1. Discuss the fundamentals of diagnosis in a patient presenting with 1.1.3.

Intensity
abdominal pain
●​ Pain intensity does not always directly correlate with the severity of the
The evaluation of acute abdominal pain requires a meticulously executed and underlying condition. For example, the early discomfort of superior
detailed history, as the most catastrophic events may be heralded by the subtlest of mesenteric artery occlusion may seem insignificant, presenting as a mild
symptoms. The chronological sequence of events in a patient's history is often more ache that is famously described as "pain out of proportion to physical
important for narrowing the differential diagnosis than the specific location of the findings".
pain. ●​ The intensity of peritoneal inflammation depends on the nature of the
irritant. Sudden release of sterile acidic gastric juice causes much more
1.1. Approach in the history intense, immediate pain than exposure to neutral, sterile feces.
●​ Parietal pain intensity is exacerbated by movement, changes in tension,
1.1.1. Description and onset
coughing, or sneezing, leading the patient to lie completely still. In
●​ Visceral vs. Parietal Pain: Visceral pain is generally midline, vague, and contrast, patients with colicky pain often thrash around in discomfort.
poorly localized. In contrast, inflammation of the parietal peritoneum
1.1.4. Timing of pain with food intake, defecation, and other factors
causes pain that is steady, aching, precise, and transmitted by somatic
nerves directly over the inflamed area. ●​ Food Intake: Eating commonly exacerbates pain in chronic pancreatitis
●​ Colicky vs. Steady Pain: Intraluminal obstruction of hollow viscera (leading to a fear of eating and subsequent weight loss) and gastric outlet
classically elicits intermittent, cramping, or "colicky" pain. However, obstruction. Pain that worsens with meals also points to mesenteric
sudden distention of the biliary tree (often termed "biliary colic") produces ischemia or irritable bowel syndrome (IBS). Conversely, typical duodenal
a steady, constant pain rather than a truly colicky one. ulcer pain occurs 90 minutes to 3 hours after a meal and is frequently
●​ Speed of Onset: A sudden and catastrophic onset often signals vascular relieved by food or antacids.
disturbances (such as embolism or thrombosis of the superior mesenteric ●​ Defecation: Pain that is relieved by defecation is characteristic of Irritable
artery) or the rupture/perforation of a hollow viscus. Conversely, acute Bowel Syndrome (IBS) or certain cases of Inflammatory Bowel Disease
appendicitis typically begins with vague, intermittent periumbilical pain (IBD).
that slowly migrates to the right lower quadrant over 12 to 24 hours, ●​ Time of Day: Pain that forcibly awakens the patient from sleep (specifically
where it becomes sharper and localized. between midnight and 3:00 A.M.) is a highly discriminating symptom found
in two-thirds of patients with duodenal ulcers.
1.1.2. Radiation The pattern of pain radiation is a critical localizing clue:
●​ Posture: Pain from distention of the pancreatic ducts is characteristically
●​ Biliary and Hepatic: Acute distension of the gallbladder frequently accentuated by recumbency and relieved when the patient sits upright.
causes right upper quadrant pain radiating to the right posterior thorax
1.1.5. Associated GI symptoms, systemic symptoms
or the tip of the right scapula.
●​ Pancreatic and Peptic Ulcer: Pain radiating to the mid-back or left ●​ [Link].1. Heartburn, Chest pain, Dysphagia
shoulder may occur with acute pancreatitis or penetrating peptic ulcers. ○​ Heartburn (Pyrosis): Characterized by a burning sensation
●​ Vascular: Abdominal pain with radiation to the sacral region, flank, or behind the sternum rising from the epigastrium. It strongly
genitalia should immediately signal the possibility of a rupturing indicates gastroesophageal reflux disease (GERD).
abdominal aortic aneurysm. ○​ Chest Pain: Esophageal pain (from GERD, esophageal spasms, or
●​ Renal/Urologic: Obstruction of the ureter causes severe flank and infections) can feel exactly like angina pectoris, manifesting as a
suprapubic pain radiating to the penis, scrotum, or inner upper thigh. pressure-like sensation radiating to the back, neck, or jaw.
●​ Referred Pain: It is essential to consider that intrathoracic diseases (e.g., Distinguishing this from life-threatening coronary artery disease is
myocardial infarction, pneumonia, or pulmonary embolism) can refer pain to critical.
the abdomen.
 ○​ Dysphagia: A key differentiator in upper GI pathology. Intermittent while determining a diagnosis; adequate analgesia will not hide or obfuscate
dysphagia exclusively to solid food implies a structural obstruction serious surgical abdominal signs.
(e.g., strictures, webs, rings, or neoplasms), whereas constant
dysphagia to both liquids and solids points to a motor 1.1.8. Current and previous illness, surgery
abnormality like achalasia.
●​ Previous Surgery: A history of abdominal surgery is the leading risk factor
●​ [Link].2. Nausea and vomiting
for intestinal obstruction due to adhesions.
○​ The chronological onset of nausea matters. In acute appendicitis,
●​ Immunocompromised States: Patients receiving chemotherapy,
nausea and emesis typically follow the onset of abdominal pain,
immunosuppressants, or those with HIV/AIDS may lack normal
distinguishing it from gastroenteritis, where nausea usually
physiologic responses to inflammation. They can present without standard
occurs first.
signs of peritonitis, and their pain might stem from opportunistic
○​ Vomiting partially digested food many hours after eating suggests
infections (e.g., CMV, Candida, or mycobacteria) affecting the GI tract.
gastric outlet obstruction.
●​ Gynecologic History: Obtaining a precise menstrual history is absolutely
○​ Clinicians must distinguish true vomiting (preceded by nausea
mandatory for female patients to rule out ectopic pregnancy, pelvic
and retching) from regurgitation (the effortless passage of
inflammatory disease, ruptured ovarian cysts, or endometriosis. Normal
gastric contents into the mouth).
anatomic relationships and laboratory values are significantly altered by a
○​ Biliary colic and acute cholecystitis are frequently accompanied
gravid uterus.
by nausea and vomiting,.
●​ [Link].3. Diarrhea and constipation 1.1.9. Current or recent medications A thorough medication review is vital, as
○​ Diarrhea: Can result from infections, malabsorption, many drugs directly cause GI pathology:
medications, or endocrine diseases. Diarrhea from
malabsorption typically improves with fasting, whereas ●​ NSAIDs & Aspirin: The most common causes of peptic ulcer disease and
secretory diarrhea persists even without oral intake. gastric erosions. They also significantly increase the risk of diverticular
○​ Constipation: Can signal mechanical bowel obstruction or motor bleeding.
disorders. An inability to pass gas or stool (obstipation) coupled ●​ Anticoagulants: Increase the risk of spontaneous intramural bleeding,
with pain and distension is a hallmark of obstruction or such as a rectus sheath hematoma, and complicate presentations of
complicated diverticular disease. diverticular bleeding.
○​ Alternating Habits: An alternating pattern of diarrhea and ●​ Pancreatitis triggers: Dozens of drugs have been linked to acute
constipation is a classic presentation of Irritable Bowel Syndrome pancreatitis, including azathioprine, statins, GLP-1 agonists, DPP-4
(IBS). inhibitors, and sulfonamides.
●​ Opiates: Cause opioid-induced bowel dysfunction and can induce
1.1.6. Previous diagnosis A patient's past medical history dramatically shapes the functional obstructions or mimic achalasia. They also increase
differential diagnosis. For instance, a patient with known gallstones has a high sphincter of Oddi tone, precipitating biliary-type pain.
probability of recurrent biliary colic or acute cholecystitis. Similarly, 10–25% of
individuals with known diverticulosis will experience recurrent symptoms of 1.1.10. Other environmental factors (occupation, stress)
symptomatic uncomplicated diverticular disease (SUDD) or diverticulitis.
●​ Stress: Psychological stress can precipitate episodes of Irritable Bowel
Previous diagnoses of atrial fibrillation or heart failure elevate the suspicion for
Syndrome (IBS) and functional dyspepsia. Severe physiologic stress
mesenteric ischemia.
(burns, trauma, shock) leads to "stress-related mucosal disease" causing
1.1.7. Treatment received from previous physicians or self-administered It is gastric ischemia and ulceration (e.g., Curling or Cushing ulcers).
important to evaluate what medications the patient has already taken. For instance, a ●​ Toxic/Occupational Exposures: Lead poisoning can cause severe
patient taking antacids that relieve their gnawing epigastric pain likely has acid colicky abdominal pain mimicking intestinal obstruction. Insect or animal
peptic disease. Furthermore, narcotics or analgesics should not be withheld envenomation (e.g., black widow spider bites) can produce intense
 abdominal muscle rigidity easily confused with an acute surgical ○​ Prior Bleeding or Ulcers: Patients with a history of H. pylori or
abdomen. peptic ulcers have a high rate of recurrence, with 10-50%
●​ Lifestyle Habits: Heavy alcohol use is a prominent trigger for acute and rebleeding within a year if untreated.
chronic pancreatitis, alcoholic liver disease, and gastritis. Cigarette ●​ Associated GI Symptoms:
smoking strongly synergizes with NSAIDs to induce peptic ulcer disease ○​ Vomiting and Retching: A classic history of vomiting, retching,
and impairs mucosal healing. Dietary changes and smoking are also or vigorous coughing immediately preceding hematemesis is the
suspected drivers of early-onset GI cancers. hallmark of a Mallory-Weiss tear.
○​ Abdominal Pain: While epigastric burning relieved by food
2. Elaborate on the fundamentals of diagnosis in a patient presenting with GI suggests PUD, >50% of ulcer-related hemorrhages occur without
bleeding any preceding warning signs or abdominal pain.
○​ Painless Bleeding: Abrupt, painless, and massive bleeding is
Gastrointestinal bleeding is the most common GI condition leading to hospitalization
highly characteristic of colonic diverticular bleeding.
and can present as either overt bleeding (visible blood) or occult bleeding (hidden
○​ Change in Bowel Habits/Systemic Symptoms: Weight loss,
blood manifesting as anemia or positive fecal tests).
early satiety, or altered bowel habits with hematochezia raises
2.1. Approach in the history the suspicion for upper or lower GI malignancies (e.g., gastric or
colorectal cancer). Bloody diarrhea with tenesmus and fever
A meticulous history is paramount, as many patients may bleed without any points to inflammatory bowel disease (IBD) or infectious colitis.
preceding warning signs, and initial laboratory tests (like hemoglobin) may be
deceptively normal since it takes up to 72 hours for extravascular fluid to enter the 2.2. Character of stool; definition of terms: melena, hematochezia
vascular space and drop the hemoglobin level. The history should focus on
The visual character of the stool provides immense localizing value:
identifying hemodynamic instability, potential bleeding sources, and risk factors.
●​ Melena: Defined as black, tarry stool. Melena indicates that blood has been
●​ Assessment of Hemodynamic Compromise: The history should
present in the gastrointestinal tract for at least 14 hours, and it can
immediately seek symptoms of acute blood loss, such as
continue to pass for as long as 3 to 5 days after the bleeding stops.
lightheadedness, syncope, angina, or dyspnea. Syncope is a heavily
●​ Hematochezia: Defined as the passage of red or maroon blood from the
weighted risk factor in assessing the severity of a bleed.
rectum.
●​ Medication History: This is a critical component of the evaluation.
●​ Minor/Anal Bleeding: Bright red blood that is passed with, or coating,
○​ NSAIDs and Aspirin: Nonsteroidal anti-inflammatory drugs
formed brown stool, or blood seen only on toilet paper, usually indicates a
(NSAIDs) are the most common cause of peptic ulcer disease
local anal, rectal, or sigmoid source, such as internal hemorrhoids or
(PUD), which accounts for ~50% of upper GI bleeding (UGIB)
anal fissures.
hospitalizations. Up to 50% of chronic NSAID users develop
●​ Occult Bleeding: Right-sided colon cancers (cecum and ascending
gastric erosions.
colon) commonly ulcerate and lead to insidious, chronic blood loss without
○​ Anticoagulants/Antiplatelets: Increased use of these medications
any visible change in the appearance of the stool, presenting only as
significantly elevates the risk of severe bleeding, particularly for
iron-deficiency anemia.
conditions like diverticular bleeding and vascular ectasias.
●​ Comorbidities and Past Medical History: 2.3. Clues in the history that will help differentiate upper and lower GI bleeding
○​ Liver Disease/Cirrhosis: A history of hepatic disease or
alcoholism strongly points to bleeding from esophageal or gastric Differentiating between an Upper GI Bleed (UGIB) and a Lower GI Bleed (LGIB) relies
varices, or portal hypertensive gastropathy. on synthesizing stool characteristics, hemodynamic status, and accompanying
○​ Cardiovascular Disease: A history of aortic stenosis coupled symptoms:
with GI bleeding suggests Heyde's syndrome (bleeding from
vascular ectasias). ●​ The Rule of Localization by Stool Character:
 ○​ Hematemesis (vomiting of red blood or "coffee-grounds" material) 3.1.1. Inspection, auscultation, percussion, palpation
definitively isolates the bleeding to an upper GI source
(esophagus, stomach, or duodenum). ●​ Inspection: A simple, critical inspection of the patient’s general
○​ Melena usually indicates an upper GI source, because the more appearance, facies, position in bed, and respiratory activity provides
proximal the bleeding site, the more likely the blood will degrade valuable clues. For instance, a patient with peritonitis typically lies
into melena. However, in older patients with slow colonic transit, completely still, while a patient with colicky pain may thrash around. The
bleeding from the small bowel or the right colon can also abdomen should be inspected for distention (suggesting obstruction,
present as melena. neoplasm, or ascites) or vascular abnormalities seen in liver disease. In
○​ Hematochezia usually represents a lower GI source (~85% of severe cases, such as necrotizing pancreatitis with hemorrhage,
cases). inspection may reveal Cullen's sign (a faint blue discoloration around the
●​ The Exception to the Rule (Massive UGIB): Hematochezia can occur from umbilicus) or Turner's sign (a blue-red-purple or green-brown discoloration
an upper GI source if the lesion bleeds so briskly that the blood transits the of the flanks).
entire bowel rapidly before it can be degraded into melena. Clues that ●​ Auscultation: Auscultation is used to detect bruits or friction rubs
hematochezia is actually an upper GI bleed include: associated with vascular disease or hepatic tumors. The quality and
○​ Concomitant hemodynamic instability (hypotension, severe frequency of bowel sounds are also assessed: a loss of bowel sounds
tachycardia). signifies an ileus, whereas high-pitched, hyperactive sounds are
○​ Rapidly dropping hemoglobin levels. characteristic of intestinal obstruction. However, auscultation is generally
○​ Hyperactive bowel sounds. considered one of the least revealing aspects of the abdominal exam;
○​ An elevated Blood Urea Nitrogen (BUN) level. catastrophic events, such as a strangulating small-intestinal obstruction
●​ BUN as a Differentiator: An elevated BUN is a strong clue for an UGIB. or a perforated appendix, can paradoxically occur in the presence of
It occurs due to a combination of intravascular volume depletion and the normal peristaltic sounds.
absorption of blood proteins as they transit through the small intestine. ●​ Percussion: Percussion is utilized to assess liver size and detect shifting
●​ Nasogastric Aspirate Caveats: If a nasogastric (NG) tube is placed, a dullness, which indicates the presence of ascites. Importantly, it is also a
nonbloody aspirate does not exclude an UGIB; this is seen in ~15% of highly effective and gentle method for eliciting signs of peritoneal
UGIB patients who present with severe hematochezia. Furthermore, a inflammation.
bile-stained appearance in the aspirate does not rule out UGIB, as ●​ Palpation: Palpation is used to assess for hepatosplenomegaly and to
reports of bile are incorrect in about half of all cases. detect neoplastic or inflammatory masses. It helps the clinician
●​ Age and Demographic Clues (Asian Context): differentiate between generalized visceral discomfort and localized
○​ If an elderly patient (>60 years) presents with abrupt, painless parietal pain accompanied by involuntary guarding or rigidity.
hematochezia, diverticular disease is the most likely cause. Of
3.1.2. Importance of doing auscultation before palpation While the sources do
note for the Asian and Philippine context: While diverticular bleeds
not explicitly dictate the sequence of the exam steps, they strongly emphasize the
stop spontaneously in 90% of Western patients, the rates of
catastrophic effects of aggressive palpation on the rest of the clinical
severe rebleeding are substantially higher in Asian populations.
assessment. Once a patient with peritoneal inflammation has been examined
○​ Painless, chronic, or occult lower GI bleeding in a patient >70
brusquely or deeply palpated, accurate assessment by the examiner becomes
years old strongly suggests vascular ectasias.
almost impossible. Aggressive palpation startles the patient and induces
3. Perform a targeted physical examination voluntary muscle spasm, which becomes superimposed on involuntary muscular
rigidity, potentially obscuring findings (such as a palpable gallbladder) and altering
The amount of information a clinician can glean from a physical examination is the natural state of the abdomen. Therefore, listening to the abdomen must be done
directly proportional to their gentleness and thoroughness. before the bowel's natural motility is disrupted or before defensive muscle guarding
is provoked by the clinician's hands.
3.1. Cardinal methods of examining the abdomen
3.1.3. Eliciting direct and rebound tenderness ●​ Detecting Malignancy: A DRE can detect a palpable pelvic mass (known
as a Blumer's shelf), which is a classic sign of metastatic spread from
●​ Direct Tenderness: The entire abdomen should be examined upper GI cancers, such as gastric adenocarcinoma.
systematically, explicitly starting in an area where the patient does not ●​ Assessing Fecal Incontinence: For patients presenting with functional
report discomfort. The clinician must palpate very gently, as aggressive bowel complaints or fecal incontinence, the DRE allows the clinician to
pressing can mask underlying pathology through induced muscle spasm. If assess sphincter tone. A weak sphincter tone and the loss of the "anal
the pain is of the abdominal wall rather than intra-abdominal, asking the wink" reflex (S1-level control) are critical clues pointing to a neurogenic
patient to perform a Valsalva maneuver or a leg lift will exacerbate the dysfunction as the root cause of the incontinence.
tenderness.
●​ Rebound Tenderness: Historically, rebound tenderness was elicited by the 5. Understand the indications of endoscopy and imaging studies
sudden release of a deeply palpating hand. However, this maneuver is now
considered cruel and unnecessary in a patient with suspected peritonitis. 5.1. Upper and lower GI endoscopy
Forceful demonstration of rebound tenderness will startle a nervous or
●​ Upper Endoscopy (Esophagogastroduodenoscopy or EGD): EGD is the
worried patient, inducing a protective muscle spasm even when true
optimal method for examining the upper GI mucosa. It is superior to
rebound tenderness is not present. Instead, the exact same clinical
barium radiography for detecting gastric ulcers and flat mucosal
information can be obtained much more humanely via:
lesions, such as Barrett's esophagus.
1.​ Gentle percussion of the abdomen, which creates rebound
○​ Diagnostic indications: Persistent or treatment-refractory
tenderness on a miniature, precise, and localizing scale.
dyspepsia, new-onset dyspepsia in patients older than 50 or with
2.​ Asking the patient to cough, which elicits true rebound tenderness
"alarm" features (weight loss, iron-deficiency anemia,
without the clinician even needing to place a hand on the
obstructive symptoms), dysphagia, upper GI bleeding,
abdomen. Alternatively, jiggling the patient's bed or bumping
malabsorption, and to biopsy radiologic abnormalities. It is also
their feet can gently elicit signs of parietal peritoneal irritation.
crucial for evaluating patients with a long-standing history (≥10
4. Know the importance of a digital rectal examination (DRE) years) of gastroesophageal reflux disease (GERD) to screen for
Barrett's esophagus.
A digital rectal examination (and pelvic examination in females) is absolutely ○​ Therapeutic indications: Hemostasis of bleeding ulcers or varices,
mandatory in every patient presenting with abdominal pain. Its importance cannot dilation of peptic or malignant strictures, removal of impacted
be overstated for the following reasons: food or foreign bodies, placement of stents, and endoscopic
mucosal resection (EMR) or submucosal dissection (ESD) for
●​ Detecting "Hidden" Peritonitis: Abdominal signs may be minimal or dysplasia or early cancer.
completely absent in cases of pelvic peritonitis. An inflamed appendix ●​ Colonoscopy: This is the gold standard for imaging the colonic mucosa.
located retrocecally or deep below the pelvic brim may cause very little ○​ Diagnostic indications: Colorectal cancer screening and
tenderness on the anterior abdominal wall. In these patients, the only surveillance, evaluation of lower GI bleeding, chronic diarrhea,
physical sign of a surgical emergency like a perforated appendix, pelvic unexplained iron-deficiency anemia, and evaluation of
diverticulitis, or a twisted ovarian cyst may be exquisite tenderness radiographic abnormalities. It is significantly more sensitive than a
elicited during a rectal or pelvic examination. barium enema for detecting colitis, colon polyps, and early
●​ Evaluating GI Bleeding: DRE is a critical step in assessing patients with GI colorectal cancer.
bleeding to confirm the presence of melena (black, tarry stool) or ○​ Therapeutic indications: Polypectomy, palliation of neoplasms,
hematochezia (red/maroon blood). Even trivial amounts of red blood foreign body removal, and placement of stents across stenotic
found on toilet tissue demand a digital examination and anoscopy to check lesions.
for internal/external hemorrhoids, anal fissures, or rectal masses. ●​ Flexible Sigmoidoscopy: Visualizes only the rectum and a variable
portion of the left colon (typically up to 60 cm from the anal verge). It is
 primarily indicated for evaluating chronic diarrhea, rectal outlet bleeding, ○​ Transabdominal US: The recommended initial diagnostic imaging
and can be used in some colorectal cancer screening protocols because modality for evaluating the hepatobiliary system. It is highly
it can be performed quickly without sedation. sensitive for diagnosing gallstones, acute cholecystitis, and
●​ Small-Bowel Endoscopy: common bile duct dilation. It also screens for hepatocellular
○​ Capsule Endoscopy: Indicated for evaluating obscure GI bleeding carcinoma (HCC) in high-risk cirrhotic patients. It is limited,
(where EGD and colonoscopy are negative), providing positive however, by severe obesity and excessive intestinal gas.
findings like vascular ectasias in 50–70% of cases. It is also used ○​ Endoscopic Ultrasound (EUS): Provides high-resolution transmural
for detecting small-intestinal Crohn's disease and tumors. images of the gut wall and adjacent organs. It is indicated for the
○​ Push and Balloon-Assisted Enteroscopy (Single- or most accurate preoperative local staging of esophageal,
Double-Balloon): Indicated when deeper intubation of the small gastric, pancreatic, and rectal malignancies. It is also highly
intestine is required following capsule endoscopy. It allows for accurate for diagnosing common bile duct stones
direct biopsy of suspicious small-intestinal masses or ulcers (choledocholithiasis), gallbladder disease, subepithelial
and therapeutic interventions, such as thermal ablation (argon lesions, chronic pancreatitis, and for guiding fine-needle
plasma coagulation) of bleeding vascular ectasias and aspiration (FNA).
polypectomy. ●​ Computed Tomography (CT) Scan:
○​ Indications: Crucial for evaluating organs and regions
5.2. Barium swallow, Barium enema inaccessible to endoscopy. It is highly accurate for diagnosing
acute appendicitis, intestinal obstruction, perforated viscus,
●​ Barium Swallow / Esophagography:
intraabdominal abscesses, and for the staging of
○​ Indications: It is the best initial diagnostic test when transfer
intraabdominal malignancies.
(oropharyngeal) dysphagia or an esophageal motility disorder
○​ Specific Protocols: Multiphasic CT with intravenous contrast is
(e.g., achalasia, diffuse esophageal spasm) is suspected. It
indicated for the staging of pancreatic cancers and to identify
provides critical assessments of esophageal function, peristaltic
the typical hypervascular "washout" hallmark of HCC. CT
integrity, and morphology that endoscopy might miss. It is also
enterography evaluates small-bowel thickening, stricturing, and
indicated to evaluate structural defects like Zenker's diverticulum,
fistulas in inflammatory bowel disease (IBD). CT angiography is
tracheoesophageal fistulas, extrinsic esophageal
used to identify the source of severe lower GI or obscure
compression, or altered postsurgical anatomy.
small-intestinal bleeding.
○​ Limitations: While its sensitivity for detecting strictures is high
○​ Pancreatitis: CT imaging is generally not recommended in the
(especially when using a 13-mm barium tablet), its overall
first 48–72 hours of mild acute pancreatitis, but it is indicated
sensitivity for detecting reflux esophagitis ranges widely (22 to
after 3-5 days to evaluate for local complications, such as
95%) and it rarely obviates the need for a subsequent EGD to
pancreatic necrosis or fluid collections.
obtain biopsies or provide therapy.
●​ Magnetic Resonance Imaging (MRI):
●​ Barium Enema:
○​ Indications: Excellent for noninvasive, detailed evaluation of the
○​ Indications: Historically used to evaluate the colon and identify
pancreatic parenchyma, soft tissues, and vascular structures
occult blood sources, but it has largely been replaced by
without ionizing radiation. MRI with Magnetic Resonance
colonoscopy. It is now primarily indicated when a colonoscopy is
Cholangiopancreatography (MRCP) has largely replaced
unsuccessful or physically contraindicated.
diagnostic Endoscopic Retrograde Cholangiopancreatography
5.3. Ultrasonography; CT scan / MRI (ERCP) for evaluating the biliary and pancreatic ducts; it is the first
choice to assess for choledocholithiasis, strictures, and
●​ Ultrasonography (US): pancreatic cystic neoplasms. MRI is also highly specific for
 characterizing liver tumors, such as focal nodular hyperplasia ○​ Philippine Context regarding Lower GI Neoplasms: Biopsies and
and hepatocellular adenomas. early detection of colorectal cancer are particularly critical in
developing or under-resourced regions. While survival rates in
6. Identify the indications for biopsy Europe, Japan, and Australia are ~60%, overall 5-year survival
rates for colorectal cancer are notably lower in the Philippines
Biopsies are essential for definitive histopathologic diagnoses, particularly to
(along with China, India, and Thailand), ranging from only 30% to
distinguish benign from malignant conditions or to isolate specific inflammatory and
42%. This underscores the critical need for prompt endoscopic
infectious etiologies.
biopsy when symptoms like iron-deficiency anemia or
●​ Upper GI Tract: hematochezia arise.
○​ Gastric Ulcers: Because gastric ulcers can represent a ●​ Liver, Pancreas, and Extraintestinal Masses:
malignancy, they must be biopsied upon discovery. Even if initial ○​ Liver Biopsy: Indicated to confirm chronic hepatitis, assess the
biopsies are negative, repeat endoscopy with biopsy is warranted extent of inflammatory activity (grade) and fibrosis (stage),
if the ulcer fails to heal. (Note: Duodenal ulcers are extremely evaluate unexplained jaundice, or rule out post-transplant
rarely malignant and do not strictly require biopsy for malignancy). rejection. Biopsy is also required to diagnose hepatocellular
○​ Barrett's Esophagus: Endoscopic biopsy is the gold standard to carcinoma (HCC) in patients without cirrhosis, or when a liver
confirm intestinal metaplasia and to assess for the presence of nodule (e.g., a LI-RADS 4 lesion) lacks the classic radiologic
low-grade dysplasia, high-grade dysplasia, or adenocarcinoma. features on both CT and MRI.
○​ Eosinophilic Esophagitis (EoE): Because the endoscopic ○​ EUS-Guided Fine-Needle Aspiration/Biopsy: Indicated for
appearance can be shared with GERD, mucosal biopsies obtaining diagnostic tissue from solid pancreatic masses,
demonstrating eosinophilic infiltration of the squamous evaluating cystic pancreatic lesions, assessing potentially
epithelium are absolutely required for diagnosis. malignant lymph nodes, and distinguishing autoimmune
○​ Infectious Esophagitis: Biopsies are indicated to differentiate pancreatitis from malignancy.
infectious causes, such as discovering the pathognomonic large
7.1. Diseases of the esophagus
nuclear/cytoplasmic inclusion bodies of Cytomegalovirus
(CMV) or testing for herpes simplex virus. 7.1.1. Inflammatory disorders
○​ Helicobacter pylori Infection: Gastric biopsy specimens are
utilized for rapid urease testing, histologic visualization (using [Link]. Gastroesophageal reflux disease (GERD) and esophagitis
Giemsa or silver stains), or culture to determine antibiotic
susceptibility. ●​ Pathophysiology: GERD is caused by excessive reflux of gastric juice
○​ Celiac Disease / Malabsorption: Duodenal biopsies are indicated (acid, pepsin, and bile) overwhelming the esophageal mucosal defenses.
to assess for celiac sprue when evaluating unexplained This occurs due to the breakdown of the esophagogastric junction's
iron-deficiency anemia or chronic diarrhea. anti-reflux barrier, driven by transient lower esophageal sphincter (LES)
●​ Lower GI Tract: relaxations, LES hypotension, anatomical distortion (such as a sliding
○​ Colitis / Diarrhea: Colonoscopic biopsies are indicated to hiatal hernia), and loss of the native flap valve. Delayed gastric emptying,
determine the etiology of colitis or ileitis (e.g., distinguishing abdominal obesity, and impaired esophageal clearance (due to weak
ulcerative colitis from Crohn's disease, diagnosing microscopic peristalsis or reduced salivation) exacerbate the exposure. The
colitis, evaluating ischemia, infection, or immune checkpoint inflammatory damage is cytokine-mediated, leading to erosions,
inhibitor-induced enterocolitis). ulcerations, or Barrett's metaplasia.
○​ Polyps and Neoplasms: Polyps detected during colonoscopy Step 1: Disruption of the Antireflux Barrier The normal esophagus is protected from the
must be removed/biopsied to assess for dysplastic changes, highly acidic gastric environment primarily by the gastroesophageal junction (GEJ), which acts
serrated histology, or progression to adenocarcinoma. as a complex valvular mechanism. This barrier depends on the intrinsic lower esophageal
sphincter (LES), the external pinch of the surrounding crural diaphragm, and the native ●​ Cytokine-Mediated Inflammation: Interestingly, current experimental evidence
subdiaphragmatic angle of His. Pathologic reflux, the first step in Gastroesophageal Reflux supports that esophagitis is not merely a direct caustic chemical burn to the
Disease (GERD), occurs when this architecture is anatomically or physiologically distorted: esophageal epithelium. Instead, the refluxate induces a cytokine-mediated
inflammatory pathway. This cascade leads to the infiltration of inflammatory cells,
●​ Transient LES Relaxations: While occasional LES relaxation is a normal physiologic causing microscopic tissue injury and macroscopic mucosal erosions or ulcers
mechanism to allow belching, patients with GERD often have increased compliance of characteristic of erosive esophagitis.
the GEJ. This leads to a wider sphincter opening during transient LES relaxations, ●​ Paradoxical Protective Factors: Interestingly, chronic Helicobacter pylori gastritis
causing a loss of the ability to prevent liquid from escaping along with gas. can occasionally have a protective effect against GERD. H. pylori can induce
●​ Anatomic Distortion and Hiatal Hernia: A breakdown of the diaphragmatic hiatus atrophic gastritis with concomitant hypoacidity; by lowering the acidity of the
and a diminished crural diaphragm sphincteric function severely compromises the stomach, the refluxate becomes less caustic to the esophagus.
barrier. This is often manifested as a sliding hiatal hernia (Type I), where the GEJ
and gastric cardia translocate cephalad into the mediastinum due to a weakened Step 5: Chronic Complications and Malignant Degeneration If the cycle of inflammatory
phrenoesophageal ligament. This leads to the loss of the intraabdominal esophageal injury and inadequate repair persists chronically, severe structural consequences emerge:
segment, completely disabling the native flap valve architecture. Furthermore, acidic
fluid retained within the hiatal hernia sac uniquely refluxes back into the esophagus ●​ Peptic Strictures: Chronic erosive esophagitis can lead to submucosal scarring and
during swallow-induced LES relaxation. fibrosis, creating mechanical narrowing (strictures) of the distal esophagus, which
●​ Basal LES Hypotension: A chronically weakened LES fails to prevent reflux during typically present as progressive solid food dysphagia.
moments of increased intraabdominal pressure, such as during inspiration or ●​ Barrett’s Esophagus (Metaplasia): In response to chronic acidic and biliary injury
straining. (typically lasting >10 years), the normal stratified squamous epithelium of the distal
esophagus is replaced by specialized intestinal-type columnar epithelium with goblet
Step 2: Exacerbation by Environmental and Physiologic Triggers Once the barrier is cells. Bile is heavily invoked as a specific cofactor in this metaplastic transformation.
compromised, reflux is exacerbated by several secondary factors: ●​ Esophageal Adenocarcinoma: Barrett’s metaplasia is a highly unstable tissue that
harbors a significantly increased risk of developing dysplasia and ultimately
●​ Increased Abdominal Pressure: Abdominal obesity, pregnancy, and gluttony progressing to esophageal adenocarcinoma. The incidence of this specific cancer has
physically force gastric contents upward. increased sixfold in recent decades, directly tracking with the rising incidence of
●​ Gastric Factors: Delayed gastric emptying or gastric hypersecretory states (such as GERD.
Zollinger-Ellison syndrome, where unregulated gastrin leads to massive acid
production) overwhelm the distal esophagus. Pharmacologic Considerations (Applicable to the Philippines Context) In the management
●​ Dietary and Chemical Triggers: The ingestion of fatty foods, alcohol, spearmint, of GERD, particularly within the Philippines and among broader Asian populations,
peppermint, coffee, and tea can inherently reduce LES pressure, making them highly pharmacogenetics plays a critical step in effective therapy. The mainstay of treating the
"refluxogenic". pathophysiology of GERD relies on Proton Pump Inhibitors (PPIs) such as omeprazole,
lansoprazole, or esomeprazole, which covalently bind to the H+,K+-ATPase pump to suppress
Step 3: Impaired Esophageal Clearance Normally, if acid enters the esophagus, primary and acid. When applying this to a Philippine/Asian demographic, it is highly relevant that Asians are
secondary peristaltic contractions rapidly return the fluid to the stomach. Following this significantly more likely to possess a specific CYP2C19 genotype that correlates with the
mechanical clearance, the residual acid is chemically neutralized by the bicarbonate contained slow hepatic metabolism of PPIs. Approximately 23% of Asians are slow metabolizers,
in swallowed saliva. In GERD, prolonged acid exposure occurs due to impaired peristaltic compared to only 3% of Caucasians or African Americans. Because PPIs are primarily
emptying (either from disrupted peristalsis or the presence of a hiatal hernia) and reduced metabolized by the hepatic cytochrome P450 system (particularly CYP2C19 and CYP3A4), this
salivation, which removes the crucial neutralizing capacity of bicarbonate. genetic variation can lead to delayed drug clearance, which may significantly heighten both the
therapeutic efficacy and the potential toxicity of standard PPI doses in Filipino patients.
Step 4: Cellular Injury and the Cytokine-Mediated Inflammatory Cascade (Esophagitis)
When clearance mechanisms fail, the esophageal epithelium is subjected to prolonged exposure ●​ Clinical Features: The classic symptoms are heartburn (pyrosis) and
to gastric juice.
regurgitation of sour or burning fluid, often worsened by recumbency or
●​ The Noxious Refluxate: While hydrochloric acid is highly damaging, it is not the only meals. Atypical or extraesophageal symptoms include noncardiac chest
destructive agent. Pepsin, pancreatic enzymes, and bile also play critical roles. Bile is pain, chronic cough, asthma, laryngitis, globus sensation, and dental
particularly insidious because it persists in the refluxate even when patients are taking erosions. Complications include dysphagia from peptic strictures or
acid-suppressing medications, and it can traverse the cell membrane to impart severe Barrett's esophagus.
cellular injury even in a weakly acidic environment.
 ●​ Diagnosis: Empirical diagnosis based on classic symptoms is common. becomes opportunistic and pathogenic, overgrowing and spreading into the
Upper endoscopy (EGD) is the test of choice to identify erosive esophagitis, esophagus.
strictures, or Barrett's esophagus, though it is normal in about two-thirds of ●​ Cytomegalovirus (CMV): Rather than a new infection, CMV esophagitis usually
results from the reactivation of a latent, pre-existing viral infection within the patient.
patients (nonerosive reflux disease). For atypical cases or refractory
●​ Herpesvirus: Herpes simplex virus (type 1 or 2) and Varicella-zoster virus can also
symptoms, ambulatory 24- to 96-hour esophageal pH/impedance
aggressively infect the esophagus in these patients.
monitoring is the gold standard to prove excess acid exposure.
●​ Management: Lifestyle modifications (weight reduction, elevating the head Step 3: Mucosal Invasion and Pathogen-Specific Cellular Injury The pathogens invade the
of the bed, avoiding late-night meals, and dietary triggers like fats, alcohol, esophageal mucosa, causing distinct patterns of tissue damage and ulceration depending on
and mint) are first-line. Pharmacotherapy relies heavily on Proton Pump the specific organism:

Inhibitors (PPIs) (e.g., omeprazole 20mg/day, lansoprazole 30mg/day), ●​ Fungal Pathophysiology (Candida): Candida invades the mucosal surface, leading
which are superior to H2-receptor antagonists and antacids for symptom to an inflammatory response characterized endoscopically by the formation of friable,
relief and mucosal healing. Baclofen or vonoprazan may be used in white plaques or thick exudates adhering to the esophageal lining.
refractory cases. For chronic or refractory GERD, laparoscopic ●​ Herpetic Pathophysiology (HSV): HSV specifically targets the squamous
fundoplication is an effective surgical option to restore the anatomical epithelium of the esophagus. The virus replicates within these cells, causing
barrier. cytopathic changes that include the formation of multinucleated giant cells,
ground-glass nuclei, and eosinophilic Cowdry’s type A inclusion bodies.
[Link]. Infectious esophagitis Macroscopically, this cellular destruction leads to the formation of mucosal vesicles
that eventually rupture, leaving behind small, superficial ulcerations.
●​ Pathophysiology: Infectious esophagitis primarily occurs in ●​ CMV Pathophysiology: In contrast to HSV, CMV tends to cause large, serpiginous
immunocompromised individuals (e.g., those with HIV/AIDS, organ (snake-like) ulcers, particularly located in the distal portion of the esophagus, often
transplants, or receiving chemotherapy), though Candida and Herpes surrounded by otherwise normal-appearing mucosa. At the cellular level, the virus
induces pathognomonic large nuclear or cytoplasmic inclusion bodies, typically found
Simplex Virus (HSV) can occasionally infect immunocompetent hosts.
at the bases of the ulcers.
Candida can also infect an esophagus with stasis due to motility
disorders. Step 4: Clinical Manifestation and Functional Impairment The culmination of this acute
mucosal inflammation, epithelial destruction, and deep ulceration leads to severe localized
Step 1: Disruption of Host Defenses or Esophageal Clearance Unlike other forms of symptoms.
esophagitis, infectious esophagitis is relatively rare in healthy individuals and almost always
begins with a breakdown of the host's systemic immune system or local esophageal defenses. ●​ The hallmark symptom of infectious esophagitis is odynophagia (severe pain caused
by or exacerbated by swallowing), which is a direct physiologic consequence of food
●​ Systemic Immunosuppression: The disease is most commonly triggered by or liquid passing over the raw, ulcerated, and inflamed tissues.
immunocompromised states, particularly the AIDS epidemic (where risk increases as ●​ The extensive inflammation and mucosal damage can also cause dysphagia (difficulty
the CD4 count declines), the use of chemotherapy, or immunosuppressive therapies swallowing), chest pain, and, because the ulcerations can erode into subepithelial
for organ transplantation and chronic inflammatory diseases. blood vessels, esophageal hemorrhage.
●​ Local Esophageal Stasis: In addition to systemic immunodeficiency, local structural
or functional abnormalities, such as esophageal stasis caused by esophageal motor
disorders or the presence of diverticula, can predispose the esophagus to infection,
particularly by fungal organisms. ●​ Clinical Features: The hallmark symptom is odynophagia (painful
swallowing), which is uniquely distinct from GERD. Dysphagia, chest pain,
Step 2: Pathogen Introduction, Overgrowth, or Reactivation Once the host's defenses are
and upper GI hemorrhage can also occur. Concomitant oral thrush or oral
lowered, the specific offending pathogen—most commonly Candida species, Herpes Simplex
herpetic vesicles strongly suggest the etiology.
Virus (HSV), or Cytomegalovirus (CMV)—initiates the infection.
●​ Diagnosis: Endoscopy with biopsy is paramount. Candida presents as
●​ Candida albicans: This fungus is normally found as a commensal organism in the white plaques, exudates, and friability. HSV presents with vesicles and
throat. However, in a compromised host or in the setting of esophageal stasis, it small, superficial ulcerations; biopsies show multinucleated giant cells
and eosinophilic Cowdry's type A inclusion bodies. Cytomegalovirus
 (CMV) presents as large, serpiginous ulcers in the distal esophagus, The uncoordinated oral cavity allows the bolus to slip backward into the hypopharynx before the
with pathognomonic large nuclear or cytoplasmic inclusion bodies. central pharyngeal swallow response has been safely and properly triggered to protect the
●​ Management: airway.

○​ Candida: Oral fluconazole (400 mg on day 1, then 200 mg daily) Step 4: Pharyngeal Phase Failure and Bolus Retention If the bolus does reach the pharynx,
for 7–14 days. Refractory cases require itraconazole, the rapid pharyngeal phase (which normally takes less than a second) fails to execute properly.
posaconazole, or IV echinocandins. Normal pharyngeal clearance relies on the pharyngeal muscles (innervated by the
○​ HSV: Acyclovir (200 mg 5x/day or IV 5 mg/kg every 8h for severe glossopharyngeal and vagus nerves) to propel the food while the larynx is elevated and pulled
cases), famciclovir, or valacyclovir for 14-21 days in forward to facilitate the opening of the upper esophageal sphincter (UES). Due to paralysis,
compromised hosts. there is poor tongue and pharyngeal propulsion, and the necessary laryngeal elevation may
not occur. This results in the severe retention of food within the pharynx and a functional
○​ CMV: IV ganciclovir (5 mg/kg every 12 h) or oral valganciclovir
obstruction at the level of the UES.
for 3-6 weeks.
Step 5: Airway Compromise and Bolus Misdirection (Transfer Dysphagia) The ultimate and
7.1.2. Motor disorders most dangerous pathophysiologic consequence of oropharyngeal paralysis is the failure to
safely transfer the bolus from the mouth to the esophagus while protecting the respiratory tract,
[Link]. Involving striated muscle
a condition known as transfer dysphagia. Because the paralyzed structural mechanisms
cannot adequately seal off the nasopharynx or the trachea, the retained or prematurely spilled
●​ [Link].1. Oropharyngeal paralysis
food and liquids are misdirected. This manifests physiologically as nasal regurgitation (food or
○​ Pathophysiology: The oral cavity, pharynx, and upper esophageal
liquid leaking out of the nose) or pulmonary aspiration into the trachea, which is frequently
sphincter (UES) consist of striated muscle innervated directly by marked by a severe, swallow-induced cough. Over time, this chronic aspiration and inability to
cranial nerves V, VII, IX, X, and XII. Paralysis results from clear the pharynx leads to severe morbidity, including malnutrition and recurrent aspiration
neurogenic or myogenic disorders, such as stroke, Parkinson's pneumonia.
disease, Amyotrophic Lateral Sclerosis (ALS), myasthenia
gravis, or polymyositis.

Step 1: Neuromuscular Insult and Loss of Innervation The pathophysiology of oropharyngeal ○​ Clinical Features: Manifests as oropharyngeal (transfer)
paralysis (often presenting clinically as bulbar palsy, pseudobulbar palsy, or neurogenic dysphagia. Symptoms include poor bolus control, drooling,
oropharyngeal dysphagia) begins with damage to the central or peripheral nervous system. The difficulty initiating swallowing, nasal regurgitation, and
normal swallow response is centrally mediated by medullary nuclei that directly innervate the tracheobronchial aspiration (manifesting as coughing or choking
oropharynx, but it is also highly dependent on the cerebral cortex. An insult such as a unilateral during swallowing).
cortical cerebrovascular accident (stroke) can cause paralysis due to asymmetry in the cortical ○​ Diagnosis: A fluoroscopic video-swallow study is the gold
representation of the pharynx. Other common neurogenic and myogenic triggers for this
standard to assess transfer mechanics and aspiration.
paralysis include Parkinson's disease, amyotrophic lateral sclerosis (ALS), brainstem tumors,
○​ Management: Directed by swallow therapists, using posture
multiple sclerosis, myasthenia gravis, and polymyositis.
alteration, head positioning, and dietary consistency
Step 2: Impairment of the Oral Phase (Bolus Formation and Control) Normal swallowing modifications. Severe cases may require enteral feeding via
begins with a voluntary oral phase where food is masticated, mixed with saliva, and pushed into gastrostomy. Underlying conditions like myasthenia gravis must
the pharynx by the tongue. In oropharyngeal paralysis, there is a functional failure of the muscles be medically treated.
of the oral cavity (innervated by the trigeminal and facial cranial nerves) and the tongue
●​ [Link].2. Cricopharyngeal bar
(innervated by the hypoglossal cranial nerve). This muscular weakness or paralysis results in
○​ Pathophysiology: A structural/functional anomaly caused by the
poor bolus formation and a profound loss of bolus control. Consequently, food is subjected
to prolonged retention within the oral cavity. Patients classically present with drooling, seepage limited distensibility of the cricopharyngeus muscle (part of the
of food out of the mouth, and a severe difficulty in simply initiating the act of swallowing. UES). It is often secondary to neuromuscular disorders impairing
UES opening. It leads to increased hypopharyngeal pressure,
Step 3: Premature Spillage into the Hypopharynx Because the paralyzed tongue and oral potentially giving rise to Zenker's diverticulum.
musculature cannot securely hold the food or liquid bolus in place, premature spillage occurs.
Step 1: Normal Physiology and the Upper Esophageal Sphincter (UES) To understand the ○​ Diagnosis: Best visualized on rapid-sequence barium swallow
formation of a cricopharyngeal bar, it is first necessary to understand the normal function of the radiography or fluoroscopy, showing a prominent posterior
upper esophageal sphincter (UES). The UES is physiologically composed of the indentation at the level of the cricoid cartilage.
cricopharyngeus muscle, the adjacent inferior pharyngeal constrictor, and the proximal portion
○​ Management: Treated by surgical or endoscopic
of the cervical esophagus. At rest, the UES remains closed to protect the airway, maintained by
cricopharyngeal myotomy when highly symptomatic.
the inherent elastic properties of the tissue and the neurogenically mediated contraction of the
cricopharyngeus muscle via the vagus nerve. During a normal swallow, the UES must open to ●​ [Link].3. Globus pharyngeus
allow the food bolus to pass. This opening requires both the cessation of vagal excitation to the ○​ Pathophysiology: Often tied to visceral hypersensitivity or
cricopharyngeus (allowing it to relax) and the simultaneous contraction of the suprahyoid and abnormal UES function. It frequently occurs in the setting of
geniohyoid muscles, which actively pull the larynx upward and forward to pull the UES open. anxiety or obsessive-compulsive disorders ("globus
Step 2: Cricopharyngeal Dysfunction (Spasm or Stenosis) The pathophysiology of a hystericus"), though clinical experience strongly links it to
cricopharyngeal bar begins with a functional or structural failure of the cricopharyngeus muscle underlying GERD.
to properly relax and distend during swallowing. This dysfunction manifests as limited
distensibility, stenosis, or frank spasm of the cricopharyngeus muscle. In some cases, this Step 1: The Perceptual Phenomenon and Absence of True Dysphagia The pathophysiology
muscular dysfunction is secondary to other underlying neuromuscular disorders that impair the of globus pharyngeus (also commonly referred to as globus sensation) begins as a distinct
carefully coordinated opening mechanisms of the UES. sensory misperception rather than a mechanical blockage. The patient experiences a persistent
Step 3: Luminal Indentation (Formation of the "Bar") Because the cricopharyngeus muscle feeling of a lump, fullness, or a foreign body that is localized in the neck or throat. A defining
fails to adequately yield to the approaching food bolus, it creates a physical restriction in the pathophysiologic feature of this condition is that the sensation occurs irrespective of swallowing
luminal space. On radiographic imaging (such as a barium swallow), this restriction appears as a and does not actually interfere with the mechanical transit of food or liquid. Paradoxically,
prominent indentation located just behind the lower third of the cricoid cartilage. This visible the uncomfortable lump sensation is often temporarily relieved by the active act of swallowing.
indentation is what clinicians refer to as the "cricopharyngeal bar". It is worth noting that while it
is a common radiographic finding, many transient cricopharyngeal bars remain entirely Step 2: Absence of Structural or Primary Motility Defects (Functional Classification) For a
asymptomatic. diagnosis of a pure functional globus disorder, the pathophysiology relies on the distinct
Step 4: Increased Hypopharyngeal Pressure When the bar becomes significant, it acts as a absence of structural lesions or major primary esophageal motility disorders (such as
functional outflow obstruction. As the pharyngeal constrictor muscles actively propel the food achalasia). When standard diagnostic esophageal testing is performed, the results are typically
bolus downward against this unyielding, stenotic, or spastic cricopharyngeus muscle, the negative, confirming that the feeling of a lump is generated without any actual physical mass,
generated force has nowhere to easily escape. This dynamic results in a dramatic increase in stricture, or overt mucosal destruction.
intraluminal pressure within the hypopharynx immediately above the level of the obstruction.
Step 5: Structural Failure and Pulsion Diverticulum (Zenker's Diverticulum) Over time, the Step 3: Triggering by Local Physiologic Irritants (GERD and UES Dysfunction) Despite its
chronically increased hypopharyngeal pressure takes a mechanical toll on the surrounding classification as a functional disorder, clinical experience dictates that the globus sensation is
tissues. The continuous high pressure causes the mucosal and submucosal layers to gradually frequently instigated by localized physiologic irritants. The most common underlying cause is
herniate outward through the muscular layer of the esophagus. This typically occurs in a specific Gastroesophageal Reflux Disease (GERD). When gastric acid refluxes into the esophagus, it
region of natural anatomic weakness located immediately proximal to the cricopharyngeus can irritate the local mucosal nerve endings, which the brain misinterprets as a retained lump in
muscle, known as Killian’s triangle. This pressure-driven herniation creates a "pulsion the throat. Additionally, dysfunction of the Upper Esophageal Sphincter (UES)—such as
diverticulum," classically known as a Zenker's diverticulum. abnormal resting tone or uncoordinated relaxation—can mechanically manifest as a persistent
Step 6: Clinical Manifestations As the cricopharyngeal bar worsens and a diverticulum fullness or foreign body sensation in the neck.
potentially forms and enlarges, patients transition from being asymptomatic to experiencing
Step 4: Visceral Hypersensitivity and Central Nervous System Dysregulation If overt acid
severe clinical consequences. They classically present with progressive oropharyngeal
reflux and UES dysfunction are excluded, the core pathophysiology shifts to the nervous
dysphagia (difficulty swallowing). If a Zenker's diverticulum develops, the pouch can retain food
system. Globus is driven by altered central mechanisms and visceral hypersensitivity. In
and saliva, leading to the regurgitation of particulate, undigested food debris, severe halitosis
these patients, the central nervous system abnormally processes normal, baseline physiological
(bad breath), and a high risk of potentially life-threatening pulmonary aspiration.
stimuli or minor motor events within the esophagus. This central dysregulation magnifies normal
sensations into the bothersome perception of a foreign body. Because the defect lies within
○​ Clinical Features: While often an asymptomatic radiographic
central pain and sensory processing pathways, neuromodulating medications such as
finding, a symptomatic bar causes transfer dysphagia. gabapentin or pregabalin are often utilized to blunt this hypersensitivity.
Step 5: Psychogenic Amplification and Affective Disorders The final step in the ○​ Management: No cure exists; treatment targets reducing LES
pathophysiologic cascade is the profound modulation of the symptom by psychological and tone. Pharmacological options (nitrates, calcium channel blockers,
emotional states. Historically referred to by the alternative name "globus hystericus," this Botox injections) are temporizing. Durable therapies include
sensation is intimately linked to affective disorders. Globus frequently occurs or is severely
pneumatic balloon dilation, Laparoscopic Heller myotomy with
exacerbated in the setting of anxiety, psychological stress, or obsessive-compulsive
partial fundoplication, or Peroral Endoscopic Myotomy (POEM).
disorders. These psychiatric and affective conditions likely lower the central nervous system's
sensory threshold, amplifying the visceral hypersensitivity and locking the patient into the ●​ [Link].2. Diffuse esophageal spasm (DES)
persistent perception of a throat lump despite a structurally normal anatomy. ○​ Pathophysiology: A rare disorder characterized by impairment of
inhibitory myenteric plexus neurons, leading to premature,
○​ Clinical Features: The perception of a lump, fullness, or foreign rapid, and uncoordinated ("spastic") contractions of the distal
body sensation localized in the neck. Crucially, it is felt irrespective esophageal smooth muscle, but with normal LES relaxation.
of swallowing and is sometimes transiently relieved by the act of ○​ Clinical Features: Episodic dysphagia to solids and liquids and
swallowing. nonexertional, squeezing chest pain that mimics angina pectoris.
○​ Diagnosis: A diagnosis of exclusion. EGD and functional tests ○​ Diagnosis: High-resolution manometry is required,
rule out strictures, achalasia, or GERD. demonstrating normal LES relaxation but short-latency,
○​ Management: Empirical PPI therapy is typically used initially. If premature distal esophageal contractions. Barium swallow may
unresponsive, neuromodulators like gabapentin or pregabalin are show a "corkscrew" or "rosary bead" appearance. Cardiac
prescribed. ischemia must be ruled out first.
○​ Management: Nitrates, calcium channel blockers, hydralazine,
[Link]. Involving smooth muscle
botulinum toxin, and anxiolytics are utilized with mixed results. In
●​ [Link].1. Achalasia intractable cases with severe weight loss, POEM or surgical distal
○​ Pathophysiology: Autoimmune-mediated degeneration of myotomy is considered.
inhibitory nitric oxide-producing ganglion cells in the ●​ [Link].3. Scleroderma
esophageal myenteric plexus. This results in two hallmark ○​ Pathophysiology: Infiltration and destruction of the esophageal
deficits: incomplete LES relaxation and aperistalsis of the muscularis propria with collagen deposition and fibrosis,
smooth muscle esophagus. Secondary pseudoachalasia can be accompanied by a reduction in the interstitial cells of Cajal. This
caused by tumors or Chagas disease. (Philippines context: causes profound hypotensive LES pressure and completely
Chagas disease is endemic to South America via the reduviid bug, absent esophageal contractility.
making Trypanosoma cruzi an unlikely cause of secondary ○​ Clinical Features: Mild dysphagia to solids that is often
achalasia in Filipino patients.) alleviated by standing upright or using liquid to wash food
○​ Clinical Features: Progressive solid and liquid food dysphagia, down. It produces incredibly severe GERD because the anti-reflux
regurgitation of undigested food (often nocturnal), difficulty barrier is destroyed, and the aperistaltic esophagus cannot clear
belching, and squeezing chest pain. Weight loss is common, refluxed acid.
and chronic stasis can lead to aspiration pneumonia and a ○​ Diagnosis: Esophageal manometry shows absent peristalsis with
highly increased risk of squamous cell carcinoma. a weak LES.
○​ Diagnosis: Barium swallow reveals a dilated esophagus with ○​ Management: Aggressive, lifelong PPI therapy for severe GERD,
poor emptying, an air-fluid level, and "beak-like" tapering at the and endoscopic dilation of peptic strictures.
LES. High-resolution manometry is the most sensitive test,
7.1.3. Other esophageal diseases
demonstrating absent peristalsis and impaired LES relaxation.
Endoscopy is required to rule out pseudoachalasia caused by a ●​ [Link]. Diverticula
mass at the cardia. ○​ Pathophysiology: Outpouchings of the esophageal wall. False
diverticula (Zenker's and epiphrenic) involve herniation of
 mucosa and submucosa through the muscularis due to high ○​ Clinical Features: Sliding hernias are usually asymptomatic but
intraluminal pressure from a distal obstruction (e.g., heavily predispose the patient to GERD by lowering LES pressure
cricopharyngeal bar for Zenker's, or achalasia for epiphrenic). True and retaining acidic fluid. Large paraesophageal hernias can cause
diverticula (midesophageal) involve all layers and are often an "upside-down stomach," leading to gastric volvulus,
caused by traction from adjacent mediastinal inflammation. strangulation, or obstruction.
(Philippines context: In the Philippines, high rates of endemic ○​ Diagnosis: Endoscopy or barium contrast radiography.
tuberculosis frequently cause granulomatous mediastinal ○​ Management: Sliding hernias are treated medically with PPIs if
lymphadenitis, which can scar and pull on the esophagus, resulting GERD is present. Symptomatic or large paraesophageal hernias
in traction midesophageal diverticula.) require surgical repair to prevent strangulation.
○​ Clinical Features: Often asymptomatic. Zenker's can cause ●​ [Link]. Mechanical trauma
progressive cervical dysphagia, regurgitation of foul-smelling, ○​ Pathophysiology: Includes instrumental perforation,
undigested food, halitosis, and aspiration. spontaneous rupture (Boerhaave's syndrome from forceful
○​ Diagnosis: Barium radiography is the best diagnostic modality. retching), Mallory-Weiss tears (non-transmural mucosal rents at
Endoscopy must be performed gently to avoid blindly entering and the GE junction from retching), caustic ingestion, and pill
perforating a Zenker's pouch. esophagitis (local chemical injury from lodged medications like
○​ Management: Symptomatic Zenker's and epiphrenic diverticula doxycycline or NSAIDs).
are treated surgically (diverticulectomy and myotomy) or via ○​ Clinical Features:
endoscopic septotomy (POEM/diverticulotomy). ■​ Perforation/Boerhaave's: Severe pleuritic retrosternal
●​ [Link]. Webs and rings pain, pneumomediastinum, and subcutaneous
○​ Pathophysiology: Webs are uncommon, thin, ledge-like emphysema.
semi-circumferential mucosal protrusions, usually in the ■​ Mallory-Weiss: Hematemesis following bouts of vomiting.
proximal esophagus. Rings (e.g., Schatzki rings) are thicker, ■​ Pill Esophagitis: Sudden onset of chest pain and
circumferential, and located distally at the squamocolumnar odynophagia.
junction. ○​ Diagnosis: Perforations are assessed with chest CT or
○​ Clinical Features: Both cause intermittent, nonprogressive solid Gastrografin swallows. Mallory-Weiss tears and pill esophagitis
food dysphagia. A Schatzki ring causes "steakhouse syndrome" are diagnosed endoscopically.
(sudden food impaction). Upper webs accompanied by severe ○​ Management: Perforations demand NPO, IV broad-spectrum
iron deficiency anemia, glossitis, and cheilosis are known as antibiotics, and prompt surgical drainage/repair or endoscopic
Plummer-Vinson syndrome. stenting. Mallory-Weiss tears usually stop spontaneously but can
○​ Diagnosis: Barium swallow or endoscopy. be treated endoscopically (clips, cautery). Pill esophagitis is
○​ Management: Esophageal dilation using through-the-scope managed supportively with PPIs.
balloons or bougies. ●​ [Link]. Esophageal varices
●​ [Link]. Hiatal hernia ○​ Pathophysiology: In portal hypertension (usually secondary to
○​ Pathophysiology: Herniation of the stomach into the mediastinum liver cirrhosis), the venous drainage from the gut bypasses the liver
through the diaphragmatic hiatus. In Type I (sliding hernias) (95% via portosystemic collateral vessels. The submucosal veins of the
of cases), the gastroesophageal junction translocates cephalad distal esophagus dilate massively to form varices.
due to a weakened phrenoesophageal ligament. In Type II, III, ○​ Clinical Features: Asymptomatic until they rupture, at which point
and IV (paraesophageal hernias), the fundus (or other viscera they present as a life-threatening upper GI hemorrhage (massive
like the colon) herniates above the cardia while the GE junction hematemesis or melena) accompanied by hemodynamic instability.
may remain fixed. ○​ Diagnosis: Upper endoscopy (EGD).
 ○​ Management: Acute bleeding requires resuscitation, IV [Link]. Pyloric stenosis Pyloric stenosis can be either congenital or acquired.
vasoactive medications (octreotide, somatostatin, or terlipressin), ●​ Congenital hypertrophic pyloric stenosis: This is the most common
and urgent endoscopic variceal band ligation. For secondary congenital form, occurring in 1 per 300 to 900 live births, and is three to
prophylaxis, nonselective beta-blockers combined with serial five times more common in males. Monozygotic twins have a high
variceal ligation are standard. Refractory bleeding is managed concordance rate, and the risk is also elevated in individuals with Turner
with a Transjugular Intrahepatic Portosystemic Shunt (TIPS). syndrome and trisomy 18. Environmental factors play a role; for example,
exposure to erythromycin or azithromycin (orally or via breast milk) in the
7.1.4. Esophageal tumors first 2 weeks of life is associated with the disorder. The condition presents
between the third and sixth weeks of life with new-onset regurgitation,
●​ Pathophysiology: There are two dominant malignancies: Squamous Cell
projectile nonbilious vomiting after feeding, and frequent demands for
Carcinoma (SCC) and Adenocarcinoma.
refeeding. Physical examination reveals a firm, ovoid, 1- to 2-cm
○​ SCC arises from the squamous epithelium, usually in the
abdominal mass in up to 90% of cases, often accompanied by abnormal
upper/mid-esophagus. Risk factors include tobacco, alcohol,
left-to-right hyperperistalsis just before vomiting. Pathophysiologically,
caustic injury, achalasia, and HPV. (Philippines context: In
the gastric outflow tract is obstructed by hyperplasia of the pyloric
high-incidence regions like parts of Asia, SCC makes up the vast
muscularis propria, with edema and inflammatory changes in the mucosa
majority of cases, driven significantly by regional risk factors such
and submucosa aggravating the narrowing. Diagnosis is primarily via
as smoking, high alcohol consumption, and dietary nitrites.)
ultrasonography, and surgical splitting of the muscularis (myotomy) is
○​ Adenocarcinoma arises almost exclusively from Barrett's
curative.
esophagus (intestinal metaplasia) in the distal third of the
●​ Acquired pyloric stenosis: This occurs in adults as a consequence of
esophagus. It is strongly linked to chronic GERD and obesity.
chronic mucosal injury, such as antral gastritis or peptic ulcers close to the
●​ Clinical Features: Progressive dysphagia starting with solids and
pylorus. It can also be caused by carcinomas of the distal stomach or
advancing to liquids, accompanied by severe weight loss. Late-stage
pancreas that narrow the pyloric channel through malignant infiltration or
invasive tumors cause odynophagia, coughing (tracheoesophageal fistula),
severe fibrosis.
or hoarseness (left recurrent laryngeal nerve invasion).
●​ Diagnosis: Upper endoscopy with biopsy provides the definitive 7.2.2. Gastritis
histologic diagnosis. Endoscopic Ultrasound (EUS), CT, and PET scans [Link]. Acute and Chronic It is vital to distinguish between gastropathy and
are used for staging the depth of invasion and checking the abundant gastritis. Inflammation of the gastric mucosa is termed gastritis when inflammatory
lymphatic spread. cells (specifically neutrophils) are present, and gastropathy when inflammatory cells
●​ Management: Overall prognosis is very poor. Very early-stage lesions or are rare or absent. The presence of neutrophils above the basement membrane
dysplasia in Barrett's esophagus can be cured with Endoscopic Mucosal signifies active inflammation.
Resection (EMR) or Endoscopic Submucosal Dissection (ESD) ●​ Acute Gastritis: The most common causes of true acute gastritis are
combined with Radiofrequency Ablation (RFA). Advanced stages require infectious.
surgical esophagectomy, chemotherapy, and radiation. For incurable ○​ Acute Helicobacter pylori infection: This induces a dense
malignant obstructions, palliation of dysphagia is achieved with expandable infiltrate of neutrophils in the mucosa, accompanied by edema
metal stents. and hyperemia. It typically presents with sudden onset of
epigastric pain, nausea, and vomiting, and can lead to transient
7.2. Diseases of the stomach and duodenum
hypochlorhydria lasting for up to 1 year.
(Note: While the provided sources do not contain specific statistics exclusively for the
○​ Phlegmonous gastritis: A rare, life-threatening bacterial infection
Philippines regarding these diseases, they do highlight data for Southeast Asian
of the stomach characterized by marked and diffuse acute
populations—specifically regarding H. pylori virulence—which is directly applicable to
inflammatory infiltrates of the entire gastric wall, sometimes
the Philippine clinical context and is integrated into the discussion below).
7.2.1. Congenital anomalies
 leading to necrosis. Organisms include streptococci, 7.2.3. Peptic ulcer disease
staphylococci, E. coli, Proteus, and Haemophilus species. [Link]. Review physiology of gastric acid secretion
○​ Other infections: Viral (e.g., Cytomegalovirus, Herpes simplex) or Gastric acid and pepsinogen are the two principal secretory products capable of
fungal infections can cause acute gastritis in inducing mucosal injury, but they are physiologically essential for protein
immunocompromised patients. digestion, absorption of iron, calcium, and vitamin B12, and killing ingested
●​ Chronic Gastritis: Identified histologically by an inflammatory cell infiltrate bacteria. Basal acid production occurs in a circadian pattern, peaking at night,
consisting primarily of lymphocytes and plasma cells, with scant driven by vagal cholinergic and local histaminergic input.
neutrophil involvement. The early phase is superficial gastritis (edema [Link].1. Factors that stimulate gastric acid production during:
and cellular infiltrates separating intact glands), progressing to atrophic ●​ [Link].1.1. Cephalic phase: This phase is activated by the sight, smell,
gastritis (destruction of glands), and finally gastric atrophy (loss of and taste of food. These sensory inputs stimulate gastric acid secretion
glandular structures). Chronic gastritis frequently leads to intestinal entirely via the vagus nerve.
metaplasia, a precursor to gastric cancer. ●​ [Link].1.2. Gastric phase: This phase is activated once food directly
○​ Type B (Antral-predominant) Gastritis: The most common form, enters the stomach. It is driven by nutrients (specifically amino acids and
caused almost exclusively by H. pylori infection. Although it amines) that stimulate G cells to release gastrin. This occurs directly (via
begins in the antrum, the inflammatory process progresses to peptone and amino acid receptors) and indirectly (via stimulation of
the body and fundus over 15–20 years, causing pangastritis, intramural gastrin-releasing peptide neurons). Additionally, distention of the
multifocal atrophic gastritis, and eventual gastric stomach wall mechanically triggers gastrin release and subsequent acid
adenocarcinoma. Southeast Asian Context: The virulence of H. production.
pylori is closely linked to the cytotoxin-associated gene A (CagA) ●​ [Link].1.3. Intestinal phase: This phase is initiated as food exits the
protein, which interferes with epithelial cytoskeletal structure and stomach and enters the intestine. It is mediated by luminal distention
induces severe inflammation. While CagA-positive strains have a and nutrient assimilation within the small bowel.
60% prevalence in Western countries, the prevalence in
Southeast Asian countries is close to 90%, which accounts for [Link].2. Discuss the factors that provide mucosal defense against gastric acid:
the significantly higher incidence of severe gastritis and The gastroduodenal mucosal defense system is a highly intricate three-level
gastric cancer in this region. barrier composed of preepithelial, epithelial, and subepithelial elements designed
○​ Type A (Body-predominant / Autoimmune) Gastritis: Involves to withstand the harsh acidic environment (pH < 2).
the fundus and body, with striking antral sparing. It is associated ●​ [Link].2.1. Mucus secretion: The first line of defense (preepithelial) is a
with circulating CD4+ T cell-mediated antibodies directed mucous gel layer secreted by surface epithelial cells. It consists of 95%
against parietal cells (specifically the H+,K+-ATPase pump) and water mixed with phospholipids and mucin glycoproteins. This mucous
intrinsic factor. The loss of parietal cells leads to achlorhydria gel functions as a nonstirred water layer that physically impedes the
(lack of acid production), which halts the feedback inhibition of diffusion of hydrogen ions and large molecules like pepsin from reaching
gastrin, resulting in massive hypergastrinemia and antral G-cell the mucosal surface.
hyperplasia. The lack of intrinsic factor leads to defective vitamin ●​ [Link].2.2. Bicarbonate secretion: Surface epithelial cells secrete
B12 absorption, culminating in pernicious anemia. bicarbonate directly into the mucous gel in a regulated manner. This traps
○​ Uncommon forms: Include eosinophilic gastritis (dense the bicarbonate at the cell surface and creates a dramatic pH gradient:
infiltrates of eosinophils causing prominent antral folds and while the gastric lumen is at a highly acidic pH of 1 to 2, the actual
systemic allergy), lymphocytic gastritis (intense T-cell epithelial cell surface is maintained at a near-neutral pH of 6 to 7.
infiltration of surface epithelium, sometimes associated with ●​ [Link].2.3. Epithelial barrier: The epithelial cells themselves form a
celiac sprue), and granulomatous gastritis (caused by Crohn's physical barrier utilizing intracellular tight junctions to prevent the
disease, sarcoidosis, or mycobacteria). back-diffusion of acid and leakage of digestive enzymes into the lamina
propria. Surface cells generate heat shock proteins (to prevent protein
 denaturation), trefoil factor family peptides, and cathelicidins for contents and pepsin are cleared appropriately and do not stagnate
protection. If the barrier is breached, adjacent epithelial cells undergo to cause ischemic or pressure-induced damage to the epithelial
restitution—rapidly migrating to cover the damaged region (a process layers.
independent of cell division, regulated by EGF, TGF-α, and FGF).
●​ [Link].2.4. Mucosal blood flow: The subepithelial defense system relies [Link]. Types of peptic ulcer disease according to location Peptic ulcer disease
on an elaborate microvascular bed within the gastric submucosa. High (PUD) encompasses both duodenal ulcers (DUs) and gastric ulcers (GUs). Ulcers
mucosal blood flow is critical because it delivers a continuous supply of are defined as breaks in the mucosal surface greater than 5 mm in size that extend
bicarbonate to neutralize any acid that breaches the epithelium, provides in depth to the submucosa.
oxygen and micronutrients, and rapidly flushes away toxic metabolic
[Link].1. Duodenal Ulcer [Link].1.1. Epidemiology DUs are estimated to occur in
by-products. The microcirculation is maintained by potent local
6–15% of the Western population. The incidence of DUs declined steadily from
vasodilators, specifically nitric oxide (NO), hydrogen sulfide, and
1960 to 1980 and has remained stable since then, with death rates, the need for
prostacyclin.
surgery, and physician visits decreasing by more than 50% over the past 30 years.
●​ [Link].2.5. Prostaglandin protection: Prostaglandins (specifically PGE2
This reduction in frequency is likely related to the decreasing frequency of H. pylori
and PGI2) play the most central role in orchestrating epithelial defense.
infections, which corresponds globally with overall improved sanitary conditions.
They directly stimulate the secretion of mucin and bicarbonate, increase
mucosal blood flow, and enhance epithelial cell restitution. Crucially, [Link].1.2. Pathophysiology The pathophysiology of DUs is heavily driven by H.
they also bind to the EP3 receptor on parietal cells to directly inhibit pylori infection and NSAID use. Specifically, H. pylori infection that manifests as
gastric acid secretion. These prostaglandins are synthesized from an antral-predominant gastritis is strongly associated with DU formation. In DU
arachidonic acid by cyclooxygenase (COX) enzymes; the COX-1 isoform patients, basal and nocturnal gastric acid secretion is abnormally increased, and
is constitutively expressed and maintains this baseline gastrointestinal bicarbonate secretion is significantly decreased in the duodenal bulb compared
integrity, while COX-2 is inducible during inflammation. Nonsteroidal to controls. Furthermore, H. pylori infection leads to increased basal and
anti-inflammatory drugs (NSAIDs) cause severe ulcers by blocking this stimulated gastrin release alongside a decrease in somatostatin-secreting D cells,
vital prostaglandin synthesis. which removes the inhibitory feedback on acid production. High acid exposure in the
●​ [Link].2.6. Neural and muscular components: duodenum can lead to gastric metaplasia, which provides a tissue surface to which
○​ Neural: The gastric mucosa and submucosal vessels are richly H. pylori can bind, thereby producing local mucosal injury secondary to the host's
innervated by primary afferent sensory neurons that form a inflammatory response.
dense plexus at the mucosal base, with nerve fibers entering
the lamina propria and ending just beneath the surface [Link].1.3. Morphology DUs occur most often in the first portion of the
epithelial cells. The Central Nervous System (CNS) provides duodenum (>95%), with approximately 90% located within 3 cm of the pyloric
extrinsic modulation, with vagal stimulation (influenced by valve. They are usually 1 cm or less in diameter but can occasionally reach 3 to 6
corticotropin-releasing factor, thyrotropin-releasing factor, and cm (referred to as a giant ulcer). Microscopically, these ulcers are solitary, sharply
melatonin) heavily regulating these protective responses. demarcated, punched-out defects with a depth that can reach the muscularis
Furthermore, the enteric nervous system works in tandem with propria. The base of the ulcer typically consists of a zone of eosinophilic necrosis
local hormones to regulate acid secretion; for example, surrounded by fibrosis and granulation tissue.
intramural gastrin-releasing peptide neurons directly stimulate
[Link].1.4. Clinical features The classic presentation of a DU involves epigastric
acid pathways during the gastric phase.
pain described as a burning, gnawing, or aching sensation, or as "hunger pain".
○​ Muscular: The muscularis mucosae and the deeper muscularis
The typical pain pattern occurs 90 minutes to 3 hours after a meal and is frequently
propria provide structural bounds and regulate luminal distention,
relieved by the ingestion of food or antacids. Pain that forcefully awakens the
which directly ties into acid secretion pathways. Proper functioning
patient from sleep, typically between midnight and 3:00 A.M., is a highly
of the gastric smooth muscle promotes organized peristalsis,
discriminating symptom, occurring in two-thirds of DU patients. Epigastric
grinding, and gastric emptying, ensuring that highly acidic
tenderness, sometimes found to the right of the midline, is the most frequent sign on [Link].1.8. Detection of H. pylori: invasive and non-invasive tests
physical examination, though it has poor overall predictive value.
●​ Invasive Tests: These require upper endoscopy and mucosal biopsy.
[Link].1.5. Prognosis, risk of malignancy The prognosis for healing is excellent ○​ Histology: Routine hematoxylin & eosin stains are insufficient;
with proper therapy, and recurrences have been dramatically reduced (by >80%) special stains like Giemsa, Warthin-Starry silver stain, or
following successful H. pylori eradication. Most importantly, unlike gastric ulcers, immunohistochemical stains are used to visualize the organisms.
malignant duodenal ulcers are extremely rare. It provides 95–100% sensitivity and specificity and allows
assessment of tissue damage.
[Link].1.6. Etiology: role of Helicobacter pylori H. pylori is an essential etiologic ○​ Rapid Urease Test: Tissue is placed in a urea-containing medium; if
factor in PUD, though its prevalence in DUs has dropped to about one-fourth of H. pylori urease is present, a pH shift yields a color change
cases due to broad eradication efforts, leaving NSAIDs as an increasingly dominant within 1 to 2 hours.
cause. ○​ Culture: Performed mainly for antimicrobial susceptibility testing
when patients fail to respond to standard treatments.
[Link].1.6.1. Morphologic classification of H. pylori H. pylori is a gram-negative,
●​ Non-invasive Tests:
microaerophilic, spiral-shaped, curved, or fusiform rod. It measures roughly 0.5
○​ Urea Breath Test (UBT): The patient ingests 13C- or 14C-labeled
to 3 μm in size and possesses multiple sheathed monopolar flagella that grant it
urea. Bacterial urease cleaves it, and the labeled CO2 is detected
motility to swim through viscous gastric mucus. Under adverse conditions, the
in exhaled breath (94–98% sensitivity and specificity). This is an
organism is capable of transforming into a dormant coccoid form to facilitate
excellent tool for confirming active infection and documenting
survival.
eradication.
[Link].1.6.2. Culture and biochemical characteristics Biochemically, H. pylori is ○​ Stool Antigen Test: Detects bacterial antigens in feces using
oxidase-positive, catalase-positive, and a notably strong producer of urease. monoclonal antibodies, which is highly accurate for diagnosing
The urease enzyme breaks down endogenous urea into ammonia and carbon active infection and verifying cure.
dioxide, allowing the bacteria to neutralize local gastric acid and survive in the harsh ○​ Serology: Assays detect IgG antibodies against H. pylori to
gastric lumen. It grows optimally at a near-neutral pH of 6.0 to 7.0. Culturing confirm exposure. Because antibodies persist long after
requires a microaerophilic and humid atmosphere at 37°C, typically taking 3 to 6 eradication, serology cannot reliably differentiate an active infection
days (and up to 14 days) to grow. Primary isolation utilizes enriched media (like from a past infection.
blood or chocolate agar) or antibiotic-containing media (e.g., Skirrow’s medium) to
[Link].2. Gastric Ulcers [Link].2.1. Epidemiology GUs tend to occur later in life
suppress competing flora. Colonies appear gray to translucent and are 1 to 2 mm
than DUs, with a peak incidence reported in the sixth decade. More than half of GUs
in diameter.
occur in males. While clinically less common than DUs, autopsy studies suggest a
[Link].1.7. Risk factors for H. pylori infection Risk factors include poor similar overall incidence, possibly because GUs are more likely to be silent until a
socioeconomic status, domestic household crowding, limited education, unsanitary complication occurs.
living conditions, unclean food or water, and birth or residence in a rural area or
[Link].2.2. Etiology, compared with that of duodenal ulcer Like DUs, the vast
developing country. Transmission is typically oral-oral or fecal-oral. Philippine and
majority of GUs are caused by H. pylori or NSAIDs. However, the proportion differs:
Southeast Asian Context: The prevalence of H. pylori differs noticeably by region; in
H. pylori is currently associated with only about one-sixth of GUs, compared to
developing nations in Southeast Asia, most children are infected by age 10, and
one-fourth of DUs. NSAID use is a massive driver for GUs, causing lesions ranging
prevalence remains extremely high (up to 90%) among adults. Furthermore, the
from superficial erosions to deep ulcerations.
virulence factor CagA (cytotoxin-associated gene A), which causes severe
inflammation and is linked to gastric cancer, has a prevalence of close to 90% in [Link].2.3. Pathophysiology; compare with that of duodenal ulcer While DUs are
Southeast Asian strains compared to 60% in Western countries, contributing heavily associated with antral-predominant gastritis and increased acid production, GUs are
to the severity of local gastric pathology. associated with H. pylori-induced pangastritis (involving the body and fundus) and
normal or decreased gastric acid output. Because acid levels are lower, the into the left hepatic lobe. Penetration alters the pain pattern, often causing
primary pathogenetic mechanism in GUs is an impairment of mucosal defense it to become constant, radiate to the back, and lose responsiveness to
factors (mucus, bicarbonate, mucosal blood flow) rather than acid hypersecretion. antacids or food.
●​ Gastric Outlet Obstruction: This is the least common complication,
[Link].2.4. Morphology Benign GUs are predominantly located along the lesser occurring in about 2% of patients. It can be acute (due to ulcer-related
curvature of the stomach near the interface of the body and antrum. They are rare inflammation, edema, and pylorospasm) or chronic (due to irreversible
in the gastric fundus. The benign GU is a solitary, sharply punched-out defect fibrous scarring and narrowing of the pyloric channel). Patients present
whose margins are level with the surrounding mucosa or slightly overhanging. insidiously with early satiety, crampy abdominal pain that worsens with
Heaped-up margins are uncharacteristic and suggest a malignant cancer instead. meals, severe nausea, vomiting of undigested food, and significant
NSAID-related GUs often lack chronic active gastritis and instead show a "chemical weight loss.
gastropathy" characterized by foveolar hyperplasia, lamina propria edema, and
epithelial regeneration without H. pylori. [Link]. Acute gastric ulceration: etiology, pathogenesis, morphology

[Link].2.5. Clinical Features GU patients also experience epigastric pain, but the ●​ Etiology: Acute gastric ulcerations (often termed stress-related mucosal
pattern often differs from DUs: in GUs, the discomfort may actually be precipitated disease) occur in patients experiencing severe physiologic stress. Major
or worsened by food intake. Consequently, nausea and significant weight loss etiologies include severe trauma, extensive burns, intracranial disease, major
(due to a fear of eating) occur more commonly in GU patients than in DU patients. surgery, serious medical illnesses, shock, and sepsis.
●​ Pathogenesis: The underlying mechanism is primarily local ischemia. This
[Link].2.6. Prognosis: discuss the risk of malignancy in gastric ulcers Unlike ischemia can result from systemic hypotension or stress-induced
DUs, which are virtually never malignant, a GU can harbor or represent a gastric splanchnic vasoconstriction, which reduces mucosal blood flow.
adenocarcinoma or lymphoma. Therefore, all GUs must be extensively biopsied Furthermore, severe stress leads to the upregulation and increased
upon discovery. Because even malignant GUs may undergo significant (though release of the vasoconstrictor endothelin-1, which actively contributes to
incomplete) healing with acid-suppressing therapy, repeat endoscopy is absolutely ischemic mucosal injury.
mandatory at 8 to 12 weeks to document complete healing. If the ulcer is still ●​ Morphology: Acute stress ulcers range from shallow erosions to deeper
present, repeat biopsy is required to rule out malignancy. lesions penetrating the mucosa. They are typically rounded, less than 1
cm in diameter, and have a characteristic base stained brown or black
[Link].3. Complications of peptic ulcer disease
due to the acid digestion of extravasated blood. Unlike chronic peptic
●​ Gastrointestinal Bleeding: This is the most common complication, ulcers that are usually solitary and located in the antrum, acute stress ulcers
occurring in 15% to 20% of PUD patients, and is responsible for 25% of can be found anywhere in the stomach and are frequently multiple.
ulcer-related deaths. It occurs more often in individuals >60 years of age, Microscopically, they are sharply demarcated with normal adjacent mucosa,
largely due to concurrent NSAID use. Notably, over 50% of patients with lacking the scarring and thickened blood vessels that define chronic peptic
ulcer-related hemorrhage bleed without any preceding warning signs or ulcers. Complete healing with re-epithelialization occurs rapidly (within days
dyspeptic symptoms. to weeks) once the underlying critical illness is treated.
●​ Perforation: Occurring in up to 5–7% of patients, this is a surgical
[Link]. Cushing and Curling Ulcers
emergency carrying a 30-day mortality rate of >20% and accounts for
two-thirds of ulcer-related deaths. It presents with a classic triad of acute Specific names are given to stress-related ulcers based on their distinct clinical
sudden abdominal pain, tachycardia, and a rigid, board-like abdomen, associations:
though elderly or immunocompromised patients may lack these classic
signs. ●​ Curling Ulcers: These are acute ulcers that occur specifically in the
●​ Penetration: Ulcers can penetrate completely through the stomach or proximal duodenum in the context of severe burns or severe trauma.
duodenal wall into adjacent structures. Posterior DUs tend to penetrate ●​ Cushing Ulcers: These are acute ulcers arising in the stomach,
into the pancreas (causing pancreatitis), whereas GUs tend to penetrate duodenum, or esophagus of patients suffering from intracranial disease.
 They are clinically notable because they carry an exceptionally high risk [Link].1. Benign
of perforation.
●​ Inflammatory and Hyperplastic Polyps: Comprising up to 75% of gastric
[Link]. Miscellaneous conditions polyps, these generally arise in a background of chronic gastritis
(frequently H. pylori-induced), which triggers reactive hyperplasia and
[Link].1. Hypertrophic gastropathy polyp growth. They usually occur in individuals aged 50–60. Morphology:
Typically smaller than 1 cm, ovoid with a smooth surface.
Hypertrophic gastropathies are uncommon diseases characterized by giant,
Microscopically, they show irregular, cystically dilated foveolar glands
"cerebriform" enlargement of the gastric rugal folds. This enlargement is due to
and an edematous lamina propria with acute and chronic inflammation.
profound epithelial hyperplasia without true inflammation. They are heavily linked
Dysplasia risk increases sharply in polyps larger than 1 cm.
to excessive growth factor release.
●​ Fundic Gland Polyps: These can be sporadic (increasingly common due to
●​ Ménétrier Disease: widespread proton pump inhibitor use, which elevates gastrin and drives
○​ Etiology and Pathogenesis: Associated with the excessive oxyntic gland growth) or syndromic (occurring in patients with Familial
secretion of transforming growth factor-alpha (TGF-α), leading Adenomatous Polyposis [FAP] or MUTYH mutations). Morphology:
to hyperactivation of the epidermal growth factor receptor Well-circumscribed, smooth lesions in the body and fundus composed
(EGFR) on gastric epithelial cells. In adults, the specific trigger is of cystically dilated glands lined by parietal, chief, and foveolar cells
often unknown, though some cases are linked to cytomegalovirus with minimal inflammation. Sporadic polyps have no cancer risk, while
(CMV) or Helicobacter pylori. FAP-associated ones carry a risk of dysplasia.
○​ Morphology: There is massive diffuse foveolar hyperplasia ●​ Gastric Adenomas: True neoplastic precursor lesions representing 10% of
(hyperplasia of the surface and glandular mucous cells) primarily in polyps. They usually develop in a background of chronic gastritis with
the body and fundus, characteristically sparing the antrum. The atrophy and intestinal metaplasia. Males are affected three times more
glands become elongated and corkscrew-like, frequently often than females. Morphology: Usually solitary antral lesions exhibiting
exhibiting cystic dilation. This is accompanied by a marked low- or high-grade dysplasia (nuclear enlargement, pseudostratification,
reduction or patchy atrophy of parietal and chief cells, leading hyperchromasia, and cribriform architectures). They carry a high risk of
to hypochlorhydria. harboring adenocarcinoma (up to 30% when >2 cm) and require
○​ Clinical Features: The hypersecretion of gastric mucus leads to a aggressive management.
severe protein-losing enteropathy, resulting in
[Link].2. Gastric carcinoma
hypoalbuminemia, weight loss, diarrhea, and edema. It is
considered by some to be premalignant, carrying an increased risk Adenocarcinomas constitute over 90% of gastric malignancies.
for gastric adenocarcinoma.
●​ Zollinger-Ellison Syndrome (ZES): ●​ Epidemiology & Philippine Context: There is marked geographic variation.
○​ Etiology and Pathogenesis: Caused by gastrin-secreting Incidence is highest in East Asia, South America, and Eastern Europe. In
neuroendocrine tumors (gastrinomas), which are almost always Southeast Asian countries, including the Philippines, the prevalence of
found in the small intestine or pancreas. highly virulent H. pylori strains containing the CagA (cytotoxin-associated
○​ Morphology: The unregulated, massive hypergastrinemia gene A) protein reaches almost 90% (compared to 60% in Western
stimulates parietal cells directly and exerts a trophic (growth) countries); this severe inflammatory trigger is a major driver of the high
action on gastric epithelial cells. This results in a massive regional gastric cancer burden. Furthermore, survival statistics reflect
hyperplasia of parietal cells, doubling the thickness of the regional healthcare disparities; while survival rates for GI malignancies like
oxyntic mucosa. colorectal and gastric cancers reach ~60% in developed nations like Japan,
overall survival rates are notably lower in the Philippines, Thailand, India,
[Link]. Gastric tumors and China, ranging from only 30% to 42%.
 ●​ Classification and Pathogenesis: synaptophysin and chromogranin A. They are clinically divided
○​ Intestinal Type: Associated strongly with H. pylori infection, into three types based on gastrin levels and metastatic potential.
dietary nitrites, atrophic gastritis, and intestinal metaplasia. ●​ Gastrointestinal Stromal Tumors (GIST): The most common
Pathogenetically, these are linked to mutations increasing Wnt mesenchymal tumor of the abdomen, arising from the interstitial cells of
signaling (loss of APC tumor suppressor, gain-of-function Cajal (pacemaker cells); over half occur in the stomach.
β-catenin) and mutations in TGFβRII, BAX, and CDKN2A. ○​ Pathogenesis: Associated with activating somatic mutations in
○​ Diffuse Type: Pathogenesis is fundamentally driven by either the cKIT or PDGFRA tyrosine kinase genes.
loss-of-function mutations in the CDH1 gene, which encodes ○​ Morphology: They form solitary, well-circumscribed, fleshy
the cell adhesion protein E-cadherin (seen in both familial and masses that can grow very large (up to 30 cm). Histologically,
sporadic cases). they are classified as spindle cell type (thin, elongated cells),
●​ Morphology: epithelioid type (plump, epithelial-appearing cells), or mixed. The
○​ Intestinal Type: Tends to form bulky, exophytic masses or vast majority of gastric GISTs strongly express the
ulcerated tumors with heaped-up margins. Neoplastic cells form immunohistochemical marker KIT (CD117). Their malignant
glandular structures and contain apical mucin vacuoles. potential is predicted by tumor size, location, and mitotic rate.
○​ Diffuse Type: Highly infiltrative. Because of E-cadherin loss, the
cells do not form glands but permeate the gastric wall as 8.1. Agents used for suppression of acid secretion
individual, discohesive cells. The cells develop massive mucin
The primary agents used for suppressing gastric acid secretion are Proton Pump
vacuoles that push the nucleus to the periphery, creating a
Inhibitors (PPIs) and Histamine H2-receptor antagonists (H2 blockers). A newer
signet-ring cell morphology. The extensive invasion elicits a
class, Potassium-Competitive Acid Blockers (P-CABs), is also emerging.
severe desmoplastic (fibrous) reaction that stiffens the stomach
wall, producing a rigid "leather bottle" appearance known as 8.1.1. Pharmacokinetics and pharmacodynamics
linitis plastica.
●​ PPIs (e.g., omeprazole, pantoprazole, esomeprazole): PPIs are prodrugs
[Link].3. Less common gastric tumors that require an acidic environment for activation. Because food stimulates
acid production, they should be administered approximately 30 minutes
●​ Gastric Lymphomas: The GI tract is the most common site for extranodal
before the first meal of the day. Once in the small bowel, they are rapidly
Non-Hodgkin’s Lymphomas (NHL). The two primary histologic subtypes
absorbed, highly protein-bound, and extensively metabolized by hepatic
are marginal zone B-cell lymphomas (MALTomas) and diffuse large
cytochrome P450 (CYP) enzymes, particularly CYP2C19 and CYP3A4.
B-cell lymphomas (DLBCL).
While their plasma half-life is remarkably short (0.5 to 3 hours), their
○​ Pathogenesis: MALTomas are heavily driven by chronic H. pylori
duration of acid suppression is prolonged (up to 24 to 48 hours) because
infection. A specific translocation, t(11;18), creates a chimeric
they irreversibly inactivate the proton pumps. Maximal suppression of
protein (API1-MALT1) that leads to the constitutive activation of
acid secretion requires several doses, taking 2 to 5 days of once-daily
nuclear factor-κB (NF-κB), a transcription factor that promotes
dosing to achieve the 70% steady-state inhibition of proton pumps.
pathological B-cell growth and survival.
○​ Philippines/Asian Context: Asians are significantly more likely than
●​ Neuroendocrine Neoplasms (Carcinoid Tumors): These arise from diffuse
Caucasians or African Americans to possess the CYP2C19
endocrine components of the gut. Gastric neuroendocrine tumors are
genotype associated with the slow metabolism of PPIs (23%
commonly associated with autoimmune atrophic gastritis, multiple
versus 3%). In the Philippine demographic, this can lead to slower
endocrine neoplasia type 1 (MEN1), and Zollinger-Ellison syndrome.
drug clearance, contributing to heightened efficacy but also
○​ Morphology: They form yellow or tan intramural/submucosal
potentially higher toxicity.
polypoid masses that are very firm due to intense desmoplasia.
●​ H2 Blockers (e.g., famotidine, ranitidine, cimetidine): These are rapidly
The cells are uniform with a characteristic "salt and pepper"
absorbed after oral administration, reaching peak serum concentrations
chromatin pattern and are positive for endocrine markers like
 within 1 to 3 hours. Their plasma half-life ranges from 1 to 3.5 hours. They B12, iron, and magnesium deficiency (hypomagnesemia); an increased
are cleared primarily by the kidneys through filtration and tubular incidence of bone fractures; and a higher susceptibility to enteric and
secretion, necessitating dose reductions in patients with decreased respiratory infections, notably hospital-acquired pneumonia and
creatinine clearance. Hepatic metabolism accounts for a smaller fraction of Clostridioides difficile colitis. Chronic use induces hypergastrinemia,
their clearance (<10% to 35%). which can lead to enterochromaffin-like (ECL) cell hyperplasia and
fundic gland polyposis. Drug Interactions: Omeprazole inhibits
8.1.2. Mode of action CYP2C19, decreasing the clearance of disulfiram and phenytoin, and it
may competitively inhibit methotrexate elimination. PPIs (except
●​ PPIs: PPIs diffuse into the parietal cells and accumulate in the acidic
potentially pantoprazole) may inhibit the CYP2C19-mediated conversion
secretory canaliculi, where they undergo a proton-catalyzed activation
of clopidogrel to its active anticoagulant form, though the clinical
to form a tetracyclic sulfenamide. This active form binds covalently to the
significance of this regarding mortality is debated.
sulfhydryl groups of cysteines on the H+,K+-ATPase (the proton pump),
●​ H2 Blockers: Side effects are rare (<3%) and include diarrhea, headache,
irreversibly inactivating the enzyme. They block the final step of acid
fatigue, and muscular pain. Central nervous system effects (delirium,
production, suppressing both basal and stimulated acid secretion
confusion, hallucinations) can occur with intravenous administration or in
regardless of the physiological stimulus.
the elderly. Cimetidine, specifically, can cause weak antiandrogenic
●​ H2 Blockers: These drugs inhibit acid production by reversibly competing
effects leading to reversible gynecomastia and impotence at high chronic
with histamine for binding to H2 receptors on the basolateral membrane
doses. Drug Interactions: Cimetidine strongly inhibits hepatic CYPs
of parietal cells.
(CYP1A2, 2C9, 2D6), significantly increasing blood levels of warfarin,
●​ P-CABs (e.g., vonoprazan): These inhibit gastric acid secretion via
phenytoin, and theophylline. Ranitidine has only 10% of cimetidine's CYP
potassium-competitive binding of the H+,K+-ATPase. They have a
affinity, while famotidine and nizatidine do not interact significantly with
longer half-life than PPIs and are increasingly used, particularly in
hepatic CYPs.
combination with antibiotics, to eradicate Helicobacter pylori. Philippines
Context: In Southeast Asia, the prevalence of the highly virulent 8.1.5. Tolerance and rebound with acid-suppressing medications
CagA-positive H. pylori strain is nearly 90%, driving high rates of gastric
cancer and making potent, reliable acid suppression via PPIs or P-CABs ●​ Tolerance: Tolerance to the acid-suppressing effects of H2 blockers
critical for successful antibiotic eradication therapies. frequently develops within 3 days of initiating treatment and may be
resistant to dose increases. This is believed to result from secondary
8.1.3. Potency of these drugs in suppressing acid secretion hypergastrinemia stimulating histamine release. Tolerance is rare with
PPIs.
●​ PPIs are the most potent suppressors of gastric acid secretion
●​ Rebound: PPIs can cause significant rebound gastric acid
available. They diminish the daily production of basal and stimulated acid
hypersecretion upon discontinuation after prolonged treatment. This
by 80% to 95%.
rebound can provoke dyspepsia and worsen GERD symptoms. It occurs
●​ H2 Blockers are less potent than PPIs, suppressing 24-hour gastric acid
due to gastrin-induced hyperplasia and hypertrophy of
secretion by about 70%. They are most effective at suppressing
histamine-secreting ECL cells. Gradual tapering of the PPI and
nocturnal and basal acid secretion (also about 70%), which makes
temporary transition to an H2 blocker can prevent this rebound.
evening dosing effective for healing duodenal ulcers, but they are
inferior to PPIs for meal-stimulated acid secretion and severe GERD.

8.1.4. Adverse effects and drug interactions --------------------------------------------------------------------------------

●​ PPIs: Generally very safe, but common mild adverse effects include
nausea, abdominal pain, constipation, flatulence, and diarrhea.
Long-term adverse effects are a growing concern and include vitamin 8.2. Agents that enhance mucosal defense
8.2.1 Prostaglandin analogs: Misoprostol [Link] Pharmacokinetics and a physical barrier that inhibits the pepsin-mediated hydrolysis of
pharmacodynamics Misoprostol is rapidly absorbed orally and extensively mucosal proteins. It also stimulates local production of prostaglandins
deesterified into misoprostol acid, its active metabolite. Food and antacids and epidermal growth factor, and binds bile salts.
decrease its rate of absorption. It inhibits acid production rapidly within 30 ●​ Indications: Used for the treatment of active duodenal ulcers and
minutes, peaking at 60 to 90 minutes, with a therapeutic effect lasting up to 3 maintenance therapy. Because it does not raise gastric pH as much as
hours. It is excreted mainly in the urine with a short elimination half-life of 20 to PPIs or H2 blockers, it is highly useful for stress ulcer prophylaxis in
40 minutes. critically ill patients, as preserving some gastric acidity reduces gastric
bacterial colonization and the subsequent risk of nosocomial aspiration
[Link] Mode of action, Indications and contraindications pneumonia. It is also used for conditions unresponsive to acid suppression,
like radiation proctitis and oral mucositis.
●​ Mode of Action: It is a synthetic analog of Prostaglandin E1 (PGE1). It
●​ Contraindications/Precautions: Because it contains aluminum, it should
binds to the EP3 receptor on parietal cells, stimulating the Gi pathway,
be avoided in patients with chronic renal failure who are at risk for
which decreases intracellular cAMP and strongly inhibits gastric acid
aluminum overload and neurotoxicity.
secretion. Cytoprotectively, it stimulates mucin and bicarbonate
secretion and increases mucosal blood flow.
●​ Indications: It is FDA-approved specifically for the prevention of
NSAID-induced mucosal injury and ulcers, as NSAIDs inherently deplete --------------------------------------------------------------------------------
the stomach of protective prostaglandins.
●​ Contraindications & Adverse Effects: It is strictly contraindicated during
pregnancy because it strongly increases uterine contractility and can
8.4. Antacids
induce abortion. It should not be used in women of childbearing potential
unless they are at very high risk for NSAID-induced complications. The 8.4.1 Therapeutic uses Antacids are used primarily as over-the-counter medications
most common limiting adverse effect is dose-related diarrhea, occurring in for the rapid, symptomatic relief of mild, infrequent acute acid reflux, heartburn, and
up to 30% of patients, alongside abdominal pain and cramps, and it can dyspepsia. They are insufficient for treating severe GERD or healing active peptic
exacerbate inflammatory bowel disease. ulcers.

8.4.2 Chemical reactions when antacids are added to gastric acid Antacids are
weak bases that chemically neutralize hydrochloric acid (HCl) in the gastric lumen.
--------------------------------------------------------------------------------
●​ Sodium bicarbonate and calcium carbonate react with HCl to release
carbon dioxide (CO2) gas and water, alongside a salt (NaCl or CaCl2).
8.3. Sucralfate ●​ Magnesium and aluminum hydroxides react with HCl to form water and
their respective chloride salts without producing CO2.
8.3.1 Pharmacokinetics and pharmacodynamics Sucralfate must be taken on an ●​ Magaldrate (a complex) converts rapidly in gastric acid into Mg(OH)2 and
empty stomach about 1 hour before meals because it requires an acidic Al(OH)3.
environment (pH < 4) for activation. It forms a viscous, sticky polymer paste that
adheres locally to epithelial cells and ulcer craters for up to 6 hours. It is poorly 8.4.3 Factors that influence the usefulness of antacids Effectiveness is
absorbed and thus lacks systemic toxicity. determined by patient palatability and the physical formulation; suspensions
have a greater neutralizing capacity than powders or tablets. The presence of food
8.3.2 Mode of action, Indications and contraindications is a critical factor: on an empty stomach, antacids are cleared in about 30 minutes,
but if taken with food, the food elevates the gastric pH to about 5 for an hour,
●​ Mode of Action: It is a complex sucrose octasulfate and aluminum
prolonging the antacid's neutralizing effect for up to 2 to 3 hours.
hydroxide salt. By forming a sticky polymer over ulcerated tissue, it acts as
8.4.4 Neutralizing capacities of common antacids Calcium carbonate (CaCO3) The primary goal in treating peptic ulcer disease (PUD) is to provide symptom relief,
rapidly and effectively neutralizes gastric protons. However, the preferred promote healing, and prevent recurrence. Documented eradication of H. pylori is
neutralizing agents are combinations of Magnesium (Mg2+) and Aluminum (Al3+) associated with a dramatic decrease in ulcer recurrence to <10–20%, compared to
hydroxides. Magnesium is rapidly reacting, while Aluminum is slowly reacting, 59% in gastric ulcer (GU) patients and 67% in duodenal ulcer (DU) patients when the
thus providing a relatively balanced and sustained neutralizing capacity. organism is not eliminated.

8.4.5 Adverse effects specific to a particular antacid General Principles of Therapy No single antibiotic agent is effective in eradicating
H. pylori, and monotherapy quickly leads to microbial resistance. Therefore,
●​ Sodium Bicarbonate: Highly water-soluble and rapidly absorbed, combination therapy featuring two or three antibiotics plus acid-suppressive therapy
presenting a risk of systemic alkalosis and dangerous sodium loads in (a proton pump inhibitor, PPI) is the standard of care. The optimal duration of
patients with cardiac or renal failure. treatment is 10 to 14 days; shorter courses (7 to 10 days) have proven less
●​ Calcium Carbonate: The release of CO2 causes belching, nausea, successful.
abdominal distention, and flatulence. It can induce "rebound" acid
secretion. Chronic ingestion of large quantities with milk can lead to the First-Line Treatment Regimens The choice of a regimen depends on patient
tolerance, prior antibiotic exposure, and local antibiotic resistance rates.
dangerous milk-alkali syndrome (systemic alkalosis, hypercalcemia, and
renal insufficiency). ●​ Bismuth Quadruple Therapy: This is now frequently recommended as the
●​ Aluminum Hydroxide: Relaxes gastric smooth muscle, causing delayed first-line therapy, especially in areas where clarithromycin resistance
gastric emptying and severe constipation. In patients with renal exceeds 15% or if the patient has had prior exposure to macrolide
insufficiency, absorbed aluminum can cause osteoporosis, antibiotics.
encephalopathy, and proximal myopathy. ○​ Regimen: PPI (standard dose twice daily) + Bismuth subcitrate
●​ Magnesium Hydroxide: Promotes bowel motility, causing diarrhea (loose (120–300 mg) or subsalicylate (300 mg) four times daily +
stools). It is contraindicated in chronic renal failure due to the risk of Tetracycline (500 mg) four times daily + Metronidazole (250–500
systemic hypermagnesemia. mg) four times daily.
○​ Duration: 10–14 days.
8.4.6 Important drug interactions with antacids By elevating urinary pH by
●​ Clarithromycin Triple Therapy: This is recommended only for patients
approximately 1 unit, antacids alter the renal elimination rates of many drugs. They
without prior macrolide exposure and who reside in areas where
alter the dissolution, bioavailability, and absorption of thyroid hormones,
clarithromycin resistance is known to be <15%.
allopurinol, and imidazole antifungals. Furthermore, Al3+ and Mg2+ antacids have a
○​ Regimen: PPI (standard or double dose twice daily) +
strong propensity to chelate other drugs in the GI tract (such as fluoroquinolones,
Clarithromycin (500 mg twice daily) + Amoxicillin (1 g twice
tetracyclines, digoxin, and iron), drastically decreasing their absorption.
daily) OR Metronidazole (500 mg three times daily).
○​ Duration: 14 days.
8.4.7 Proper dosing and timing of antacids To maximize their duration of action
●​ Concomitant Therapy: Developed as an alternative to triple therapy to
utilizing the buffering effect of meals, antacids should be given orally 1 and 3 hours
overcome resistance, this non-bismuth quadruple therapy is highly
after meals and at bedtime. For severe, acute symptoms, they can be given as
effective.
frequently as every 30 to 60 minutes. To avoid chelation or altering the
○​ Regimen: PPI (standard dose twice daily) + Clarithromycin (500
absorption of other medications, antacids should be ingested at least 2 hours
mg) + Amoxicillin (1 g) + Nitroimidazole/Metronidazole (500 mg)
before or after the administration of other drugs. They should specifically not be
all given twice daily.
used within 30 minutes of a dose of sucralfate, as sucralfate requires acidic pH to
○​ Duration: 10–14 days.
activate.
●​ Sequential Therapy: A 10- to 14-day regimen designed to prevent
8.5. Regimens recommended for Helicobacter pylori infection resistance.
 ○​ Regimen: PPI + Amoxicillin (1 g twice daily) for 5 to 7 days, the virulence of H. pylori is linked to the cytotoxin-associated gene A (CagA) protein.
followed by PPI + Clarithromycin (500 mg twice daily) + While CagA-positive strains have a 60% prevalence in Western countries, the
Nitroimidazole (500 mg twice daily) for 5 to 7 days. prevalence in Southeast Asian countries is close to 90%. CagA strongly induces
severe inflammation, atrophic gastritis, and intestinal metaplasia, explaining the
Salvage Therapies for Refractory Infection Eradication failure occurs in 15–25% of significantly higher incidence of gastric cancer in this part of the world. Furthermore,
patients treated with first-line therapy, usually due to poor medication compliance, due to high and rising rates of resistance to metronidazole and clarithromycin in
inadequate acid suppression, or antibiotic-resistant bacterial strains. When developing nations, empirical first-line treatment in the Philippines should strongly
initial therapies fail, salvage options include: favor robust regimens like Bismuth Quadruple Therapy or Concomitant Therapy
to maximize initial eradication success and mitigate the severe oncologic risks
●​ Levofloxacin Triple Therapy: PPI + Amoxicillin (1 g twice daily) +
associated with the local CagA-positive strains.
Levofloxacin (500 mg once daily) for 14 days.
●​ Rifabutin Triple Therapy: PPI (standard dose twice daily) + Rifabutin (300
mg once daily) + Amoxicillin (1 g twice daily) for 10 days. This yields an
86% cure rate in resistant strains. --------------------------------------------------------------------------------
●​ High-Dose Dual Therapy: PPI (standard to double dose three or four
times daily) + Amoxicillin (1 g three times daily or 750 mg four times
daily) for 14 days.
8.6. Therapy of NSAID-related Gastric or duodenal injury
Adjunctive Therapies and Novel Approaches
NSAID-induced mucosal injury is mediated both by direct topical damage (increasing
●​ Potassium-Competitive Acid Blockers (P-CABs): Vonoprazan, a highly epithelial permeability) and, more importantly, by systemic inhibition of
potent acid suppressor, has demonstrated superiority to conventional PPIs cyclooxygenase (COX-1), which depletes the stomach of cytoprotective
when combined with antibiotics (amoxicillin and clarithromycin) for H. pylori prostaglandins (PGE2 and PGI2) necessary for mucus/bicarbonate production and
eradication and has received Fast Track status by the FDA for this mucosal blood flow. Up to 87% of patients with NSAID-induced ulcers present
indication. directly with catastrophic complications (bleeding, perforation) without any preceding
●​ Probiotics: While probiotics (e.g., Lactobacillus spp., Saccharomyces spp.) dyspeptic symptoms, making active management and prophylaxis critical.
do not significantly alter the absolute eradication rates, they markedly
Treatment of an Active NSAID-Induced Ulcer
decrease antibiotic-associated side effects (like nausea, diarrhea, and
dysgeusia), thereby enhancing patient tolerability and compliance. 1.​ Discontinuation of the offending agent: The ideal first step is to stop the
●​ Statins: Atorvastatin has shown some success as an adjunct to NSAID immediately.
quadruple therapy, though it requires further validation. 2.​ Pharmacotherapy based on NSAID status:
○​ If the NSAID is successfully discontinued: Both Histamine
Post-Treatment Documentation Eradication must be definitively documented 4
H2-receptor antagonists and PPIs are highly effective for
weeks after the completion of antibiotic therapy. The preferred tests are the validated
healing.
monoclonal stool antigen test or the urea breath test (UBT). The patient must be
○​ If the NSAID must be continued (due to severe underlying
off all antisecretory agents (PPIs) for at least 7 days prior to testing to prevent
inflammatory disease): Only PPIs have the potency required to heal
false negatives. Serologic testing is entirely useless for this follow-up, as IgG
gastric or duodenal ulcers independent of continued NSAID
antibodies remain elevated long after successful eradication.
ingestion. H2 blockers and misoprostol are inferior in this setting.
The Philippines and Southeast Asian Context The epidemiology and virulence of Therapy must usually be extended (≥ 8 weeks).
H. pylori are deeply tied to geography and socioeconomic status. In developing 3.​ H. pylori Assessment: All patients with NSAID-related ulcers must be
regions, particularly Southeast Asia, most individuals are infected during childhood, tested and treated for H. pylori. The two factors are synergistic and
and the prevalence remains extraordinarily high—up to 90% among adults. Crucially, independent causes of ulceration. Eradicating H. pylori reduces the
 likelihood of GI complications in high-risk NSAID users to the level of an Pathophysiology Acute appendicitis is thought to be initiated by a progressive
average-risk user. increase in intraluminal pressure that compromises venous outflow. In 50% to
80% of cases, this is caused by overt luminal obstruction, most commonly by a
Primary Prevention and Prophylactic Therapy For patients requiring long-term fecalith (a small stone-like mass of stool), but it can also be caused by gallstones,
NSAID therapy, primary prevention is determined by evaluating both their GI risk and tumors, or a mass of worms (Oxyuriasis vermicularis). Peri-appendiceal lymphoid
cardiovascular (CV) risk. Preventive strategies include: hyperplasia, which can occur after a viral infection, may also compress and obstruct
the lumen. This stasis allows for bacterial proliferation, leading to ischemia and
●​ Proton Pump Inhibitors (PPIs): PPIs (e.g., Esomeprazole 20–40 mg/day,
inflammation. Without intervention, vascular thrombosis, ischemic necrosis, and
Lansoprazole 15 mg/day, Pantoprazole 20 mg/day) are the most effective
eventual perforation of the distal appendix can occur, though uncomplicated
and best-tolerated agents for preventing NSAID-induced ulcers. They are
appendicitis does not invariably progress to perforation.
superior to both H2 blockers and misoprostol for preventing recurrence.
●​ Misoprostol: This synthetic PGE1 analog directly replaces the
Clinical Features Acute appendicitis is the most common acute general surgery
prostaglandins depleted by NSAIDs. While effective for prophylaxis at
emergency, predominantly affecting individuals between 10 and 19 years of age. It
doses of 200 μg four times daily, it is severely limited by side effects. Up
classically begins with nonspecific symptoms, such as changes in bowel habits,
to 30% of patients develop dose-related diarrhea and severe abdominal
malaise, and vague, crampy epigastric or periumbilical pain. Over 12 to 24 hours,
cramping. Most importantly, it is strictly contraindicated during
the pain migrates to the right lower quadrant (RLQ), becoming sharper and
pregnancy and in women of childbearing potential because it increases
localized as the inflammation irritates the parietal peritoneum. Crucially, nausea and
uterine contractility and can induce abortion.
vomiting typically follow the onset of pain, helping distinguish it from
●​ Selective COX-2 Inhibitors (e.g., celecoxib): These agents spare the
gastroenteritis, and anorexia is so common that its absence should make the
COX-1 enzyme, offering 100 times more selectivity for COX-2 and reducing
clinician question the diagnosis. Physical examination classically reveals maximal
GI mucosal injury to rates comparable with placebo. However, COX-2
tenderness at McBurney’s point (two-thirds of the distance from the umbilicus to
inhibitors are associated with an increased risk of severe adverse
the right anterior superior iliac spine). Other signs of peritoneal irritation include
cardiovascular events (myocardial infarction and strokes). Furthermore, their
Rovsing's sign (pain in the RLQ upon palpation of the LLQ), the psoas sign, and the
gastroprotective advantage is completely negated if the patient is
obturator sign. Atypical presentations are common in children, the elderly, and
simultaneously taking low-dose aspirin for cardioprotection.
pregnant women, whose enlarging uterus may push the appendix into the right
Risk Stratification Guide to NSAID Therapy (ACG Guidelines) The selection of an upper quadrant.
NSAID and gastroprotective strategy should strictly follow a risk-stratification matrix
(Table 335-7): Histopathologic Features In early acute appendicitis, subserosal vessels are
congested, and a mild perivascular neutrophilic infiltrate is seen. However, the
●​ No/Low GI Risk & No CV Risk: A traditional nonselective NSAID may be diagnostic hallmark of acute appendicitis requires neutrophilic infiltration of the
used without gastroprotection. muscularis propria. As the disease progresses, a prominent neutrophilic exudate
●​ Moderate GI Risk & No CV Risk: Use a COX-2 inhibitor alone, or a generates a serosal fibrinopurulent reaction. Focal abscesses may form within the
traditional NSAID paired with a PPI or misoprostol. wall, termed acute suppurative appendicitis. Further vascular compromise results
●​ High GI Risk & No CV Risk: Avoid NSAIDs if possible. If required, use a in ischemia, hemorrhagic ulceration, and full-thickness necrosis, known as acute
COX-2 inhibitor plus a PPI or misoprostol. gangrenous appendicitis, which precedes rupture.
●​ CV Risk present (requires low-dose aspirin): Avoid COX-2 inhibitors Diagnosis Diagnosis relies heavily on history and physical examination, but
entirely due to thrombotic risks. Consider a non-NSAID analgesic. If an adjunctive tests are vital. Laboratory testing typically reveals a mild to moderate
NSAID is necessary, use a traditional NSAID with lower CV risk (like leukocytosis (10,000–18,000 cells/μL) with a "left shift" toward immature
naproxen) combined with a PPI or misoprostol to prevent the synergistic polymorphonuclear leukocytes in >95% of cases. Computed tomography (CT) is
bleeding risk created by the NSAID + aspirin combination. highly accurate (sensitivity >0.94) and is the superior imaging modality,
demonstrating appendiceal dilation >6 mm with wall thickening, a lumen that fails
9. Acute Appendicitis
to fill with enteric contrast, and surrounding fatty tissue stranding. adenoma, lacks typical cytologic dysplasia but possesses malignant potential via
Ultrasonography is highly operator-dependent but is useful in children and pregnant the mismatch repair pathway.
women to identify wall thickening and free fluid. 10.1.3. Familial polyposis Familial Adenomatous Polyposis (FAP) is an autosomal
Management Patients require preparation with intravenous fluid resuscitation and dominant disorder caused by somatic mutations in the APC tumor suppressor
electrolyte correction. Appendectomy (laparoscopic or open) is the standard and gene. Patients develop hundreds to thousands of adenomatous polyps by their
curative treatment. If a patient presents with a contained mass, phlegmon, or teenage years. If untreated, colorectal adenocarcinoma develops in 100% of FAP
abscess, they are typically managed non-operatively initially with broad-spectrum patients, usually before age 50, making prophylactic colectomy the standard of care.
antibiotics, bowel rest, and percutaneous drainage (for abscesses >3 cm), Variants include Gardner syndrome (associated with osteomas and desmoid tumors)
followed by an interval appendectomy 6 to 12 weeks later once inflammation has and Turcot syndrome (associated with brain tumors).
subsided. 10.1.4. Colorectal neoplasms
[Link]. Epidemiology and risk factors Colorectal cancer (CRC) is the most
common GI cancer and the second leading cause of cancer death in the US. While
-------------------------------------------------------------------------------- incidence generally peaks between 60 to 70 years, there is a steady and alarming
increase in incidence among patients under age 50. Major risk factors include diets
high in animal fat and low in fiber, obesity, and tobacco use. Inflammatory Bowel
10. Intestinal Tumors
Disease (IBD), particularly ulcerative colitis, significantly elevates risk; cancer may
10.1.1. Non-neoplastic polyps
develop in 8–30% of patients depending on disease severity and duration.
●​ Hyperplastic Polyps: These are benign, usually <5 mm, and most
Hereditary syndromes (FAP, Lynch syndrome) and Streptococcus bovis bacteremia
commonly found in the left colon and rectum. They result from decreased
are also prominent risk factors.
epithelial turnover and delayed shedding, causing a piling up of goblet and
[Link]. Pathogenesis Carcinogenesis follows two major distinct molecular
absorptive cells. Histologically, they feature a serrated surface
pathways:
architecture restricted to the upper third of the crypt, distinguishing
1.​ APC/β-catenin (Chromosomal Instability) Pathway: Accounts for ~80%
them from potentially malignant sessile serrated adenomas.
of sporadic CRC. It begins with the loss of the APC tumor suppressor gene,
●​ Inflammatory Polyps: Formed by chronic cycles of injury and healing. A
followed by sequential mutations in oncogenes (KRAS, BRAF) and
classic example is the solitary rectal ulcer syndrome caused by impaired
ultimately the loss of the TP53 and SMAD tumor suppressor genes.
relaxation of the anorectal sphincter, leading to abrasion, ulceration, and
2.​ Mismatch Repair (Microsatellite Instability) Pathway: Characterized by
fibromuscular hyperplasia.
defects in DNA mismatch repair genes (e.g., MLH1, MSH2), leading to the
●​ Hamartomatous Polyps: Include sporadic or syndromic lesions. Juvenile
accumulation of mutations in microsatellite repeats. This pathway is a
polyps are typical in children <5 years old, causing rectal bleeding, and
hallmark of Lynch syndrome and a subset of sporadic cancers, eventually
feature cystically dilated glands filled with mucin and inflammatory debris. In
causing mutations in genes regulating growth and apoptosis like TGFBR2
Juvenile Polyposis Syndrome (e.g., SMAD4 mutations), there is a high risk
and BAX.
of colonic adenocarcinoma. Peutz-Jeghers polyps (STK11 mutation)
feature an arborizing network of smooth muscle and connective tissue and [Link]. Common location Adenocarcinomas are distributed approximately equally
are associated with a greatly increased lifetime risk of GI and extra-GI over the entire length of the colon. However, in younger adults (under age 50), there
cancers. is a gradual increase in left-sided (descending colon and rectal) cancers, whereas
older adults show a shift toward predominantly right-sided (cecal and ascending)
10.1.2. Adenomas Adenomas are the neoplastic precursors to the majority of
cancers.
colorectal adenocarcinomas, present in ~30% of Western adults by age 60. The
[Link]. Morphology
morphologic hallmark is epithelial dysplasia (nuclear hyperchromasia, elongation,
●​ Right-sided tumors typically grow as exophytic, polypoid masses that
and stratification). They are architecturally classified into tubular (small,
extend along the wall of the large-caliber cecum and ascending colon. They
pedunculated with rounded glands) and villous (larger, sessile with slender
rarely cause obstruction.
projections; higher risk of harboring cancer). A distinct variant, the sessile serrated
 ●​ Left-sided tumors tend to be annular, producing "napkin-ring" or characteristically present with left lower quadrant abdominal pain, fever,
"apple-core" constrictions that narrow the lumen and cause obstruction. anorexia, and obstipation. The best diagnostic tool is a contrast-enhanced
Microscopically, both are typically composed of tall columnar cells abdominal and pelvic computed tomography (CT) scan, which will reveal
resembling dysplastic adenoma epithelium, eliciting a strong desmoplastic thickened colonic walls (>4 mm), the presence of diverticula, and
stromal response making them firm. Poorly differentiated variants may inflammation within the pericolic fat. Complicated diverticular disease (such
produce abundant mucin or contain signet-ring cells, both indicating a poor as abscesses, strictures, or fistulas) is staged using the Hinchey
prognosis. classification system (Stages I through IV) based on the extent of localized
or generalized peritonitis and abscess formation.
[Link]. Clinical features Cancers develop insidiously. Right-sided cancers often ●​ Evaluation of Diverticular Bleeding: Hemorrhage from a colonic
ulcerate and bleed chronically, leading to fatigue, weakness, and iron-deficiency diverticulum is the most common cause of hematochezia (passage of red or
anemia. It is a clinical maxim that unexplained iron-deficiency anemia in an adult maroon blood) in patients over 60 years of age. The bleeding is typically
(especially older men or postmenopausal women) mandates evaluation for GI abrupt in onset, painless, sometimes massive, and often originates from the
cancer. Left-sided cancers are more likely to present with occult bleeding, changes right colon. The initial evaluation to localize the bleeding includes
in bowel habits, cramping, left lower quadrant discomfort, or frank hematochezia colonoscopy (after an oral lavage solution), multiplanar CT angiography, or a
(rectosigmoid lesions). nuclear medicine tagged red blood cell scan. If the patient presents with
[Link]. Diagnosis and morphology Diagnosis is definitively established via hemodynamic instability and a rapidly dropping hemoglobin level, upper
colonoscopy with endoscopic tissue biopsy. Radiographic barium enemas endoscopy must first be performed to rule out a massive upper
classically reveal "apple-core" constrictions in left-sided lesions. For asymptomatic gastrointestinal bleed mimicking a lower source.
screening, fecal immunochemical tests (FIT) and multitarget fecal DNA testing are ●​ Management of Diverticular Bleeding: Most diverticular bleeds are
highly sensitive for detecting adenocarcinoma. Once diagnosed, CT and MRI are self-limited and will stop spontaneously with bowel rest. If the bleeding site
utilized for preoperative staging of the tumor and detecting metastatic spread. is localized during colonoscopy, endoscopic therapy such as banding,
[Link]. Treatment and Prognosis Treatment primarily relies on surgical resection, placement of a detachable snare, or an over-the-scope hemoclip can
supplemented by systemic chemotherapy and/or radiation for advanced stages. The effectively achieve hemostasis and prevent emergent surgery. If the patient
most critical prognostic factors are the depth of tumor invasion (T stage) and the is stable but has ongoing bleeding, highly selective mesenteric angiography
presence of lymph node metastasis (N stage). Philippine Context on Prognosis: with coil embolization is highly successful (80% of cases) with a low risk of
Survival rates for colorectal cancer underscore severe disparities in global acute rebleeding (<25%) and colonic ischemia (<10%). If the patient is
healthcare. While 5-year survival rates in developed nations (e.g., Europe, Japan, refractory to endoscopic and angiographic interventions, remains
Australia, US) range around 60%, the overall survival rates for colorectal cancer in hemodynamically unstable, or requires massive blood transfusions, surgical
the Philippines are notably lower, ranging from only 30% to 42%. This highlights intervention is necessary. This involves a segmental resection if the bleeding
challenges in early screening access, late-stage presentations, and healthcare site is definitively known, or a subtotal colectomy with primary anastomosis
delivery in the region. if the exact site remains unidentified.
●​ Philippine and Asian Context: In Western nations, diverticula
predominantly affect the left and sigmoid colon, sparing the rectum.
11.1. Diverticulitis
However, in Asian populations, including the Philippines, the anatomical
11.1.1. Evaluation and management of diverticulosis and diverticular bleeding distribution is distinctly different, with 70% of diverticula occurring in the
right colon and cecum. Furthermore, while colonic diverticula stop bleeding
●​ Evaluation of Diverticulosis and Diverticulitis: Diverticulosis refers to the spontaneously in ≥90% of Western patients with a very low rebleeding rate
presence of diverticula, which are herniations of the mucosal and (~15% over 4–5 years), the rates of recurrent severe bleeding are
submucosal layers through the muscularis propria of the colon (specifically substantially higher in Asian populations, which may prompt earlier
where the nutrient artery, or vasa recta, penetrates the wall), creating a angiographic or surgical intervention in the Philippine clinical setting.
pseudodiverticulum. Patients with acute uncomplicated diverticulitis
11.2. Hemorrhoidal diseases, Anorectal abscess, fistula-in-ano, anal fissures 11.2.2. Presentation and evaluation

11.2.1. Anatomy and pathophysiology ●​ Hemorrhoidal Diseases: Patients typically present with bright red bleeding
(often noted only on toilet paper or coating the stool) and painless
●​ Hemorrhoidal Diseases: Hemorrhoidal cushions are a normal, highly protrusion of tissue. Pain is generally a dull ache from engorgement, but
vascularized part of the anal canal that aid in fecal continence by protecting severe, acute pain indicates a thrombosed hemorrhoid. Evaluation relies on
the sphincter muscle from damage. There are three main hemorrhoidal visual perianal inspection, a careful digital rectal examination (DRE), and
complexes: the left lateral, right anterior, and right posterior. Pathologically, anoscopy to stage the disease. The presentation must be differentiated
prolonged venous engorgement (due to straining, constipation, low-fiber from full-thickness rectal prolapse. In any patient presenting with bleeding
diets, or the venous stasis of pregnancy) weakens the anatomic connective and anemia, a colonic neoplasm must be ruled out with endoscopy,
tissue support system, causing this tissue to prolapse into the anal canal. especially with the rising rates of early-onset colorectal cancer.
Hemorrhoids are classified as external (originating below the dentate line, ●​ Anorectal Abscess: The hallmark symptoms are unrelenting perianal pain
covered by squamous epithelium) or internal (originating above the dentate and fever, sometimes accompanied by difficulty voiding and bloody stools.
line, covered by mucosa and transitional zone epithelium). They can also Physical examination reveals a large, visible, fluctuant, and exquisitely
develop as collateral anal varices secondary to portal hypertension. tender mass. Laboratory evaluation shows an elevated white blood cell
●​ Anorectal Abscess: An anorectal abscess is an abnormal fluid-containing (WBC) count. For recurrent or complex abscesses, a CT scan or MRI (80%
cavity resulting from an infection of the anal glands surrounding the anal accuracy for detecting incomplete drainage) is indicated, and a
canal. Normally, these glands release lubricating mucus into the canal; sigmoidoscopy may be performed to rule out underlying Crohn's disease or
however, when fecal matter accidentally enters the glands, bacterial proctitis.
infection ensues. Abscesses are categorized by their anatomic location: ●​ Fistula-in-ano: Patients complain of constant or intermittent purulent
perianal (40–50%), ischiorectal (20–25%), intersphincteric (2–5%), and drainage from the perianal region associated with tenderness, often
supralevator (2.5%). beginning approximately one month after the treatment of an abscess.
●​ Fistula-in-ano: An anal fistula is a chronic communication between an Evaluation under anesthesia is the best diagnostic method. During surgery,
abscess cavity and an identifiable internal opening within the anal canal, injecting hydrogen peroxide into the external opening can help trace the
most commonly located at the dentate line where the anal glands enter. tract to the internal opening. Tracts are mapped using Goodsall's rule: a
Between 30% and 40% of anorectal abscesses will eventually give rise to a posterior external opening will track to the posterior midline, while an
fistula. They are anatomically classified by their relation to the anal sphincter anterior opening will track straight to the nearest crypt in a radial fashion
muscles: intersphincteric (70%), transsphincteric (23%), suprasphincteric (unless the opening is >3 cm from the anal verge, which may have a
(5%), and extrasphincteric (2%). Ten percent of fistulas are secondary to complex upward extension). Preoperative MRI is highly effective (80%
other pathologies like inflammatory bowel disease (IBD), tuberculosis, accuracy) for mapping complex tracts.
radiation, or malignancy. ●​ Anal Fissures: The classic presentation is sharp, severe, relentless pain
●​ Anal Fissures: A fissure is a tear in the anal mucosa resulting from strongly associated with the act of defecation. Bright red bleeding may
mechanical trauma during defecation (usually passing hard stool). Fissures occur but is typically less extensive than with hemorrhoids and is usually
are most commonly located in the posterior or anterior midline of the anal only seen on wiping. Acute fissures look like a simple tear, but chronic
canal. The local trauma causes irritation that significantly increases the fissures (present for >6 weeks) develop classical anatomical markers: a
resting pressure (spasm) of the internal anal sphincter. Because the blood hypertrophied anal papilla at the proximal end, a sentinel pile (skin tag) at
supply to the sphincter enters laterally, this sustained increased tone results the distal end, and exposed circular fibers of the internal sphincter visible at
in relative local ischemia at the anterior/posterior poles, preventing the the base of the ulcer. Diagnosis is made easily on clinical history and gentle
mucosal injury from healing. Fissures located laterally are highly suspicious inspection.
for systemic etiologies such as tuberculosis, syphilis, Crohn's disease, or
malignancy. 11.2.3. Treatment
●​ Hemorrhoidal Diseases: Treatment is strictly tailored to the stage of the ●​ Anal Fissures: The goal of therapy is to relax the hypertonic internal
hemorrhoid. sphincter to restore mucosal blood flow.
○​ Stage I & II (Bleeding with no or spontaneously reducing ○​ Acute Fissures (<6 weeks): Conservative medical therapy including
protrusion): Medical management with fiber supplementation, stool stool softeners, dietary fiber, topical anesthetics, glucocorticoids,
softeners, and short courses of cortisone suppositories. and warm sitz baths heals 60–90% of cases.
Office-based procedures including rubber band ligation (causes ○​ Chronic Fissures (>6 weeks): Medical therapies aimed at
local ischemia and proximal fixation), infrared coagulation, and chemically relaxing the sphincter include the application of topical
sclerotherapy (injection of sodium tetradecyl sulfate) are also nitrates, calcium channel blockers, or targeted injections of
utilized. botulinum toxin into the internal sphincter (with >80% healing
○​ Stage III & IV (Protrusion requiring manual reduction or irreducible): rates).
Surgical management is required. Options include excisional ○​ Surgical Management: If medical therapy fails, a lateral internal
hemorrhoidectomy (Milligan-Morgan), stapled hemorrhoidopexy sphincterotomy is performed, wherein approximately one-third of
(Procedure for Prolapse and Hemorrhoids [PPH]), the hypertrophied internal sphincter muscle is surgically divided.
transhemorrhoidal dearterialization (THD) using ultrasound While highly effective at preventing recurrence, it carries a distinct
guidance, and bipolar electrocautery ligation (LigaSure). long-term risk of minor fecal incontinence, particularly in women.
○​ Acutely thrombosed external hemorrhoids: Best treated with an
elliptical excision and clot extraction under local anesthesia within 12.1.1. Cholelithiasis & Cholecystitis
the first 48 hours of onset.
Cholelithiasis (Gallstones)
●​ Anorectal Abscess: The absolute "gold standard" of treatment is prompt
surgical incision and drainage. Simple abscesses can be drained in an office ●​ Pathogenesis: Gallstones are formed due to abnormal bile composition
setting by making an incision close to the anal verge and placing a and are divided into cholesterol and pigment stones.
Mallenkot catheter for up to 1 week. Patients who are diabetic, ○​ Cholesterol stones (>50% cholesterol): Form due to four primary
immunocompromised, or have complex abscesses must be drained in the conditions: (1) supersaturation of bile with cholesterol (often due to
operating room to prevent necrotizing fasciitis. Antibiotics play a very limited hepatic hypersecretion); (2) gallbladder hypomotility leading to
role and are strictly reserved for patients exhibiting extensive surrounding stasis; (3) accelerated nucleation of cholesterol monohydrate
cellulitis or those who are significantly immunocompromised. crystals; and (4) hypersecretion of mucus, which traps crystals to
●​ Fistula-in-ano: Surgical intervention is mandatory, usually beginning with form stones. Risk factors include obesity, female sex hormones
the placement of a seton catheter into the tract to allow continuous (pregnancy, oral contraceptives), age, and genetics.
drainage and reduction of acute inflammation over 4 to 6 weeks. Definitive ○​ Pigment stones: Composed of calcium bilirubinate. Black pigment
treatment depends on the tract's location: stones are linked to sterile bile in patients with chronic hemolytic
○​ Sphincter-cutting procedures (Fistulotomy/Fistulectomy): Used for anemias or ileal disease. Brown pigment stones contain cholesterol
intersphincteric and low transsphincteric fistulas (involving less and calcium soaps and are heavily linked to chronic bacterial
than one-third of the sphincter muscle). They have a 94% success infections or parasitic infestations of the biliary tree.
rate but carry a 13% risk of mild fecal incontinence. ○​ Philippine & Asian Context: While cholesterol stones dominate
○​ Sphincter-sparing procedures: Used for high transsphincteric Western countries, pigment stones are highly prevalent in
fistulas to prevent severe incontinence. These include anorectal non-Western and Asian populations. Biliary infections caused by
advancement flaps, ligation of the intersphincteric fistula tract (LIFT enteric bacteria (E. coli) or endemic parasites (such as Ascaris
procedure), and the injection of fibrin or cyanoacrylate glue. These lumbricoides or the liver fluke Clonorchis sinensis) release
preserve continence entirely and have a success rate of up to microbial β-glucuronidases that deconjugate bilirubin, leading to
78%. the precipitation of brown pigment stones.
 ●​ Clinical Features: 70–80% of patients remain asymptomatic throughout subcostal palpation). Jaundice is unusual and suggests common bile duct
their lives. When symptomatic, the hallmark is "biliary colic"—a misnomer, obstruction.
as the pain is usually constant, not colicky. It presents as a steady ache or ●​ Diagnosis: Made based on the clinical triad of sudden RUQ tenderness,
fullness in the epigastrium or right upper quadrant (RUQ), frequently fever, and leukocytosis (typically 10,000–15,000 cells/μL with a left shift).
radiating to the right scapula or interscapular area. It is often precipitated by Ultrasound demonstrates gallstones, gallbladder wall thickening, and
a fatty meal and lasts 30 minutes to 5 hours. pericholecystic fluid. A radionuclide (HIDA) scan confirms the diagnosis if
●​ Diagnosis: Transabdominal ultrasound is the procedure of choice, the bile ducts are imaged but the gallbladder fails to visualize (indicating
accurately identifying >95% of stones as echogenic opacities that cast an cystic duct obstruction).
acoustic shadow and move with gravity. Plain abdominal X-rays have a low ●​ Management: Medical stabilization includes fasting (NPO), IV fluids, and
yield but can detect the 10-20% of cholesterol stones and 50-75% of black intravenous antibiotics (e.g., piperacillin-tazobactam or ceftriaxone plus
pigment stones that contain enough calcium to be radiopaque. metronidazole). Early laparoscopic cholecystectomy (within 72 hours) is the
●​ Management: Prophylactic cholecystectomy is generally not recommended treatment of choice. For critically ill, unstable patients with acalculous or
for asymptomatic patients due to a low cumulative risk of complications. complicated cholecystitis, percutaneous cholecystostomy drainage is
For symptomatic patients, laparoscopic cholecystectomy is the "gold performed.
standard," boasting minimal disability and a mortality rate <0.1%. Medical
dissolution using oral ursodeoxycholic acid (UDCA) is reserved for poor 12.1.2. Choledochal Cysts
surgical candidates with small (<5–10 mm), radiolucent cholesterol stones in
●​ Pathogenesis: Congenital dilations of the extrahepatic biliary tree, most
a functioning gallbladder, though recurrence rates are high.
commonly the free portion of the common bile duct. They may also occur
Cholecystitis as diverticula in the intraduodenal segment or alongside intrahepatic duct
dilations (Caroli disease). The anomaly predisposes patients to stone
●​ Pathogenesis: Inflammation of the gallbladder, almost always associated formation, stenosis, and recurrent cholangitis.
with gallstones. ●​ Clinical Features: They present most often in children before age 10,
○​ Acute calculous cholecystitis (90%): Initiated by a gallstone though ~20-50% present in adulthood. There is a strong female predilection
obstructing the cystic duct or gallbladder neck. Distention (3:1 to 4:1 ratio). Patients classically present with a triad of jaundice,
increases intraluminal pressure, causing ischemia. Mucosal recurrent abdominal pain, and a palpable abdominal mass (though only
phospholipases hydrolyze lecithin to toxic lysolecithin, causing one-third exhibit the full triad). Notably, patients with choledochal cysts are
chemical inflammation. Bacterial superinfection (e.g., E. coli, at a highly increased risk of developing cholangiocarcinoma.
Klebsiella, Enterococcus) eventually develops in 50–85% of cases. ●​ Diagnosis: Ultrasound, abdominal CT, or MRCP reliably demonstrate the
○​ Acute acalculous cholecystitis (10%): Occurs in the absence of cystic dilation separate from the gallbladder and its connection to the
stones, typically in severely ill hospitalized patients (e.g., sepsis, extrahepatic bile ducts.
major trauma, burns, prolonged fasting). It is driven by gallbladder ●​ Management: Complete surgical excision of the cyst combined with a
ischemia and stasis of viscous bile/sludge. biliary-enteric anastomosis (e.g., Roux-en-Y hepaticojejunostomy) is
○​ Chronic cholecystitis: Associated with cholelithiasis in >90% of required to relieve symptoms and eliminate the malignant risk.
cases, resulting from repeated bouts of acute inflammation or
continuous mechanical irritation from stones. It features 12.1.3. Tumors of the Gallbladder (Benign and Pre-malignant)
subepithelial fibrosis and mucosal outpouchings known as
●​ Pathogenesis & Morphology:
Rokitansky-Aschoff sinuses.
○​ Hyperplastic Cholecystoses: Benign proliferations of normal
●​ Clinical Features: Progressive RUQ pain lasting >6 hours, fever, anorexia,
tissues. Adenomyomatosis involves benign epithelial proliferation
nausea, and vomiting. Examination classically reveals localized RUQ
with extramural sinuses and strictures. Cholesterolosis ("strawberry
tenderness, marked by Murphy's sign (inspiratory arrest during deep
 gallbladder") is characterized by the abnormal deposition of recommended for patients who achieve complete (R0) resection.
cholesteryl esters within macrophages in the lamina propria. The 5-year survival rate for resectable cases ranges from 60–90%
○​ Gallbladder Polyps: Include cholesterol polyps, inflammatory depending on invasion depth.
polyps, adenomyomas, and adenomas. Their prevalence is 3–6% ○​ Advanced/Unresectable Disease: Tumors with distant metastases
in adults. or severe local invasion are treated with palliative intent. First-line
●​ Clinical Features: Most benign tumors and polyps are asymptomatic and systemic therapy includes a combination of gemcitabine, cisplatin,
discovered incidentally on ultrasound. and an immunomodulator (durvalumab), yielding a median overall
●​ Diagnosis & Management: No intervention is needed for asymptomatic survival of 10 to 12 months. Percutaneous transhepatic drainage is
cholesterolosis or small polyps. Cholecystectomy is recommended for utilized to relieve symptomatic biliary obstruction. Radiotherapy is
symptomatic patients or asymptomatic patients >50 years old whose considered ineffective for this cancer.
polyps are >10 mm, are growing on serial ultrasound, or are accompanied
by gallstones, due to the substantial risk of malignant transformation. 13.1.1. Regulation of pancreatic secretion (physiology)

12.1.4. Carcinoma of the Gallbladder The exocrine pancreas secretes between 1500 and 3000 mL of isosmotic, alkaline
(pH >8) fluid daily, containing approximately 20 enzymes essential for digestion.
●​ Pathogenesis: It is the most common malignancy of the extrahepatic biliary Secretion is regulated in a phasic manner (cephalic, gastric, and intestinal phases)
tract. Gallstones are present in 95% of cases. Chronic inflammation of the through complex neuro-hormonal pathways:
gallbladder mucosa—from gallstones, chronic bacterial/parasitic infection,
or primary sclerosing cholangitis—acts as the primary catalyst for malignant ●​ Water and Electrolyte Secretion: Gastric acid entering the duodenum
transformation. Another notable risk factor is a "porcelain gallbladder" stimulates S cells in the duodenal mucosa to release secretin. Secretin
(extensive dystrophic calcification of the gallbladder wall from chronic binds to basolateral receptors on pancreatic ductal cells, increasing
cholecystitis). intracellular cyclic AMP, which opens the cystic fibrosis transmembrane
○​ Philippine/Asian Context: The incidence of biliary tract cancers is conductance regulator (CFTR) chloride channel on the apical surface to
strongly correlated with the regional prevalence of endemic risk promote the secretion of water and bicarbonate. This bicarbonate
factors. Asian regions with high rates of liver fluke infestations and neutralizes gastric acid and creates an optimal pH for digestive enzymes.
hepatolithiasis (intrahepatic stones) experience elevated incidences ●​ Enzyme Secretion: The presence of long-chain fatty acids and essential
of cholangiocarcinomas and gallbladder malignancies. amino acids in the duodenum triggers Ito cells to release cholecystokinin
●​ Clinical Features: The clinical presentation is notoriously insidious, leading (CCK). CCK evokes an enzyme-rich secretion from pancreatic acinar cells.
to late diagnoses. Early-stage cancer is almost exclusively discovered In humans, CCK works primarily as a neuromodulator by stimulating
incidentally during routine cholecystectomy for gallstone disease. In afferent vagal and intrapancreatic nerves rather than binding directly to
advanced stages, patients present with symptoms mimicking chronic acinar cells.
cholecystitis or biliary obstruction: right upper quadrant pain, painless ●​ Neural Modulation: The parasympathetic nervous system (via the vagus
jaundice, anorexia, and significant weight loss. nerve) exerts significant control, particularly during the cephalic phase.
●​ Diagnosis: Magnetic Resonance Cholangiopancreatography (MRCP) is the Acetylcholine and vasoactive intestinal peptide (VIP) strongly potentiate
most accurate imaging modality to define staging and the extent of vascular ductal and acinar cell secretion,.
and biliary tract invasion. CT and PET scans are used for preoperative ●​ Feedback Inhibition: Pancreatic secretion is counterbalanced by inhibitory
staging of distant or lymph node metastases. neuropeptides such as somatostatin, pancreatic polypeptide, and peptide
●​ Management: YY. Furthermore, an enteropancreatic axis relies on a peptide called
○​ Local/Resectable Disease (only ~20% of cases): The mainstay of CCK-releasing factor (CCK-RF); when intraluminal dietary proteins are fully
curative intent is surgical resection via simple or radical digested, free pancreatic proteases degrade CCK-RF, terminating CCK
cholecystectomy (involving partial hepatectomy and regional lymph release and halting further enzyme secretion.
node dissection). Adjuvant chemotherapy (capecitabine) is
13.1.2. Auto protection of the pancreas ●​ Chronic Pancreatitis: This is a syndrome of irreversible pancreatic
damage.
To prevent the pancreas from digesting itself (autodigestion), several highly ○​ Etiology: Long-term, heavy alcohol use is the most common
coordinated protective mechanisms are in place: cause, and cigarette smoking is a major independent,
dose-dependent risk factor that accelerates disease progression,,.
1.​ Zymogen Packaging: Digestive proteases (e.g., trypsin, chymotrypsin,
About 25% of cases are idiopathic, and up to 25% have a genetic
elastase) are synthesized as inactive proenzymes (zymogens) and packaged
basis,.
within secretory granules,,. They normally remain inactive until they reach
○​ Pathogenesis: Repeated episodes of acute acinar cell injury lead to
the duodenum, where the brush-border enzyme enteropeptidase
the release of profibrogenic cytokines (e.g., TGF-β and PDGF).
(enterokinase) cleaves trypsinogen into active trypsin, which then initiates
These cytokines activate pancreatic stellate cells (periacinar
a cascade activating the other enzymes,.
myofibroblasts), shifting their function toward fibrogenesis, leading
2.​ Intracellular Calcium Homeostasis: Low intracellular calcium levels in the
to irreversible collagen deposition, parenchymal fibrosis, and
acinar cell cytosol promote the spontaneous destruction of any prematurely
acinar cell loss,,.
activated trypsin.
3.​ Trypsin Inhibitors: Acinar and ductal cells synthesize and secrete specific [Link]. Clinical and laboratory features
trypsin inhibitors, such as serine protease inhibitor Kazal type 1
(SPINK1), which binds and inactivates up to 20% of intracellular trypsin ●​ Acute Pancreatitis:
activity,. Chymotrypsin C is also present to lyse and inactivate trypsin. ○​ Clinical: Presents with steady, severe, "boring" epigastric pain that
frequently radiates to the back, accompanied by nausea, vomiting,
13.1.3. Acute and chronic pancreatitis and abdominal distention. Severe necrotizing cases may present
with shock and periumbilical bruising (Cullen's sign) or flank
[Link]. Etiology and pathogenesis
bruising (Turner's sign) due to tissue breakdown.
●​ Acute Pancreatitis: Acute pancreatitis results from the inappropriate ○​ Laboratory: Serum lipase and amylase elevated greater than
intrapancreatic activation of trypsin, which triggers autodigestion, three times the upper limit of normal strongly support the
microvascular leak, edema, fat necrosis, and an intense systemic diagnosis. Lipase is preferred as it is more specific and remains
inflammatory response,,. elevated for 8 to 14 days (compared to 3–5 days for amylase),.
○​ Etiology: Gallstones and heavy alcohol use account for 80–90% Leukocytosis, hemoconcentration (hematocrit >44%), elevated
of cases in the United States,. Other causes include severe blood urea nitrogen (BUN), and hypocalcemia (from saponification
hypertriglyceridemia (>1000 mg/dL), endoscopic retrograde of fat) are common.
cholangiopancreatography (ERCP), trauma, hypercalcemia, and ●​ Chronic Pancreatitis:
drugs (e.g., azathioprine, statins, DPP-4 inhibitors),,. Genetic ○​ Clinical: Presents with intermittent or constant abdominal/back
mutations (PRSS1, SPINK1, CFTR) can also predispose to pain. Disease progression leads to exocrine insufficiency
recurrent acute attacks,,. Infections such as mumps and (steatorrhea, fat-soluble vitamin deficiencies, weight loss) and
coxsackievirus can directly injure acinar cells,. endocrine insufficiency (diabetes mellitus),.
○​ Asian/Philippine Context: While cholesterol gallstones dominate in ○​ Laboratory: Serum amylase and lipase are usually not strikingly
Western countries, populations in Asia and rural areas have a high elevated because of massive acinar cell dropout,. Diagnosis relies
prevalence of pigment gallstones driven by chronic biliary tract on tests of exocrine function, such as decreased fecal elastase-1
infections and endemic parasitic infestations (e.g., Ascaris (<100 μg/g indicates severe insufficiency) and an abnormal
lumbricoides, Clonorchis sinensis),,. These pathogens release secretin stimulation test (peak bicarbonate <80 mEq/L),,,.
microbial β-glucuronidases that precipitate pigment stones,
[Link]. Morphology of the pancreas
creating a high regional risk for biliary tract obstruction and
secondary gallstone pancreatitis,.
 ●​ Acute Pancreatitis: The morphology ranges from interstitial edematous 13.1.4. Pancreatic pseudocysts
pancreatitis (diffuse gland enlargement and peripancreatic fluid) to
necrotizing pancreatitis,. The basic alterations include microvascular leak, Pancreatic pseudocysts are local complications that account for 75% of all
acute inflammation, fat necrosis (characterized by blue granular calcium pancreatic cysts.
soaps due to saponification), parenchymal autodigestion, and blood vessel
●​ Pathogenesis & Morphology: They are formed when areas of
destruction leading to interstitial hemorrhage (red-black discoloration),.
intrapancreatic or peripancreatic hemorrhagic fat necrosis are walled off by
●​ Chronic Pancreatitis: Characterized by parenchymal fibrosis, acinar
fibrosis and granulation tissue following an attack of acute pancreatitis or
atrophy and dropout, and variable ductal dilation. Grossly, the gland is
trauma. They are termed "pseudocysts" because they lack a true
hard with dilated ducts containing inspissated eosinophilic protein plugs or
epithelial lining,. Maturation usually requires >4 weeks after the onset of
calcified concretions,. The islets of Langerhans are relatively spared until
acute interstitial pancreatitis.
late in the disease. Autoimmune pancreatitis type 1 specifically displays a
●​ Clinical Course: They are usually solitary, ranging from 2 to 30 cm in
unique dense lymphoplasmacytic inflammation rich in IgG4-secreting
diameter, and frequently localize in the lesser omental sac. While many
plasma cells, storiform fibrosis, and obliterative phlebitis,.
resolve spontaneously, some persist and become symptomatic, causing
[Link]. Factors that adversely affect the survival pain by compressing adjacent structures, or they may become secondarily
infected or perforate,. Symptomatic pseudocysts require endoscopic
●​ Acute Pancreatitis: The critical clinical parameter that dictates mortality is transpapillary or transmural drainage, or surgical intervention,.
persistent organ failure (>48 hours) involving the respiratory,
cardiovascular, or renal systems,,. Other major adverse prognostic 13.1.5. Carcinoma of the pancreas
indicators include the presence of infected pancreatic necrosis,
Infiltrating ductal adenocarcinoma of the pancreas is one of the most lethal
hemoconcentration, admission azotemia (rising BUN), and the Systemic
malignancies, representing the third leading cause of cancer deaths in the United
Inflammatory Response Syndrome (SIRS),,. Mortality approaches 50% if
States with a 5-year survival rate of only 10%.
multiorgan failure develops.
●​ Chronic Pancreatitis: Long-term outlook is poor, with a 50% mortality rate ●​ Pathogenesis: Greater than 90% of pancreatic cancers arise from
over 20 to 25 years. Survival is adversely affected by malnutrition, diabetes microscopic, noninvasive precursor lesions called pancreatic
mellitus complications, and the significantly increased risk of pancreatic intraepithelial neoplasia (PanIN). Progression from normal ducts to
cancer. Patients with hereditary PRSS1 mutations carry a massive 40% invasive carcinoma follows a stepwise accumulation of mutations. Telomere
lifetime risk of developing pancreatic cancer,. shortening and activating mutations in the KRAS oncogene occur early,.
Subsequent inactivation of tumor suppressor genes, specifically CDKN2A
[Link]. Course and Complications
(p16), TP53, SMAD4, and BRCA2, drive the transition to high-grade PanIN
●​ Acute Pancreatitis: Most cases (85-90%) are mild and self-limited, and invasive cancer,.
resolving in 3-7 days,. Complications typically develop in the "late phase" ●​ Risk Factors: Primarily a disease of older adults (>60 years). Cigarette
(>2 weeks) and include local structural issues: acute peripancreatic fluid smoking is the strongest environmental influence, doubling the risk. Other
collections, acute necrotic collections (ANC), and walled-off necrosis risks include chronic pancreatitis, obesity, and diabetes mellitus (new-onset
(WON),,,. Perivascular complications can include splanchnic venous diabetes in an elderly patient may herald an occult pancreatic cancer).
thrombosis (splenic vein) and ruptured pseudoaneurysms,. Approximately 10% of patients have germline mutations (BRCA2, PALB2,
●​ Chronic Pancreatitis: Characterized by relentless, irreversible progression. STK11/Peutz-Jeghers, PRSS1),.
Complications include intractable chronic abdominal pain (often leading to ●​ Morphology: 60% of carcinomas arise in the head of the pancreas, 15% in
narcotic dependence), stricturing of the common bile duct or pancreatic the body, and 5% in the tail. They are highly invasive and characteristically
duct, metabolic bone disease (osteoporosis in ~65% of patients), and elicit an intense desmoplastic response, leading to the deposition of
pancreatic pseudocysts,,. dense collagen that creates a hard, stellate, gray-white mass. The tumors
 rapidly invade local nerves (perineural invasion), blood vessels, and the
retroperitoneum.
●​ Clinical Features: The disease remains silent until advanced. Carcinomas
in the head of the pancreas frequently obstruct the distal common bile duct,
presenting with painless obstructive jaundice and a palpable, nontender
gallbladder (the Courvoisier sign). Tumors in the body and tail do not
impinge the biliary tract and spread widely before detection. Advanced
disease presents with severe pain, extreme weight loss, anorexia, and
sometimes Trousseau sign (migratory thrombophlebitis caused by
tumor-elaborated procoagulants). Because of aggressive local invasion and
metastasis (principally to the liver and lungs), >80% of patients have
unresectable disease at the time of diagnosis,.