Management of Upper GI

Bleeding

Meremo A. J., MD, MMED

 Background

• Upper GI bleeding is a common medical emergence

that results in high morbidity, mortality and medical
care cost

• In TZ the most common cause of UGIB on endoscopic

study were1
– peptic ulcer (40.9%)
– oesophageal varices (16.4%) and
– mucosal lesions (7.4%)

1. DH Mwakyusa et al.Trop Geogr Med. 1983 Jun;35 (2):173-8 6604353 (P,S,E,B )

2
 Gastrointestinal Bleeding
• Definition:
Intraluminal blood loss anywhere from the
oropharynx to the anus.
– Upper GI Bleed (UGIB): above the ligament of
Treitz (point where the duodenum becomes the jejunum)
– Lower GI Bleed (LGIB): below the ligament of
Treitz
 Signs of GI Bleeding
– Coffee-ground emesis: digested blood in vomitus
• UGIB
– Hematemesis: blood in vomitus
• UGIB
– Hematochezia: blood in stools
• Rapid UGIB
• LGIB
– Melena: Black tarry stools from digested blood
• Usually UGIB, but LGIB can cause melena with
bleeding in small bowel & the right colon.
 Etiologies of UGIB
– Oropharyngeal bleeding & Epistaxis ->
swallowed blood
– Erosive esophagitis (10%)
• Immunocompetent person: GERD/ Barrett’s
esophagus, XRT (x-ray radiation therapy)
• Immunocompromised person: Candida,
CMV, HSV
– Mallory-Weiss tear (10%)
• GE junction tear due to forceful vomiting
against closed glottis
– Varices (10%)
• Secondary to portal hypertension secondary
to cirrhosis or schistosomiasis
 Etiologies of UGIB (cont)
– Gastritis/Gastropathy (15%)
• NSAIDs, alcohol, physiologic stress (burn
patients), portal gastropathy
– Peptic Ulcer Disease (PUD) (50%)
• NSAID-induced
• H. pylori-induced
– Vascular malformations
• AVMs
– Neoplasm
• Esophageal or gastric
 Clinical Clues
• UGIB > LGIB: • LGIB > UGIB:
– Nausea – Diarrhea
- Hematemesis – Tenesmus
– Coffee ground – BRBPR
emesis
– Maroon stool
– Melena
– Lightheadedness
– Syncope
 PEPTIC ULCER DISEASE (PUD)
• A peptic ulcer is an excoriated area of stomach or
intestinal mucosa caused principally by the digestive
action of gastric juice or upper small intestinal
secretions.
Sites of peptic ulcers.
 Sites of peptic ulcers
• Duedenum 1st portion (few cms from the pyloric ring)
anterior portion is most affected.
• stomach,. Usually antrum lesser curvature
(common); anterior, posterior wall and greater
curvature less common.
• In the margin of gastroenterestomy (stomach ulcer).
• In the deudenum, stomach or jejunum in patients
with Zollinger- Ellison Syndrome.
• Within or adjacent to meckel’s diverticulum that
contains ectopic gastric mucosa.
• A marginal ulcer also often occurs wherever a
surgical opening such as a gastrojejunostomy has been
made between the stomach and the jejunum of the
small intestine
• Under normal conditions, a physiologic balance
exists between peptic acid secretion and
gastroduodenal mucosal defense.
• Mucosal injury and, thus, peptic ulcer occur when the
balance between the aggressive factors and the
defensive mechanisms is disrupted.
• Aggressive factors, such as NSAIDs, H pylori, alcohol,
bile salts, acid, and pepsin can alter the mucosal
defense by allowing back diffusion of hydrogen ions
and subsequent epithelial cell injury.
• The defensive mechanisms include tight intercellular
junctions, mucus, mucosal blood flow, cellular
restitution, and epithelial renewal.
Gastric ulcer with punched-out ulcer base with
whitish fibrinoid exudates.
• The epithelial cells of the stomach and duodenum
secrete mucus in response to irritation of the
epithelial lining and as a result of cholinergic
stimulation.
• A portion of the gastric and duodenal mucus exists in
the form of a gel layer, which is impermeable to acid
and pepsin.
• Other gastric and duodenal cells secrete bicarbonate,
which aids in buffering acid that lies near the mucosa.
• Prostaglandins of the E type (PGE) have an
important protective role, because PGE increases the
production of both bicarbonate and the mucous layer.
• In the event of acid and pepsin entering the epithelial
cells, additional mechanisms are in place to reduce
injury.
• Within the epithelial cells, ion pumps in the
basolateral cell membrane help to regulate
intracellular pH by removing excess hydrogen ions.
• Through the process of restitution, healthy cells
migrate to the site of injury.
• Mucosal blood flow removes acid that diffuses
through the injured mucosa and provides bicarbonate
to the surface epithelial cells.
 Basic Cause of Peptic Ulceration.

• The usual cause of peptic ulceration is an imbalance

between the rate of secretion of gastric juice and the
degree of protection afforded by

(1) the gastro duodenal mucosal barrier and

(2) the neutralization of the gastric acid by duodenal

juices.
• It will be recalled that all areas normally exposed to
gastric juice are well supplied with mucous glands.
• Beginning with compound mucous glands in the
lower esophagus plus the mucous cell coating of the
stomach mucosa, the mucous neck cells of the gastric
glands, the deep pyloric glands that secrete mainly
mucus.
• Finally, the glands of Brunner of the upper
duodenum, which secrete a highly alkaline mucus.
• In addition to the mucus protection of the mucosa, the
duodenum is protected by the alkalinity of the small
intestinal secretions.
• Especially important is pancreatic secretion, which
contains large quantities of sodium bicarbonate that
neutralize the hydrochloric acid of the gastric juice.
• Thus also inactivating pepsin and preventing
digestion of the mucosa.
• In addition, large amounts of bicarbonate ions are
provided in

-(1) the secretions of the large Brunner's glands in the

first few centimeters of the duodenal wall and

-(2) in bile coming from the liver.

• Finally, two feedback control mechanisms normally
ensure that this neutralization of gastric juices is
complete, as follows:

When excess acid enters the duodenum, it reflexly

inhibits gastric acid secretion and peristalsis in the
stomach, both by nervous reflexes and by hormonal
feedback from the duodenum, thereby decreasing the
rate of gastric emptying.
• The presence of acid in the small intestine liberates
secretin from the intestinal mucosa, which then
passes by way of the blood to the pancreas to promote
rapid secretion of pancreatic juice.
• This juice also contains a high concentration of
sodium bicarbonate thus making still more sodium
bicarbonate available for neutralization of the acid.
• Therefore, a peptic ulcer can be caused in either of
two ways:

(1) excess secretion of acid and pepsin by the gastric

mucosa or

(2) diminished ability of the gastroduodenal mucosal

barrier to protect against the digestive properties of
the stomach acid-pepsin secretion.
 Specific Causes of PUD

1. Helicobacter pylori.
• Many peptic ulcer patients have been found to have
chronic infection of the terminal portions of the gastric
mucosa and initial portions of the duodenal mucosa,
infection most often caused by the bacterium
Helicobacter pylori.
• Currently, 70% of all gastric ulcers occurring in the
United States can be attributed to H pylori infection.
• In addition to an increase in acid secretion, H pylori
infection also predisposes patients to ulcer disease by
disrupting mucosal integrity.
• The H. pylori is capable of penetrating the mucosal
barrier both
By virtue of its physical capability to burrow through
the barrier and
By releasing bacterial digestive enzymes that liquefy
the barrier.
• H. pylori secretes urease (generates ammonia),
protease (breaks down glycoprotein in the gastric
mucus) or phospholipases.
• The bacterium's spiral shape and flagella facilitate its
penetration into the mucous layer and its attachment to
the epithelial layer.
• Subsequently, it releases phospholipase andproteases,
which cause further mucosal damage.
• A cytotoxin-associated gene (cag A) has been isolated
in approximately 65% of the bacteria.
• The products of this gene are associated with more
severe gastritis, gastric ulcer, gastric cancer, and
lymphoma.
• Once this infection begins, it can last a lifetime unless
it is eradicated by antibacterial therapy.
• Infection with H pylori is likely pathogenic by means
of a variety of indirect mechanisms as the organism
does not generally colonize the duodenum.
• The mechanisms are described as follows :

H pylori infection that follows an antral predominant

pattern leads to an inflammatory state in which high
levels of tumor necrosis factor-alpha (TNF-alpha) and
other cytokines are produced.
• These stimulate gastric acid production directly by
increasing gastrin release from G cells and inhibit
somatostatin production by antral D cells.
• This leads to a net increase in gastric acid secretion,
which leads to an increased acid load in the
duodenum, overwhelming the mucosal defense.
• Duodenal acid exposure can lead to gastric
metaplasia, whereby the duodenal mucosa can take
on characteristics of gastric mucosa.
• H pylori can then colonize the duodenal mucosa and
adhere to cells.
• This adherence leads to a variety of second-
messenger signals, which invoke an immunologic
response against those cells causing mucosal damage
by host neutrophils and other inflammatory cells.
• The cellular immune response in the H pylori–
infected gastric mucosa is predominantly the T helper
cell type 1 (Th1). Interleukin (IL)-18 levels are
increased in this setting.
• The acidic environment of the gastric lumen induces
the gastric mucosal production of IL-8, which is
involved in the proinflammatory pathways.
• The secretion of soluble triggering receptor is
increased in H pylori –positive persons with gastric
but not duodenal ulcers, suggesting that the host
response may determine the site of ulceration.
• The age of the host may also influence the type of
immune mechanism(s) involved in the pathogenesis
of the H pylori –associated gastroduodenal disease.
• Duodenal ulcer in an elderly patient who
presented with melena and hypotension.
2. Zollinger-Ellison syndrome (ZES)

• ZES is a rare disorder characterized by one or more

tumors in the pancreas, duodenum, or both. The
tumors cause the stomach to make too much acid,
leading to peptic ulcers in the duodenum.
• The tumors are sometimes cancerous and spread to
other areas of the body.
3. NSAIDs
• NSAIDs are pathogenic through their inhibition of
the cyclooxygenase-1 (COX-1) pathway, which
normally produces protective prostaglandins.
• These prostaglandins are protective as they augment
both bicarbonate and mucous production, as
mentioned above.
• However, perhaps more important, prostaglandins
augment mucosal blood flow, and their inhibition
leads to impairment of blood flow, leaving the
mucosa vulnerable to damage.
• NSAID-induced ulcers account for approximately
26% of gastric ulcers, and they are believed to be
secondary to a decrease in prostaglandin production
resulting from the inhibition of cyclooxygenase.
• However, the risk of gastroduodenal ulcer is not
diminished with parental or rectal use of NSAIDs
indicating injury occurring from the systemic effect
of NSAIDs on the gastrointestinal mucosa.
• Selective COX-2 (cyclooxygenase) inhibitors, like
celecoxib (Celebrex), rofecoxib (Vioxx), and
valdecoxib (Bextra), have been shown to cause
gastroduodenal ulcers at a rate comparable to placebo
(4%).
• Other medications that predispose patients to
gastroduodenal ulcers include potassium chloride,
chemotherapeutic agents, and bisphosphonates.
3. Smoking
• Cigarette smoking can affect gastric mucosal defense
adversely.
• Cigarette smoking is believed to play a facultative
role in H pylori infection.
• Smoking, presumably causes an increased nervous
stimulation of the stomach secretory glands.
• People who smoke tend to develop more frequent and
recurrent ulcers and their ulcers are more resistant to
therapy.
• Alcohol tends to break down the mucosal barrier, no
evidence indicates that dietary habits or alcohol
consumption predisposes individuals to gastric ulcer.
 Other Causes of Ulceration.
• Studies in both animals and human beings have shown that
excess secretion of gastric juices for any reason (eg; even
in psychic disturbances) may cause peptic ulceration.
Clinical presentation
History
• Epigastric pain (the most common symptom)

– Gnawing or burning sensation

– Occurs 2-3 hours after meals

– Relieved by food or antacids

– Patient awakens with pain at night.

– May radiate to the back (consider penetration)

• Nausea &Vomiting,

• Dyspepsia, including belching, bloating, distention,

and fatty food intolerance
• Heartburn

• Chest discomfort

• Anorexia, weight loss

• Hematemesis or melena
Physical findings
• In uncomplicated PUD, clinical findings are few and
nonspecific.
– Epigastric tenderness

– Guaiac-positive stool

– Melena

– Succussion splash
 Workup
Laboratory Studies
• CBC,

• Liver function tests (LFTs)

• Amylase, and lipase

 Imaging Studies
• Upper gastrointestinal series

– Double-contrast radiography. However, it has been

replaced largely by diagnostic endoscopy, when
available.
Other Tests
• Rapid urease tests

• Histopathology

• Culture

• Serum H pylori antibody detection

• Fecal antigen tests

• Urea breath tests

• A fasting serum gastrin level

• A secretin stimulation test

Procedures
• Upper GI endoscopy

– Preferred diagnostic test

– Highly sensitive for the diagnosis ulcers

– Allows for biopsies and cytologic brushings in

gastric ulcer to differentiate a benign ulcer from a
malignant lesion.
– Allows antral biopsies for a rapid urease test
and/or histopathology.
• Medical Care
Treatment.

Most patients with PUD are treated successfully with

cure of H pylori infection and/or avoidance of
NSAIDs and use of antisecretory therapy.
 Proton pump inhibitor (PPI)-based triple therapy- 14
days on more
 Administration of an acid-suppressant drug,
especially ranitidine.
• In the past, before these approaches to peptic ulcer
therapy were developed, it was often necessary to
remove as much as four fifths of the stomach, thus
reducing stomach acid-peptic juices enough to cure
most patients.
• Another therapy was to cut the two vagus nerves that
supply parasympathetic stimulation to the gastric glands.
• This often cured the ulcer or ulcers within 1 week after
the operation was performed.
• However, much of the basal stomach secretion returned
after a few months, and in many patients the ulcer also
returned.
Surgical Care
Indications
 Refractory, symptomatic peptic ulcers

 Obstruction

 Penetration / perforation

 Bleeding
 Upper GI Bleeding Protocol
• Due to frequency of admissions for upper GI
bleeding, we think a streamlined protocol for the
evaluation and management of these patients will
improve outcomes.
 Aims of the Protocol
• The protocol aims to guide the accomplishment of 8
major goals:
– Attaining quick history
– Attaining quick physical
– Triaging the patient
– Stabilizing the patient
– Administering medications based on the proposed
etiology of their UGI bleed
– Early endoscopy
– Starting maintenance medications once the pt is
stable
 IV’s and fluid rates
• The volume administered through an IV greatly
increases with small increases in the diameter of the
IV:
– 22 gg = 35 cc/min
– 20 gg = 70 cc/min
– 18 gg = 125 cc/min
– 16 gg = 250 cc/min

*With two 16 gg IV’s, one can administer 1L of crystalloid in 2 minutes! *

 Medical Management
• Octreotide bolus and infusion has been shown to have
an 84% success rate in controlling variceal bleeding
<Lancet 342:637, 1993>
• Endoscopic banding alone has >90% success rate and
octreotide infusion in conjunction with banding has
>95% success <New England Journal of Medicine
333:555, 1995>
 Medical Management
• Given prophylactic antibiotics during an acute
variceal bleed is now standard management.
• Several studies have shown that this prevents the
development of infections particularly SBP which can
worsen PHTN and in turn worsen variceal bleeds.
• Generally a 3rd generation cephalosporin or a
quinolone are used
 Medical Management
Infusion of high-dose omeprazole before
endoscopy
– accelerates the resolution bleeding in ulcers, by
stabilizing clots and initiating healing
– reduces the need for endoscopic therapy
– No improvement in mortality
<NEJM 336: 1054, 1997, NEJM 356: 1631, 2007>
 Medical Management
• Infusion should be continued 24h after bleed stops
particularly if patient was endoscopically intervened
upon.
• No role for IV H2 blockers
• Unclear what the role of PO PPI’s are during active
bleed.
 Endoscopic Management
• Varices should be banded depending on:
– Size of the varices
– Location of varices (near the EG junction are more
likely to bleed)
 Endoscopic Management
• Predictors of rebleed and mortality:
– Active bleeding
– Non-bleeding visible vessel present
– Adherent clot present
*In turn, arteries should be clipped, cauterized, or
injected (with saline, epinephrine) if these are
found.

<BMJ 2005;330:568>