Epigastric Pain

Epigastric pain is discomfort localized to the upper central abdomen, commonly arising from gastric, duodenal, pancreatic, or biliary pathology.

Epigastric pain is pain localised to the upper central region of the abdomen, bounded superiorly by the xiphisternum, inferiorly by the transumbilical plane, and laterally by the midclavicular lines bilaterally. It corresponds roughly to the epigastrium — one of the nine regions of the abdomen.

"Epigastric" breaks down as: epi- (Greek: upon/above) + gastric (Greek: gaster = stomach) — literally "upon the stomach." This is logical because the stomach and adjacent foregut structures sit directly behind this region.

Epigastric pain is not a diagnosis; it is a presenting complaint that encompasses a vast differential ranging from benign functional dyspepsia to life-threatening emergencies such as perforated peptic ulcer, acute pancreatitis, ruptured abdominal aortic aneurysm, and even acute myocardial infarction. The clinical approach therefore demands a systematic framework linking anatomy, referred pain pathways, and pathophysiology to narrow the differential efficiently.

Key Concept

Epigastric pain is a symptom, not a disease. Your job is to work backwards from the pain to the organ, then from the organ to the pathology, using the character, timing, radiation, and associated features to narrow the differential.

Relationship to Dyspepsia

Dyspepsia is a broader syndrome defined by the Rome IV criteria (updated from Rome III) as one or more of ^[1]^[2]:

Postprandial fullness
Early satiety
Epigastric pain
Epigastric burning

These symptoms must be prominent enough to affect daily activities. Approximately 75% of patients with dyspepsia have functional dyspepsia (no identifiable organic cause), while 25% have an underlying organic cause ^[1]^[2].

Alarm features in dyspepsia (mandating urgent investigation) include ^[1]^[2]:

Age ≥ 40 years (in Asian populations; ≥ 55 years in Western guidelines) with newly onset dyspepsia
Family history of upper GI cancer
Jaundice
Unintended weight loss
Dysphagia or odynophagia
GI bleeding (haematemesis, melaena)
Unexplained iron-deficiency anaemia
Persistent vomiting
Palpable mass or lymphadenopathy

High Yield: In Hong Kong, the age threshold for OGD is typically ≥ 40 years with new-onset dyspepsia (lower than Western guidelines) because of higher gastric cancer prevalence in East Asia ^[2].

Epidemiology and Risk Factors

Condition	Epidemiological Highlights (HK/Asia Focus)
Functional dyspepsia	Prevalence 10–20% among Chinese; most common cause of epigastric discomfort; F > M = 2:1; usually < 40 years ^[2]
Peptic ulcer disease	Incidence ~1/1000/year, lifetime risk ~10%, falling trend (↓ H. pylori, ↓ smoking); M:F = 3:1 for DU ^[1]^[3]
GERD	Rising incidence in HK (2.5% in 2002 → 3.7% in 2011); Asians present atypically with less severe oesophagitis ^[4]
Gastric cancer	6th in incidence, 4th in cancer mortality; ↑ in Asia (Japan, Korea, China); 90% adenocarcinoma; distal stomach MC site ^[5]^[6]
Pancreatic carcinoma	Head (60%), body (15%), tail (5%), diffuse (20%); 90% ductal adenocarcinoma ^[7]^[8]
Acute pancreatitis	Gallstones MC cause in HK; alcohol second; incidence rising globally ^[1]^[9]
Biliary colic / cholecystitis	Gallstones affect ~10–15% of adults; 80% remain asymptomatic; higher prevalence in females (4F's: Female, Forty, Fat, Fertile) ^[9]
Acute MI (inferior)	Must always be considered; epigastric pain can be the sole presenting complaint, especially in diabetics (autonomic neuropathy masks chest pain)

Anatomy and Function

Understanding which organs sit in or refer pain to the epigastrium is essential. The key concept is the distinction between visceral pain and somatic (parietal) pain.

Feature	Visceral Pain	Somatic (Parietal) Pain
Origin	Distension, ischaemia, or spasm of hollow viscera / capsular stretch of solid organs	Inflammation of parietal peritoneum
Nerve fibres	Autonomic (sympathetic) afferents; poorly localised	Somatic (spinal) afferents; well-localised
Character	Dull, vague, crampy, midline	Sharp, localised, constant
Location	Referred to dermatome of embryological origin	Directly over the inflamed area
Associated features	Nausea, vomiting, sweating (autonomic)	Guarding, rigidity, rebound tenderness

Why is foregut pain felt in the epigastrium? The foregut (stomach, duodenum D1–D2, liver, gallbladder, pancreas, spleen) is innervated by the coeliac (splanchnic) plexus, which enters the spinal cord at T5–T9. The brain interprets this afferent input as coming from the T5–T9 dermatomes, which map to the epigastrium. This is why gastric ulcer pain, biliary colic, and early appendicitis (midgut = T10) all start as poorly localised midline pain before parietal peritoneal involvement causes localisation.

Etiology (Hong Kong Focus) and Pathophysiology

Below are the major causes of epigastric pain, organised by system, with their pathophysiological mechanisms explained from first principles.

1. Peptic Ulcer Disease (PUD)

Definition: A defect in the gastric or duodenal mucosa that extends through the muscularis mucosae into the submucosa or deeper ^[1]^[3].

Sites ^[3]:

Duodenal ulcer (75%): usually solitary, in D1 (anterior wall perforates; posterior wall bleeds from gastroduodenal artery)
Gastric ulcer (20%): usually lesser curvature / corpus-antrum junction
Lower oesophagus, Meckel's diverticulum (ectopic gastric epithelium), stomal ulcer

H. pylori infection ^[1]^[3]:

Present in 92% of DU and 70% of GU
Microaerophilic Gram-negative coccobacillus
Strong urease activity — hydrolyses urea → ammonia + CO₂ → neutralises surrounding acid → creates a "protective cloud" allowing survival
Spiral shape, flagella, and mucolytic enzymes — facilitates penetration through the mucus layer to reach the gastric surface epithelium
Induces chronic active gastritis → direct epithelial injury by toxins (CagA, VacA) + host inflammatory response → disruption of mucosal defence → ulceration
In duodenal ulcer: H. pylori colonises gastric metaplasia in duodenum; promotes antral-predominant gastritis → ↑ gastrin → ↑ acid load to duodenum → duodenal injury
In gastric ulcer: pangastritis → mucosal atrophy → ↓ acid (paradoxically) but ↓ mucosal defence even more → ulceration

NSAIDs (including aspirin) ^[1]^[3]:

Present in 5% of DU and 25% of GU
Gastric and duodenal mucosa use COX-1 for prostaglandin synthesis
Prostaglandins (PGE₂) protect mucosal lining via: mucin production, mucosal bicarbonate secretion, maintaining mucosal blood flow, and inhibiting gastric acid secretion
NSAIDs non-selectively inhibit COX-1 and COX-2 → impaired prostaglandin production → disruption of mucosal barrier → increased mucosal permeability to H⁺ ions → acid-mediated damage
Selective COX-2 inhibitors spare COX-1-mediated GI protection
Risk factors for NSAID ulcers: advanced age ( > 75 years), prior ulcer history, high-dose / long-duration NSAIDs, concurrent corticosteroids / anticoagulants ^[1]

Other aetiologies ^[1]^[3]:

Stress ulcers — burns (Curling's ulcer), head injury (Cushing's ulcer — vagal-mediated acid hypersecretion), mechanical ventilation, coagulopathy; due to impaired mucosal perfusion + biliary reflux
Smoking — 2× risk; impairs mucosal blood flow and bicarbonate secretion, accelerates gastric emptying of acid into duodenum
Alcohol — direct mucosal irritant
Zollinger-Ellison syndrome — gastrinoma (usually pancreatic or duodenal) → hypergastrinaemia → massive acid hypersecretion → ulcers at atypical locations (D2, jejunum); suspect when recurrent ulcers despite adequate treatment, ulcers in unusual locations, H. pylori-negative, no NSAID use ^[1]

Epidemiology: ↓ trend globally but ↑ in Asia; 6th in incidence, 4th in cancer mortality; adenocarcinoma (90%) > lymphoma (5%) > GIST, metastasis; site: distal stomach (antrum/pylorus) > cardia (↑ trend) > OGJ ^[5]^[6].

Risk factors ^[5]^[6]:

Compensatory epithelial cell proliferation:
- H. pylori → chronic atrophic gastritis → intestinal metaplasia → body/distal CA (intestinal type)
- Chronic gastric reflux (e.g., Barrett's oesophagus) → proximal CA
- History of gastric resection → bile reflux (e.g., Billroth II) → chronic gastritis
- Chronic atrophic gastritis associated with pernicious anaemia and Ménétrier's disease
Environmental factors: smoking, smoked/pickled food, nitrosamines, alcohol
Host factors: hereditary diffuse gastric carcinoma (HDGC: E-cadherin mutation), HNPCC, FAP, Peutz-Jeghers syndrome ^[5]^[6]
Adenomatous polyps ^[6]
Previous partial gastrectomy ( > 20 years) ^[6]
EBV infection (~10%) ^[5]
Industrial exposure (dusty, high temperature, rubber, coal mining, metal processing, chromium production) ^[6]
Pernicious anaemia ^[6]
Common variable immunodeficiency (CVID) ^[6]

Classification (Lauren) ^[5]:

Feature	Intestinal Type	Diffuse Type
Differentiation	Well-differentiated, better prognosis	Undifferentiated, poorer prognosis
Risk factors	H. pylori, environmental	HDGC (E-cadherin mutation)
HER2	+ve in 15%	-ve; signet ring cells +ve
Spread	Haematogenous	Transmural (linitis plastica) and lymphatic
Demographics	Elderly male, distal stomach	Young female, proximal stomach

Pathophysiology of epigastric pain in gastric cancer: The tumour invades the gastric wall → serosal irritation and involvement of the coeliac plexus → constant, dull epigastric pain. Antral tumours may cause gastric outlet obstruction → distending pain with vomiting. Ulceration within the tumour mimics peptic ulcer pain.

Classification of Epigastric Pain

Category	Examples
Acute ( < 24–48 hours)	Perforated PU, acute pancreatitis, biliary colic, acute cholecystitis, acute MI, ruptured AAA, gastric volvulus
Subacute (days–weeks)	Gastritis, PUD, cholangitis, GOO
Chronic ( > 4 weeks)	Functional dyspepsia, GERD, chronic pancreatitis, gastric cancer, pancreatic cancer

Mechanism	Character	Examples
Visceral (distension/spasm)	Dull, vague, midline, ± N/V	Biliary colic, early appendicitis, functional dyspepsia, gastric distension
Somatic (peritoneal irritation)	Sharp, well-localised, ↑ with movement	Perforated PU, cholecystitis with localised peritonitis
Referred	Pain felt distant from source	Inferior MI → epigastric; diaphragmatic irritation → shoulder tip
Inflammatory	Constant, progressive	Pancreatitis, cholecystitis
Neoplastic	Constant, progressive, with weight loss	Gastric cancer, pancreatic cancer

Source	Conditions
Oesophagus	GERD, oesophagitis, oesophageal spasm, Mallory-Weiss tear, Boerhaave's perforation
Stomach	Gastritis, gastric ulcer, gastric cancer, gastric volvulus, gastroparesis
Duodenum	Duodenal ulcer, duodenitis, periampullary tumour
Hepatobiliary	Biliary colic, cholecystitis, cholangitis, hepatitis, liver abscess, HCC
Pancreas	Acute/chronic pancreatitis, pancreatic cancer
Vascular	AAA, mesenteric ischaemia, SMA syndrome
Cardiac	Acute MI (inferior), myopericarditis
Other	Herpes zoster (T5–T9 dermatome), musculoskeletal, DKA, Addisonian crisis

Clinical Features

A. Symptoms with Pathophysiological Basis

Feature	Significance	Pathophysiological Basis
Site: epigastric	Foregut structures (T5–T9)	Visceral afferents from stomach, duodenum, pancreas, gallbladder all converge on T5–T9 segments
Onset: sudden	Perforation, vascular event	Sudden peritoneal contamination (PPU) or acute ischaemia (MI, AAA)
Onset: gradual	Inflammatory or functional	Accumulating inflammation (pancreatitis) or ongoing functional derangement (FD)
Character: burning	Acid-related	Mucosal contact with H⁺ ions → nociceptor activation in exposed submucosa
Character: sharp, constant	Peritoneal irritation	Parietal peritoneum has somatic innervation → sharp, well-localised pain
Character: dull, crampy	Visceral distension/spasm	Hollow viscus distension (biliary colic) or smooth muscle spasm stimulates poorly-localised autonomic afferents
Character: tearing	Aortic dissection	Intimal tear with propagating haematoma stretching the aortic wall
Radiation: to back	Pancreatitis, pancreatic CA, penetrating posterior DU	Retroperitoneal location of pancreas → inflammation/invasion of coeliac/superior mesenteric plexus ^[7]^[9]
Radiation: to right shoulder	Biliary pathology	Phrenic nerve (C3–C5) irritation by diaphragmatic inflammation from gallbladder → referred to C3–C5 dermatome (shoulder)
Radiation: interscapular	Aortic dissection	Descending aorta posterior to heart → pain referred to interscapular region

Pattern	Condition	Why?
Pain immediately after meals → afraid of eating	Gastric ulcer	Food stimulates acid secretion → acid contacts exposed ulcer base → pain ^[3]
Pain 2 hours after meals; relieved by eating	Duodenal ulcer	Food buffers gastric acid temporarily → relief; 2–3 hours later as stomach empties, acid bolus enters duodenum → pain ^[3]
Pain after fatty meals	Biliary colic	Fat → CCK release → gallbladder contraction against impacted stone → pain
Pain after heavy meals, worse lying flat	GERD	Large meal → gastric distension → ↑ transient LES relaxation + ↑ intra-abdominal pressure → reflux
Pain exacerbated by movement	Peritonitis (e.g., PPU)	Movement stretches inflamed parietal peritoneum → somatic pain ^[3]
Pain relieved by leaning forward	Acute pancreatitis, CA pancreas	Leaning forward takes pressure off the inflamed retroperitoneal pancreas by moving it away from the vertebral column and coeliac plexus ^[9]

Symptom	Conditions	Pathophysiology
Nausea and vomiting	Most causes of epigastric pain	Vagal afferent stimulation from visceral inflammation → vomiting centre in medulla
Non-bilious projectile vomiting of undigested food	Gastric outlet obstruction	Obstruction proximal to the ampulla of Vater → bile cannot enter stomach → vomitus contains food/gastric juice but no bile ^[10]
Bilious vomiting	Obstruction distal to ampulla	Bile from CBD enters duodenum proximal to obstruction → refluxes into stomach → bilious vomit
Haematemesis (fresh blood)	Severe/acute UGIB (PUD, varices, Mallory-Weiss)	Rapid bleeding from arterial erosion or variceal rupture — blood does not remain long enough for acid digestion
Coffee-ground vomiting	Slow UGIB	Haemoglobin exposed to gastric acid → oxidised to acid haematin (dark brown) → coffee-ground appearance
Melaena	UGIB (PUD, gastric CA)	Blood digested through GI tract → haemoglobin broken down by bacteria → dark, tarry, foul-smelling stool ^[6]
Early satiety	Gastric CA (linitis plastica), FD, GOO	Linitis plastica: diffuse infiltration → non-compliant, rigid stomach → cannot accommodate food; FD: impaired gastric accommodation reflex
Dysphagia	CA oesophagus/cardia, GERD stricture	Luminal narrowing → progressive difficulty swallowing solids then liquids (mechanical) vs. solids and liquids from the start (motility)
Steatorrhoea	Chronic pancreatitis, pancreatic CA	↓ Pancreatic lipase → undigested fat in stool → pale, greasy, foul-smelling, floating stools
Heartburn and regurgitation	GERD	Acid contacts squamous epithelium → burning; LES incompetence → gastric content flows retrogradely to throat ^[4]

Symptom	Conditions	Pathophysiology
Unintended weight loss	Gastric CA, pancreatic CA, chronic pancreatitis	Malignancy: catabolic state + anorexia; pancreatic insufficiency: malabsorption ^[6]^[7]
Fever	Acute cholecystitis, cholangitis, pancreatitis, perforated PU	Infection/SIRS → pyrogens → hypothalamic thermostat reset
Painless progressive jaundice	CA head of pancreas	Tumour gradually obstructs CBD → conjugated bilirubin cannot drain → regurgitates into blood → jaundice ^[7]^[8]
Jaundice with pain	Choledocholithiasis, cholangitis	Stone intermittently/acutely obstructs CBD → pain (distension) + jaundice (obstruction)
New-onset diabetes	Pancreatic CA	Destruction of islets of Langerhans → ↓ insulin → hyperglycaemia ^[7]
Trousseau syndrome (migratory thrombophlebitis)	Pancreatic CA	Mucin-secreting adenocarcinoma releases tissue factor and procoagulants → hypercoagulable state ^[7]

B. Signs with Pathophysiological Basis

Sign	Conditions	Pathophysiology
Pallor	UGIB, gastric CA with chronic blood loss	Chronic GI bleeding → iron deficiency → microcytic anaemia → ↓ haemoglobin → pallor
Jaundice	Biliary obstruction, pancreatic CA, hepatitis	↑ Serum bilirubin > 35–50 μmol/L → deposits in skin and sclerae
Cachexia	Advanced malignancy (gastric CA, pancreatic CA)	Tumour-secreted cytokines (TNF-α, IL-6) → increased basal metabolic rate + anorexia → muscle wasting
Distress, lying still	Peritonitis (PPU)	Any movement stretches inflamed parietal peritoneum → patient instinctively avoids motion
Restlessness	Biliary/ureteric colic, mesenteric ischaemia	Visceral pain with no position of comfort → patient writhes and moves about
Trousseau's sign of malignancy	Pancreatic CA	Migratory superficial thrombophlebitis → tender, erythematous, cord-like superficial veins ^[7]

Sign	Conditions	Pathophysiology
Epigastric tenderness	PUD, gastritis, pancreatitis	Inflammation of underlying organ → visceral nociceptors activated → tenderness on palpation
Guarding (voluntary → involuntary)	Peritonitis (PPU, perforated cholecystitis)	Reflex contraction of abdominal wall muscles to "guard" the inflamed peritoneum → progresses to involuntary as inflammation worsens
Board-like rigidity	Generalised peritonitis (PPU)	Intense involuntary contraction of the rectus abdominis due to widespread parietal peritoneal irritation
Rebound tenderness	Peritonitis	Sudden release of palpating hand → inflamed peritoneum snaps back → momentary sharp pain
Succussion splash	GOO, gastric outlet obstruction	Retained gastric content (food + fluid + air) in a dilated stomach → shaking patient produces audible splash ^[10]
Palpable epigastric mass	Gastric CA, pancreatic CA	Advanced tumour large enough to be palpated in the epigastrium ^[6]^[7]
Murphy's sign (+ve)	Acute cholecystitis	Palpation of RUQ during inspiration → inflamed gallbladder descends with diaphragm → contacts examiner's hand → patient arrests inspiration due to pain
↓ Liver dullness	Pneumoperitoneum (PPU)	Free air rises to beneath anterior abdominal wall → abolishes normal liver dullness on percussion
Cullen's sign	Severe acute pancreatitis	Retroperitoneal haemorrhage tracks along the falciform ligament to the periumbilical region → bluish discolouration ^[9]
Grey Turner's sign	Severe acute pancreatitis	Retroperitoneal haemorrhage tracks laterally to the flanks → flank ecchymosis ^[9]
Fox's sign	Severe acute pancreatitis	Retroperitoneal blood tracks to inguinal ligament region
Palpable gallbladder (Courvoisier's sign)	Pancreatic head CA, periampullary tumour	Non-fibrotic gallbladder distends when CBD is gradually obstructed by tumour (in contrast to gallstone disease where the GB is fibrotic and cannot distend) ^[7]^[8]^[9]
Virchow's node (left supraclavicular)	Gastric CA, pancreatic CA	Metastasis via thoracic duct → left supraclavicular lymph node (also called "Troisier's sign")
Sister Mary Joseph nodule	Gastric CA (advanced), ovarian CA	Peritoneal metastasis tracking along the falciform ligament or umbilical ligaments to the umbilicus

Don't Forget the ECG!

In any patient presenting with acute epigastric pain — especially if elderly, diabetic, or with cardiovascular risk factors — perform an ECG. Inferior MI (occlusion of the right coronary artery) can mimic acute abdominal pathology and is immediately life-threatening.

Condition	Character	Timing	Radiation	Key Associated Features
Gastric ulcer	Burning, gnawing	Worse with food	Epigastric	Weight loss (afraid to eat), UGIB
Duodenal ulcer	Burning, hunger pain	Relieved by food; 2h post-meal	Epigastric	Good appetite, nocturnal pain
GERD	Burning	Post-prandial, lying flat	Retrosternal → throat	Heartburn, regurgitation, water brash
Biliary colic	Steady, severe	After fatty meal	Right shoulder/scapula	N/V, resolves < 6h
Acute cholecystitis	Constant, severe	Persistent > 6h	Right shoulder	Fever, Murphy's +ve
Acute pancreatitis	Severe, constant	Rapid onset (gallstone) or less abrupt (alcohol)	Radiates to back	Relieved leaning forward, N/V, Cullen's/Grey Turner's
Pancreatic CA	Constant, dull → severe	Progressive	Back	Painless jaundice (head), weight loss, new-onset DM
Gastric CA	Persistent, dull	Constant	Variable	Weight loss, early satiety, anaemia, haematemesis/melaena, palpable mass
PPU	Sudden, excruciating	Sudden onset	Generalises to whole abdomen	Board-like rigidity, pneumoperitoneum
GOO	Distending, waxing-waning	Post-prandial	Epigastric	Non-bilious projectile vomiting, succussion splash
Inferior MI	Heavy, squeezing	Acute	Jaw, left arm	Diaphoresis, dyspnoea, ECG changes

High Yield Summary

Epigastric pain is a symptom, not a diagnosis — work backwards from pain character, timing, radiation, and associated features to the organ and then the pathology.
Foregut structures (stomach, D1–D2, liver, gallbladder, pancreas) all refer visceral pain to the epigastrium via T5–T9 sympathetic afferents.
PUD pathophysiology = imbalance between aggressive factors (acid, pepsin) and protective factors (mucus, bicarbonate, prostaglandins, mucosal blood flow). H. pylori (92% DU) and NSAIDs (25% GU) are the dominant causes.
NSAIDs cause ulcers by inhibiting COX-1 → ↓ prostaglandins → ↓ mucosal defence → acid-mediated injury. COX-2 selective inhibitors spare GI protection.
Gastric ulcer pain worsens with food; duodenal ulcer pain improves with food and recurs 2 hours later.
Pain radiating to the back = think retroperitoneal (pancreatitis, pancreatic CA, penetrating posterior DU, AAA).
Painless progressive obstructive jaundice + palpable gallbladder (Courvoisier's law) = periampullary tumour (CA head of pancreas) until proven otherwise.
Always ECG for acute epigastric pain — inferior MI is a life-threatening mimic.
Alarm features requiring urgent OGD: age ≥ 40 (Asia), weight loss, UGIB, dysphagia, anaemia, FHx of UGI cancer, palpable mass.
Functional dyspepsia is the commonest cause of epigastric discomfort (prevalence 10–20% in Chinese), but is a diagnosis of exclusion. Pathophysiology involves gastric dysmotility, visceral hypersensitivity, altered microbiome, and psychological factors.
Acute pancreatitis — gallstones MC cause; severe constant epigastric pain radiating to back, relieved by leaning forward; Cullen's and Grey Turner's signs indicate retroperitoneal haemorrhage.
Gastric cancer — 6th incidence, 4th mortality; risk factors include H. pylori, atrophic gastritis, intestinal metaplasia, E-cadherin mutation (HDGC), smoking, pickled food; Lauren classification (intestinal vs diffuse).

Active Recall - Epigastric Pain (Definition, Epidemiology, Anatomy, Etiology, Clinical Features)

Differential Diagnosis of Epigastric Pain

The differential diagnosis of epigastric pain is one of the broadest in clinical medicine. The key to narrowing it down efficiently is understanding why each condition produces epigastric pain — this always comes back to the anatomy (which organ?), the innervation (visceral vs somatic, which spinal segments?), and the pathological process (inflammation, obstruction, ischaemia, neoplasia).

Think of the differential in three tiers:

Life-threatening emergencies — must be excluded first
Common organic causes — the bread-and-butter diagnoses
Less common but important causes — conditions you must not forget

These must be actively excluded in any acute epigastric pain presentation. Missing them is catastrophic.

Condition	Why Epigastric Pain?	Key Discriminating Features
Perforated peptic ulcer	Anterior DU/GU perforates → gastric acid spills onto parietal peritoneum → immediate chemical peritonitis (somatic pain via T5–T9) → secondary bacterial peritonitis ^[3]^[12]	Sudden onset, maximal from the start; board-like rigidity; pain ↑ by movement → lies still; pneumoperitoneum on erect CXR (↓ liver dullness); Hx of NSAIDs/PUD. Note: pain and guarding may ↓ after 4–6h as acid diluted — but peritonitis is still progressing ^[3]
Ruptured / expanding AAA	Aorta lies retroperitoneally at T12–L2 directly behind the epigastrium → aneurysmal expansion or rupture irritates retroperitoneal nerves → epigastric + back pain ^[13]	Tearing pain at epigastrium radiating to back; shock; pulsatile abdominal mass; elderly male with vascular risk factors
Aortic dissection	Intimal tear → propagating haematoma stretches aortic wall → visceral afferents from thoracic/abdominal aorta → chest ± epigastric pain depending on extent of dissection ^[11]^[13]	Sudden, excruciating, tearing/ripping pain; radiating to interscapular region of back or into abdomen; ↑↑↑ BP or Hx of HTN; Hx of connective tissue disorder (Marfan, EDS); ± branch vessel occlusion signs (stroke, limb ischaemia, AKI) ^[11]
Acute mesenteric ischaemia	SMA occlusion (embolus or thrombosis) → small bowel ischaemia → visceral afferent activation (T9–T12) → periumbilical / epigastric pain; as bowel infarcts, transmural necrosis → peritonitis ^[3]	"Pain out of proportion to physical findings" early on; vascular risk factors (AF, recent MI, atherosclerosis); rapid deterioration; lactic acidosis; late: peritoneal signs, bloody diarrhoea
Acute MI (inferior wall)	Inferior LV wall sits on diaphragm → ischaemic afferents travel with phrenic nerve and cardiac sympathetic chain → referred to epigastrium. Especially in diabetics with autonomic neuropathy who lack typical chest pain ^[11]	Risk factors for IHD; diaphoresis, dyspnoea, nausea; ECG: ST elevation in II, III, aVF; troponin ↑. Always ECG + troponin in acute epigastric pain!
Severe acute pancreatitis	Premature trypsin activation → autodigestion → retroperitoneal inflammation → coeliac plexus irritation → severe epigastric pain radiating to back ^[1]^[9]	Severe constant pain; radiates to back; relieved leaning forward; N/V; Cullen's/Grey Turner's signs; amylase/lipase ≥ 3× ULN; organ failure

Life-Threatening DDx Mnemonic

For life-threatening causes of acute epigastric pain, remember "PRAMS": Perforated peptic ulcer, Ruptured AAA, Acute MI (inferior), Mesenteric ischaemia, Severe pancreatitis. Some add DKA, Addisonian crisis, and ruptured ectopic pregnancy to complete the list of abdominal emergencies ^[1]^[13].

Tier 2: Common Organic Causes

These are the conditions you encounter most frequently in clinical practice and exams.

Condition	Why Epigastric Pain?	Discriminating Features
GERD / Oesophagitis	Refluxing of acid from stomach up through LES onto squamous epithelium of oesophagus → pain ^[3]^[4]	Retrosternal burning (heartburn); precipitated by bending, stooping, heavy lifting; occurs when lying flat; acid regurgitation with bitter taste ± cough; dysphagia suggests stricture ^[3]^[4]. Note: GERD is overdiagnosed in dyspepsia — do NOT conclude GERD unless typical symptoms present ^[2]
Oesophageal spasm	Diffuse oesophageal spasm → uncoordinated, high-amplitude contractions of oesophageal smooth muscle → visceral pain via vagal and sympathetic afferents → retrosternal/epigastric pain	Retrosternal burning pain associated with supine position and recent eating/drinking; may radiate to back; may be a/w dysphagia; may be relieved by nitrates or warm water ^[11]
Mallory-Weiss tear	Forceful retching/vomiting → longitudinal mucosal tear at GEJ → bleeding from submucosal arteries → haematemesis with epigastric pain	Preceding forceful vomiting (often alcohol-related); haematemesis; usually self-limiting

Condition	Why Epigastric Pain?	Discriminating Features
Gastritis / Gastropathy	Mucosal inflammation or epithelial injury (H. pylori, NSAIDs, alcohol, stress) → nociceptor activation in mucosa/submucosa → visceral epigastric pain ^[3]^[14]	Non-specific dyspepsia (epigastric pain, nausea, vomiting); drug Hx (NSAIDs, alcohol, iron); may present with UGIB; endoscopy diagnostic ^[14]
Gastric ulcer	Irritation of gastric/duodenal mucosa due to ↓ mucosal defence → acid contacts exposed submucosa/muscularis → nociceptor stimulation ^[3]	Usually pain immediately after meal → often afraid of eating; ↓ by vomiting; epigastric tenderness ± guarding ^[3]. Drug Hx: ask about ANY drug ingested, esp aspirin, NSAIDs, alendronate ^[3]
Gastric cancer	Tumour invades gastric wall → serosal irritation; ulceration within tumour mimics PUD; antral tumours cause GOO → distension pain ^[5]^[6]	Could be asymptomatic; distending discomfort, vomiting (splash); anaemia, pallor, melaena, haematemesis; perforation with acute peritonitis (rare); epigastric pain ^[6]. Persistent and progressive epigastric discomfort/pain as disease progresses; early satiety, bloating esp linitis plastica; constitutional symptoms (LOW, LOA, cachexia) ^[15]. Metastatic signs: Virchow's node, Sister Joseph nodule, Krukenberg tumour
Gastric volvulus	Rotation > 180° → closed-loop obstruction → gastric wall ischaemia and distension → intense visceral pain ^[10]	Borchardt's triad: severe epigastric pain + retching without vomiting + inability to pass NG tube
Gastroparesis	Delayed gastric emptying without mechanical obstruction → gastric distension → stretch-activated visceral afferents → pain	N/V, early satiety, postprandial fullness, bloating; causes: DM neuropathy, drugs (CCB, GLP-1 agonists), post-surgical
Gastric outlet obstruction	Mechanical obstruction at pylorus/duodenum → proximal gastric distension → stretch-activated visceral afferents → epigastric pain ^[10]	Waxing-and-waning epigastric pain; repeated non-bilious projectile vomiting of undigested food; early satiety; weight loss; succussion splash on examination; malignant until proven otherwise (80% malignant, 20% benign) ^[10]

Condition	Why Epigastric Pain?	Discriminating Features
Duodenal ulcer	↓ pain after eating → usually good appetite; pain ~2h after meal — food buffers acid temporarily; as stomach empties, acid bolus hits duodenal ulcer ^[3]	Hunger pain; nocturnal pain (circadian acid secretion maximal at night); relieved by antacids; 4 major risk factors: H. pylori, NSAIDs, stress, excess gastric acid ^[1]^[12]
Duodenitis	Mucosal inflammation of duodenum (same mechanisms as gastritis — H. pylori, NSAIDs) → visceral pain	Clinically indistinguishable from DU without endoscopy; usually self-limited
Periampullary tumour	Tumour at ampulla of Vater → obstructs CBD/pancreatic duct → obstructive jaundice ± pancreatitis → epigastric pain	Painless jaundice (may have intermittent pain); ampullary tumours may present with melaena (ulceration)

Condition	Why Epigastric Pain?	Discriminating Features
Biliary colic	Gallbladder contracts against transient obstruction (Hartmann's pouch/cystic duct) → ↑ intra-gallbladder pressure → visceral pain via splanchnic afferents → RUQ/epigastric ^[9]^[11]	RUQ/epigastric pain esp after fatty meal (fat intolerance); steady (not truly colicky); radiates to right shoulder/scapula; N/V; resolves < 6h; afebrile; no peritoneal signs ^[9]^[11]. Biliary pain is episodic, constant, NON-colicky, intense, dull — NOT ↑ by movement, NOT ↓ by squatting or bowel movements ^[2]
Acute cholecystitis	Persistent cystic duct obstruction → GB distension → mucosal ischaemia → inflammation extends to serosa → parietal peritoneal irritation (somatic pain) ^[1]^[9]	RUQ/epigastric pain lasting > 6h ± tenderness ^[11]; fever; Murphy's sign +ve; pain does NOT subside (cf. biliary colic); leukocytosis; USG: GB wall thickening, pericholecystic fluid, sonographic Murphy's ^[1]
Choledocholithiasis / Cholangitis	Stone in CBD → duct distension → visceral pain; if infected → cholangitis (Charcot's triad: fever + jaundice + RUQ pain) ^[1]	Obstructive jaundice pattern on LFT (↑ ALP, ↑ conjugated bilirubin); Reynolds' pentad adds hypotension + altered mental status in suppurative cholangitis
Hepatitis (acute)	Hepatocyte inflammation → liver capsular stretch (Glisson's capsule innervated by phrenic nerve + lower intercostal nerves) → RUQ/epigastric pain	Jaundice, dark urine, pale stools; ↑↑ transaminases; ask about viral risk factors, drugs, alcohol
HCC	Tumour expansion → capsular stretch → pain; or rupture → haemoperitoneum → acute abdomen	Background of chronic liver disease/cirrhosis; AFP ↑; irregular hepatomegaly

Condition	Why Epigastric Pain?	Discriminating Features
Acute pancreatitis	Premature enzyme activation → autodigestion → retroperitoneal inflammation → coeliac plexus irritation ^[1]^[9]^[16]	Severe constant epigastric pain radiating to back; relieved leaning forward; ↑ by movement; N/V (90%); initially little peritoneal signs ("pain out of proportion to findings"); amylase/lipase ≥ 3× ULN ^[16]. D/dx to consider: PUD (long-standing intermittent pain, normal amylase/lipase), PPU (early florid peritoneal signs, free gas, lipase < 3× ULN), cholangitis (obstructive jaundice, normal amylase), cholecystitis (RUQ, Murphy's, amylase rarely > 3× ULN), IO (imaging discernible), mesenteric ischaemia (periumbilical, vascular RFs, less marked enzyme rise) ^[16]
Chronic pancreatitis	Progressive fibrosis and destruction of pancreatic parenchyma → ductal hypertension, perineural inflammation → chronic epigastric pain radiating to back ^[1]	Recurrent episodes; steatorrhoea; new-onset DM; pancreatic calcifications on imaging; alcohol Hx
Pancreatic carcinoma	Head: CBD obstruction → painless jaundice; Body/tail: retroperitoneal infiltration → severe epigastric pain radiating to back ^[7]^[8]	Painless progressive obstructive jaundice (head); severe epigastric pain radiating to back (body/tail); constitutional symptoms; steatorrhoea; new-onset DM; Trousseau syndrome; Courvoisier's sign (palpable GB) ^[7]^[8]

High Yield: When distinguishing pancreatitis from PUD — PUD has long-standing intermittent epigastric pain, NSAID use/HP infection, and normal amylase and lipase; PPU has early florid peritoneal signs, free gas under diaphragm on erect CXR, and lipase/amylase < 3× ULN ^[16].

Condition	Why Epigastric Pain?	Discriminating Features
Acute MI (inferior)	Inferior wall ischaemia → afferents via phrenic nerve and cardiac sympathetic chain → referred to epigastrium	Prolonged epigastric ± substernal pain ^[11]; diaphoresis; dyspnoea; ECG changes (ST elevation II, III, aVF); troponin ↑; IHD risk factors
Myopericarditis	Sharp, pleuritic pain of variable duration, may be positional (↑ when sitting up and leaning forward due to pressure on parietal pericardium); retrosternal, radiating to shoulder/neck; insidious onset, may be a/w prodromal viral illness ^[11]	Positional pain; pericardial rub; diffuse ST elevation on ECG; recent viral illness
Aortic dissection	Sudden, excruciating, tearing/ripping pain radiating to interscapular region or abdomen; may occur with heavy isometric exercise or ↑↑↑ BP; ± occlusion of aortic branches ^[11]	BP differential between arms; widened mediastinum on CXR; CT aortogram diagnostic
Mesenteric ischaemia	SMA occlusion → small bowel ischaemia → visceral pain (T9–T12); late: transmural infarction → peritonitis	Pain out of proportion; AF or recent MI (embolus); lactic acidosis; CT angiography

Condition	Why Epigastric Pain?	Discriminating Features
Functional dyspepsia	Gastric dysmotility + visceral hypersensitivity + psychological factors → chronic epigastric discomfort without structural disease ^[2]	Commonest cause of epigastric discomfort; prevalence 10–20% in Chinese; young ( < 40y), F > M; diagnosis of exclusion after OGD and HP testing negative ^[2]. Overlap with GERD and IBS common in Chinese
Drug-induced dyspepsia	Direct mucosal irritation (NSAIDs, iron, bisphosphonates) or systemic effects (digoxin, metronidazole) → mucosal injury or altered GI motility → epigastric pain ^[2]	Drugs: NSAIDs, steroids, oral antibiotics, iron, digoxin, metronidazole, alendronate, slow K ^[2]; temporal relationship with drug initiation; resolves on drug withdrawal
Herpes zoster	Varicella-zoster virus reactivation in T5–T9 dorsal root ganglia → dermatomal neuropathic pain → epigastric region ^[11]^[13]	Severe, unilateral dermatomal burning pain; ± vesicular eruption ^[11]; dermatomal hyperaesthesia ^[13]; rash may come after pain or without pain (zoster sine herpete)
Abdominal wall pain	Myofascial trigger points or nerve entrapment in rectus sheath → somatic pain localised to epigastrium	Carnett sign positive (↑ local tenderness during muscle tensing → indicates abdominal wall origin) ^[2]
Metabolic	DKA: gastroparesis + metabolic acidosis → vomiting + abdominal pain; Hypercalcaemia: ↑ Ca²⁺ → ↑ gastric acid secretion + constipation + pancreatitis; Hyperkalaemia: smooth muscle dysfunction → abdominal pain ^[1]^[2]	DKA: Kussmaul breathing, ketotic breath, hyperglycaemia; hyperCa: "bones, stones, groans, thrones, moans"
Referred pain from chest	Basal pneumonia or PE → diaphragmatic irritation → phrenic nerve (C3–C5) → referred to epigastrium/shoulder	Pleuritic pain; cough; dyspnoea; CXR findings; D-dimer / CTPA for PE
Pancreatitis (referred from retro-peritoneum) ^[13]	Already discussed above but worth remembering as a common "forgotten" cause in acute abdominal pain ^[13]

Don't Forget These!

"Have you forgotten?" — In any acute abdominal pain, always consider ^[13]:

Hernia (inguinal or femoral) — incarceration/strangulation
Ruptured AAA or aortic dissection — tearing epigastric pain radiating to back + shock
Herpes zoster — dermatomal hyperaesthesia, vesicular eruption
Pancreatitis
Retention of urine
Non-specific abdominal pain

This table is extremely high yield for exams — it distils the discriminating features of the most commonly confused causes.

Feature	Gastric Ulcer	Duodenal Ulcer	Biliary Colic	Acute Cholecystitis	Acute Pancreatitis	Pancreatic CA	Gastric CA	Inferior MI
Pain timing	Worse with food	Better with food; 2h post-meal	After fatty meal	Persistent > 6h	Acute onset	Progressive	Persistent	Acute onset
Radiation	Epigastric	Epigastric	R shoulder	R shoulder	Back	Back	Variable	L arm, jaw
Character	Burning	Burning/hunger	Steady, severe	Constant	Severe, boring	Dull → severe	Dull, aching	Heavy, squeezing
Relieved by	Vomiting	Food, antacids	Resolves spontaneously	Nothing (needs Tx)	Leaning forward	Nothing	Nothing	GTN (sometimes)
Key signs	Epigastric tenderness	Epigastric tenderness	Afebrile, no peritoneal signs	Murphy's +ve, fever	Cullen's/Grey Turner's (severe)	Courvoisier's sign, jaundice	Mass, Virchow's node	ECG changes
Lab clue	Normal amylase	Normal amylase	Normal LFT (or mild ↑)	Leukocytosis, ↑ LFT	Amylase/lipase ≥ 3× ULN	↑ ALP, ↑ bilirubin, CA19-9	↓ Hb (chronic blood loss)	↑ Troponin

Differential Diagnosis by Clinical Presentation Pattern

Sometimes it's more useful to think about the differential based on what the patient presents with, rather than organ-by-organ:

System	Condition	Key Clue
Oesophageal	GERD	Heartburn, regurgitation, positional
	Oesophageal spasm	Retrosternal pain relieved by nitrates/warm water
Gastric	Gastric ulcer	Pain ↑ with food
	Gastric cancer	Alarm features, persistent pain, weight loss
	GOO	Non-bilious projectile vomiting, succussion splash
	Gastric volvulus	Borchardt's triad
Duodenal	Duodenal ulcer	Pain ↓ with food, 2h post-meal recurrence
Biliary	Biliary colic	Steady RUQ/epigastric pain after fatty meal, < 6h
	Cholecystitis	> 6h, fever, Murphy's +ve
	Cholangitis	Charcot's triad / Reynolds' pentad
Pancreatic	Acute pancreatitis	Severe, radiates to back, leaning forward relieves
	Chronic pancreatitis	Recurrent, steatorrhoea, calcifications
	Pancreatic CA	Painless jaundice (head) / back pain (body-tail)
Vascular	Ruptured AAA	Pulsatile mass, shock, back pain
	Mesenteric ischaemia	Pain out of proportion, AF, lactic acidosis
Cardiac	Inferior MI	ECG changes, troponin ↑, diaphoresis
Other	Functional dyspepsia	Young, no alarm features, normal investigations
	Drug-induced	Temporal relation to NSAID/iron/alendronate
	Herpes zoster	Dermatomal, unilateral, vesicles
	DKA / hyperCa	Metabolic derangement

High Yield Summary

Organise the DDx anatomically — oesophagus, stomach, duodenum, biliary, pancreas, vascular, cardiac, other — then prioritise by acuity.
Life-threatening DDx to exclude first: Perforated PU, ruptured AAA, acute MI, mesenteric ischaemia, severe pancreatitis (mnemonic: PRAMS).
Most common cause overall: Functional dyspepsia (60% of dyspepsia presentations), but this is a diagnosis of exclusion.
Most common organic cause of UGIB: Peptic ulcer disease.
Gastric ulcer pain ↑ with food; duodenal ulcer pain ↓ with food and recurs 2h later.
Biliary colic: steady (NOT colicky), < 6h, afebrile, no peritoneal signs. Acute cholecystitis: > 6h, fever, Murphy's +ve.
Pancreatitis vs PUD: PUD has normal amylase/lipase; pancreatitis has amylase/lipase ≥ 3× ULN. PPU has early florid peritoneal signs and pneumoperitoneum.
Always ECG in acute epigastric pain — inferior MI is a life-threatening mimic.
Don't forget: hernia, herpes zoster, ruptured AAA, retention of urine, non-specific abdominal pain.
ZES: recurrent ulcers at unusual sites, refractory to PPI, H. pylori-negative, no NSAIDs, ± diarrhoea → check fasting serum gastrin.
Valentino's sign: PPU mimics appendicitis as duodenal contents track down right paracolic gutter to RIF.

Active Recall - Differential Diagnosis of Epigastric Pain

References

^[1] Senior notes: felixlai.md (Dyspepsia, Peptic Ulcer Disease, Acute Pancreatitis, Biliary sections) ^[2] Senior notes: Ryan Ho Fundamentals.pdf (p263–264, Approach to Dyspepsia); Ryan Ho GI.pdf (p53–54) ^[3] Senior notes: Ryan Ho GI.pdf (p94, Causes of Upper Abdominal Pain); Ryan Ho Fundamentals.pdf (p268) ^[4] Senior notes: Ryan Ho GI.pdf (p56–57, GERD) ^[5] Senior notes: felixlai.md (Gastric Cancer — Etiology, Classification) ^[6] Lecture slides: GC 212. Weight loss and vomiting gastric cancer; abdominal imaging.pdf (p24) ^[7] Senior notes: maxim.md (Pancreatic carcinoma section) ^[8] Lecture slides: WCS 056 - Painless jaundice and epigastric mass - by Prof R Poon.ppt (1).pdf ^[9] Senior notes: maxim.md (Biliary colic, Acute cholecystitis, Acute pancreatitis sections); felixlai.md (Biliary sections) ^[10] Senior notes: maxim.md (GOO, Gastric volvulus, Valentino's sign sections) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p56, Chest pain differentials — aortic dissection, myopericarditis, GERD, biliary, gastritis/PU, herpes zoster) ^[12] Senior notes: felixlai.md (Upper GI Bleeding — Differential diagnosis) ^[13] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf (p44) ^[14] Senior notes: Ryan Ho GI.pdf (p75, Gastritis) ^[15] Senior notes: Ryan Ho GI.pdf (p84, Gastric cancer clinical features) ^[16] Senior notes: Ryan Ho GI.pdf (p340–341, Acute pancreatitis — DDx) ^[17] Senior notes: Ryan Ho Endocrine.pdf (p102, Gastrinoma / Zollinger-Ellison Syndrome)

Formal Diagnostic Criteria for Major Conditions

Diagnostic criteria: ≥ 2 out of 3 ^[9]^[16]:

Criterion	Details	Why?
Clinical	Acute onset of persistent, severe epigastric pain often radiating to the back	Retroperitoneal pancreatic inflammation irritating coeliac plexus
Biochemical	Serum amylase or lipase ≥ 3× upper limit of normal (ULN)	Leakage of pancreatic enzymes into blood from damaged acinar cells
Radiological	Characteristic findings on transabdominal USG, contrast-enhanced CT, or MRI	Direct visualisation of pancreatic oedema, necrosis, or peripancreatic fluid

Key points ^[9]^[16]:

Pancreatic enzyme elevation is NOT indicative of severity — it tells you the diagnosis, not the prognosis ^[9]
Imaging is usually only needed if the diagnosis is in doubt (i.e., amylase/lipase is equivocal but clinical suspicion is high) ^[16]
Early CT scan ( < 3 days) will not show necrotic/ischaemic areas — necrosis takes 48–72 hours to demarcate ^[16]

Diagnostic criteria (Sensitivity 91.2%, Specificity 96.9%) ^[18]^[19]:

Component	Criteria
A: Local signs of inflammation	Murphy's sign; RUQ mass/pain/tenderness
B: Systemic signs of inflammation	Fever; leukocytosis; elevated CRP ( > 3 mg/dL)
C: Imaging findings	Imaging findings characteristic of acute cholecystitis

Interpretation ^[18]^[19]:

Suspected diagnosis = 1× item in A + 1× item in B
Definite diagnosis = 1× item in A + 1× item in B + 1× item in C

Why this structure? Because you want both clinical and radiological confirmation — clinical signs alone have limited specificity (Murphy's sign: Sens 50–65%, Spec 79–96%), and imaging alone may show incidental cholecystitis in asymptomatic patients ^[19].

The Diagnostic Algorithm

Investigation Modalities — Systematic Review

Investigation	What It Tells You	Key Findings
ECG	Rule out acute MI (inferior wall) ^[3]^[11]^[18]	ST elevation in II, III, aVF = inferior MI; diffuse ST elevation with PR depression = pericarditis; normal ECG does not exclude ACS (repeat in 6–12h)
Urinalysis	Rule out urological causes (UTI, renal colic) ^[3]^[18]	Haematuria → renal colic; nitrites + leukocytes → UTI; glucose + ketones → DKA
Urine pregnancy test	Rule out ectopic pregnancy in women of childbearing age ^[3]^[18]	Always check before CT scan (radiation)

Investigation	What It Tells You	Key Findings & Interpretation
CBC	Infection, chronic blood loss, haemoconcentration	↑ WBC with left shift → infection/inflammation (cholecystitis, cholangitis, pancreatitis); ↓ Hb (microcytic) → chronic GI blood loss (PUD, gastric CA); ↑ Hb/Hct → haemoconcentration in pancreatitis (prognostic) ^[3]^[18]
LFT	Hepatocellular vs obstructive pattern	Parenchymal (↑↑ AST/ALT, mild ↑ ALP): hepatitis; Ductal/Obstructive (↑↑ ALP, ↑ GGT, ↑ conjugated bilirubin): choledocholithiasis, cholangitis, pancreatic head tumour ^[18]^[21]. ↑ bilirubin/GGT in cholecystitis should raise suspicion of CBD obstruction ^[19]
RFT	Hydration, electrolytes, renal function	HypoK/hypoCl → prolonged vomiting; ↑ urea:creatinine ratio ( > 100:1) → UGIB (Hb digestion in gut + reduced renal perfusion); Cr → suitability for contrast scans ^[3]^[18]
Serum amylase	Pancreatic injury	Rise within 6–12h of onset, normalise in 3–5 days; ≥ 3× ULN diagnostic of acute pancreatitis; prolonged elevation suggests complications (e.g., pseudocyst); false positives: PPU, ruptured AAA, DKA, macroamylasaemia ^[9]^[16]. If equivocal/delayed: urine amylase (rises within 24–48h, persists 1 week) ^[9]
Serum lipase	Pancreatic injury (preferred for delayed presentations)	Rise within 4–8h of onset, normalise in 8–14 days (longer half-life); more specific than amylase; preferred for delayed presentation > 24h ^[9]^[16]
Cardiac markers (Troponin)	Rule out myocardial infarction as a differential diagnosis of epigastric pain ^[1]^[3]^[18]	↑ cTnI or cTnT with dynamic rise/fall pattern → MI. Repeat troponin at 6–12h if first is normal but clinical suspicion remains ^[20]
CRP	Inflammatory marker	↑ CRP supports inflammatory/infective process (cholecystitis, pancreatitis); CRP > 150 mg/L at 48h in pancreatitis predicts severe disease ^[16]
Glucose	DKA, new-onset DM (pancreatic CA)	Hyperglycaemia → DKA (with ketones) or pancreatic exocrine/endocrine destruction ^[7]
Calcium, Phosphate	Aetiology of pancreatitis; metabolic cause of abdominal pain	Hypercalcaemia → can cause pancreatitis AND cause epigastric pain directly; Hypocalcaemia in pancreatitis → fat saponification (fatty acids precipitate with calcium) ^[9]
ABG / VBG + Lactate	Metabolic status	Metabolic acidosis + ↑ lactate → intestinal ischaemia; metabolic alkalosis → prolonged vomiting; respiratory alkalosis → early sepsis ^[3]^[18]
Clotting profile	Coagulopathy, pre-operative baseline	↑ INR in obstructive jaundice (vitamin K malabsorption — fat-soluble vitamin requires bile salts); responsive to IV vitamin K (cf. hepatocellular failure where it is not) ^[21]
Tumour markers	Prognostic/monitoring (NOT diagnostic screening)	CA19-9: elevated in ~80% pancreatic CA, but NOT sensitive and NOT specific for early diagnosis; also ↑ in HCC, cholangioCA, gastric CA, chronic pancreatitis, cholangitis; used for monitoring after treatment ^[7]^[8]. CEA: raised in 30–60% pancreatic CA

Amylase vs Lipase — Know the Difference

A common exam mistake is confusing the two. Serum lipase has a longer half-life (normalises in 8–14 days vs 3–5 days for amylase) and is more specific for pancreatic injury. Always prefer lipase for delayed presentations ( > 24h). Amylase can be falsely elevated in many non-pancreatic conditions (PPU, DKA, macroamylasaemia). The cut-off for diagnosis is ≥ 3× ULN for either, NOT an absolute value ^[9]^[16].

C. Radiological Investigations

Why order it? It is rapid, cheap, and answers three critical questions at once ^[3]^[18]^[22]:

Finding	Diagnosis	Why?
Free gas under diaphragm	Perforated peptic ulcer (or other viscus)	Air escapes from the perforated hollow viscus into the peritoneal cavity → rises to highest point (under diaphragm on erect film) ^[22]
Left-sided pleural effusion	Acute pancreatitis (or Boerhaave's)	Pancreatic inflammation tracks via the oesophageal hiatus or diaphragmatic lymphatics to the left pleural space; amylase-rich effusion
Widened mediastinum	Aortic dissection	Haematoma around the aortic arch widens the mediastinal silhouette
Basal consolidation	Pneumonia (referred epigastric pain)	Lower lobe pneumonia irritates the diaphragm → phrenic nerve → referred epigastric/shoulder pain

Finding	Diagnosis	Pathophysiological Explanation
Sentinel loop sign	Acute pancreatitis	Localised ileus of a single jejunal loop adjacent to the inflamed pancreas → the loop becomes dilated and gas-filled ^[9]^[16]^[18]
Colonic cut-off sign	Acute pancreatitis	Functional spasm of the descending colon secondary to pancreatic inflammation → colon dilated from ascending to mid-transverse, then abrupt paucity of gas distal to splenic flexure ^[9]^[16]
Pancreatic calcification	Chronic pancreatitis	Intraductal protein plugs calcify over time → visible calcification in the pancreatic bed ^[16]
Radio-opaque stones	Gallstones (only 15%), urinary stones (90%)	Only pigmented gallstones are radio-opaque (calcium bilirubinate); majority cholesterol stones are radiolucent; urinary stones (calcium oxalate/phosphate) are usually radio-opaque ^[18]
Air-fluid levels ( > 5)	Intestinal obstruction	Dilated bowel loops with fluid trapped behind the obstruction → gravity-dependent fluid with gas above it on erect film
Ground-glass appearance	Peripancreatic fluid collection	Hazy opacification of the abdomen due to free fluid
Obliteration of psoas outline	Retroperitoneal fluid/haemorrhage	Retroperitoneal fluid accumulation (pancreatitis, AAA leak) obliterates the normally visible psoas muscle shadow ^[9]

USG is the first-line imaging for biliary pathology and is readily available, quick, and non-invasive ^[18]^[19].

Target	Findings	Interpretation
Gallstones	Hyperechoic focus with posterior acoustic shadowing, gravity-dependent (rolling stone sign on lateral decubitus)	USG sensitivity for gallstones ~95% ^[9]^[18]
Acute cholecystitis	Thickened GB wall ( > 3 mm), distended GB with sludge, sonographic Murphy's sign, pericholecystic fluid	Sensitivity 88%, Specificity 80% ^[19]. Sonographic Murphy's sign = tenderness maximal when USG probe presses on the visualised gallbladder ^[18]^[19]
CBD dilatation	CBD diameter > 6 mm (or > 10 mm post-cholecystectomy)	Suggests distal obstruction — choledocholithiasis, pancreatic head tumour
Pancreas	Diffusely enlarged and hypoechoic (acute pancreatitis); peripancreatic anechoic fluid collection	May be absent in initial phase; may be obscured by bowel gas due to ileus ^[16]
Liver	Hepatomegaly, focal lesions, dilated intrahepatic ducts	HCC, metastatic disease, biliary obstruction

Limitations: operator-dependent; limited by body fat and bowel gas (especially for distal CBD and pancreas) ^[9].

Site of pain	Imaging of choice
RUQ	USG
LUQ	CT
RLQ	CT with IV contrast
LLQ	CT with IV contrast
Suprapubic	USG (transabdominal or transvaginal)

This table from the lecture notes is useful as a quick reference — RUQ pain defaults to USG because the most common pathology is biliary, and USG is the gold standard for gallstones ^[18].

CT is the workhorse of abdominal imaging for complex or unclear presentations. Different "protocols" are used depending on the clinical question ^[7]^[16]^[18]:

Protocol	What It Evaluates	Key Findings
Standard CT abdomen with IV contrast	Most acute abdomen presentations	PPU: free gas + free fluid; cholecystitis: GB wall thickening + fat stranding (seen better than USG); appendicitis: distended appendix + fat stranding; AAA: aneurysmal dilatation ± retroperitoneal haematoma ^[18]
CT with pancreas protocol (thin-sliced, triphasic: arterial + pancreatic + portovenous phases)	Pancreatic carcinoma	Ill-defined hypoattenuating mass within pancreas; double duct sign (dilated pancreatic duct + CBD) — present in 62–77% of CA head of pancreas; determine resectability: encasement of SMA, hepatic artery, coeliac trunk, SMV, portal vein ^[7]^[8]
CT abdomen with contrast for pancreatitis	Acute pancreatitis (when diagnosis in doubt or assessing severity ≥ 3 days)	Focal or diffuse enlargement with homogeneous enhancement; peripancreatic fat stranding; necrosis shown as hypoenhancement on contrast CT; early CT will NOT show necrotic areas ^[16]
CT angiography	Mesenteric ischaemia, AAA, aortic dissection	Filling defect in SMA/SMV; intestinal pneumatosis (air in bowel wall); aortic intimal flap; contrast extravasation (active bleeding)

High Yield: Contrast is essential in pancreatitis CT to detect pancreatic necrosis — a non-enhanced CT cannot distinguish viable from necrotic tissue. Necrosis = hypoenhancement = failure to take up contrast ^[1]^[16].

Modality	What It Does	When To Use
MRCP (Magnetic Resonance Cholangiopancreatography)	Non-invasive delineation of biliary and pancreatic ductal anatomy	Alternative to ERCP; ↑ popularity because ERCP is associated with ↑↑↑ risks (pancreatitis, perforation, bleeding); used to confirm CBD stones, cholangiocarcinoma, define anatomy before surgery ^[7]
ERCP (Endoscopic Retrograde Cholangiopancreatography)	Therapeutic + diagnostic: cannulation of ampulla of Vater → inject contrast → visualise ducts; can perform sphincterotomy, stone extraction, stenting	Suspected cholangitis or CBD stones needing intervention; diagnostic doubt; brush cytology/biopsy for biliary strictures ^[7]

Upper Endoscopy (OGD — Oesophago-gastro-duodenoscopy)

OGD is the definitive investigation for the upper GI tract. It is both diagnostic and therapeutic ^[1]^[3].

Indications ^[1]:

Symptom-based: anaemia, haematemesis, melaena, epigastric pain, dysphagia, acid reflux, indigestion
Disease-based: PUD follow-up, suspected oesophageal/gastric cancer, oesophageal variceal treatment, foreign body ingestion

Contraindications ^[1]: Known/suspected perforation; recent MI

Key findings and their significance ^[1]:

Finding	Diagnosis	Endoscopic Features
Benign ulcer	Peptic ulcer disease	Smooth, regular, rounded edges; flat smooth ulcer base often filled with exudate ^[1]
Malignant ulcer	Gastric cancer	Ulcerated mass protruding into lumen; irregular or thickened ulcer margins; folds surrounding ulcer crater are nodular, clubbed, fused ^[1]
Oesophagitis	GERD	Mucosal breaks at the GEJ (Los Angeles classification A–D)
Gastritis	H. pylori, NSAIDs, alcohol	Erythema, erosions, petechiae
Varices	Portal hypertension	Dilated submucosal veins in oesophagus/fundus

Forrest classification — endoscopic stigmata of recent haemorrhage (SRH), used to prognosticate rebleeding risk and guide therapy ^[1]:

Class	Stigmata	Prevalence	Rebleeding Risk	Management
Ia	Spurting haemorrhage	10%	55–100%	Endoscopic therapy required
Ib	Oozing haemorrhage	10%		Endoscopic therapy required
IIa	Non-bleeding visible vessel	25%	40–50%	Endoscopic therapy required
IIb	Adherent clot	10%	20–30%	Consider endoscopic therapy
IIc	Flat pigmented spot	10%	10%	Acid suppression alone
III	Clean base	35%	5%	Acid suppression alone

High Yield: Forrest Class I and IIa/IIb are high risk and require endoscopic haemostasis. Class IIc and III are low risk and can be managed with acid suppression alone ^[1].

Biopsy protocol at OGD:

All gastric ulcers must be biopsied (to exclude malignancy) — duodenal ulcers are rarely malignant and do not routinely need biopsy
H. pylori testing should be done on biopsy sample (rapid urease test / histology) ^[2]
Follow-up OGD for gastric ulcers at 6–8 weeks to confirm healing and re-biopsy if not healed

AVOID Endoscopy in Acute Abdomen!

AVOID endoscopy for acute abdomen — a sealed-off perforation may open by gas insufflation during endoscopy ^[18]. If perforation is suspected (peritonism, free gas on CXR), do NOT proceed with OGD. This is a critical safety point.

H. pylori testing is central to the diagnostic approach to epigastric pain, because it determines management for both PUD and functional dyspepsia ^[1]^[2].

Test	Type	How It Works	Sensitivity / Specificity	Notes
Rapid urease test (CLO test)	Invasive (biopsy at OGD)	Biopsy placed in urea-containing medium → H. pylori urease converts urea to ammonia → pH change → colour change	High	Requires OGD; affected by recent PPI/antibiotics (must stop PPI ≥ 2 weeks, antibiotics ≥ 4 weeks before testing)
Histology	Invasive (biopsy at OGD)	Direct visualisation of organisms on gastric biopsy	Gold standard	Also assesses gastritis, metaplasia, dysplasia
Urea breath test (UBT)	Non-invasive	Patient ingests ¹³C- or ¹⁴C-labelled urea → H. pylori urease hydrolyses it to labelled CO₂ → detected in breath samples ^[1]	Sens ~95%, Spec ~95%	Best non-invasive test; used for test-and-treat AND confirmation of eradication (≥ 4 weeks post-treatment)
Stool antigen test	Non-invasive	Detects H. pylori antigens in stool using monoclonal antibodies	Sens ~95%, Spec ~95%	Good alternative to UBT; useful in children
Serology (IgG)	Non-invasive	Detects antibodies to H. pylori in blood	Moderate	Cannot distinguish current from past infection; NOT useful for confirming eradication; useful in epidemiological studies

Why stop PPI before HP testing? PPIs suppress H. pylori replication and reduce urease activity → false-negative results on urease-based tests (CLO test, UBT). Always stop PPI ≥ 2 weeks and antibiotics ≥ 4 weeks before testing ^[1]^[2].

Study	Evaluates	Indications	Key Findings
Barium meal	Stomach and duodenum	Dyspepsia and epigastric pain; weight loss; suspected stomach cancer; suspected PPU ^[22]	Ulcer crater (niche); filling defect (tumour); mucosal irregularity; gastric outlet narrowing; contrast leak (perforation — use water-soluble contrast, NOT barium, if perforation suspected)
Barium swallow	Hypopharynx, oesophagus	Dysphagia, odynophagia	Stricture, achalasia ("bird's beak"), mucosal irregularity, hiatus hernia
Water-soluble contrast meal	Stomach/duodenum when perforation suspected	Suspected PPU or oesophageal perforation	Contrast extravasation at perforation site — barium NEVER used if perforation suspected (causes severe peritonitis)

Condition	Key Investigation	Specific Findings
ZES / Gastrinoma	Fasting serum gastrin + gastric pH	Gastrin > 10× ULN with pH < 2 diagnostic; secretin stimulation test for equivocal cases ^[17]
Chronic pancreatitis	Plain AXR, USG, CT, MRCP, ± secretin-stimulated MRCP, faecal elastase	AXR: pancreatic calcification (30%); CT: ductal dilatation, calcification, pseudocysts; amylase/lipase usually NORMAL due to burnout effect ^[16]; faecal elastase < 200 μg/g → exocrine insufficiency
Gastric cancer staging	CT chest + abdomen + pelvis, ± PET-CT, EUS	EUS for T and N staging; CT for distant metastases (liver, peritoneal, lung); diagnostic laparoscopy for peritoneal disease
Pancreatic cancer staging	CT pancreas protocol, ± MRCP, ± EUS-FNAC, ± PET-CT	Double duct sign; hypoattenuating mass; vascular encasement (SMA, hepatic artery, coeliac trunk, SMV, portal vein) determines resectability ^[7]^[8]
GERD	PPI trial → if refractory: 24h pH/impedance monitoring, oesophageal manometry	pH monitoring: gold standard for acid exposure; manometry for motility assessment before anti-reflux surgery
Mesenteric ischaemia	CT angiography, ± conventional angiography	SMA filling defect (embolus/thrombus); intestinal pneumatosis; portal venous gas; bowel wall thickening

Clinical Scenario	First-Line Investigations	Second-Line / Definitive
Acute severe epigastric pain	ECG, troponin, CBC, LRFT, amylase/lipase, VBG/lactate, erect CXR	CT abdomen, OGD (if no perforation suspected), ± CT angiography
Chronic/recurrent epigastric pain, age ≥ 40 or alarm features	CBC, LFT, OGD with biopsy + HP testing	CT abdomen, USG abdomen, tumour markers if malignancy suspected
Chronic/recurrent epigastric pain, age < 40, no alarm features	Non-invasive HP test (UBT or stool Ag)	OGD if HP eradication fails or symptoms persist despite PPI
RUQ / biliary-type pain	USG abdomen, CBC, LFT, amylase	MRCP, ERCP if CBD stones/cholangitis
Suspected pancreatic pathology	Amylase/lipase, USG, LFT, Ca²⁺, glucose	CT pancreas protocol, MRCP, EUS-FNAC
Suspected UGIB	CBC, clotting, X-match, LRFT, VBG	Urgent OGD (within 24h; within 12h if high-risk)

High Yield Summary

Functional dyspepsia is diagnosed by Rome IV criteria PLUS exclusion of organic disease by OGD — it is a diagnosis of exclusion.
Acute pancreatitis: ≥ 2/3 of clinical (epigastric pain radiating to back), biochemical (amylase/lipase ≥ 3× ULN), radiological. Enzyme elevation is diagnostic, NOT prognostic.
Acute cholecystitis: Tokyo 2013 — suspected = local signs + systemic signs; definite = local + systemic + imaging.
Acute MI: rise/fall of cTn above 99th URL + ≥ 1 of symptoms, ECG changes, Q waves, imaging, or thrombus.
Always ECG + troponin in acute epigastric pain to exclude inferior MI.
Erect CXR: pneumoperitoneum (PPU), pleural effusion (pancreatitis), widened mediastinum (dissection).
AXR: sentinel loop sign and colonic cut-off sign → pancreatitis; radio-opaque stones → 90% urinary, only 15% gallstones.
USG is first-line for biliary pathology (sensitivity 95% for gallstones); sonographic Murphy's sign confirms acute cholecystitis.
CT pancreas protocol (triphasic) is essential for pancreatic carcinoma — hypoattenuating mass, double duct sign, vascular encasement determines resectability.
Forrest classification at OGD guides management: Class I/IIa–b = high risk → endoscopic therapy; Class IIc/III = low risk → acid suppression alone.
Stop PPI ≥ 2 weeks and antibiotics ≥ 4 weeks before H. pylori testing (urease-based tests) to avoid false negatives.
AVOID endoscopy if perforation is suspected — gas insufflation can open a sealed perforation.
EUS-guided FNAC is preferred over percutaneous biopsy for pancreatic masses (higher sensitivity, lower seeding risk). Tissue diagnosis is NOT mandatory if the lesion is potentially resectable.

Active Recall - Diagnostic Criteria, Algorithm, and Investigations for Epigastric Pain

Phase 1: Immediate Stabilisation (Acute Presentations)

Any patient presenting with acute severe epigastric pain needs the ABCDE approach before any specific treatment ^[23]^[24]:

Step	Action	Why
A — Airway	Secure airway; consider cuffed ETT + NGT if massive haematemesis or impaired consciousness	Massive UGIB → aspiration risk; peritonitis → septic shock → reduced GCS
B — Breathing	High-flow O₂; monitor SpO₂; assess for respiratory distress	Pancreatitis → ARDS / pleural effusion; peritonitis → splinting → shallow breathing
C — Circulation	NPO, 2 large-bore IV cannulae (16G); IV NS 2L fast rate to maintain BP/pulse + urine output; blood transfusion if Hb < 7 or massive haemorrhage; withhold anticoagulants/antiplatelets (balance thrombotic risk) ^[23]	Hypovolaemic shock from UGIB, pancreatitis (third-spacing), or AAA rupture
D — Disability	GCS, glucose, pupils	DKA can cause epigastric pain; altered consciousness in Reynolds' pentad (cholangitis)
E — Exposure	Full abdominal examination, PR exam	Look for peritonism, Cullen's/Grey Turner's signs, hernia

When epigastric pain is accompanied by haematemesis/melaena ^[23]^[24]:

Bloods: CBC (baseline Hb), clotting, cross-match, LRFT, VBG (acidosis)
RFT: elevated urea:creatinine ratio ( > 100:1) — because Hb digestion in the gut generates urea + reduced renal perfusion from hypovolaemia ^[23]
Pre-endoscopic PPI: IV esomeprazole 80 mg stat → 8 mg/h infusion until OGD (only if early endoscopy cannot be arranged; raising gastric pH stabilises clots) ^[23]
Risk stratification:

Score	Components	Use
Glasgow-Blatchford Score (GBS)	Clinical + Lab (endoscopic results NOT required)	Predicts need for endoscopy; GBS = 0 can be safely discharged ^[23]
Rockall Score	Clinical (Age, BP, Comorbidities) + Endoscopy (Diagnosis, Evidence of bleeding)	Predicts rebleeding and mortality ^[23]
AIMS65	Albumin < 30, INR > 1.5, altered Mental status, Systolic BP ≤ 90, age > 65	Predicts in-patient mortality ^[24]

Phase 2: Cause-Specific Management

A. Peptic Ulcer Disease (PUD)

PUD management has three pillars: eradicate the cause, heal the ulcer, and prevent recurrence.

If H. pylori is detected, eradication is mandatory — it cures the ulcer in the vast majority and prevents recurrence ^[1]^[2]^[25]:

Regimen	Components	Duration	Notes
Standard triple therapy	PPI (bd) + Amoxicillin 1g bd + Clarithromycin 500 mg bd	7–14 days	First-line in areas with clarithromycin resistance < 15% ^[25]
Bismuth quadruple therapy	PPI (bd) + Bismuth subsalicylate + Metronidazole + Tetracycline	10–14 days	First-line if clarithromycin resistance ≥ 15% or previous macrolide exposure
Concomitant therapy	PPI (bd) + Amoxicillin + Clarithromycin + Metronidazole (all bd)	14 days	Alternative first-line; higher eradication rates than sequential

Post-treatment testing: Confirm eradication with non-invasive tests (UBT or stool antigen) ≥ 4 weeks after completing all drugs. Do NOT use serology (positive for life). Stop PPI ≥ 2 weeks before testing ^[25].

Causes of failure of triple therapy ^[25]:

Poor compliance
Inappropriate dose and duration
Smoking: nicotine can ↓ efficacy of antibiotics
True antibiotic resistance

If first-line fails → switch to alternative regimen or guide treatment by sensitivity studies.

Drug Class	Mechanism	Indications	Key Points
Proton pump inhibitors (PPI)	Irreversibly inhibit H⁺/K⁺-ATPase (proton pump) on parietal cell apical membrane → blocks the final common pathway of acid secretion	Full-dose PPI × 4–8 weeks for non-HP non-NSAID PUD; × 8 weeks for NSAID PUD ^[2]^[25]	All PPIs except dexlansoprazole should be taken 30 min–1 hour before meals for maximal efficacy (pump must be active to be inhibited) ^[1]. Examples: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
H₂-receptor antagonists (H₂RA)	Competitively block histamine H₂ receptors on parietal cells → ↓ basal and stimulated acid secretion	Alternative if PPI intolerant; second-line	Regular use leads to tolerance and loss of therapeutic effect → use intermittently ^[1]. Examples: famotidine, ranitidine (withdrawn in many markets due to NDMA concerns)
Antacids	Directly neutralise gastric acid (Al(OH)₃, Mg(OH)₂, CaCO₃)	Symptomatic relief only	Do NOT heal ulcers; provide rapid but short-lived relief
Sucralfate	Forms a viscous gel that binds to the ulcer base → physical barrier protecting from acid and pepsin	Adjunctive in stress ulcer prophylaxis	Must be taken on empty stomach; can impair absorption of other drugs
Misoprostol	PGE₁ analogue → replaces the prostaglandins inhibited by NSAIDs → restores mucosal defence	Co-therapy for NSAID gastroprotection ^[25]	Side effects: diarrhoea, abdominal cramps; contraindicated in pregnancy (uterotonic → can induce abortion)

Why PPI Before Meals?

PPIs are prodrugs that require an acidic environment for activation. They are absorbed in the small intestine, circulate to the parietal cell, and are trapped in the secretory canaliculus (pH ~1) where they are activated. But the proton pump must be actively secreting acid for the PPI to bind and inhibit it. Eating stimulates acid secretion → pumps are active → PPI works best. Taking PPI 30–60 minutes before a meal ensures peak plasma levels coincide with maximal pump activity.

Indications for surgery ^[1]^[10]:

Complicated PUD (haemorrhage, perforation, GOO)
Refractory to medical treatment (exclude ZES before elective surgery)
Suspicious of malignancy (non-healing GU > 3 months)

Ulcer Type	Surgical Options	Rationale
DU (acid reduction)	Highly selective vagotomy (nerve of Latarjet preserved); Truncal vagotomy + drainage (pyloroplasty / gastrojejunostomy); Antrectomy + Billroth II / Roux-en-Y ^[10]	DU is acid-driven → reduce acid secretion by dividing vagal supply to parietal cells (vagotomy) or removing gastrin-producing antrum (antrectomy)
GU Type I	Distal gastrectomy + Billroth II	Type I is on lesser curvature, normal/low acid → remove ulcer to exclude malignancy
GU Type II/III	Truncal vagotomy + antrectomy + Billroth II	Type II/III have high acid → need acid reduction + ulcer excision
GU Type IV	Subtotal gastrectomy extending to ulcer + Billroth I/II/Roux-en-Y	High lesser curvature → technically difficult, needs wider resection

B. Management of PUD Complications

This is the leading cause of death in PUD (5–15% mortality).

Step-wise approach:

Endoscopic treatment modalities — usually dual therapy (adrenaline injection + one other modality) ^[1]^[24]:

Modality	Mechanism	Key Points
Chemical: Adrenaline injection	Volume effect (tamponade) + vasoconstriction + platelet aggregation	Should NOT be used as monotherapy — high rate of rebleeding after absorption (~1h) ^[1]^[24]
Thermal: Heater probe / bipolar cautery	Coaptive coagulation — compress vessel walls together + seal with heat	Risk of perforation (immediate or delayed)
Mechanical: Haemoclips	Physically clamp the bleeding vessel	Useful for large visible vessels
Haemospray (TC-325)	Nanopowder with large surface area → induces mechanical haemostasis	Usually when other modalities fail; good for diffuse oozing
Argon plasma coagulation	Non-contact thermal → lower energy depth → lower perforation risk	Useful for diffuse superficial oozing (gastritis, angiodysplasia) ^[24]

Post-endoscopy ^[24]:

IV PPI × 72h to ↑ pH for clot stabilisation (for Forrest IIa and above, or adherent clot resistant to vigorous irrigation)
Close monitoring for rebleeding (3–10%): keep inpatient ≥ 3 days
Signs of rebleeding: ↑ pulse rate, haematemesis, fresh blood from NGT, fresh melaena, sudden ↓ Hb

Transcatheter arterial embolisation (TAE) ^[1]^[10]:

Angiography of coeliac trunk and SMA → identify contrast extravasation → selective coiling of bleeding vessel
Equally effective as surgery for failed endoscopic haemostasis with fewer complications
Consider when patient is high-risk for surgery
Reduces need for surgery without increasing mortality

Surgical treatment ^[10]^[24]:

DU: suture ligation of bleeding vessel (usually GDA) → ± partial gastrectomy or vagotomy + pyloroplasty
GU: partial gastrectomy (risk of malignant ulcer → need histology)

Perforated peptic ulcer (PPU) is a surgical emergency:

Initial management: NPO, IV PPI (high-dose), IV broad-spectrum antibiotics (cover gut flora — e.g., co-amoxiclav or cefuroxime + metronidazole), IV fluids, NG decompression, urinary catheter
Definitive: Emergency laparoscopic or open omental patch repair (Graham patch) — suturing a pedicled omental flap over the perforation
Post-operatively: H. pylori eradication, review NSAIDs, PPI therapy

Boey score (prognostic for PPU mortality) ^[10]:

Risk Factor	Points
Time from perforation to admission > 24 hours	1
Pre-operative systolic BP < 100 mmHg	1
Any systemic illness (heart disease, liver disease, renal disease, DM)	1
Mortality: Score 0 = 0%, 1 = 10%, 2 = 45.5%, 3 = 100%

C. GERD Management [1][4][25]

Step	Treatment	Details
1. Lifestyle modification	Weight loss, smoking cessation, reduce alcohol, elevate head of bed, avoid late meals ( < 2–3h before bed), avoid precipitants (chocolate, coffee, fatty food, spicy food) ^[1]	Reducing intra-abdominal pressure (weight loss) and decreasing LES relaxation (avoiding triggers) reduces reflux
2. Medical therapy	Full-dose PPI × 4–8 weeks for healing of oesophagitis ^[25]	PPI only changes acidic reflux into non-acidic reflux → relieves heartburn and oesophagitis but regurgitation often remains uncorrected since reflux mechanism is unaffected ^[1]
3. Maintenance	Lowest dose PPI if symptoms recur; offer H₂RA if inadequate PPI response ^[25]
4. Severe oesophagitis	Full-dose PPI × 8 weeks or long-term; double-dose PPI or switch PPI if failed ^[25]

D. Acute Pancreatitis Management [1][9][16][27]

Management is primarily supportive — there is no specific drug that "treats" pancreatitis. The focus is on:

Aggressive IV fluid resuscitation
Pain control
Nutritional support
Aetiology-directed treatment
Management of complications

Component	Details	Rationale
Aggressive IV fluids	5–10 mL/kg/h isotonic crystalloids (Lactated Ringer's may be superior to NS in reducing SIRS); adjust according to clinical assessment, Hct, and urea ^[1]^[16]^[27]	Pancreatitis causes massive third-space fluid loss → hypovolaemia → end-organ ischaemia; aggressive early resuscitation ↓ pancreatic necrosis. Aim for urine output 0.5–1.0 mL/kg/h ^[1]
Analgesia	Opioids preferred: fentanyl, hydromorphone, tramadol, pethidine; morphine should be AVOIDED ^[1]^[27]	Morphine can cause sphincter of Oddi spasm → theoretically worsens ductal hypertension (though evidence is debated, it remains standard teaching to avoid it). NSAIDs NOT preferred: can worsen pancreatitis and cause renal failure ^[27]
O₂ supplementation	Pulse oximetry and ABG monitoring	Pancreatitis → SIRS → ARDS; diaphragmatic inflammation → pleural effusion → hypoxia
Electrolyte correction	Correct hypocalcaemia (tetany from fat saponification), hypokalaemia, hyperglycaemia	Metabolic derangements common; hypocalcaemia is prognostic
NPO + NG suction	NPO only if nausea/vomiting; NG suction if ileus or protracted vomiting ^[1]
Monitoring	HDU care if severe; serial vitals, electrolytes, glucose, ABG
Stress ulcer prophylaxis	PPI	Critically ill patients at risk of stress ulceration

Complication	Management
Acute peripancreatic fluid collection	None needed — majority resolves spontaneously ^[27]
Acute necrotic collection (sterile)	Conservative management for ≥ 4 weeks (necrotic tissue is poorly demarcated early on → early debridement is incomplete and harmful) ^[27]
Infected necrosis	Empirical antibiotics → percutaneous/endoscopic drainage → surgical necrosectomy if failed (step-up approach); leading cause of morbidity/mortality; usually occurs > 10 days post-onset ^[27]
Pseudocyst (walled-off collection)	Observe if asymptomatic; drain if symptomatic/infected/causing organ dysfunction; endoscopic (EUS-guided), percutaneous, or surgical drainage
Pseudoaneurysm	Endoscopic drainage absolutely contraindicated → angiographic embolisation or surgical resection ^[27]
Abdominal compartment syndrome	IAP > 20 mmHg + new organ failure → surgical decompression ^[27]

Definitive treatment: Early laparoscopic cholecystectomy (LC) — ideally within 72 hours of symptom onset. This is supported by current guidelines because:

Early LC has comparable morbidity to delayed LC
↓ Overall hospital stay
↓ Risk of recurrent attacks while waiting for interval surgery

Severity (TG13)	Management
Grade I (Mild)	IV antibiotics + early LC (within 72h)
Grade II (Moderate)	IV antibiotics + early LC if safe; percutaneous cholecystostomy (drainage) if high surgical risk
Grade III (Severe)	Organ support + IV antibiotics + percutaneous cholecystostomy for drainage → interval LC when stable

Step	Treatment	Rationale
1. Reassurance	Explain that no serious organic disease has been found	Reduces anxiety, which itself perpetuates symptoms
2. Dietary changes	Avoid known precipitants, low-fat diet, ↓ FODMAPs, ↓ lactose ^[2]	Dietary triggers exacerbate gastric dysmotility and visceral hypersensitivity
3. HP eradication	If HP +ve: eradication therapy → offers symptomatic benefit in a small subgroup ^[2]	NNT ~14 — modest benefit, but worthwhile as HP is a modifiable factor
4. Empirical PPI	Low-dose PPI or H₂RA × 4 weeks if symptoms persist after HP excluded ^[25]	Effective in Western populations but effect not clearly demonstrated in Asians; effective in ulcer-like/reflux-like but NOT in dysmotility-like FD ^[2]
5. Prokinetics	Metoclopramide for refractory cases	Enhances gastric emptying → helps postprandial distress symptoms. Side effects: extrapyramidal (dopamine antagonist)
6. Neuromodulators	TCAs (e.g., amitriptyline) and SSRIs (e.g., escitalopram) ^[2]	Modulate visceral hypersensitivity via central and peripheral mechanisms; TCAs also have anticholinergic effects that may ↓ gastric motility (paradoxical) — use at low doses
7. Others	Simeticone (Mylicon): anti-foaming agent for belching symptoms ^[2]	Commonly used in GOPC; reduces gas bubble surface tension

High Yield: Reinvestigate by OGD if symptoms persist despite multiple treatments — do not keep treating empirically indefinitely ^[2].

Stage	Approach
Early gastric cancer (T1N0)	Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD); HP eradication; > 90% 5-year survival ^[5]
Resectable invasive CA	Gastrectomy (distal/subtotal/total depending on site) + D2 lymphadenectomy + perioperative chemotherapy
Unresectable / metastatic	Palliative chemotherapy ± targeted therapy (trastuzumab if HER2+ve); local palliation for GOO (stenting / bypass), bleeding (radiotherapy / endoscopic)

Criteria for unresectability ^[5]:

Distant metastasis
Invasion of major vascular structures (aorta)
Encasement/occlusion of coeliac axis, proximal splenic artery, or hepatic artery (distal splenic artery involvement is NOT a contraindication)

Assess resectability — this is the central decision point ^[7]^[8]:

Category	Management
Resectable (no vascular involvement)	Surgery: Whipple's procedure (pancreaticoduodenectomy) for head tumours; distal pancreatectomy + splenectomy for body/tail; ± adjuvant chemotherapy
Borderline resectable	Neoadjuvant chemotherapy ± chemoradiation → reassess → surgery if responds
Unresectable / locally advanced	Palliative chemotherapy (FOLFIRINOX or gemcitabine + nab-paclitaxel); biliary stenting for jaundice; coeliac plexus block for pain
Metastatic	Palliative chemotherapy; best supportive care

Vascular encasement by SMA, hepatic artery, coeliac trunk, SMV, or portal vein determines resectability on CT pancreas protocol ^[7]^[8].

Condition	Treatment Protocol
Uninvestigated dyspepsia	HP testing and eradication (test-and-treat); empirical full-dose PPI × 4 weeks; offer H₂RA if inadequate PPI response
Functional dyspepsia	HP eradication if HP+ve; low-dose PPI or H₂RA × 4 weeks if symptoms persist after HP excluded; lowest dose PPI/H₂RA if symptoms recur
Peptic ulcer disease	HP eradication if HP+ve; full-dose PPI or H₂RA × 4–8 weeks for non-HP non-NSAID PUD; × 8 weeks for NSAID PUD
GERD	Full-dose PPI × 4–8 weeks for oesophagitis; × 8 weeks or long-term for severe oesophagitis; lowest-dose PPI for recurrent symptoms; H₂RA if PPI inadequate

High Yield Summary

Management of epigastric pain is cause-directed — stabilise first (ABCDE), diagnose (Ix), then treat the specific cause.
PUD: eradicate H. pylori (triple therapy 7–14 days) + PPI for ulcer healing (4–8 weeks) + review NSAIDs.
Bleeding PUD: IV PPI 80 mg bolus + 8 mg/h infusion → urgent OGD → endoscopic haemostasis (dual therapy: adrenaline + heater probe/clip) for Forrest Ia–IIb → IV PPI 72h post-endoscopy. Adrenaline alone is NOT sufficient.
Failed endoscopic haemostasis → TAE (if unfit) or surgery (suture ligation ± acid-reducing procedure for DU; partial gastrectomy for GU).
PPU: emergency omental patch repair + IV PPI + IV antibiotics + HP eradication. Boey score predicts mortality.
GERD: lifestyle + PPI 4–8 weeks → lowest maintenance dose → fundoplication if PPI-dependent/refractory. Nissen (360°) is more durable but more dysphagia; partial wraps preferred in Chinese.
Acute pancreatitis: aggressive IV fluids (LR 5–10 mL/kg/h) + opioid analgesia (NOT morphine) + early enteral feeding ( < 48–72h) + ERCP within 24–72h if biliary cause with cholangitis/CBD stones. Prophylactic antibiotics NOT routinely recommended.
Cholecystectomy for ALL gallstone pancreatitis patients — during same admission if mild, interval if severe.
Acute cholecystitis: early LC within 72h + IV antibiotics. Percutaneous cholecystostomy if too sick for surgery.
Cholangitis: IV antibiotics + ERCP for biliary decompression. ERCP complications: perforation, bleeding, pancreatitis.
Functional dyspepsia: reassurance → dietary changes → HP eradication if +ve → low-dose PPI → prokinetics/TCA if refractory → reinvestigate by OGD if persistent.
Gastric cancer: EMR/ESD for T1N0; gastrectomy + D2 LN dissection + perioperative chemo for resectable; palliative chemo ± targeted therapy for unresectable.
Pancreatic cancer: Whipple's for resectable head tumours; assess vascular encasement (SMA, hepatic artery, coeliac trunk, SMV, PV) for resectability; neoadjuvant chemo for borderline; palliative chemo + stenting for unresectable.

Active Recall - Management of Epigastric Pain

^[1] Senior notes: felixlai.md (PUD treatment, NSAID management, aspirin in bleeding ulcer, PUD complications, Acute pancreatitis treatment, Cholecystectomy for gallstone pancreatitis, GERD medical treatment) ^[2] Senior notes: Ryan Ho GI.pdf (p54–55, Functional Dyspepsia management); Ryan Ho Fundamentals.pdf (p264–265) ^[3] Senior notes: Ryan Ho Fundamentals.pdf (p268, Perforated peptic ulcer) ^[4] Senior notes: Ryan Ho GI.pdf (p56–57, GERD pathophysiology and treatment) ^[5] Senior notes: Ryan Ho GI.pdf (p86, Gastric cancer staging and management) ^[6] Lecture slides: GC 212. Weight loss and vomiting gastric cancer; abdominal imaging.pdf ^[7] Senior notes: maxim.md (Pancreatic carcinoma — Investigations, resectability) ^[8] Lecture slides: WCS 056 - Painless jaundice and epigastric mass - by Prof R Poon.ppt (1).pdf ^[9] Senior notes: maxim.md (Biliary colic, Acute pancreatitis — Investigation, diagnostic criteria, management) ^[10] Senior notes: maxim.md (PUD surgical management, Boey score, GOO, PUD complications — haemorrhage) ^[16] Senior notes: Ryan Ho GI.pdf (p340–346, Acute pancreatitis diagnosis, management, complications) ^[19] Senior notes: Ryan Ho GI.pdf (p247–248, Acute cholecystitis — Tokyo guidelines, management) ^[23] Senior notes: maxim.md (UGIB initial management, pre-endoscopy management, risk stratification) ^[24] Senior notes: Ryan Ho Fundamentals.pdf (p255–257, Endoscopic Tx modalities, post-endoscopy management, surgery for bleeding ulcers) ^[25] Senior notes: Ryan Ho GI.pdf (p55, p78–79, NICE guidelines, HP eradication, NSAID ulcer management); Ryan Ho Fundamentals.pdf (p265) ^[26] Senior notes: maxim.md (GERD surgical treatment, fundoplication types and complications) ^[27] Senior notes: Ryan Ho GI.pdf (p344–346, Pancreatitis supportive management, antibiotics, nutritional support, management of complications) ^[28] Lecture slides: GC 200. RUQ pain, jaundice and fever Cholecytitis and cholangitis Imaging of GI system.pdf (p14, ERCP for cholangitis)

1. Complications of Peptic Ulcer Disease

The four classic PUD complications can be remembered by the mnemonic "4 Bs" — Bleed, Burst (perforation), Block (GOO), and Burrow (penetration/fistulisation) ^[1]^[25].

Pathophysiology: Chronic ulcer penetrates completely through the bowel wall into an adjacent hollow viscus, creating an abnormal communication ^[1].

Fistula Type	Consequence
Gastrocolic or duodenocolic fistula	Feculent vomiting, postprandial diarrhoea (colonic bacteria contaminate small bowel), dyspepsia, weight loss ^[1]
Choledochoduodenal fistula	Pneumobilia (air in biliary tree)
Aortoduodenal fistula	Massive, often fatal UGIB (rare; more common post-aortic graft)

GERD complications result from chronic acid exposure to the squamous epithelium of the lower oesophagus ^[1]^[4].

Complication	Pathophysiology	Clinical Significance
Oesophagitis	Acid erodes squamous epithelium → inflammation → mucosal breaks (Los Angeles A–D)	Pain (odynophagia), bleeding
Oesophageal ulceration	Deep mucosal erosion into submucosa	Bleeding, pain, perforation (rare)
Oesophageal stricture	Chronic inflammation → fibrosis → luminal narrowing	Progressive dysphagia (solids then liquids) ^[1]
Barrett's oesophagus	Chronic acid injury → metaplasia of squamous epithelium to specialised intestinal-type columnar epithelium	Pre-malignant condition; risk of progression: non-dysplastic → low-grade dysplasia → high-grade dysplasia → adenocarcinoma (~0.5%/year progression rate to cancer) ^[1]
Oesophageal adenocarcinoma	Malignant transformation of Barrett's epithelium	Rising incidence; poor prognosis if diagnosed late
Oesophageal haemorrhage	Ulceration of Barrett's or oesophagitic mucosa → vessel erosion	Haematemesis, anaemia

High Yield: Barrett's oesophagus (described as "chronic reflux → stricture → Barrett's oesophagus (10%) → metaplasia → adenocarcinoma (7% of Barrett's)") ^[26]. ALL patients with Barrett's should receive PPI regardless of symptoms. Surveillance: non-dysplastic → every 3–5 years; low-grade → every 6 months for 1 year then annually; high-grade → EMR + RFA or oesophagectomy ^[1].

3. Complications of Acute Pancreatitis

Acute pancreatitis complications can be classified by timing (early vs late) and type (local vs systemic) using the Revised Atlanta Classification ^[9]^[16]^[27].

Severity	Definition	Mortality
Mild	NO organ failure, NO local/systemic complications	< 2%
Moderately severe	Transient organ failure < 48h OR local/systemic complications	~5%
Severe	Persistent organ failure > 48h	10–30%

Timing	Interstitial Oedematous Pancreatitis (90–95%)	Necrotising Pancreatitis (5–10%)
Early ( < 4 weeks)	Acute peripancreatic fluid collection (APFC, 30–50%): inflammatory rupture of pancreatic duct → fluid/debris in lesser sac; CT: wall not well-defined, homogeneous; most resolve spontaneously in 7–10 days; does NOT require intervention ^[27]	Acute necrotic collection (ANC): similar but contains necrotic tissue (heterogeneous, solid debris); Infected pancreatic necrosis: usually > 1 week, secondary to enteric G⁻ bacilli; CT: extraluminal gas in/around pancreas; leading cause of morbidity/mortality; requires drainage + antibiotics ± necrosectomy ^[27]
Late ( > 4 weeks)	Pseudocyst: mature APFC with well-defined wall (only 6.8% of APFCs); Sx: pain, visceral obstruction, vascular occlusion, fistulation, pseudoaneurysm	Walled-off necrosis (WON): mature ANC with well-defined wall; may be sterile or infected; drainage/debridement if symptomatic, infected, or causing organ failure ^[27]

Why does infected necrosis develop? Pancreatic necrosis creates a devitalised tissue bed — an ideal medium for bacterial colonisation. Gut bacteria (mainly Gram-negative bacilli) translocate across the inflamed, permeable intestinal wall into the peripancreatic tissue via the portal circulation or lymphatics. This typically occurs after > 7–10 days of disease onset ^[27].

Complication	Pathophysiology	Clinical Features	Management
Splenic vein thrombosis (~11% of necrotising pancreatitis)	Pancreatic inflammation → venous endothelial injury → thrombosis → left-sided portal hypertension → blood drains via short gastric veins → gastric varices ^[16]^[27]	UGIB from gastric varices, splenomegaly, ascites	Anticoagulation if extends into portal/SMV; splenectomy if isolated splenic vein thrombosis with variceal bleeding
Pseudoaneurysm	Pancreatic enzyme-rich fluid erodes into adjacent arteries (splenic, GDA, pancreaticoduodenal) → weakened arterial wall → pseudoaneurysm formation	Unexplained GI bleed, anaemia, sudden ↑ size of fluid collection	Endoscopic drainage of pancreatic collection is ABSOLUTELY CONTRAINDICATED (risk of fatal haemorrhage); Mx: angiographic embolisation or surgical resection ^[27]
Portosplenomesenteric venous thrombosis (~50% of necrotising pancreatitis)	Extension of splenic vein thrombosis into portal/SMV system	Left-sided portal HTN, ascites, bowel ischaemia (if SMV involved)	Anticoagulation; monitor for bowel ischaemia ^[27]

Complication	Pathophysiology	Key Points
Organ failure (respiratory/cardiovascular/renal)	SIRS → cytokine storm (TNF-α, IL-1, IL-6) → capillary leak, endothelial damage → multi-organ dysfunction	Persistent organ failure > 48h defines severe pancreatitis ^[9]
ARDS	Circulating pancreatic enzymes + inflammatory mediators → pulmonary capillary damage → non-cardiogenic pulmonary oedema	Dyspnoea; bilateral infiltrates on CXR; PaO₂/FiO₂ < 300
Pleural effusion	Pancreatic inflammation tracks via oesophageal hiatus or diaphragmatic lymphatics → amylase-rich effusion (usually left-sided)	Dyspnoea; diagnostic thoracentesis shows ↑ amylase
AKI	Hypovolaemia (third-spacing) → pre-renal AKI; or cytokine-mediated intrinsic renal injury	Oliguria, ↑ creatinine; aggressive fluid resuscitation is key to prevention
Hypocalcaemia	Fat saponification: lipolysis of peripancreatic fat → release of fatty acids → precipitate with calcium → transient hypocalcaemia → tetany ^[9]	Positive Trousseau's and Chvostek's signs; correct with IV calcium gluconate
DIC	Systemic inflammation → activation of coagulation cascade → consumption of clotting factors + platelets	Bleeding + thrombosis; ↑ PT/aPTT, ↓ platelets, ↑ D-dimer, ↓ fibrinogen
Hyperglycaemia	Islet cell damage → ↓ insulin secretion; stress response → ↑ cortisol/catecholamines → insulin resistance	May require insulin infusion
Abdominal compartment syndrome	Tissue oedema + ascites + ileus → ↑ intra-abdominal pressure > 20 mmHg → ↓ venous return, ↓ renal perfusion, ↓ diaphragmatic excursion → new organ failure	Mx: surgical decompression ^[27]

Never Drain a Pseudoaneurysm Endoscopically!

If a patient with pancreatitis has a fluid collection and you suspect a pseudoaneurysm (suggested by unexplained bleeding, anaemia, or sudden ↑ in collection size), endoscopic drainage is absolutely contraindicated — puncturing a pseudoaneurysm causes fatal haemorrhage. Always get angiographic confirmation and embolisation first ^[27].

Chronic pancreatitis has a distinct complication profile arising from progressive fibrosis and ductal destruction ^[16].

Complication	Pathophysiology	Clinical Features
Pseudocyst (10%)	Ductal disruption → fluid collects in lesser sac → encapsulated by inflammatory tissue	Abdominal pain, visceral obstruction, vascular occlusion, fistulation (pancreatico-enteric, pancreaticopleural), pseudoaneurysm ^[16]
CBD / duodenal obstruction (5–10%)	Inflammation and fibrosis of head of pancreas or pseudocyst compresses CBD/duodenum	Obstructive jaundice, secondary biliary cirrhosis (biliary); postprandial pain, early satiety (duodenal) ^[16]
Pancreatic ascites and pleural effusion	Disrupted pancreatic duct or ruptured pseudocyst → fistulation into peritoneal/pleural cavity	Abdominal distension, dyspnoea; ↑↑ amylase in ascitic/pleural fluid ^[16]
Splenic vein thrombosis (11%)	Chronic inflammation → venous injury → thrombosis → left-sided portal HTN → gastric varices	UGIB, splenomegaly
Pancreatic cancer	2–3× increased risk of pancreatic ductal adenocarcinoma; chronic inflammation → dysplasia → carcinoma	Weight loss, new/changed pain pattern, jaundice; EUS or MRCP screening indicated in hereditary pancreatitis ^[16]
Exocrine insufficiency	Progressive loss of acinar cells → ↓ pancreatic enzymes; clinically significant only when > 90% of exocrine mass is lost	Steatorrhoea, malabsorption, fat-soluble vitamin deficiency (A, D, E, K)
Endocrine insufficiency	Progressive islet cell destruction → diabetes mellitus (30%); α-cells also destroyed → ↑↑ risk of hypoglycaemia	Brittle diabetes; need careful insulin titration

Complications of gallstone disease ^[28]^[29]:

Complication	Pathophysiology	Key Features
Acute cholecystitis	Persistent cystic duct obstruction → GB distension → mucosal ischaemia → secondary bacterial infection	RUQ pain > 6h, fever, Murphy's +ve
Mucocele of gallbladder	Cystic duct obstruction → GB distends with mucus (sterile)	Palpable non-tender GB
Empyema of gallbladder	Mucocele becomes secondarily infected → pus fills the GB	Septic patient, high fever, RUQ mass
Gallbladder perforation	Gangrenous cholecystitis → wall necrosis → perforation	Peritonitis, sepsis; may be contained (pericholecystic abscess) or free (generalised peritonitis)
Acute cholangitis	Stone in CBD → bile stasis → ascending bacterial infection	Charcot's triad (fever, jaundice, RUQ pain); Reynolds' pentad adds hypotension + altered mental status
Acute biliary pancreatitis	Stone impacts at ampulla → duct obstruction → reflux + ductal hypertension → premature enzyme activation	Epigastric pain radiating to back + amylase/lipase ≥ 3× ULN
Cholecystoduodenal (cholecystoenteric) fistula	Chronic cholecystitis → adhesions between GB and duodenum → erosion → fistula	Pneumobilia (air in biliary tree on AXR/CT)
Gallstone ileus	Large stone passes through cholecystoenteric fistula → impacts in terminal ileum (narrowest part of small bowel) → mechanical small bowel obstruction	Rigler's triad: SBO + pneumobilia + ectopic gallstone; Bouveret syndrome = gallstone impacts in duodenum causing GOO
Liver abscess	Ascending infection via biliary system → pyogenic liver abscess	Fever, RUQ pain, hepatomegaly, sepsis
Mirizzi syndrome	Large stone in Hartmann's pouch or cystic duct → extrinsic compression of common hepatic duct → obstructive jaundice	Jaundice + cholecystitis; easily confused with cholangioCA

Complications of gastric cancer ^[1]^[5]:

Complication	Pathophysiology	Clinical Features
Bleeding	Tumour ulceration → erosion into gastric vessels	Iron-deficiency anaemia (chronic occult blood loss); haematemesis and melaena (acute) ^[1]
Gastric outlet obstruction	Antral/pyloric tumour → mechanical luminal obstruction	Abdominal distension, vomiting, dehydration; hypokalaemic hypochloraemic metabolic alkalosis ^[1]
Perforation	Tumour necrosis → full-thickness wall erosion → peritonitis	Rare; acute peritonitis ^[1]
Gastrocolic fistula	Tumour invades through posterior gastric wall into transverse colon	Feculent vomiting, diarrhoea
Linitis plastica → non-compliant stomach	Diffuse type (signet ring) → transmural infiltration → rigid, non-distensible stomach	Severe early satiety, weight loss
Metastatic complications	Haematogenous (liver), lymphatic (Virchow's node, Irish's node), transcoelomic (peritoneum, Krukenberg tumour, Sister Joseph nodule)	Jaundice (liver mets), ascites (peritoneal carcinomatosis), bowel obstruction (peritoneal deposits)

Complication	Pathophysiology	Clinical Features
Obstructive jaundice	Head tumour → CBD obstruction → conjugated hyperbilirubinaemia	Painless jaundice, dark urine, pale stools, pruritus
Acute cholangitis	Biliary stasis → secondary infection	Fever, jaundice, RUQ pain ^[1]
Acute pancreatitis	Tumour obstructs main pancreatic duct → ductal hypertension → enzyme activation	Can be the presenting feature of early pancreatic cancer ^[1]
Pancreatic exocrine insufficiency	Duct obstruction + parenchymal destruction → ↓ enzyme output	Steatorrhoea, malabsorption, weight loss
New-onset diabetes mellitus	Islet cell destruction by tumour	Hyperglycaemia; may resolve after Whipple's (suggesting tumour-mediated β-cell dysfunction) ^[7]
Trousseau syndrome	Mucin-secreting adenocarcinoma → hypercoagulable state	Migratory superficial thrombophlebitis; DVT/PE
GOO	Large tumour or duodenal invasion → mechanical obstruction	Vomiting, unable to tolerate oral intake

8. Post-Surgical Complications (Gastrectomy / Whipple's)

These are important because many patients with epigastric pain are post-surgical — the complications themselves cause new epigastric pain.

General ^[29]:

Immediate: bleeding, injury to nearby organs (pancreas, duodenum)
Early: wound infection, chest infection, post-op ileus
Late: recurrence (usually at gastric bed)

Anastomosis-Related ^[1]^[5]^[29]:

Complication	Pathophysiology	Clinical Features
Anastomotic leak	Technical failure at suture line → GI content leaks into peritoneal cavity	Fever, tachycardia, peritonitis; usually POD 7–10 ^[29]
Duodenal stump blowout	In Billroth II: duodenal stump closure fails → bile and pancreatic juice leak	Peritonitis, sepsis; life-threatening
Afferent loop syndrome	Kinking, anastomotic narrowing, adhesions, or volvulus of afferent limb in Billroth II → accumulation of biliary/pancreatic secretions → risk of duodenal stump blowout, obstructive jaundice, ascending cholangitis, pancreatitis ^[1]^[29]	Post-prandial epigastric pain, nausea, non-bilious vomiting (bilious after obstruction relieved); ↑ amylase ^[29]. Mx: revise GJ, convert to Roux-en-Y, or Braun's enteroenterostomy ^[29]
Efferent loop syndrome	Obstruction of efferent limb → GOO	Epigastric pain, distension, bilious vomiting ^[29]

Motility-Related ("Post-Gastrectomy Syndromes") ^[1]^[5]^[29]:

Complication	Pathophysiology	Clinical Features
Dumping syndrome (20%)	Loss of pylorus → rapid gastric emptying of hyperosmolar carbohydrates → fluid drawn into intestinal lumen by osmosis + inappropriate GI hormone release ^[29]	Early (15–30 min): abdominal pain, N/V/D, vasomotor symptoms (sweating, flushing, palpitations — because of ↓ circulating volume from fluid shift). Late (2–3h): post-prandial hyperinsulinaemic hypoglycaemia (PHH) — rapid glucose absorption → exaggerated insulin spike → rebound hypoglycaemia ^[1]^[29]
Alkaline reflux gastritis	Billroth II: bile refluxes into gastric remnant → chronic chemical gastritis	Epigastric burning pain, nausea, bilious vomiting; unresponsive to PPI
Roux stasis syndrome	Disrupted normal motility in Roux limb → ectopic pacemakers → net propulsive activity proximal (towards stomach) rather than distal ^[1]^[29]	Chronic abdominal pain, nausea, vomiting aggravated by eating
Gastric stasis	Impaired gastric emptying due to post-op atony or vagal denervation	Early satiety, nausea, vomiting
Small stomach syndrome	Inadequate reservoir function after subtotal/total gastrectomy	Early satiety; recommend small frequent meals ^[1]

Nutritional Deficiencies ^[5]^[29]:

Deficiency	Mechanism	Consequence
Vitamin B₁₂ deficiency	↓ Gastric acid + ↓ intrinsic factor (parietal cells removed)	Megaloblastic anaemia, neuropathy; Mx: IM B₁₂ every 3 months ^[29]
Iron deficiency	↓ Gastric acid needed to cleave Fe³⁺ from food + duodenal bypass (Billroth II)	Microcytic anaemia
Calcium deficiency	↓ Gastric acid needed for Ca²⁺ absorption + duodenal bypass	Osteoporosis
Fat-soluble vitamins (A, D, E, K)	Loss of duodenal continuity → ↓ bile-pancreatic mixing	Coagulopathy (K), osteomalacia (D), neuropathy (E)
Steatorrhoea	Impaired mixing of food with bile/pancreatic enzymes; rapid transit	Fatty stools, weight loss

Timing	Complication	Details
Early	Anastomotic leak	PJ leak (30%) > CJ > GJ — highest risk for pancreaticojejunostomy due to digestive enzymes + small, soft duct ^[29]. Severe PJ leak may require completion distal pancreatectomy
	Pancreatic fistula	Persistent amylase-rich drainage from PJ anastomosis; may lead to pseudoaneurysm (GDA stump), splenic vein thrombosis
	Delayed gastric emptying	Especially in pylorus-preserving PD; mechanisms: injury to nerve of Latarjet, disrupted pacemaker cells, ↓ CCK (high concentration in duodenum) ^[29]
	Haemorrhage	From GDA stump pseudoaneurysm (eroded by pancreatic fistula), or surgical site
Late	Exocrine insufficiency	Malabsorption, steatorrhoea; Mx: pancreatic enzyme replacement therapy (PERT)
	Endocrine insufficiency	New-onset DM (16%) ^[29]; brittle diabetes
	Dumping syndrome	Loss of pylorus (classic Whipple) → same mechanism as post-gastrectomy
	Recurrence	Locally at surgical bed, liver metastases, peritoneal carcinomatosis

ERCP is a critical therapeutic tool but carries significant procedure-specific risks ^[1]^[28]:

Complication	Incidence	Pathophysiology
Post-ERCP pancreatitis	~2% (MOST frequent complication)	Manipulation of pancreatic ductal system → oedema at papilla → ductal obstruction → enzyme activation ^[1]
Cholangitis (0.6%)	Manipulation of obstructed biliary system → introduction of bacteria	Fever, jaundice, RUQ pain after procedure
Bleeding	After sphincterotomy → cutting through papilla disrupts submucosal vessels	Increased risk in thrombocytopenia and coagulopathy ^[1]
Perforation	Instrument-related or sphincterotomy-related → duodenal/retroperitoneal perforation	Retroperitoneal air on CT; may need surgery ^[1]
Papillary stenosis	Long-term: scarring at sphincterotomy site → ampullary stricture	Recurrent biliary obstruction
Stent stenosis or migration	Plastic stents occlude with biofilm/sludge (~3 months); metal stents may migrate	Recurrent jaundice, cholangitis

Preventing Post-ERCP Pancreatitis

Two proven strategies: (1) PR indomethacin (NSAID) immediately before or after ERCP — inhibits phospholipase A₂ and ↓ inflammation; (2) Temporary prophylactic pancreatic duct stenting — maintains ductal drainage to prevent oedema-induced obstruction ^[9].

Primary hyperparathyroidism can cause epigastric pain through multiple mechanisms ^[30]:

Mechanism	Pathophysiology
↑ Gastric acid secretion	Calcium stimulates gastrin release → ↑ HCl → PUD
Pancreatitis	Hypercalcaemia → premature activation of trypsinogen within pancreatic duct → autodigestion
Constipation	Calcium → ↓ smooth muscle motility → constipation → abdominal pain
Renal colic	Hypercalciuria → calcium stones → ureteric colic (may radiate to epigastrium)

The classic mnemonic for hypercalcaemia: "Bones, stones, groans, thrones, and psychic overtones" — bone pain/fractures, renal stones, abdominal groans (GI pain including epigastric pain/dyspepsia), polyuria (thrones), confusion/depression ^[30].

High Yield Summary

PUD "4 Bs": Bleed, Burst, Block, Burrow. Posterior DU bleeds (GDA); anterior DU perforates; chronic scarring blocks (GOO); penetration burrows into pancreas/adjacent organs.
Bleeding PUD is the leading cause of death — IV PPI post-endoscopy raises pH > 6 to stabilise clots. Signs of rebleeding: haematemesis, fresh melaena, tachycardia, falling Hb.
PPU: chemical peritonitis → "silent interval" (acid dilution) → bacterial peritonitis. Pain and guarding may ↓ after 4–6h but peritonitis is progressing.
GOO from PUD → hypokalaemic, hypochloraemic metabolic alkalosis from vomiting.
GERD progression: oesophagitis → ulceration → stricture → Barrett's → adenocarcinoma.
Acute pancreatitis complications (Atlanta): APFC (resolves, no Rx) vs ANC → infected necrosis (leading cause of death; > 7–10 days; step-up approach). Pseudoaneurysm: NEVER drain endoscopically.
Hypocalcaemia in pancreatitis: fat saponification (fatty acids + calcium → soap).
Gallstone complications: mucocele, empyema, perforation, cholangitis, biliary pancreatitis, cholecystoenteric fistula → gallstone ileus / Bouveret syndrome.
Post-gastrectomy syndromes: dumping (early = osmotic fluid shift; late = hyperinsulinaemic hypoglycaemia), afferent/efferent loop syndrome, alkaline reflux gastritis, nutritional deficiencies (B₁₂, iron, calcium, ADEK).
Post-Whipple's: PJ leak (30%, highest risk), delayed gastric emptying, pancreatic fistula → pseudoaneurysm, new-onset DM (16%).
Post-ERCP pancreatitis is the most frequent ERCP complication (~2%); preventable with PR indomethacin and pancreatic duct stenting.

Active Recall - Complications of Conditions Causing Epigastric Pain

^[1] Senior notes: felixlai.md (PUD complications — bleeding, perforation, penetration, GOO, fistulisation; Barrett's oesophagus; Gastric cancer complications; Post-gastrectomy syndromes; ERCP complications; Gallstone pancreatitis prevention) ^[3] Senior notes: Ryan Ho Fundamentals.pdf (p268, Perforated peptic ulcer — pathology, clinical features) ^[4] Senior notes: Ryan Ho GI.pdf (p56–57, GERD pathophysiology and complications) ^[5] Senior notes: Ryan Ho GI.pdf (p84, p86, p88, Gastric cancer clinical features, staging, post-gastrectomy complications) ^[7] Senior notes: maxim.md (Pancreatic carcinoma — complications, Whipple's complications) ^[9] Senior notes: maxim.md (Acute pancreatitis — Revised Atlanta classification, severity, complications) ^[10] Senior notes: maxim.md (PUD complications — haemorrhage, perforation, GOO, Boey score, surgical options) ^[16] Senior notes: Ryan Ho GI.pdf (p340–342, p345–346, p350, Acute pancreatitis — complications, local collections, vascular complications; Chronic pancreatitis complications) ^[24] Senior notes: Ryan Ho Fundamentals.pdf (p255–257, Endoscopic Tx modalities, post-endoscopy management) ^[25] Senior notes: Ryan Ho GI.pdf (p78–79, PUD complications — bleed/burst/block/burrow) ^[26] Senior notes: maxim.md (GERD — relationship with Barrett's and oesophagitis, complications) ^[27] Senior notes: Ryan Ho GI.pdf (p342, p345–346, Revised Atlanta classification of local complications, vascular complications, management of pancreatitis complications) ^[28] Lecture slides: GC 200. RUQ pain, jaundice and fever Cholecytitis and cholangitis Imaging of GI system.pdf (p5, Complications of gallstone disease; p14, ERCP complications) ^[29] Senior notes: maxim.md (Post-gastrectomy complications — afferent/efferent loop, dumping, nutritional; Whipple complications — PJ leak, DGE); felixlai.md (Post-gastrectomy syndromes — afferent/efferent loop, Roux stasis, dumping, nutritional deficiencies) ^[30] Senior notes: Ryan Ho Endocrine.pdf (p42, Hyperparathyroidism — GI complications, bones stones groans)

Epigastric Pain

Relationship to Dyspepsia

Epidemiology and Risk Factors

Anatomy and Function

Etiology (Hong Kong Focus) and Pathophysiology

1. Peptic Ulcer Disease (PUD)

Classification of Epigastric Pain

Clinical Features

A. Symptoms with Pathophysiological Basis

B. Signs with Pathophysiological Basis

Active Recall - Epigastric Pain (Definition, Epidemiology, Anatomy, Etiology, Clinical Features)

Differential Diagnosis of Epigastric Pain

Organising Framework

Tier 2: Common Organic Causes

Differential Diagnosis by Clinical Presentation Pattern

Active Recall - Differential Diagnosis of Epigastric Pain

References

Formal Diagnostic Criteria for Major Conditions

The Diagnostic Algorithm

Investigation Modalities — Systematic Review

C. Radiological Investigations

Upper Endoscopy (OGD — Oesophago-gastro-duodenoscopy)

Active Recall - Diagnostic Criteria, Algorithm, and Investigations for Epigastric Pain

Phase 1: Immediate Stabilisation (Acute Presentations)

Phase 2: Cause-Specific Management

A. Peptic Ulcer Disease (PUD)

B. Management of PUD Complications

C. GERD Management [1][4][25]

D. Acute Pancreatitis Management [1][9][16][27]

Active Recall - Management of Epigastric Pain

1. Complications of Peptic Ulcer Disease

3. Complications of Acute Pancreatitis

8. Post-Surgical Complications (Gastrectomy / Whipple's)

Active Recall - Complications of Conditions Causing Epigastric Pain

On this page

Epigastric Pain

Definition and Overview

Relationship to Dyspepsia

Epidemiology and Risk Factors

Epidemiology of Epigastric Pain (by Major Causes)

General Risk Factors for Conditions Causing Epigastric Pain

Anatomy and Function

Visceral vs Somatic Pain — A First Principles Explanation

Organs in or Referring Pain to the Epigastrium

Stomach Anatomy (Detailed)

Gastric Mucosal Defence — Why Doesn't the Stomach Digest Itself?

Pancreatic Anatomy

Biliary System Anatomy

Etiology (Hong Kong Focus) and Pathophysiology

1. Peptic Ulcer Disease (PUD)

Aetiology

Pathophysiology Summary

2. Gastro-oesophageal Reflux Disease (GERD)

3. Functional Dyspepsia

4. Gastric Cancer

5. Pancreatic Carcinoma

6. Acute Pancreatitis

7. Biliary Colic and Acute Cholecystitis

8. Gastric Outlet Obstruction (GOO)

9. Other Important Causes

Classification of Epigastric Pain

By Onset and Duration

By Mechanism

By Anatomical Source

Clinical Features

A. Symptoms with Pathophysiological Basis

1. Pain Characteristics (SOCRATES Framework)

2. Relationship to Meals

3. Associated GI Symptoms

4. Associated Systemic Symptoms

5. Key History Points

B. Signs with Pathophysiological Basis

1. General Inspection

2. Abdominal Examination

Important Patterns of Epigastric Pain — Summary Table

Active Recall - Epigastric Pain (Definition, Epidemiology, Anatomy, Etiology, Clinical Features)

References

Differential Diagnosis of Epigastric Pain

Systematic Differential Diagnosis by System

Organising Framework

Tier 1: Life-Threatening Emergencies

Tier 2: Common Organic Causes

A. Oesophageal

B. Gastric

C. Duodenal

D. Hepatobiliary

E. Pancreatic

F. Cardiac and Vascular

G. Non-GI / Miscellaneous

Differentiating the Key Conditions: A Practical Comparison

Differential Diagnosis by Clinical Presentation Pattern

Pattern 1: Acute Severe Epigastric Pain

Pattern 2: Chronic/Recurrent Epigastric Pain

Pattern 3: Epigastric Pain with Jaundice

Pattern 4: Epigastric Pain with UGIB

Pattern 5: Epigastric Pain with Weight Loss

Zollinger-Ellison Syndrome — A Special Differential

Valentino's Sign — A Diagnostic Trap

A Practical Clinical Approach to Narrowing the DDx

Summary Table: Differential Diagnosis at a Glance

Active Recall - Differential Diagnosis of Epigastric Pain

References

Diagnostic Criteria, Algorithm, and Investigations for Epigastric Pain

Formal Diagnostic Criteria for Major Conditions

1. Functional Dyspepsia — Rome IV Criteria

2. Acute Pancreatitis — Revised Atlanta Classification (2013)

3. Acute Cholecystitis — Tokyo Guidelines 2013 (TG13)

4. Acute Myocardial Infarction — 4th Universal Definition (2018)

5. Peptic Ulcer Disease — No Formal "Diagnostic Criteria"

6. GERD — Clinical + Response to PPI

The Diagnostic Algorithm

Overarching Principle

Master Algorithm for Epigastric Pain

Key Decision Points Explained

Investigation Modalities — Systematic Review