment-related complications

• Post-band ulceration and esophageal stricture after ligation; TIPS precipitates new or worsened encephalopathy and can cause high-output heart failure.
• Balloon tamponade: pressure necrosis, esophageal rupture, and airway obstruction if the balloon migrates — limit duration and intubate first.
• Transfusion: TACO/TRALI, citrate-related hypocalcemia and dilutional coagulopathy in massive transfusion.
• Chronic PPI use: hypomagnesemia, C. difficile and enteric infection, and impaired calcium absorption.

• Elevated BUN with normal creatinine (BUN:Cr ratio markedly raised) is the classic clue that blood is being digested and absorbed as protein in the small bowel — it points to an upper source even when the patient reports only melena.
• Single best next step in a cirrhotic with hematemesis: resuscitate, then start octreotide plus IV ceftriaxone before EGD. Antibiotic prophylaxis is one of the few interventions with a demonstrated mortality benefit in variceal bleeding (AASLD) and is the item most often omitted on exam stems.
• Transfuse to a hemoglobin near 7 g/dL, not higher (ACG). The distractor is "transfuse to 10" — over-transfusion raises portal pressure and increases variceal rebleeding.
• Epinephrine injection alone is never adequate: it must be paired with clips or thermal therapy. A stem offering "inject epinephrine and observe" is wrong.
• Posterior duodenal ulcer erodes the gastroduodenal artery (brisk bleeding); anterior duodenal ulcer perforates into the peritoneum (free air, peritonitis). This anterior/posterior pairing is the single anatomy association examiners repeat.
• Herald bleed weeks after aortic graft repair = aortoenteric fistula. Next step is CT angiography (or EGD looking at the third portion of the duodenum) and vascular surgery — do not settle for "routine EGD and PPI."
• Massive hematochezia with hemodynamic instability can be an upper source: get EGD first rather than going straight to colonoscopy.
• Do not give tranexamic acid in acute UGIB — ACG recommends against it; it is a favored distractor.
• Buzzwords: coffee-ground emesis (oxidised hemoglobin, slower bleed); watermelon stomach (GAVE); Dieulafoy lesion (large submucosal arteriole near the GE junction, spurting, no ulcer); Forrest Ia spurting vessel; cherry-red spots on varices predicting rupture.
• **After ulcer hemostasis, test and treat *H. pylori*** and confirm eradication; a negative test during acute bleeding can be falsely negative and must be repeated.