Sandbox:Aditya

# 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.
- 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 .
- 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
- 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
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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.

## 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:
- A history of epigastric pain, dyspepsia, or prior peptic ulcer may suggest the diagnosis of peptic ulcer disease.
- A history of documented prior upper GI bleeding is important because approximately 60% of upper GI bleeders are rebleeding from the same site.
- Prior use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) is important because these patients have an increased risk of gastric ulcer and a fourfold risk of significant GI bleeding compared with other patients.
- A history of alcoholism increases the likelihood of cirrhosis and consequently of bleeding from esophageal varices or congestive gastropathy but alcoholics also frequently have peptic ulcers or gastritis.
- Cigarette smokers have a significantly higher rate of the recurrent duodenal ulcer as compared with nonsmokers and a history of cigarette smoking should be elicited.
- Vomiting, coughing, or retching before bleeding is suggestive of a Mallory-Weiss tear.
A directed history may also alert to consider unusual causes.
- A history of pancreatitis suggests possible hemorrhage from a pancreatic pseudocyst. Erosion of a pancreatic pseudocyst into the duodenum or stomach may cause massive hematemesis, and the patient may present in shock.
- Patients with prior abdominal aortic aneurysm repair may present with severe GI hemorrhage from an aortoenteric. This fistula often presents with a herald bleed followed within 4 to 96 hours by massive bleeding.
- A personal or family history of recurrent epistaxis may suggest the diagnosis of Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia), and a careful examination for skin telangiectasias should be performed.
- Patients with renal failure frequently have GI bleeding. This bleeding is often due to peptic ulcer disease or angiodysplasia. This bleeding may be severe because of clotting dysfunction associated with renal disease.
===Symptoms===

# 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 -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 -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 -blockers plus EVL is the best option for secondary prophylaxis of UGIB from varices.
- The nonselective -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.
- 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.

## Scoring systems
Two scoring systems identify those at risk for adverse outcomes from UGIB:
- The Glasgow Blatchford Score (GBS)
- The Rockall score

## The Glasgow Blatchford Score (GBS)
- The Glasgow Blatchford Score (GBS) helps in identifying low-risk patients with UGIB who can be managed safely as outpatients without an urgent endoscopy.
- GBS parameters include
Blood urea nitrogen level
Hematocrit level
Heart rate
Systolic blood pressure
Presence of syncope or melena, as well as presence of comorbid heart and liver disease.
- Blood urea nitrogen level
- Hematocrit level
- Heart rate
- Systolic blood pressure
- Presence of syncope or melena, as well as presence of comorbid heart and liver disease.
- GBS is the more effective system for predicting the need for transfusion in patients with UGIB.

## The Rockall score
- The complete Rockall score identifies those patients with evidence of acute UGIB on endoscopy who are at low risk for further bleeding or death.
- The score is based upon
Age
Presence of shock
Comorbidity diagnosis
Endoscopic ulcer characteristics
Stigmata of recent hemorrhage.
- Age
- Presence of shock
- Comorbidity diagnosis
- Endoscopic ulcer characteristics
- Stigmata of recent hemorrhage.

# Complications
Complications of UGIB include:
- End-organ damage
Cardiac ischemia
Renal failure
Ischemic hepatitis
Anoxic brain injury
- Cardiac ischemia
- Renal failure
- Ischemic hepatitis
- Anoxic brain injury
- Iron-deficiency anemia

# Classification
According to The American Gastroenterological Association, upper GI bleeding can be classified based on the rate of blood loss into overt(acute), occult or obscure(chronic) forms.
- Overt GI bleeding:- Overt GI bleeding is defined as acute bleeding which is visible and can present in the form of hematemesis, coffee-ground emesis, melena, or hematochezia.
- Occult or chronic GI bleeding:- Occult GI bleeding  is defined as a microscopic hemorrhage which can present as Hemoccult-positive stools with or without iron deficiency anemia. It is the initial presentation in patients with no evidence of visible blood loos and is positive on fecal occult blood test(FOBT).
- Obscure GI bleeding:- Obscure GI bleeding is defined as recurrent bleeding in which a source is not identified after upper endoscopy and colonoscopy. It can be either overt or occult.

# 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.

## Mucosal barrier
- The gastric mucosa is protected from the acidic environment by mucus, bicarbonate, prostaglandins, and blood flow.
- This mucosal barrier consists of three protective components which include:
Layer of epithelial cell lining.
Layer of mucus, secreted by surface epithelial cells and foveolar cells.
Layer of bicarbonate ions, secreted by the surface epithelial cells.
- Layer of epithelial cell lining.
- Layer of mucus, secreted by surface epithelial cells and foveolar cells.
- Layer of bicarbonate ions, secreted by the surface epithelial cells.
The following table demonstrates the defense mechanisms of gastric mucosal barrier

## Pathogenesis
The main inciting event in the pathogeneis of upper GI bleeding is damage to mucosal injury. This mucosal injury can occur at various levels of GI tract. If the damage and bleeding is confined up to ligament of Treitz, it is defined as upper GI bleeding.

## Pathogenesis
- Regardless of etiology, if the balance of gastric acid secretion and mucosal defenses is disrupted, acid interacts with the epithelium to cause damage.
Varices are large, tortuous veins and protrude into the lumen, rupturing.
Helicobacter pylori disrupts the mucosal barrier and causes inflammation of the mucosa of the stomach and duodenum.
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.
NSAIDs inhibit cyclooxygenase, leading to impaired mucosal defenses by decreasing mucosal prostaglandin synthesis.
During stress, there is acid hypersecretion; therefore, the breakdown of mucosal defenses leads to injury of the mucosa and subsequent bleeding.
Mucosal defects along with dilated and tortuous vessels in dieulafoy lesion put them at risk for rupture because of necrosis of the arterial wall from exposure to gastric acid.
- Varices are large, tortuous veins and protrude into the lumen, rupturing.
- Helicobacter pylori disrupts the mucosal barrier and causes inflammation of the mucosa of the stomach and duodenum.
- 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.
- NSAIDs inhibit cyclooxygenase, leading to impaired mucosal defenses by decreasing mucosal prostaglandin synthesis.
- During stress, there is acid hypersecretion; therefore, the breakdown of mucosal defenses leads to injury of the mucosa and subsequent bleeding.
- Mucosal defects along with dilated and tortuous vessels in dieulafoy lesion put them at risk for rupture because of necrosis of the arterial wall from exposure to gastric acid.

## Gross and Microscopic Pathology

# Diagnosis
In patients with acute Upper GI bleeding who are unstable rapid assessment and resuscitation should be initiated even before diagnostic evaluation. Once hemodynamic stability is achieved, a proper clinical history, physical examination, and initial laboratory findings are crucial not only in determining the likely sources of bleeding but also in directing the appropriate intervention. The hematocrit level is measured soon after the onset of bleeding, but will not accurately reflect the amount of blood loss. Equilibration between the intravascular and extravascular spaces is not complete until 24 to 72 hours after bleeding has occurred. Low mean corpuscular volume, low iron and ferritin levels, and high transferrin and total iron-binding capacity (TIBC) confirm iron deficiency. Blood urea nitrogen (BUN) level may be elevated out of proportion to any increase in the creatinine level in patients with UGIB, secondary to the breakdown of blood proteins to urea by intestinal bacteria. Platelet count and coagulation studies should be checked, especially in patients with known or suspected coagulopathy. Nasogastric lavage should be performed if the presence or source of bleeding is unknown. Upper gastrointestinal endoscopy is the primary diagnostic tool, performed for both diagnosis and treatment of active bleeding. The American Society of Gastrointestinal Endoscopy guidelines recommend that upper endoscopy be performed within 24 hours of presentation in all patients with UGIB. Angiography and tagged erythrocyte scan are rarely needed, but may be used to diagnose (and embolize) active UGIB, particularly in patients who cannot tolerate EGD. Also, upper gastrointestinal tract radiographic studies using barium are generally not advised, as they may obscure visualization during EGD.

# Initial Laboratory Studies
- The hematocrit level is used to identify the degree of blood loss and suggests the acuity or chronicity of blood loss.
- Serial complete blood count (CBC) tests are important for monitoring the presence of ongoing blood loss.
- Initial CBC may not fully reflect the actual degree of acute blood loss.
- Qualitatively, on peripheral blood smear prepared with Wright-Giemsa stain, normal erythrocytes should be smaller than the nucleus of a normal lymphocyte, and the central clear area should not be overly prominent.
- In iron-deficiency anemia associated with chronic blood loss, erythrocytes are smaller (microcytic) and appear lighter (hypochromic) than normal cells.
- Mild to moderate thrombocytopenia (>30  103/L) does not usually result in spontaneous bleeding, although patients with a pre-existing lesion may bleed in the presence of even mild thrombocytopenia.
- Platelet count may rise in response to significant gastrointestinal bleeding and may fall with multiple blood transfusions.
- Low ferritin level is the most specific test for iron-deficiency anemia. This finding together with a low iron and high TIBC levels are helpful in diagnosing iron-deficiency anemia, a common complication of ongoing or significant UGIB.
- BUN level may be elevated out of proportion to any increase in the creatinine level in patients with UGIB, secondary to breakdown of blood proteins to urea by intestinal bacteria.
- In patients with esophageal varices, acquired coagulopathies are common due to cirrhosis.

# Naso-Gastric Lavage
- Nasogastric lavage is only indicated when the diagnosis of UGIB doubtful.
- It is rarely used now
- Nasogastric lavage also helps in documenting active or recent UGIB and the need for urgent endoscopy.
- Occasionally used to empty gastric contents in preparation for endoscopy.

## Complicatiions
Complications of the procedure include:
- Bleeding from trauma during tube passage in patients with coagulopathy is a possible complication.
- Other rare complications include
Pharyngeal and esophageal perforation
Cardiac arrest
Ethmoid sinus fracture with brain trauma
Bronchial intubation.
- Pharyngeal and esophageal perforation
- Cardiac arrest
- Ethmoid sinus fracture with brain trauma
- Bronchial intubation.

## Interpretation
- Evidence of old (brown colored or 'coffee grounds') or fresh blood documents presence of UGIB.
- Evidence of bilious material rules out bleeding distal to the pylorus.
- Any other appearances of GI contents are non-diagnostic.
- There is no evidence that performing a nasogastric lavage to clear clots or otherwise manage bleeding improves clinical outcome.

## Contraindications
- Avoid gastric lavage in patients with suspected perforated abdominal viscus.

# Upper GI Endoscopy
- Upper GI Endoscopy is considered investigation of choice for diagnosing and assessing the source of UGIB.
- The American Society of Gastrointestinal Endoscopy guidelines recommend that upper gastrointestinal endoscopy be performed within 24 hours of presentation in all patients with UGIB

## Indications
- Active UGIB
- Used for biopsy lesions for tissue diagnosis and to treat currently bleeding lesions.

## Complications
Complications include
- Aspiration
- Esophageal perforation
- Cardiopulmonary complications secondary to anesthesia
- Increased bleeding while attempting therapeutic intervention

# Other Diagnostic studies
In cases where the source of bleeding is unidentified after upper endoscopy, the utilization of subsequent diagnostic modalities depends upon the hemodynamic stability of the patient. Other diagnostic studies include:
- CT angiography
- Catheter angiography
- Radionuclide imaging

# Differentiating UGIB
Blood that originates from the oro-pharynx, if swallowed, can present as melena, leading to a false concern of a gastrointestinal source. Examination of nasal area and mouth will help to identify source of bleeding.

# Management
The management of GI bleeding includes
- Initial resuscitation and pharmacotherapy
- Risk stratification
- Surgery
Pre-endoscopy management
Initial management of antithrombotic agents (anticoagulants and antiplatelet agents)
Pharmacological therapy
Role of gastric lavage and prophylactic endotracheal intubation
Timing of endoscopy
Endoscopic management
Endoscopic diagnosis
Endoscopic therapy
- Pre-endoscopy management
Initial management of antithrombotic agents (anticoagulants and antiplatelet agents)
Pharmacological therapy
Role of gastric lavage and prophylactic endotracheal intubation
Timing of endoscopy
- Initial management of antithrombotic agents (anticoagulants and antiplatelet agents)
- Pharmacological therapy
- Role of gastric lavage and prophylactic endotracheal intubation
- Timing of endoscopy
- Endoscopic management
Endoscopic diagnosis
Endoscopic therapy
- Endoscopic diagnosis
- Endoscopic therapy
- Management following endoscopy/endoscopic hemostasis

## Initial resuscitation
- The initial steps in the management of a patient with UGIB is to assess the severity of bleeding, and then institute fluid and blood resuscitation as needed.
- Any patient with hemodynamic instability or who is actively bleeding should be admitted to the ICU for monitoring and resuscitation
- The patients hemodynamic status is of great importance in determining the degree of severity and triage status.
- The rate of fluid resuscitation is proportional to the severity of bleeding with the goal of restoring and maintaining the patients blood pressure.
- Two large caliber (16-gauge or larger) peripheral catheters or a central venous line should be inserted in patients who are hemodynamically unstable. *Supportive care includes administration of supplemental oxygen and monitoring of urine output.
- Patients with severe bleeding will need to be transfused; the indications for transfusion in patients with less severe bleeding should be based on the patients age and presence of comorbid conditions.
- The target hematocrit value varies according to age and clinical conditions.
In the elderly patient, the target hematocrit is 30%.
In younger, healthy patients, the target hematocrit is 25%.
In patients with portal hypertension, the target hematocrit should not be above 27% or 28%, so as not to raise portal venous pressure.
- In the elderly patient, the target hematocrit is 30%.
- In younger, healthy patients, the target hematocrit is 25%.
- In patients with portal hypertension, the target hematocrit should not be above 27% or 28%, so as not to raise portal venous pressure.
- 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
- The National Institute for Health and Care Excellence (NICE) guidline on blood product management in upper GI bleeding:
- Platelets should only be given if the patient is actively bleeding or hemodynamically unstable and has a platelet count of <50109/L.
- Fresh frozen plasma should be given if the fibrinogen level is 1.5 times normal.
- Prothrombin complex should be provided to those on warfarin and actively bleeding.
- Recombinant factor VIIa should only be used when all of the above measures have failed.

## Endoscopic intervention
- In UGIB, diagnostic and therapeutic endoscopy may be performed simultaneously.
- Therapeutic upper gastrointestinal endoscopy should be performed in all patients with suspected UGIB to evaluate and possibly treat the source of bleeding.
- The urgency of endoscopy depends on the anticipated source of bleeding, rapidity of blood loss, and hemodynamic stability of the patient.
- Endoscopic intervention should be undertaken within 24 hours, as early intervention is associated with reduced transfusion needs and a decreased length of stay in high-risk patients with nonvariceal bleeding.

### Endoscopic procedures
- The most common procedures used to manage bleeding caused by peptic ulcer disease are injection, coagulation (thermal, electric, and argon plasma), and hemostatic clips.
- The most common procedures used to manage esophageal varices are sclerotherapy and variceal band ligation
- There is evidence supporting the use of two different endoscopic procedures, rather than a single procedure to better control bleeding and decrease the incidence of rebleeding
- Other successful methods for controlling bleeding are available when endoscopy fails:
Balloon tamponade and TIPS are temporizing measures for patients with actively bleeding esophageal varices who cannot be managed endoscopically.
Emergency surgery for bleeding peptic ulcers that cannot be managed endoscopically involves oversewing of the ulcer to ligate the bleeding artery plus truncal vagotomy to decrease acid secretion and pyloroplasty to improve gastric drainage.
- Balloon tamponade and TIPS are temporizing measures for patients with actively bleeding esophageal varices who cannot be managed endoscopically.
- Emergency surgery for bleeding peptic ulcers that cannot be managed endoscopically involves oversewing of the ulcer to ligate the bleeding artery plus truncal vagotomy to decrease acid secretion and pyloroplasty to improve gastric drainage.
- EBL involves the placement of elastic circular ring ligatures around the varices to cause strangulation, while the patient is under sedation and analgesia. *Bands are typically delivered at the gastroesophageal junction first, then proximally; six to ten bands may be delivered with a single intubation.
- The primary drawback of EBL is that during active bleeding, operator visibility is limited by the device holding the bands prior to their delivery.  *Endotracheal intubation is prudent in patients with active bleeding to reduce the risk of aspiration pneumonia.
- Systemic antibiotics should be considered in patients with ascites to reduce the risk of bacterial infection
- Follow-up endoscopies are recommended at various intervals depending on the size/appearance of varices and severity of liver disease.
- Typically, visits every 2 to 4 weeks until obliteration. An interval of 1 to 3 months is recommended for initial surveillance of recurrence of varices, then every 6 to 12 months
- Endoscopic therapy can halt bleeding in 80% to 90% of patients
- EBL is equivalent to EIS in establishing initial control of bleeding, but EBL is challenging in the actively bleeding patient
- EBL is widely favored over EIS for primary prevention due to similar or superior efficacy with fewer complications

### Endoscopic injection sclerotherapy (EIS)
- Comprises endoscopic delivery of a sclerosant, such as ethanol, morrhuate sodium, polidocanol, or sodium tetradecyl sulfate, while patient is under sedation and analgesia.
- Injections may be intravariceal or be delivered into the esophageal wall near the varices.
- Bucrylate is an adhesive that has been used successfully.
- Typical injection volume is 1 to 2 mL per injection, for a total volume of 10 to 15 mL. Interval between injections varies according to patient tolerance and response, and complications
- After an initial injection to control bleeding, there is usually a follow-up injection 2 to 3 days later, followed by weekly or biweekly procedures until complete obliteration of the varices is achieved, which usually takes five or six sessions

## Pharmacotherapy

# Physical examination
Common physical exam findings include:

## Vitals
- Hypotension
- Tachycardia
- Thready pulse
- Hypoxia

## Abdomen
- +Bowel sounds
- Abdominal tenderness
- Hepatomegaly
- Splenomegaly
- Caput medusa
- Spider angiomata

## Skin
- Palmar erythema
- Cold clammy extremities

## Neurological examination
- Altered sensations
- Poor mentation
- Drowsiness

## Rectal examination
- Occult blood
- Gross blood
Bright red blood per rectum
Melena
Burgundy stools
Blood coating stools versus within stools
Bloody diarrhea
- Bright red blood per rectum
- Melena
- Burgundy stools
- Blood coating stools versus within stools
- Bloody diarrhea

# Surgery

## TIPS
TIPS is a complex nonsurgical shunt which involves insertion of an expandable metal stent that bridges the hepatic vein and an intrahepatic branch of the portal vein. TIPS can halt bleeding in almost all patients, including those with bleeding refractory to other therapies.
Indications
- For treatment of bleeding varices that are refractory to banding or sclerosant injection.
- For treatment of refractory variceal bleeding as a bridge to liver transplantation.
Procedure
- TIPS involves the percutaneous puncture of the right internal jugular vein and insertion of a vascular sheath into the inferior vena cava and the hepatic vein.
- A needle is inserted through the sheath, into the liver parenchyma, and then into the portal vein.
- Aspiration of blood and injection of contrast media ensure accurate placement.
- An angioplasty balloon catheter is used to dilate the tract between the hepatic and portal veins, and a stent is then placed across the tract.
- Portal venography is used to confirm the placement
- Patients should be monitored closely for bleeding for 12 to 24 hours
Complications
- Hepatic encephalopathy
- Hemolytic anemia
- Intra-abdominal bleeding during stent placement

## Balloon tamponade
Balloon tamponade is only used as a temporary measure in patients who fail to respond to pharmacologic and endoscopic intervention. Balloon tamponade stabilizes patients until more definitive treatment can be instituted (TIPS or liver transplantation).
Procedure
- Balloon tamponade involves the passage of a specialized nasogastric tube, fitted with an inflatable balloon.
- When the balloon is inflated, direct pressure staunches bleeding by compressing the varices.
- Controls active bleeding in 80% to 90% of patients although rebleeding after balloon deflation is common.
Indications
- For bleeding varices that are refractory to banding or sclerosant injection.
Complications
- Rebleeding upon balloon deflation
- Esophageal rupture

## Emergency laparotomy
Emergency laparotomy is performed as a last resort for complications such as bleeding and perforation. Emergency laparotomy involving open exploration of the abdomen, oversewing of the ulcer (to ligate the bleeding artery), plus truncal vagotomy (to decrease acid secretion) and pyloroplasty (for improved gastric drainage).
Indications
- Treatment of bleeding ulcer that cannot be managed with endoscopy
- Treatment of patients who cannot tolerate endoscopy
Complications
- Risks of major surgery and general anesthesia
The following is a list of diseases that present with acute onset severe lower abdominal pain:

# Diagnosis
- The presence of renal tubular acidosis (RTA) should be considered in any patient with an otherwise unexplained normal anion gap (hyperchloremic) metabolic acidosis.
- The first step in the diagnosis of a patient with a reduced serum bicarbonate and elevated chloride concentration is to confirm that metabolic acidosis is present by measuring the blood pH.
- The next steps in the diagnosis of possible RTA in patients who have a normal anion gap metabolic acidosis are measurement of the urine pH and estimation of urinary ammonium excretion.

## Urine PH
- Patients with normal renal function and normal renal acidification mechanisms who develop metabolic acidosis usually have a urine pH of 5.3 or less.
- In most cases of distal RTA, the urine pH is persistently 5.5 or higher, reflecting the primary defect in distal acidification, and a urine pH below 5.5 generally excludes distal (but not proximal) RTA.
- However, the urine pH can be reduced below 5.5 in occasional patients (2 of 17 in one study) with distal RTA.
- In contrast to the persistently elevated urine pH in distal RTA, the urine pH is variable in proximal RTA, a disorder characterized by diminished proximal bicarbonate reabsorption.
- The urine pH will be inappropriately elevated if patients with proximal RTA are treated with alkali, increasing the serum bicarbonate concentration enough to produce a filtered bicarbonate load that exceeds the reduced proximal reabsorptive capacity; this most commonly occurs when alkali is given for the diagnosis or treatment of this disorder.
- In patients presenting with a normal anion gap metabolic acidosis, two scenarios can produce a misleading elevation in the urine pH that incorrectly suggests the presence of RTA:
Urinary tract infections with urea-splitting organisms may increase the urine pH because urea is converted to ammonia and bicarbonate.
Thus, assessment of the urine pH should include a urinalysis and, if indicated, a urine culture.
Severe volume depletion (which indirectly and reversibly limits hydrogen ion secretion by reducing distal sodium delivery) can impair urine acidification.
Thus, reliable interpretation of an inappropriately high urine pH requires that the urine sodium concentration be greater than 25 meq/L.
- Urinary tract infections with urea-splitting organisms may increase the urine pH because urea is converted to ammonia and bicarbonate.
Thus, assessment of the urine pH should include a urinalysis and, if indicated, a urine culture.
- Thus, assessment of the urine pH should include a urinalysis and, if indicated, a urine culture.
- Severe volume depletion (which indirectly and reversibly limits hydrogen ion secretion by reducing distal sodium delivery) can impair urine acidification.
Thus, reliable interpretation of an inappropriately high urine pH requires that the urine sodium concentration be greater than 25 meq/L.
- Thus, reliable interpretation of an inappropriately high urine pH requires that the urine sodium concentration be greater than 25 meq/L.

## Urine ammonium excretion
- Urine ammonium excretion is reduced in distal RTA  Thus, either direct measurement or indirect estimation of the urine ammonium concentration can be helpful in establishing the correct diagnosis.
- Urinary NH4 excretion cannot be directly measured in most clinical laboratories. However, an indirect estimate can be obtained by measurement of the urine anion gap and/or the urine osmolal gap.
- Estimation of NH4 excretion is not useful in patients with proximal RTA.