Dyspepsia is a symptom complex of recurrent epigastric pain or discomfort, often accompanied by bloating, nausea, early satiety, or postprandial fullness, originating from the gastroduodenal region.

Dyspepsia — Definition, Epidemiology, Risk Factors, Anatomy, Etiology, Pathophysiology, Classification, and Clinical Features

2. Epidemiology

3. Anatomy and Functional Considerations

Understanding the anatomy of the upper GI tract is essential because dyspepsia can originate from any structure between the lower oesophagus and the duodenum (and even from extra-GI sources).

3.2 Stomach

The stomach is divided into cardia, fundus, body (corpus), antrum, and pylorus ^[3].

Understanding gastric acid secretion is fundamental to understanding dyspepsia:

Cell Type	Location	Secretion	Function
Parietal cells	Body/fundus	HCl, intrinsic factor	Acid production via H⁺/K⁺-ATPase (proton pump)
Chief cells	Body/fundus	Pepsinogen	Converted to pepsin by acid; digests proteins
G cells	Antrum	Gastrin	Stimulates parietal cells → ↑ acid
D cells	Antrum/duodenum	Somatostatin	Inhibits gastrin and acid secretion
ECL cells	Body/fundus	Histamine	Stimulates parietal cells via H2 receptors
Mucous cells	Throughout	Mucus + HCO₃⁻	Protective mucosal barrier

The mucosal defence system relies on:

Mucus-bicarbonate barrier — traps HCO₃⁻ near epithelium to neutralise acid
Prostaglandins (especially PGE₂) — stimulate mucus/bicarbonate secretion, maintain mucosal blood flow, inhibit acid secretion
Mucosal blood flow — washes away back-diffusing H⁺ ions, delivers oxygen and nutrients for cell repair
Epithelial cell renewal — rapid turnover every 3–5 days

Why do NSAIDs cause ulcers? Because COX-1 inhibition → ↓ prostaglandin synthesis → loss of all four protective mechanisms simultaneously ^[3].

4. Etiology and Pathophysiology

The causes of dyspepsia can be divided into organic (~25%) and functional (~75%). Let us go through each systematically, with their pathophysiology.

4.1 Organic Causes

A. Gastrointestinal Causes

PUD accounts for the majority of organic dyspepsia. The fundamental mechanism is an imbalance where aggressive factors overwhelm protective mechanisms ^[6].

Risk Factors and their Pathophysiology:

Risk Factor	Pathophysiology
H. pylori infection (92% DU, 70% GU) ^[6]	Microaerophilic Gram-negative spiral bacillus. Strong urease activity hydrolyses urea → ammonia → neutralises local acid, creating a protective alkaline cloud for the bacterium ^[3]. Flagella + mucolytic enzymes help it burrow through the mucus layer. It causes chronic inflammation → disrupts mucosal defences → ↑ acid secretion (in antral-predominant infection) via ↑ gastrin release from G-cells. In corpus-predominant infection → atrophic gastritis → ↓ acid → ↑ gastric cancer risk.
NSAIDs including aspirin ^[3]^[6]	Gastric and duodenal mucosa use COX-1 for prostaglandin (PGE₂) synthesis. PGE₂ protects mucosa by: mucin production, bicarbonate secretion, maintaining mucosal blood flow, inhibiting acid secretion. NSAIDs non-selectively inhibit COX-1 and COX-2 → ↓ PGE₂ → disruption of mucosal barrier → ↑ permeability to H⁺ ions → acid-mediated damage ^[3]. COX-2 selective inhibitors (e.g. celecoxib) preserve GI mucosal protection because COX-1 is left intact.
Smoking (2× risk) ^[6]	↓ mucosal blood flow, ↓ bicarbonate secretion, ↑ gastric acid output, impairs ulcer healing
Stress ^[6]	Stress ulcers are due to biliary reflux, uraemic toxins and impaired perfusion to stomach, leading to impairment of mucosal protection ^[6]. Especially in ICU patients on mechanical ventilation or with coagulopathy.
Zollinger-Ellison syndrome ^[6]^[7]	Gastrinoma → hypersecretion of gastrin → 4–6× gastric acid output via trophic effect on parietal cells and ECL cells ^[7]. Features: multiple ulcers at atypical positions, often complicated (bleeding, stricture, perforation), PPI-resistant ulcers, ulcers in unusual locations (distal duodenum, jejunum) ^[7].
Alcohol ^[6]	Direct mucosal irritant, stimulates acid secretion
Drugs: antiplatelets, steroids ^[6]	Steroids ↓ mucosal cell turnover; antiplatelets impair platelet plug formation at ulcer sites

NSAID ulcer risk factors ^[3]:

Advanced age ( > 75 years)
Prior history of ulcer disease or complications
High dose / long duration / relatively toxic NSAIDs
Concurrent use of corticosteroids or anticoagulants

PUD Clinical Pattern:

Epigastric pain aggravated by any food and relieved by antacids indicates chronic gastric ulcer ^[1]
Pain before meals relieved by food indicates chronic duodenal ulcer ^[1]
- Why? In DU, fasting allows acid to bathe the exposed ulcer; food buffers the acid temporarily. In GU, food stimulates acid secretion and gastric motility, which irritates the ulcer.
Pain may radiate to the back (atypical — suggests posterior ulcer penetrating into pancreas)
Associated with postprandial belching, epigastric fullness, early satiety, fatty food intolerance, nausea and vomiting ^[3]

Cause	Mechanism
Chronic pancreatitis	Ongoing pancreatic inflammation → epigastric pain radiating to back; fat maldigestion → steatorrhoea
Infiltrative gastric diseases (e.g. Crohn's disease)	Transmural inflammation of gastric/duodenal wall → pain, stricture, GOO
Coeliac disease	Immune-mediated villous atrophy → malabsorption; can cause vague upper abdominal discomfort
Intestinal parasitic infestation	Direct mucosal irritation, inflammation
Bowel ischaemia due to coeliac artery compression	Median arcuate ligament syndrome → post-prandial pain ("intestinal angina")
Other abdominal cancers (HCC, HBP malignancies)	Mass effect, capsular stretching (liver), biliary obstruction
Gastroparesis ^[4]	Delayed gastric emptying without mechanical obstruction → early satiety, postprandial fullness, N/V, bloating. Causes: DM neuropathy, drugs (CCB, GLP-1 agonists), post-surgical, scleroderma
Gastric outlet obstruction ^[4]	Mechanical obstruction → epigastric pain, projectile non-bilious vomiting of undigested food, succussion splash. Malignant (80%) until proven otherwise

This is where clinicians get caught out. Dyspepsia is not always from the gut!

Cause	Mechanism / Explanation
Drug-induced dyspepsia ^[1]^[2]	NSAIDs, steroids, oral antibiotics, iron, digoxin, metronidazole, alendronate, slow K — direct mucosal irritation and/or ↓ mucosal protection. Drug history is important, especially NSAID use ^[1].
Abdominal wall pain ^[2]	Musculoskeletal origin; detected by Carnett sign (↑ local tenderness during abdominal wall muscle tensing — if pain increases with tensing, it is from the wall, not the viscera) ^[2]
Electrolyte disturbances (hyperCa, hyperK) ^[2]	Hypercalcaemia → ↑ gastrin secretion → ↑ acid; also impairs GI motility
Thyroid and parathyroid diseases ^[2]	Hyperthyroidism → ↑ GI motility; hyperparathyroidism ^[1] → hypercalcaemia → ↑ gastrin
Chronic renal failure ^[2]	Uraemic toxins damage gastric mucosa; ↑ gastrin levels (reduced renal clearance)
Coronary artery disease (basal myocardial ischaemia) ^[1]^[2]	Inferior MI / ischaemia can present as epigastric pain via shared T5–T9 dermatome innervation with the stomach. In particular, care should be taken to consider and perhaps exclude ischaemic heart disease ^[1].
Congestive cardiac failure ^[1]	Hepatic congestion from right heart failure → hepatomegaly → RUQ/epigastric discomfort
Depression ^[1]	Somatic manifestation of depression can present as vague upper abdominal discomfort
Diabetes ^[1]	Diabetic gastroparesis (autonomic neuropathy → vagal dysfunction → delayed gastric emptying)
Pregnancy (early) ^[1]	hCG → stimulates the chemoreceptor trigger zone; progesterone → relaxes LES and slows GI motility

The Masquerades Checklist

Depression, diabetes, drugs (especially NSAIDs/aspirin) are listed in Murtagh's "masquerades checklist" ^[1]. These are conditions that mimic other diseases. Always consider them in undifferentiated dyspepsia. Anxiety and stress are common associations of which patients are often unaware. Consider irritable bowel syndrome ^[1].

Rare Causes [1]

Hyperparathyroidism → hypercalcaemia → mechanisms as above
Mesenteric ischaemia → "intestinal angina" — post-prandial epigastric pain in patients with atherosclerotic risk factors
Zollinger-Ellison syndrome ^[1]^[7] — gastrinoma causing hypergastrinaemia
Kidney failure ^[1] — uraemic gastropathy
Scleroderma ^[1] — fibrosis of GI smooth muscle → dysmotility → delayed emptying, GERD

Functional dyspepsia: dyspepsia in the absence of detectable organic diseases ^[2]. This is a diagnosis of exclusion.

Pathophysiology [2]

FD pathophysiology is NOT well understood, but is postulated to be multifactorial:

Mechanism	Explanation
Gastric dysmotility and impaired compliance ^[2]	The fundus normally relaxes (accommodates) to receive food. In FD, impaired gastric accommodation → the stomach doesn't expand properly → food causes early distension → postprandial fullness and early satiation. Additionally, antral hypomotility → delayed gastric emptying in ~25–35% of FD patients.
Visceral hypersensitivity ^[2]	↓ Threshold for pain when gastric compliance is normal — the stomach distends normally but the brain perceives it as painful. This is analogous to allodynia in pain syndromes. Peripheral sensitisation of gastric afferents + central amplification in the brain.
H. pylori infection ^[2]	Evidence weak but HP eradication associated with relief in minority of patients — NNT ~14 (i.e. you need to treat 14 patients with HP eradication for 1 to benefit). The mechanism may involve low-grade mucosal inflammation altering sensory nerve function.
Altered gut microbiome ^[2]	Quantitative and qualitative changes in gut bacteria may alter mucosal immunity and visceral sensation. Duodenal eosinophilia and mast cell infiltration have been demonstrated in FD — these cells release mediators that sensitise sensory neurons.
Psychological factors ^[2]	Multiple studies reveal association between anxiety/depression and FD — likely via the brain–gut axis. Stress activates the HPA axis and autonomic nervous system → altered gastric motility and visceral perception.
Other factors ^[2]	Diet, genetics — certain foods (high fat, spicy) may trigger symptoms; genetic polymorphisms in GNβ3 (G-protein subunit) have been associated with FD.
Duodenal micro-inflammation	Emerging evidence (post-2020) suggests that low-grade duodenal inflammation (eosinophilic/mast cell infiltration) may be a key driver, potentially triggered by infections, food antigens, or altered microbiome. This disrupts mucosal barrier → activates submucosal sensory neurons.
Post-infectious FD	~10% of FD cases begin after acute gastroenteritis (similar to post-infectious IBS). Salmonella, Campylobacter, and norovirus are implicated. Mechanism: persistent low-grade mucosal inflammation + visceral sensitisation.

5. Classification

Category	Proportion	Examples
Functional dyspepsia	~60–75% ^[3]	No organic cause found
Peptic ulcer disease	~15–20%	Gastric ulcer, duodenal ulcer
GERD / oesophagitis	~5–15%	Reflux oesophagitis
Malignancy	~1–2%	Gastric, oesophageal, pancreatic CA
Other organic	~5%	Biliary, pancreatitis, drugs, metabolic

Subtype	Predominant Symptoms	Old Name	Postulated Mechanism
Postprandial distress syndrome (PDS)	Bothersome postprandial fullness + bothersome early satiation	"Dysmotility-like"	Impaired gastric accommodation + delayed emptying
Epigastric pain syndrome (EPS)	Bothersome epigastric pain or burning, NOT necessarily related to meals, NOT related to defecation/passing flatus	"Ulcer-like"	Visceral hypersensitivity + acid sensitivity

Exam Trap: EPS vs IBS

Symptoms relieved by evacuation of feces or gas should generally NOT be considered as part of dyspepsia ^[3]. If abdominal pain is characteristically associated with defecation — think IBS, not dyspepsia ^[8]. The overlap is real (many patients have both), but the distinction matters for classification.

This is a classic clinical reasoning framework — extremely high yield for clinical exams:

Category	Conditions
Probability diagnosis	Irritable upper GIT (functional dyspepsia), gastro-oesophageal reflux, gastritis, oesophageal motility disorder ^[1]
Serious disorders not to be missed	Cancer (stomach, pancreas, oesophagus), cardiovascular (IHD, CCF), pancreatitis, peptic ulcer ^[1]
Pitfalls (often missed)	Myocardial ischaemia, food allergy (e.g. lactose intolerance), pregnancy (early), biliary motility disorder, other gallbladder disease, post-vagotomy, duodenitis ^[1]
Rarities	Hyperparathyroidism, mesenteric ischaemia, Zollinger-Ellison syndrome, kidney failure, scleroderma ^[1]
Masquerades checklist	Depression, diabetes (rarely), drugs (esp. NSAIDs, aspirin) ^[1]
Is the patient trying to tell me something?	Anxiety and stress are common associations of which patients are often unaware. Consider IBS. ^[1]

6. Clinical Features

These are critical — they mandate urgent investigation (usually upper endoscopy) to rule out malignancy and serious pathology.

Alarming features in dyspepsia ^[1]^[2]^[3]:

Alarm Feature	Pathophysiological Basis
Age ≥ 55 (some guidelines say > 40) with newly onset dyspepsia	↑ incidence of malignancy with age; gastric CA rare < 40y
Family history of upper GI cancer	Genetic susceptibility (e.g. HDGC, HNPCC, FAP)
Jaundice	Biliary obstruction (pancreatic head CA, cholangioCA, metastatic disease)
Unintended weight loss	Catabolic state from malignancy; also occurs in chronic pancreatitis, coeliac disease
Dysphagia	Oesophageal stricture, oesophageal CA, extrinsic compression
Odynophagia	Oesophageal ulceration, severe oesophagitis, pill oesophagitis, infection (CMV, Candida, HSV in immunocompromised)
GI bleeding (haematemesis/melaena)	Ulcer erosion into vessel, variceal bleeding, malignancy
Unexplained iron-deficiency anaemia	Occult GI blood loss from ulcer or malignancy
Persistent vomiting	GOO from pyloric stenosis (PUD-related or malignant), gastroparesis
Palpable mass or lymphadenopathy	Advanced malignancy (e.g. Virchow's node = left supraclavicular LN = Troisier's sign → gastric CA metastasis)

High Yield: Age Threshold for Endoscopy

The lecture slides and senior notes use age > 40 as the cut-off for recommending OGD in uninvestigated dyspepsia ^[2]. Some Western guidelines (NICE, AGA) use 55–60. For HKUMed exams, use age > 40 as per the local practice and Ryan Ho's notes ^[2]. This reflects the higher incidence of gastric CA in East Asia compared to the West.

6.2 Symptoms

Symptom	Pathophysiological Basis
Postprandial fullness	Impaired gastric accommodation → fundus doesn't relax → early gastric distension → afferent signals to brain perceived as "fullness"
Early satiation (unable to finish a normal-sized meal)	Same mechanism as above; also possible antral hypomotility → food pools in stomach
Epigastric pain	Visceral hypersensitivity — normal gastric distension/acid exposure triggers pain via sensitised vagal afferents → dorsal horn → brain
Epigastric burning	Acid exposure to hypersensitive mucosa; also may indicate H. pylori-related duodenal micro-inflammation
Morning symptoms characteristic ^[2]	Overnight fasting → acid accumulates in empty stomach → morning pain in EPS subtype
Nausea, bloating, excessive belching ^[3]	Related to gastric dysmotility, aerophagia, and visceral hypersensitivity
Psychiatric comorbidities	± anxiety, depression ^[2] — brain-gut axis dysregulation

Important Supportive Remarks from Rome IV

Postprandial epigastric pain/burning, bloating, excessive belching and nausea can also be present ^[3]
Pain may be induced or relieved by ingestion of a meal or may occur while fasting ^[3]
Pain does not fulfill biliary pain criteria ^[3]
Vomiting warrants consideration of another disorder ^[3] — persistent vomiting is NOT typical of FD

Symptom	Pathophysiological Basis
Epigastric pain — gnawing, burning, hunger-like	Acid bathing the ulcer crater stimulates exposed nerve endings in the submucosa
Pain before meals relieved by food (DU) ^[1]	Fasting → acid accumulates → exposed ulcer base irritated; food buffers acid temporarily
Pain aggravated by food (GU) ^[1]	Food → ↑ acid secretion + gastric motility → irritates the gastric ulcer
Night pain (DU)	Nocturnal acid secretion peaks at ~2 AM (circadian pattern); no food buffer
Pain radiating to back	Posterior ulcer penetrating into pancreas — pancreatic nerve plexus irritation
Postprandial belching, fullness, early satiety, fatty food intolerance, N/V ^[3]	Gastric inflammation → impaired motility; fatty foods ↑ CCK → slows gastric emptying
Periodicity	Symptoms come and go over weeks/months — ulcers heal and recur

Symptom	Pathophysiological Basis
Heartburn	Acid contact with oesophageal squamous epithelium (which lacks the protective mucus barrier of gastric columnar epithelium) → mucosal injury → pain via oesophageal nociceptors
Regurgitation	Retrograde flow of gastric content into pharynx — reflux past an incompetent LES
Water brash	Reflex salivary gland stimulation as acid enters throat ^[5] — a vagal reflex
NCCP (non-cardiac chest pain)	Shared T1–T5 spinal innervation between oesophagus and heart → referred pain pattern identical to angina
Posturally aggravated	Characteristically increased by bending, straining or lying down ^[5] — gravity no longer assists clearance
Chronic cough, hoarseness, throat tightness	Laryngo-pharyngeal reflux (LPR) ^[5] — acid reaching larynx/pharynx → chemical irritation of vocal cords and airways
Asthma	Correlated with GERD, reason incompletely understood ^[5] — possibly micro-aspiration or vagal reflex bronchoconstriction
Dental erosion	Acid reaches oral cavity → dissolves enamel (palatal surfaces of upper incisors characteristically affected)

Symptom	Pathophysiological Basis
Episodic constant pain in RUQ/epigastrium ^[2]	Gallbladder distension against obstructing stone → visceral pain via splanchnic afferents
Radiation to back or right scapula ^[2]	Phrenic nerve irritation (gallbladder on undersurface of liver near diaphragm) → referred pain to shoulder tip / scapula
Diaphoresis, nausea, vomiting ^[2]	Vagal stimulation from visceral distension → parasympathetic activation
Post-prandial timing	Fatty meal → CCK → gallbladder contraction against stone

Symptom	Pathophysiological Basis
Triple loss of appetite, weight and colour ^[1]	Cancer-related cachexia (TNF-α, IL-6) → anorexia, muscle wasting, anaemia from chronic disease or occult blood loss
Progressive dysphagia	Oesophageal CA → progressive luminal narrowing → solids first, then liquids
New-onset dyspepsia in elderly	High pre-test probability of malignancy

Symptom Pattern	Think Of	Why
Epigastric pain + exertional, + risk factors for CVD	Myocardial ischaemia ^[1]	Inferior wall of heart and stomach share T5–T9 afferent innervation → pain referred to epigastrium
Dyspepsia + peripheral oedema, JVP, hepatomegaly	CCF ^[1]	Right heart failure → hepatic congestion → capsular distension → RUQ/epigastric pain
Drug history +ve	Drug-induced ^[1]^[2]	NSAID, aspirin, steroids, iron, etc.
Polyuria, polydipsia, constipation, confusion	Hyperparathyroidism / hypercalcaemia ^[1]	↑ Ca²⁺ → ↑ gastrin → ↑ acid; also Ca²⁺ → impaired GI smooth muscle contractility

Physical examination usually normal ^[2] — this is a key teaching point. Dyspepsia is largely a symptom-based diagnosis. However, certain signs are diagnostically valuable:

Sign	Significance	Pathophysiological Basis
Epigastric tenderness	Non-specific — epigastric discomfort is NOT diagnostically valuable ^[2]	Present in FD, PUD, GERD, pancreatitis, etc.
Carnett sign (+ve)	Indicates abdominal wall origin ^[2] — ↑ local tenderness during muscle tensing	If pain increases when the patient tenses their abdominal wall (e.g. by lifting head off pillow), the source is the abdominal wall (e.g. muscle strain, nerve entrapment), NOT the viscera. Visceral pain would be LESS tender with muscle tensing because the tense wall "shields" the viscera from palpation.
Anaemia	Occult GI bleeding (ulcer, CA), coeliac disease, chronic disease	Chronic blood loss → iron depletion; malabsorption → ↓ iron/B12/folate
Jaundice	Biliary obstruction, hepatic disease, pancreatic CA	Obstruction → conjugated hyperbilirubinaemia → yellow sclera/skin
Wasting / cachexia	Malignancy, chronic pancreatitis, coeliac disease	↑ catabolism, ↓ nutrient absorption
Abdominal mass	Gastric CA, pancreatic CA, hepatomegaly	Advanced tumour growth
Lymphadenopathy	Metastatic disease — Virchow's node (left supraclavicular) = classic gastric CA; Sister Mary Joseph nodule (periumbilical) = GI malignancy	Lymphatic spread from intra-abdominal malignancy
Ascites	Peritoneal carcinomatosis, hepatic disease	Malignant deposits on peritoneum → exudative ascites; portal hypertension → transudative ascites
Succussion splash	Gastric outlet obstruction ^[4]	Retained fluid in a dilated stomach; splash heard when shaking the patient > 4 hours post-meal
Hepatomegaly	Liver metastases, CCF, hepatitis	Tumour infiltration or congestion from right heart failure
Courvoisier sign	Palpable non-tender gallbladder + painless jaundice → pancreatic head CA	Gradual obstruction of CBD → gallbladder distension without inflammation (cf. gallstones cause chronic fibrosis → gallbladder cannot distend)

High Yield Summary

Definition: Dyspepsia = chronic/recurrent upper abdominal pain or discomfort. It is a syndrome, not a diagnosis.

Rome IV for FD: ≥1 of postprandial fullness, early satiation, epigastric pain, epigastric burning — with NO structural disease — for ≥ 3 months (onset ≥ 6 months ago).

Epidemiology: ~25% population prevalence; ~75% functional, ~25% organic. FD prevalence 10–20% in Chinese.

Main organic causes: PUD (HP, NSAIDs), GERD, malignancy, biliary disease, drugs.

Don't miss: Myocardial ischaemia, pancreatic CA, drugs, depression, pregnancy.

Alarm features (mandate OGD): Age > 40 with new onset, weight loss, dysphagia, GI bleeding, IDA, persistent vomiting, mass/LN, jaundice, FHx UGI CA.

Clinical patterns: DU pain = fasting/before meals, relieved by food; GU pain = worse with food; GERD = heartburn + regurgitation, posturally aggravated; Biliary = constant RUQ pain + radiation to back/scapula.

FD subtypes: PDS (postprandial distress — dysmotility-like) vs EPS (epigastric pain — ulcer-like).

Key exam findings: Usually normal. Look for Carnett sign (abdominal wall pain), anaemia, jaundice, mass, LN (Virchow's node), succussion splash.

Murtagh's Diagnostic Tips: Epigastric pain + food aggravation + antacid relief → GU. Pain before meals + food relief → DU. Appetite/weight/colour loss → gastric CA. Always consider IHD.

Active Recall - Dyspepsia: Definition, Epidemiology, Etiology & Clinical Features

Differential Diagnosis of Dyspepsia

The entire point of evaluating dyspepsia is differential diagnosis — because dyspepsia is a symptom complex, not a disease. Your job at the bedside is to sort through the differentials systematically, pick out the dangerous ones early, and arrive at the right diagnosis. Let's think about this like a clinician on a ward round.

This is a must-know framework for clinical exams — it forces you to think about common things first while never forgetting the dangerous ones.

Category	Differentials	Why It's Here
Probability diagnosis	Irritable upper GIT (functional dyspepsia)	60–75% of all dyspepsia — by far the commonest cause ^[3]
	Gastro-oesophageal reflux	Very common; often overlaps with dyspepsia in Chinese populations ^[2]
	Gastritis	Mucosal inflammation (HP, alcohol, NSAIDs, stress) without ulceration — self-limiting
	Oesophageal motility disorder (dysmotility)	e.g. achalasia, diffuse oesophageal spasm — can present with epigastric discomfort + dysphagia
Serious disorders not to be missed	Cancer: stomach, pancreas, oesophagus	Must be excluded in any patient with alarm features. Triple loss of appetite, weight and colour is a feature of cancer of the stomach ^[1].
	Cardiovascular: ischaemic heart disease, congestive cardiac failure	In particular, care should be taken to consider and perhaps exclude ischaemic heart disease ^[1]. Inferior MI shares T5–T9 afferents with the stomach → referred epigastric pain. CCF → hepatic congestion → RUQ/epigastric discomfort.
	Pancreatitis	Acute or chronic — epigastric pain radiating to back, worsened by eating
	Peptic ulcer (PU)	Serious because of complications: bleeding, perforation, GOO. Epigastric pain aggravated by any food and relieved by antacids indicates chronic gastric ulcer. Pain before meals relieved by food indicates chronic duodenal ulcer. ^[1]
Pitfalls (often missed)	Myocardial ischaemia	The classic "missed diagnosis" — elderly patient with epigastric pain put down to "gastritis" but actually having an inferior STEMI
	Food allergy (e.g. lactose intolerance)	Undigested lactose → bacterial fermentation → gas, bloating, cramping. Easy to miss if you don't ask about dairy
	Pregnancy (early)	hCG → CTZ stimulation → nausea; progesterone → ↓ LES tone + slowed motility. Always check β-hCG in reproductive-age women!
	Biliary motility disorder	Sphincter of Oddi dysfunction — episodic biliary-type pain with normal imaging
	Other gallbladder disease	Cholecystitis, choledocholithiasis — post-prandial RUQ/epigastric pain
	Post vagotomy	Disrupted gastric motility → dumping syndrome, bile reflux gastropathy
	Duodenitis	Inflammation without frank ulceration — often H. pylori or NSAID-related
Rarities	Hyperparathyroidism	↑ Ca²⁺ → ↑ gastrin secretion → ↑ acid production; also impairs GI smooth muscle motility
	Mesenteric ischaemia	"Intestinal angina" — post-prandial pain due to inadequate splanchnic blood flow in setting of atherosclerotic disease (coeliac/SMA stenosis)
	Zollinger–Ellison syndrome	Gastrinoma → massive acid hypersecretion → multiple/atypical ulcers, diarrhoea, PPI-resistant symptoms ^[7]
	Kidney failure	Uraemic toxins → direct mucosal damage; ↑ gastrin (reduced renal clearance)
	Scleroderma	Fibrosis of GI smooth muscle → oesophageal dysmotility, gastroparesis, GERD
Masquerades checklist	Depression	Somatic presentation of depression → vague epigastric discomfort, LOA
	Diabetes (rarely)	Autonomic neuropathy → gastroparesis → postprandial fullness, nausea, early satiety
	Drugs, esp. NSAIDs, aspirin	Drug history and past history is important, especially NSAID use ^[1]. Direct mucosal injury + COX-1 inhibition → ↓ PGE₂ → ↓ mucosal protection
"Is the patient trying to tell me something?"	Anxiety and stress are common associations of which patients are often unaware. Consider irritable bowel syndrome. ^[1]	Brain–gut axis: psychological distress → altered visceral perception, abnormal motility. IBS overlaps significantly with FD, especially in Chinese ^[2].

The Pitfall of Pitfalls

Myocardial ischaemia is the most dangerous diagnosis to miss. An inferior MI can present purely as epigastric pain (sometimes with nausea and diaphoresis but NO chest pain). In any patient > 50y with risk factors for coronary artery disease presenting with acute epigastric discomfort — get an ECG before reaching for the endoscopy referral form. The shared T5–T9 spinal innervation between the heart and the stomach makes this referral pattern neuroanatomically inevitable ^[1]^[9].

3. Systematic Organ-System Differential Diagnosis

Now let's organise the same differentials by mechanism and organ system, which is more useful when you need to be comprehensive.

Differential	Key Distinguishing Features	Pathophysiological Basis
Peptic ulcer disease	Epigastric pain aggravated by food (GU) or relieved by food (DU) ^[1]; periodicity; night pain; NSAID/HP history; GI bleeding	Mucosal defect extending to muscularis mucosae — acid + pepsin eroding an area where protective mechanisms have failed (HP infection disrupts mucus layer; NSAIDs inhibit COX-1 → ↓ PGE₂) ^[3]^[6]
GERD	Heartburn + regurgitation — posturally aggravated, worse lying down/bending ^[2]^[5]; water brash; chronic cough; NCCP	Incompetent LES → reflux of acid/pepsin/bile into oesophageal squamous epithelium (which lacks the protective mucus-bicarbonate barrier of gastric columnar epithelium) → mucosal inflammation ^[5]
Gastritis / Duodenitis	Often indistinguishable from PUD clinically; diagnosed on OGD	Mucosal inflammation without ulcer crater — can be HP-related, chemical (alcohol, bile reflux, NSAIDs), or autoimmune (corpus gastritis with pernicious anaemia)
Gastric cancer	Triple loss of appetite, weight and colour ^[1]; progressive dysphagia (cardia tumour); GOO (distal tumour); early satiety (linitis plastica); palpable mass; Virchow's node ^[8]	Adenocarcinoma (90%) — intestinal type arises through Correa cascade (HP → chronic atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma); diffuse type (E-cadherin mutation) infiltrates transmurally ^[8]
Oesophageal cancer	Progressive dysphagia (solids → liquids), weight loss, odynophagia	Squamous cell CA (upper/middle oesophagus — smoking, alcohol) or adenocarcinoma (lower oesophagus / GOJ — Barrett's oesophagus from chronic GERD)
Pancreatic cancer	Epigastric pain radiating to back, painless obstructive jaundice (head), new-onset DM, weight loss, Courvoisier sign	Ductal adenocarcinoma (90%) — head tumours obstruct CBD → conjugated hyperbilirubinaemia; body/tail tumours invade coeliac plexus → severe back pain
Biliary pain ^[2]	Episodic constant NON-colicky intense dull pain in RUQ or epigastrium ± radiation to back or scapula; diaphoresis, nausea, vomiting; NOT increased by movement; can be associated with post-prandial discomfort ^[2]	Gallbladder distension against obstructing stone → visceral pain. Fatty meal → CCK release → GB contraction against stone → pain. Biliary colic can be associated with post-prandial pain, as eating a fatty meal is a common trigger for GB contraction ^[2].
Chronic pancreatitis ^[2]^[3]	Epigastric pain radiating to back, steatorrhoea, DM (endocrine insufficiency), weight loss; history of alcohol or recurrent acute pancreatitis	Chronic inflammatory destruction of pancreatic parenchyma → fibrosis → loss of exocrine (lipase, amylase) and endocrine (insulin) function
Infiltrative gastric diseases (e.g. Crohn's disease) ^[2]	Other Crohn's features (mouth ulcers, perianal disease, skip lesions); granulomatous inflammation on biopsy	Transmural inflammation → gastric/duodenal stricture, fistula, ulceration
Coeliac disease ^[2]	Diarrhoea, steatorrhoea, IDA, dermatitis herpetiformis, bloating; often vague upper abdominal discomfort	Immune-mediated villous atrophy of small bowel (anti-tTG antibodies) → malabsorption of Fe, folate, Ca, fat-soluble vitamins
Intestinal parasitic infestation ^[2]	Travel history, eosinophilia, diarrhoea	Direct mucosal invasion/irritation by parasites (e.g. Giardia, Strongyloides)
Bowel ischaemia due to coeliac artery compression ^[2]	Post-prandial pain ("intestinal angina"), weight loss (food fear), abdominal bruit	Median arcuate ligament syndrome — extrinsic compression of coeliac artery → inadequate splanchnic blood flow when demand increases post-prandially
Other abdominal cancers (HCC, HBP malignancies) ^[2]	Hepatomegaly, jaundice, ascites; HBV/HCV history (HCC); weight loss	Mass effect, capsular stretching of liver, biliary obstruction
Gastroparesis	Postprandial fullness, nausea, vomiting, bloating, early satiety; DM history	Impaired gastric emptying without mechanical obstruction — vagal neuropathy (DM), drugs (GLP-1 agonists, CCB), post-surgical ^[4]
Gastric outlet obstruction	Projectile non-bilious vomiting, succussion splash, weight loss	Malignant (80%) until proven otherwise — gastric CA most common cause; benign causes include PUD-related pyloric stenosis ^[4]
Oesophageal motility disorder	Dysphagia to solids AND liquids simultaneously (unlike mechanical obstruction which is solids first), chest pain, regurgitation of undigested food	Achalasia: failure of LES relaxation + absent oesophageal peristalsis (loss of inhibitory neurons in myenteric plexus). Diffuse oesophageal spasm: uncoordinated contractions.

Differential	Key Distinguishing Features	Pathophysiological Basis
Drug-induced dyspepsia ^[1]^[2]	Temporal relationship to drug use; NSAIDs, steroids, oral antibiotics, iron, digoxin, metronidazole, alendronate, slow K ^[2]	Direct mucosal irritation (iron, alendronate, KCl) or systemic COX inhibition (NSAIDs → ↓ PGE₂). Steroids ↓ epithelial cell turnover. Digoxin stimulates CTZ → nausea.
Coronary artery disease (basal myocardial ischaemia) ^[1]^[2]	Exertional, CVD risk factors, associated diaphoresis/dyspnoea; may be relieved by GTN	Inferior wall ischaemia → cardiac afferents travel via T5–T9 → converge on same dorsal horn neurons as gastric afferents → brain misinterprets origin as epigastric ^[9]
CCF ^[1]	Peripheral oedema, ↑ JVP, orthopnoea, hepatomegaly	Right heart failure → ↑ hepatic venous pressure → hepatic congestion → capsular distension → RUQ/epigastric pain; also gut wall oedema → dysmotility
Electrolyte disturbances (hyperCa, hyperK) ^[2]^[3]	Polyuria, polydipsia (hyperCa); weakness, ECG changes (hyperK)	HyperCa → ↑ gastrin → ↑ acid; ↓ GI smooth muscle contractility → constipation, nausea. HyperK → GI smooth muscle dysfunction
Thyroid / parathyroid diseases ^[2]	Thyrotoxic features (tremor, weight loss, tachycardia) or hyperparathyroid features (stones, bones, moans, groans)	Hyperthyroidism → ↑ GI motility → discomfort. Hyperparathyroidism ^[1] → hypercalcaemia → mechanisms as above
Chronic renal failure ^[2]	Elevated creatinine, uraemic symptoms (nausea, anorexia, pruritis, metallic taste)	Uraemic toxins → direct gastric mucosal damage (uraemic gastropathy); ↓ renal clearance of gastrin → hypergastrinaemia
Abdominal wall pain ^[2]	Carnett sign: ↑ local tenderness during muscle tensing → indicates abdominal wall origin ^[2]	Nerve entrapment (anterior cutaneous nerve entrapment syndrome — ACNES), muscle strain, hernia. The positive Carnett sign differentiates wall from visceral pain because tensing the rectus sheath compresses the trapped nerve/injured muscle
Depression ^[1]	Low mood, anhedonia, sleep disturbance, fatigue; somatic symptoms without organic cause	Brain–gut axis: depression → altered serotonin signalling in both CNS and enteric nervous system → abnormal visceral perception + dysmotility
Diabetes ^[1]	Known DM, signs of peripheral/autonomic neuropathy	Diabetic autonomic neuropathy → vagal dysfunction → gastroparesis
Early pregnancy ^[1]	Reproductive-age woman, amenorrhoea, breast tenderness	hCG stimulates chemoreceptor trigger zone → nausea/vomiting; progesterone → relaxes LES (reflux) + slows gastric emptying

Differential	Key Features	Pathophysiological Basis
Functional dyspepsia ^[2]^[3]	Diagnosis of exclusion — dyspepsia in the absence of detectable organic diseases ^[2]. Two subtypes: PDS (postprandial fullness, early satiation) and EPS (epigastric pain/burning)	Multifactorial: impaired gastric accommodation, visceral hypersensitivity, altered microbiome, duodenal micro-inflammation, psychological factors ^[2]
IBS overlap	Abdominal pain related to defecation (distinguishing feature from dyspepsia); altered bowel habits	Considerable overlap with GERD and IBS in Chinese ^[2]. IBS and FD share pathophysiological mechanisms (visceral hypersensitivity, brain–gut axis dysfunction) and commonly coexist

FD vs IBS: The Key Distinguishing Feature

Symptoms that are relieved by evacuation of feces or gas should generally NOT be considered as part of dyspepsia ^[3]. If abdominal pain is characteristically associated with defecation → think IBS. If centred in the epigastrium and related to meals or fasting but NOT to bowel movements → think FD. In practice, ~30–50% of FD patients also meet criteria for IBS, so the overlap is huge — but the distinction matters for classification and targeted treatment.

The following table summarises how the history and examination help you move from the broad differential list to the likely diagnosis. This is the clinical reasoning that examiners want to see.

Clinical Feature	Points Towards	Points Away From
Epigastric pain aggravated by food, relieved by antacids ^[1]	Gastric ulcer	DU (food relieves DU)
Pain before meals, relieved by food ^[1]	Duodenal ulcer	GU
Heartburn + regurgitation ^[2]	GERD	FD (heartburn is NOT a dyspeptic symptom per Rome IV)
Pain related to defecation / passage of flatus	IBS	Dyspepsia
Episodic constant pain, RUQ/epigastric, radiation to scapula, NOT increased by movement ^[2]	Biliary pain	PUD, GERD
Triple loss of appetite, weight and colour ^[1]	Gastric cancer	FD (no weight loss / anaemia in FD)
Exertional pain, CVD risk factors, diaphoresis	Myocardial ischaemia / angina	GI cause
Temporal relationship with NSAID use	Drug-induced / PUD	FD
Positive Carnett sign ^[2]	Abdominal wall pain	Visceral cause
Young woman, amenorrhoea, nausea	Early pregnancy	—
Multiple atypical ulcers, diarrhoea, PPI-resistant	Zollinger–Ellison syndrome ^[1]^[7]	Simple PUD
Known DM + postprandial fullness/vomiting	Gastroparesis	Mechanical GOO

Clinical Clue	Suspect	Why
Recurrent ulcers despite adequate HP eradication and NSAID cessation; ulcers in unusual locations (D2, jejunum); diarrhoea + weight loss	Zollinger-Ellison syndrome ^[7]	Gastrinoma → 4–6× gastric acid output; multiple ulcers at atypical positions, often complicated; PPI-resistant ^[7]. Diagnosed by fasting serum gastrin > 10× ULN while pH < 2 ^[7].
Epigastric pain after eating in elderly with known atherosclerotic disease, weight loss ("food fear"), abdominal bruit	Mesenteric ischaemia ^[1]	Coeliac/SMA stenosis → inadequate post-prandial splanchnic blood flow → "intestinal angina"
"Stones, bones, moans, groans" + dyspepsia	Hyperparathyroidism ^[1]	↑ PTH → ↑ Ca²⁺ → ↑ gastrin → ↑ acid; ↓ GI motility
Raynaud's, skin tightening, dysphagia + reflux	Scleroderma ^[1]	Fibrosis of oesophageal/gastric smooth muscle → dysmotility, GERD, gastroparesis
Known MEN1 + recurrent PUD	ZES (gastrinoma)	20–30% of gastrinomas are associated with MEN1 ^[7]

High Yield Exam Pearl

When the question gives you a patient with recurrent peptic ulcers despite treatment, ulcers at unusual locations (beyond D1), or diarrhoea with PUD — think Zollinger-Ellison syndrome ^[1]^[7]. When it gives you epigastric pain + CVD risk factors + diaphoresis — do NOT assume it's GI; get an ECG to exclude myocardial ischaemia ^[1]^[9].

High Yield Summary

Framework: Use Murtagh's Diagnostic Strategy — probability (FD, GERD, gastritis) → serious (cancer, IHD, CCF, PUD, pancreatitis) → pitfalls (MI, pregnancy, biliary, food allergy) → rarities (ZES, hyperparathyroidism, mesenteric ischaemia, scleroderma, CKD) → masquerades (depression, DM, drugs) → psychosocial (anxiety/IBS).

Most common cause: Functional dyspepsia (60–75%), but this is a diagnosis of exclusion.

Most dangerous to miss: Myocardial ischaemia (shared T5–T9 innervation), gastric/pancreatic/oesophageal cancer.

Key discriminators: Food–pain relationship (GU vs DU), heartburn/regurgitation (GERD), pain with defecation (IBS not dyspepsia), alarm features (cancer), drug history (NSAID), Carnett sign (abdominal wall), biliary pattern (constant, radiation to scapula).

HK-specific: Lower OGD age threshold (> 40), high HP prevalence, rising GERD, HBV-related HCC, FD-IBS-GERD overlap in Chinese.

ZES clues: Atypical ulcer location, PPI-resistant, multiple ulcers, diarrhoea, fasting gastrin > 10× ULN with pH < 2.

Active Recall - Differential Diagnosis of Dyspepsia

References

^[1] Lecture slides: murtagh merge.pdf (Dyspepsia, pp. 38–39) ^[2] Senior notes: Ryan Ho GI.pdf (pp. 53–54, Section 2.1.4) and Ryan Ho Fundamentals.pdf (pp. 263–264, Section 3.3.4) ^[3] Senior notes: felixlai.md (Dyspepsia section, pp. 490–492) ^[4] Senior notes: maxim.md (Gastroparesis, GOO sections, pp. 130–133) ^[5] Senior notes: Ryan Ho GI.pdf (pp. 56–57, Section 2.2.1 — GERD) ^[6] Senior notes: Ryan Ho GI.pdf (p. 76, Section 2.3.2 — PUD) ^[7] Senior notes: Ryan Ho Endocrine.pdf (p. 102, Section 4.2.3 — Gastrinoma/ZES) ^[8] Senior notes: Ryan Ho GI.pdf (p. 84 — Gastric cancer clinical features) ^[9] Senior notes: Ryan Ho Cardiology.pdf (p. 54, Section 2.1 — Chest Pain/Angina)

Diagnostic Criteria, Diagnostic Algorithm and Investigation Modalities for Dyspepsia

1. Diagnostic Criteria

The Rome IV criteria (2016, current standard) require ALL of the following:

≥1 of:

Bothersome postprandial fullness

Bothersome early satiation

Bothersome epigastric pain

Bothersome epigastric burning

AND: No evidence of structural disease (including on upper endoscopy) that is likely to explain the symptoms

Duration: Criteria fulfilled for the last 3 months with symptom onset ≥ 6 months before diagnosis ^[3]

Subtypes (important because they guide treatment):

Subtype	Criteria	Old Name
Postprandial Distress Syndrome (PDS)	Bothersome postprandial fullness (occurring after ordinary-sized meals, ≥ 3 days/week) AND/OR bothersome early satiation (preventing finishing a regular meal, ≥ 3 days/week)	"Dysmotility-like"
Epigastric Pain Syndrome (EPS)	Bothersome epigastric pain AND/OR bothersome epigastric burning (severe enough to impact usual activities, ≥ 1 day/week). NOT necessarily related to meals. NOT related to defecation/passing flatus ^[2]	"Ulcer-like"

Supportive Remarks from Rome IV (Examinable)

Postprandial epigastric pain or burning, epigastric bloating, excessive belching and nausea can also be present ^[3]
Pain may be induced by or relieved by ingestion of a meal or may occur while fasting ^[3]
Pain does NOT fulfil biliary pain criteria ^[3]
Vomiting warrants consideration of another disorder ^[3]
Heartburn is NOT a dyspeptic symptom but may often coexist ^[3]
Symptoms relieved by evacuation of feces or gas should generally NOT be considered as part of dyspepsia ^[3] — this feature should prompt you to think about IBS instead

Alarm features in dyspepsia mandate upper endoscopy (OGD) as the first-line investigation regardless of age ^[1]^[2]:

#	Alarm Feature
1	Age > 40y (HK/East Asia practice) with new-onset dyspepsia ^[2]
2	Unintentional weight loss ^[2]
3	Dysphagia or odynophagia ^[2]
4	Unexplained iron-deficiency anaemia ^[2]
5	Persistent vomiting ^[2]
6	Upper GI bleeding (haematemesis/melaena) ^[2]
7	Palpable mass or lymphadenopathy ^[2]
8	Family history of upper GI cancers ^[2]

Additional alarm features from Felix Lai's notes ^[3]: jaundice, which indicates biliary obstruction or hepatic disease.

Why Age > 40 and Not > 55?

Western guidelines (ACG, NICE 2024) use age ≥ 60 as the OGD threshold. However, in East Asia including Hong Kong, the incidence of gastric cancer is substantially higher and peaks earlier. HKUMed and local practice use age > 40 as the cut-off for recommending OGD in uninvestigated dyspepsia ^[2]. For your summative exams, use > 40.

2. Diagnostic Algorithm

The clinical approach to dyspepsia follows a stepwise algorithm driven by the presence or absence of alarm features and the patient's age. The main aim is to rule out organic causes of dyspepsia ^[2].

The evaluation depends on setting and presence of alarm symptoms ^[2]. There are essentially three pathways:

Pathway	Who Gets It	What It Involves	Rationale
Upper endoscopy (OGD)	Age > 40y; unexplained weight loss or anaemia; UGIB, vomiting; dysphagia or odynophagia; FHx +ve for UGI cancers ^[2]	Upper endoscopy for any organic disease. H. pylori testing should be done on biopsy sample ^[2]. If organic cause found → treat. If HP +ve on biopsy → eradicate. If both negative → treat as functional dyspepsia ^[2].	Endoscopy is the gold standard for visualising mucosal pathology and obtaining tissue diagnosis. In older patients or those with alarm features, the pre-test probability of organic disease (especially malignancy) is high enough to warrant direct endoscopy.
H. pylori testing ("test-and-treat")	Age < 40y and NO alarm features; HP not tested in previous OGD ^[2]	Urea breath test or stool antigen test ^[2]. If HP +ve → HP eradication therapy ^[2]. If HP -ve → treat as functional dyspepsia ^[2].	In young patients without alarm features, the probability of malignancy is very low. The most treatable organic cause is H. pylori-related disease. Testing and treating HP first is cost-effective and avoids unnecessary endoscopy.
Empirical drug therapy (treat as FD)	Age < 40y and NO alarm features; persistent symptoms despite documented HP eradication ^[2]	Empirical antisecretory therapy: PPI proven to ↓ dyspepsia symptoms. Prokinetics and TCA if fail PPI treatment. Should be reinvestigated by OGD should symptoms persist despite multiple treatments ^[2].	When HP has been excluded or eradicated and there are no alarm features, the most likely diagnosis is FD. Empirical PPI addresses acid-mediated symptoms; prokinetics address dysmotility; TCAs address visceral hypersensitivity.

3. Investigation Modalities — Detailed Breakdown

Now let's go through each investigation in detail, explaining what it is, why we do it, what we look for, and how to interpret the findings.

Test	What It Tells You	Key Findings & Interpretation
Urine dipstick + microscopy	Rule out urological causes of abdominal pain ^[10]^[11]	Haematuria → renal/ureteric stones; leucocytes/nitrites → UTI; proteinuria → renal disease
Urine pregnancy test	Rule out early pregnancy ^[10]^[11]	+ve β-hCG → pregnancy (ectopic or early intrauterine) — always check in reproductive-age women with "dyspepsia" + nausea
ECG	Rule out basal MI ^[10]^[11]	ST elevation in II, III, aVF → inferior STEMI mimicking epigastric pain. In particular, care should be taken to consider and perhaps exclude ischaemic heart disease ^[1].
Capillary blood glucose	Rule out DKA ^[10]^[11]	DKA can present with severe abdominal pain and vomiting mimicking an acute abdomen

ECG in Dyspepsia — Don't Forget!

This is the single most commonly forgotten bedside test in dyspepsia. If your patient is > 50, has CVD risk factors, or has acute-onset epigastric pain with diaphoresis — do an ECG before anything else. Missing an inferior MI because you assumed it was "gastritis" is a career-defining error.

Test	What It Tells You	Key Findings & Interpretation
CBC with differentials ^[3]^[10]	Chronic bleeding, infection, malignancy	Anaemia (↓ Hb): microcytic hypochromic → iron deficiency from chronic occult GI bleeding (PUD, malignancy) or malabsorption (coeliac). Note: takes 48h for haemodilution to set in after acute bleeding ^[10] — a normal Hb does NOT exclude acute haemorrhage. Leucocytosis → infection/inflammation. Thrombocytosis → reactive to chronic bleeding/inflammation.
Electrolyte profile ^[3]	Metabolic causes of dyspepsia	Hyperkalaemia → GI smooth muscle dysfunction, cardiac risk. Hypercalcaemia ^[3] → ↑ gastrin → ↑ acid; ↓ GI motility → nausea, constipation. Think hyperparathyroidism ^[1]. HypoK/hypoCl → prolonged vomiting ^[10] (loss of HCl in vomitus → metabolic alkalosis with paradoxical aciduria).
LFT ^[3]^[10]	Hepatobiliary disease	↑ ALP + ↑ GGT (obstructive pattern) → biliary obstruction (stones, pancreatic head CA). ↑ ALT/AST (hepatocellular pattern) → hepatitis, drug-induced liver injury. ↑ bilirubin → jaundice (obstructive vs hepatocellular).
RFT (renal function tests) ^[10]	CKD, hydration status	↑ Cr/urea → chronic renal failure (uraemic gastropathy). HypoK/hypoCa → can cause ileus but can arise from 3rd spacing ^[10]. Also needed to assess suitability for contrast scans.
Amylase/lipase ^[10]^[12]	Acute pancreatitis	Amylase peaks at 6–24h; > 1000 diagnostic of acute pancreatitis ^[10]. Lipase is more specific and stays elevated longer (preferred in current practice).
Cardiac enzymes (troponin) ^[10]	Rule out ACS	↑ Troponin → myocardial injury. ± Cardiac enzymes, ECG to rule out basal MI ^[10].
Iron studies	Assess iron deficiency	↓ Ferritin, ↓ serum iron, ↑ TIBC → iron-deficiency anaemia → occult GI blood loss
CRP/ESR ^[12]	Inflammation	Non-specific; elevated in pancreatitis, malignancy, IBD, infection
Glucose ^[10]	DKA, diabetes	± Glucose to rule out DKA ^[10]. Also assess for DM → diabetic gastroparesis
ABG ^[10]	Metabolic derangement	Metabolic acidosis with ↑ lactate → intestinal ischaemia. Metabolic alkalosis → prolonged vomiting ^[10].
TFTs	Thyroid disease	Hyperthyroidism → ↑ GI motility → dyspepsia; hypothyroidism → gastroparesis
Fasting serum gastrin	ZES screening	> 10× ULN with gastric pH < 2 → diagnostic of gastrinoma ^[7]
Coeliac screen (anti-tTG IgA)	Coeliac disease	Positive in coeliac disease → villous atrophy → malabsorption

Blood Tests — Focused Not Shotgun

Do not overinvestigate ^[1]. In an otherwise well young patient with no alarm features, you do NOT need a full metabolic work-up. The core bloods for uninvestigated dyspepsia are: CBC (anaemia?), basic metabolic panel (electrolytes, renal function), and HP test. Add LFT if biliary symptoms, amylase if pancreatic symptoms, cardiac enzymes/ECG if cardiac concern, and iron studies/coeliac screen if anaemia.

3C. H. pylori Testing

This is one of the most important investigations in dyspepsia. There are invasive (require OGD) and non-invasive methods.

Test	Principle	Sensitivity / Specificity	Key Points
Urea breath test (UBT) ^[2]^[3]	Patient ingests ¹³C- or ¹⁴C-labelled urea. If HP is present, its urease enzyme hydrolyses urea → ammonia + labelled CO₂, which is detected in exhaled breath.	~95% / ~95%	Gold standard non-invasive test. Must stop PPI for ≥ 2 weeks and antibiotics for ≥ 4 weeks before testing (both suppress HP without eradicating it → false negative). Used for both initial diagnosis and confirmation of eradication (repeat UBT ≥ 4 weeks after completing eradication therapy) ^[3].
Stool antigen test (SAT) ^[2]^[3]	Detects HP antigens in stool using monoclonal antibodies	~95% / ~95%	As accurate as UBT. Useful when UBT is unavailable. Same PPI/antibiotic washout rules apply. Convenient for patients who cannot perform breath test (e.g. children).
Serology (IgG antibodies)	Detects past or current HP exposure via anti-HP IgG	~85% / ~80%	Cannot distinguish active from past infection — IgG remains positive for months to years after eradication. Therefore NOT useful for confirming eradication. May be useful in epidemiological studies or when patient cannot stop PPI.

Test	Principle	Key Points
Rapid urease test (CLO test)	Biopsy specimen placed in urea-containing medium + pH indicator. If HP present, urease hydrolyses urea → ammonia → pH rises → colour change (yellow → pink).	Quick (~1 hour). First-line invasive test when OGD is performed. Same PPI/antibiotic washout applies. Take biopsy from antrum AND corpus for best yield.
Histology	Biopsy examined under microscopy (H&E, Giemsa stain). Visualise spiral organisms on surface epithelium.	Allows simultaneous assessment of mucosal pathology (gastritis, intestinal metaplasia, dysplasia, malignancy). Gold standard for tissue diagnosis.
Culture	Biopsy cultured on selective media under microaerophilic conditions	Allows antibiotic sensitivity testing — crucial for treatment failure (clarithromycin resistance is rising globally, ~20–30% in HK). Technically difficult; not routine.

HP Testing: When to Use What

First presentation, age < 40, no alarm features → UBT or stool antigen test ^[2] (non-invasive, "test-and-treat" strategy).

OGD being performed → Rapid urease test (CLO test) on biopsy ^[2] + histology. H. pylori testing should be done on biopsy sample ^[2].

Confirming eradication → UBT ≥ 4 weeks after completing therapy ^[3]. This was demonstrated in the case study: "A urea breath test was performed 1 week earlier (4 weeks after completing her drug therapy course) and was negative" ^[3].

Treatment failure / antibiotic resistance → Culture with sensitivity testing on biopsy.

3D. Upper Endoscopy (OGD — Oesophago-Gastro-Duodenoscopy)

The investigation of choice is gastroscopy ^[1]. This is the gold standard for evaluating organic causes of dyspepsia.

Finding	Diagnosis	Key Features
Mucosal erythema, oedema, erosions	Gastritis / duodenitis	Patchy or diffuse; antral predominant in HP; chemical pattern in NSAIDs/bile reflux
Ulcer crater	PUD (gastric or duodenal)	Gastric ulcer: usually lesser curvature / corpus-antrum junction — MUST biopsy (to rule out malignancy). Duodenal ulcer: usually D1 — biopsy NOT required (almost never malignant).
Mucosal break in distal oesophagus	Reflux oesophagitis	Graded by LA classification (A–D) based on extent of mucosal breaks
Mass, ulcerated mass, mucosal irregularity	Gastric / oesophageal CA	Multiple biopsies needed (at least 6–8 from margin of ulcer/mass). Linitis plastica may show rigid, non-distensible stomach with reduced peristalsis.
Barrett's oesophagus	Intestinal metaplasia of distal oesophagus	Salmon-pink mucosa extending above GOJ. Prague classification (circumferential + maximal extent). Biopsy for dysplasia grading.
Normal mucosa	Functional dyspepsia (after HP testing)	If OGD is normal AND HP is negative → diagnosis of FD by exclusion ^[2]
Mosaic/snakeskin pattern	Portal hypertensive gastropathy	Friable mucosa with ectatic vessels; context of liver cirrhosis ^[4]
Submucosal lesion	GIST, lipoma, carcinoid	Smooth overlying mucosa; may need EUS for further characterisation

3E. Imaging Studies

Study	Findings	Significance
Erect CXR	Free gas under diaphragm ^[10]	→ Perforation (e.g. perforated peptic ulcer). Sensitivity ~75% — a normal erect CXR does NOT exclude perforation.
Supine AXR	Sentinel loop sign (localised dilated bowel loop) ^[10]	→ Local inflammation (e.g. pancreatitis) ^[10]. Also look for pancreatic calcification → chronic pancreatitis ^[10].
	Radio-opaque stones	→ 90% urinary stones, only 15% gallstones (majority cholesterol stones are radiolucent; only pigmented stones are radio-opaque) ^[10]

Indication	Findings	Interpretation
Biliary pathology	Gallstones: highly sensitive, 95% positive ^[10]	USS is the gold standard for detecting gallstones (better than AXR because most gallstones are radiolucent)
Acute cholecystitis	Thickened GB wall ( > 3mm), pericholecystic fluid, stone at neck of HB, sonographic Murphy's sign ^[10]	Sonographic Murphy's sign = tenderness is maximal when US probe presses on visualised gallbladder ^[10]
Hepatobiliary	Dilated CBD ( > 6mm, or > 10mm post-cholecystectomy), liver masses, ascites	Obstruction, HCC, metastatic disease
Pancreas	Often limited by overlying bowel gas; may show pancreatic mass, pseudocyst, calcification	Consider CT for better pancreatic imaging
Abdominal masses	Solid vs cystic, size, location	Further characterisation often needs CT

Study	Evaluates	Indications in Dyspepsia Context	Key Findings
Barium meal	Stomach, duodenum ^[13]	Dyspepsia and epigastric pain; weight loss; assessment for suspected stomach cancer; suspected perforation of peptic ulcer ^[13]	Ulcer niche (barium-filled crater), filling defect (mass), mucosal irregularity, "leather bottle" stomach (linitis plastica)
Barium swallow	Hypopharynx, oesophagus ^[13]	Dysphagia workup; OGD-negative suspected mechanical obstruction	Bird's beak sign (achalasia), shouldering (smooth if benign, right-angled if malignant stricture), corkscrew appearance (diffuse oesophageal spasm) ^[6]

In modern practice, barium studies have been largely superseded by OGD (which allows biopsy) and CT (which provides cross-sectional imaging). However, they remain useful when OGD is contraindicated or when assessing motility (e.g. achalasia).

Indication	Key Findings
Suspected pancreatic pathology	Pancreatic mass, calcification (chronic pancreatitis), peripancreatic fluid (acute pancreatitis), dilated pancreatic duct
Suspected malignancy (staging)	Liver metastases, lymphadenopathy, peritoneal deposits, ascites
Acute mesenteric ischaemia (CTA) ^[10]	Arterial occlusion/thrombus, pneumatosis intestinalis (gas in bowel wall), portal venous gas
Retroperitoneal structures ^[10]	Leaking AAA, renal stones
Suspected GOO	Level and cause of obstruction; gastric dilatation

Indication	How It Works	Key Points
Suspected gastroparesis	Patient eats a low-fat egg-white meal (fat slows gastric emptying — so you use low-fat to standardise the test) labelled with ⁹⁹ᵐTc. Serial images taken at 0, 1, 2, 4 hours.	> 10% retention at 4 hours = delayed gastric emptying. Used after excluding mechanical obstruction (CXR/AXR, CT, OGD) ^[4].

Test	Indication	Principle	Key Findings
24-hour oesophageal pH monitoring / impedance	Suspected GERD with negative OGD or atypical symptoms	Thin catheter placed in oesophagus measures acid exposure over 24 hours. Impedance also detects non-acid reflux.	Acid exposure time > 6% = abnormal. DeMeester score > 14.7 = positive. Gold standard for GERD diagnosis.
High-resolution manometry (HRM)	Suspected oesophageal motility disorder	36 circumferential channels each with 12 sensors down oesophagus. Gold standard for assessing oesophageal motility ^[6].	Achalasia (absent peristalsis + failed LES relaxation), diffuse oesophageal spasm, hypercontractile oesophagus (jackhammer). Chicago classification ^[6].
Fasting serum gastrin + gastric pH	Suspected ZES	Fasting gastrin level measured when patient is off PPI (PPI falsely elevates gastrin). Gastric pH measured simultaneously.	Serum gastrin > 10× ULN while pH < 2 = diagnostic ^[7] of gastrinoma. If equivocal → secretin stimulation test (paradoxical rise in gastrin after IV secretin = positive for gastrinoma) ^[7].
Coeliac serology (anti-tTG IgA)	Suspected coeliac disease	IgA antibody against tissue transglutaminase (the autoantigen in coeliac)	Positive → confirm with duodenal biopsy (villous atrophy, crypt hyperplasia, intraepithelial lymphocytes). Check total IgA (IgA deficiency → false negative).

Important: Stop PPI Before Gastrin Testing

PPI should be stopped before evaluation for ZES ^[7]. PPIs profoundly suppress gastric acid → compensatory hypergastrinaemia (the body tries to make more acid). This creates a false positive for ZES. PPIs should be stopped for at least 1 week (ideally 2 weeks) before measuring fasting gastrin. H2 receptor antagonists can be used as a bridge to manage symptoms during the washout period.

The outcome of OGD determines the next steps:

OGD Finding	Next Step	Rationale
Gastric ulcer	Multiple biopsies (≥ 6 from margin) + CLO test. Repeat OGD in 6–8 weeks to confirm healing.	Must exclude malignancy — gastric CA can look exactly like a benign ulcer on gross appearance. Non-healing ulcer at repeat OGD → suspect malignancy → re-biopsy.
Duodenal ulcer	CLO test + histology for HP. No need to biopsy the ulcer itself.	DU is almost never malignant. Focus is on identifying and eradicating HP.
Oesophagitis	Grade by LA classification (A–D). If Barrett's suspected → multiple biopsies per Seattle protocol.	Guide GERD treatment intensity and surveillance intervals for Barrett's.
Mass / suspicious lesion	Multiple biopsies + staging CT (chest/abdomen/pelvis)	Tissue diagnosis essential before planning treatment (surgery, chemo, targeted therapy).
Normal OGD, HP +ve on biopsy	HP eradication therapy ^[2]	HP may be causing subclinical mucosal inflammation contributing to symptoms. NNT ~14 for symptom improvement in FD.
Normal OGD, HP -ve	Treat as functional dyspepsia ^[2]	Diagnosis of FD by exclusion is now established.

High Yield Summary

Diagnostic criteria for FD (Rome IV): ≥ 1 of bothersome postprandial fullness, early satiation, epigastric pain, epigastric burning — with NO structural disease — for ≥ 3 months (onset ≥ 6 months). Two subtypes: PDS (dysmotility-like) and EPS (ulcer-like).

Alarm features (8 key ones): Age > 40 + new onset, weight loss, dysphagia/odynophagia, IDA, persistent vomiting, UGIB, mass/LN, FHx UGI CA → all mandate OGD.

Algorithm: Alarm features or age > 40 → OGD. No alarm features + age < 40 → non-invasive HP test (UBT or SAT). HP +ve → eradicate. HP -ve → empirical PPI. Refractory → prokinetics → TCA → re-scope.

Key investigations: OGD (gold standard for organic disease), UBT/SAT (gold standard non-invasive HP test), bloods (CBC, electrolytes, LFT, RFT, amylase), USS (biliary), ECG (rule out MI), erect CXR (perforation). Special: gastric emptying study (gastroparesis), fasting gastrin + pH (ZES — stop PPI first), 24h pH monitoring (GERD), manometry (motility disorders).

HP testing rules: Stop PPI ≥ 2 weeks and antibiotics ≥ 4 weeks before UBT/SAT. Confirm eradication with UBT ≥ 4 weeks after completing therapy.

OGD rules: Biopsy ALL gastric ulcers (rule out CA). Do NOT need to biopsy duodenal ulcers. Always take antrum + corpus biopsies for HP. Repeat OGD for gastric ulcers at 6–8 weeks to confirm healing.

Active Recall - Diagnostic Criteria, Algorithm & Investigations for Dyspepsia

References

^[1] Lecture slides: murtagh merge.pdf (Dyspepsia, pp. 38–39) ^[2] Senior notes: Ryan Ho GI.pdf (pp. 53–54, Section 2.1.4) and Ryan Ho Fundamentals.pdf (pp. 263–264, Section 3.3.4) ^[3] Senior notes: felixlai.md (Dyspepsia section, pp. 490–495) ^[4] Senior notes: maxim.md (Gastroparesis section, p. 133) ^[6] Senior notes: Ryan Ho GI.pdf (p. 36, OGD/Barium investigations) ^[7] Senior notes: Ryan Ho Endocrine.pdf (p. 102, Section 4.2.3 — Gastrinoma/ZES) ^[10] Senior notes: Ryan Ho GI.pdf (p. 105) and Ryan Ho Fundamentals.pdf (p. 279 — Investigations for acute abdomen) ^[11] Senior notes: maxim.md (p. 87 — Acute abdomen investigations) ^[12] Lecture slides: murtagh merge.pdf (Abdominal pain investigations, p. 13) ^[13] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p. 19 — GI Fluoroscopy Studies)

Management Algorithm and Treatment Modalities for Dyspepsia

3. Management by Diagnosis

Drug history and past history is important, especially NSAID use ^[1].

Step	Action	Rationale
1	Stop or switch the offending drug	Remove the causative agent. If NSAIDs are essential (e.g. for rheumatological disease), switch to less ulcerogenic NSAIDs or COX-2 inhibitors ^[3]. COX-2 selective inhibitors (e.g. celecoxib) spare COX-1 → preserve prostaglandin-mediated mucosal protection.
2	Short course of PPI (4 weeks)	Allows mucosal healing while the offending agent is withdrawn.
3	Co-prescribe PPI if NSAID cannot be stopped	Gastroprotection — the PPI suppresses acid, reducing the "aggressive factor" side of the ulcer equation, partially compensating for the loss of prostaglandin protection.

Aspirin-specific management ^[3]:

Bleeding peptic ulcer: Resume aspirin with PPI treatment once haemostasis is secured to minimise cardiovascular risk ^[3] — the CV risk of stopping aspirin outweighs the GI risk of continuing it under PPI cover
Non-bleeding peptic ulcer: Continue aspirin with PPI treatment ^[3]

3B. H. pylori Eradication Therapy

This is the cornerstone of managing HP-positive dyspepsia (whether PUD or FD). The principle: eradicate the bacterium → remove the inflammatory stimulus → allow mucosal healing → reduce ulcer recurrence from ~70% to < 5%.

Triple therapy (PPI-based or bismuth-based) ^[3]:

Regimen	Components	Duration	Notes
Standard PPI triple therapy	PPI (standard dose BD) + Clarithromycin 500mg BD + Amoxicillin 1g BD	14 days	First-line where clarithromycin resistance is < 15%. In HK, clarithromycin resistance is ~20–30%, so this regimen is increasingly suboptimal.
Bismuth quadruple therapy	PPI (standard dose BD) + Bismuth subsalicylate/subcitrate QDS + Metronidazole 500mg TDS + Tetracycline 500mg QDS	14 days	First-line where clarithromycin resistance is ≥ 15% (i.e. most of East Asia including HK). Bismuth has direct antimicrobial action + forms a protective coat over ulcer base.
Concomitant quadruple therapy	PPI BD + Clarithromycin 500mg BD + Amoxicillin 1g BD + Metronidazole 500mg BD	14 days	Alternative non-bismuth quadruple that overcomes some resistance; widely used in current practice.

Why 14 days? Earlier regimens used 7 days, but meta-analyses show 14-day courses achieve ~5–10% higher eradication rates. Given rising antibiotic resistance globally, 14 days is now the standard recommendation (Maastricht VI/Florence 2022 consensus, ACG 2024 guidelines).

Understanding the drug names:

Clarithro-mycin → "clari" = clear; "-mycin" = antibiotic from Streptomyces (macrolide) — binds 50S ribosomal subunit → inhibits bacterial protein synthesis
Amoxicillin → β-lactam (penicillin class) — inhibits bacterial cell wall synthesis by binding penicillin-binding proteins (PBPs)
Metronidazole → "metro" + "ni" (nitro) + "dazole" (imidazole ring) — prodrug activated by anaerobic organisms' nitroreductase → forms cytotoxic free radicals → damages bacterial DNA
Tetracycline → "tetra" = four, "cycline" = ring — binds 30S ribosomal subunit → inhibits protein synthesis
Bismuth → heavy metal that directly damages bacterial cell membrane, inhibits urease, and forms protective barrier over ulcerated mucosa

If first-line fails (documented by positive UBT ≥ 4 weeks after completing therapy):

Regimen	Components	When to Use
Bismuth quadruple	If PPI triple was first-line	Switch strategy — use different antibiotic backbone
Levofloxacin triple	PPI BD + Levofloxacin 500mg OD + Amoxicillin 1g BD × 14 days	Second-line option; avoid if fluoroquinolone resistance is high
Culture-guided therapy	Based on HP culture and sensitivity from biopsy	After two failed eradication attempts — OGD with culture is recommended to guide antibiotic selection

3C. Peptic Ulcer Disease (PUD)

Clinical Scenario	Treatment Protocol
H. pylori-positive PUD	H. pylori eradication therapy ^[2] + PPI for ulcer healing (DU: 4 weeks; GU: 8 weeks)
Non-HP, non-NSAID PUD	Full-dose PPI or H2RA × 4–8 weeks ^[2]
NSAID-related PUD	Full-dose PPI or H2RA × 8 weeks ^[2]. Withdraw NSAIDs during PPI treatment ^[3]. If NSAIDs essential → switch to COX-2 inhibitor + co-prescribe PPI.

Drug Class	Mechanism	Potency	Role in Dyspepsia
Proton pump inhibitors (PPIs)	Irreversibly bind and inhibit the H⁺/K⁺-ATPase (proton pump) on the luminal surface of parietal cells. This is the final common pathway of all acid secretion (regardless of stimulus — histamine, gastrin, or ACh).	Most potent acid suppressant available. ↓ gastric acid by ~95%.	Empirical PPI proven to ↓ dyspepsia symptoms ^[2]. First-line for PUD, GERD, and empirical FD therapy.
H2 receptor antagonists (H2RAs)	Competitively block histamine H2 receptors on parietal cells → ↓ cAMP → ↓ acid secretion. Only blocks the histamine pathway (gastrin and ACh pathways remain active).	Less potent than PPIs. ↓ acid by ~70%.	Offer H2RA if inadequate response to PPI ^[2]. Also used as step-down from PPI.

Common PPIs (all are pro-drugs activated in acidic environment): Omeprazole (Losec), Esomeprazole (Nexium), Pantoprazole (Pantozol), Lansoprazole, Rabeprazole.

Standard dose: Omeprazole 20mg OD, Esomeprazole 20mg OD, Pantoprazole 40mg OD, Lansoprazole 30mg OD
Take 30 minutes before meals — the drug needs to be absorbed, reach the parietal cell, and be activated by acid. Proton pumps are most active when stimulated by a meal, so taking PPI before eating ensures maximal inhibition.

Common H2RAs: Ranitidine (withdrawn in many countries due to NDMA contamination), Famotidine (Pepcid) — now the main H2RA in use.

Rarely required now ^[14] due to the effectiveness of PPI and HP eradication. However, surgery is still indicated for:

Uncomplicated ulcers refractory to medical treatment ^[3]^[14]
Complicated ulcers — haemorrhage, perforation, GOO ^[14]
Risk of malignancy: non-healing GU > 3 months ^[14]
Zollinger-Ellison syndrome should be excluded before performing elective surgery for PUD ^[3]

Ulcer Type	Surgical Options	Rationale
DU (aim: ↓ acid)	Highly selective vagotomy; Truncal vagotomy + drainage (pyloroplasty/gastrojejunostomy); Gastrectomy (antrectomy) + reconstruction ^[14]	Vagotomy reduces acid secretion by removing vagal drive to parietal cells. "Highly selective" preserves nerve of Latarjet (antral motor innervation) so gastric emptying is maintained, but is technically difficult. Truncal vagotomy sacrifices Latarjet → needs drainage procedure to prevent gastric stasis.
GU (aim: prevent malignancy)	Type I: distal gastrectomy + Billroth II. Type II/III: truncal vagotomy + antrectomy + Billroth II. Type IV: subtotal gastrectomy + Billroth I/II/Roux-en-Y ^[14]	GU carries malignancy risk → resection needed for definitive histology. Type and extent of resection depend on Johnson classification (ulcer location and acid secretion status).

Step	Treatment	Details
1	Lifestyle modifications	Weight loss (↓ intra-abdominal pressure), head-of-bed elevation (gravity assists oesophageal clearance), avoid late meals (allows gastric emptying before lying down), avoid trigger foods (fat, chocolate, alcohol, coffee, smoking — all ↓ LES tone)
2	Full-dose PPI × 4–8 weeks for healing of oesophagitis ^[2]	Heals ~85% of erosive oesophagitis at 8 weeks
3	Full-dose PPI × 8 weeks or even long-term maintenance if severe oesophagitis ^[2]	LA grade C/D oesophagitis often requires prolonged therapy
4	If severe oesophagitis failed healing, consider double-dose PPI, switch to another PPI at full- or double-dose ^[2]	Different PPIs have varying bioavailability and metabolism (CYP2C19 polymorphisms affect omeprazole more than rabeprazole/esomeprazole)
5	Lowest dose possible PPI if symptoms recur after initial treatment ^[2]	Step-down strategy to minimise long-term PPI exposure
6	Offer H2RA if inadequate response to PPI ^[2]	H2RAs can be added at bedtime (nocturnal acid breakthrough — histamine is the dominant drive for nocturnal acid secretion, so H2RA adds benefit)
7	Surgical referral	Young and fit PPI-dependent patients (to avoid lifelong PPI); GERD/complications unresponsive to medical treatment ^[15]. Laparoscopic fundoplication (Nissen 360° or partial — partial preferred in Chinese due to less dysphagia ^[15]).

This is the core exam topic — the systematic, stepwise approach to managing FD when organic causes have been excluded.

Treatment approach to functional dyspepsia: PPIs (OR) Triple therapy → TCA → Prokinetics ^[3]

Step	Treatment	Mechanism	Evidence & Notes
0	Reassurance after ruling out organic pathologies ^[2]	Addresses illness anxiety; breaks the cycle of symptom-hypervigilance-anxiety-worsening symptoms	Provide education and reassurance that the condition is benign and non-life threatening ^[3]. This alone improves symptoms in many patients.
1	Dietary changes: avoid known precipitants, low fat diet, ↓ FODMAPs, ↓ lactose ^[2]	Low fat → ↓ CCK release → ↓ slowing of gastric emptying. FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) → fermented by gut bacteria → gas, bloating, distension → reducing them ↓ symptom triggers.	Benefit variable; some patients clearly identify dietary triggers
2a	HP eradication (if HP +ve)	Removes mucosal inflammation that may contribute to visceral hypersensitivity; NNT ~14 ^[2]	HP eradication: offer symptomatic benefit in a small subgroup of FD patients ^[2]. Always offer if HP +ve because it also ↓ future PUD/gastric cancer risk.
2b	Empirical PPI (if HP -ve or symptoms persist post-eradication)	Suppresses gastric acid → ↓ acid-mediated mucosal stimulation → ↓ visceral nociceptor activation	Can offer H2RA or PPI (if failed H2RA) as PRN at lowest dose possible ^[2]. Effective in Western populations but effect not demonstrated in Asians ^[2]. Effective in ulcer-like or reflux-like dyspepsia but NOT in dysmotility-like or unspecified ones ^[2].
2c	Simeticone (Mylicon)	Anti-foaming agent — reduces surface tension of gas bubbles in GI tract → allows coalescence and easier passage → ↓ bloating, belching	Anti-foaming agent for symptoms of belching, commonly used in GOPC ^[2]. Harmless, cheap, OTC — good first step for gas-predominant symptoms.
3	Prokinetics, e.g. metoclopramide ^[2]	Metoclopramide is a dopamine D2 receptor antagonist + 5-HT4 agonist → enhances gastric motility and accelerates gastric emptying → addresses the dysmotility component of FD. Also has central antiemetic action (blocks D2 in CTZ).	For refractory cases ^[2]. Use with caution due to extrapyramidal side effects (acute dystonia, tardive dyskinesia — dopamine blockade in basal ganglia). Limit to ≤ 5 days per European guidelines (EMA) or use at lowest effective dose for short courses. Alternatives: domperidone (peripheral D2 blocker, does not cross BBB as readily → fewer CNS side effects but risk of QT prolongation), itopride (D2 antagonist + AChE inhibitor — available in Asia, fewer side effects).
4	Antidepressants: TCAs (e.g. amitriptyline) and SSRIs (e.g. escitalopram) may be useful ^[2]	TCAs (tricyclic antidepressants) modulate visceral pain perception at sub-antidepressant doses (10–25mg amitriptyline at bedtime). Mechanism: ↓ noradrenaline and serotonin reuptake at spinal dorsal horn → ↓ ascending nociceptive transmission from gut. Also have anticholinergic properties → slow GI transit (helpful in diarrhoea-predominant but potentially harmful in constipation-predominant). SSRIs modulate brain-gut axis serotonergic signalling → ↓ visceral hypersensitivity.	Empirical antisecretory therapy → Prokinetics and TCA if fail PPI treatment ^[2]. TCAs are preferred for EPS (pain-dominant). SSRIs may be preferred when comorbid anxiety/depression is prominent.
5	Psychological therapy (CBT, relaxation training)	Addresses the cognitive-behavioural component: catastrophising about symptoms, symptom hypervigilance, illness anxiety. Relaxation training, e.g. progressive muscle relaxation, diaphragmatic breathing. CBT: to target underlying health beliefs and expectations ^[16].	Reserved for refractory cases or those with prominent psychological comorbidity. Note that 70–90% decline psychotherapy ^[16] — so framing and patient engagement is crucial.
6	Reinvestigate by OGD should symptoms persist despite multiple treatments ^[2]	Ensures no organic pathology was missed on initial evaluation (sampling error, early malignancy, rare conditions like eosinophilic gastroenteritis)	Safety net — if nothing new is found, reinforces the FD diagnosis and supports ongoing symptom management.

Matching FD Subtype to Treatment

PDS (postprandial distress / dysmotility-like): Dietary modification + prokinetics are more logical (targeting impaired gastric accommodation and delayed emptying). PPI less effective. Fundic relaxants (e.g. acotiamide — approved in Japan/Asia) may help.
EPS (epigastric pain / ulcer-like): PPI and TCA are more logical (targeting acid sensitivity and visceral hypersensitivity). PPI effective in ulcer-like or reflux-like dyspepsia but NOT in dysmotility-like ^[2].

This is a high-yield exam table — know it cold.

Condition	Treatment Protocol
Uninvestigated dyspepsia	H. pylori testing and eradication (test-and-treat strategy). Empirical full-dose PPI × 4 weeks. Offer H2RA if inadequate response to PPI. ^[2]
Functional dyspepsia	H. pylori eradication therapy if H. pylori-positive. Low-dose PPI or H2RA × 4 weeks if symptoms persist after HP excluded. Lowest dose possible PPI/H2RA if symptoms recur after initial treatment. ^[2]
Peptic ulcer disease	H. pylori eradication therapy if H. pylori-positive. Full-dose PPI or H2RA × 4–8 weeks for non-HP, non-NSAID PUD. Full-dose PPI or H2RA × 8 weeks for NSAID PUD. ^[2]
GERD	Full-dose PPI × 4–8 weeks for healing of oesophagitis. Full-dose PPI × 8 weeks or even long-term maintenance if severe oesophagitis. If severe oesophagitis failed healing, consider double-dose PPI, switch to another PPI at full- or double-dose. Lowest dose possible PPI if symptoms recur after initial treatment. Offer H2RA if inadequate response to PPI. ^[2]

Drug	Class	Mechanism	Indication	Key Side Effects / Contraindications
Omeprazole / Esomeprazole / Pantoprazole / Lansoprazole / Rabeprazole	PPI	Irreversible inhibition of H⁺/K⁺-ATPase (proton pump) on parietal cells — final common pathway of acid secretion	PUD, GERD, FD (empirical), HP eradication (component of regimen), stress ulcer prophylaxis	Long-term: ↑ fracture risk, ↓ Mg²⁺, ↑ C. difficile, ↓ B12, rebound hypersecretion. Take 30 min before meals.
Famotidine	H2RA	Competitive antagonism of histamine H2 receptor on parietal cells	Step-down from PPI; nocturnal acid breakthrough; FD if PPI fails	Generally well tolerated. Less potent than PPI.
Clarithromycin	Macrolide antibiotic	Binds 50S ribosomal subunit → inhibits protein synthesis	HP eradication (triple/quadruple therapy)	GI upset, metallic taste; QT prolongation; many drug interactions (CYP3A4 inhibitor). Resistance rising (20–30% in HK).
Amoxicillin	β-lactam (penicillin)	Inhibits bacterial cell wall synthesis	HP eradication	Allergy (rash, anaphylaxis); diarrhoea. CI: penicillin allergy → substitute metronidazole.
Metronidazole	Nitroimidazole	Prodrug activated in anaerobes → cytotoxic free radicals → DNA damage	HP eradication (bismuth quadruple); substitute for amoxicillin in penicillin-allergic	Disulfiram-like reaction with alcohol; metallic taste; peripheral neuropathy with prolonged use.
Tetracycline	Tetracycline	Binds 30S ribosomal subunit → inhibits protein synthesis	HP eradication (bismuth quadruple)	Photosensitivity; CI in children < 8 and pregnancy (teeth discolouration, bone growth inhibition).
Bismuth subsalicylate / subcitrate	Heavy metal compound	Direct antimicrobial against HP; forms protective barrier over ulcer; stimulates mucus/bicarbonate secretion	HP eradication (bismuth quadruple)	Black tongue/stool (harmless); CI: salicylate allergy (subsalicylate form).
Metoclopramide	Prokinetic (D2 antagonist + 5-HT4 agonist)	↑ Gastric motility, ↑ gastric emptying, antiemetic (CTZ blockade)	FD (PDS/dysmotility-like); gastroparesis	Extrapyramidal effects (acute dystonia, akathisia, tardive dyskinesia — especially in young women). Limit duration. CI: phaeochromocytoma (can cause hypertensive crisis), mechanical bowel obstruction, epilepsy.
Domperidone	Prokinetic (peripheral D2 antagonist)	Same as metoclopramide but does not cross BBB significantly → fewer CNS side effects	Alternative prokinetic for FD, gastroparesis	QT prolongation → cardiac arrhythmia. CI: hepatic impairment, concurrent QT-prolonging drugs. ECG monitoring advised.
Amitriptyline	TCA	↓ Noradrenaline + serotonin reuptake → modulates visceral pain at sub-antidepressant doses; anticholinergic → slows GI transit	FD (EPS/pain-dominant); refractory FD	Dry mouth, constipation, urinary retention, drowsiness, weight gain. CI: recent MI, arrhythmia, urinary retention, narrow-angle glaucoma. Start low (10mg nocte), titrate slowly.
Escitalopram	SSRI	Selective serotonin reuptake inhibition → modulates brain-gut axis serotonin signalling	FD with comorbid anxiety/depression	Nausea (serotonergic), sexual dysfunction, serotonin syndrome (with other serotonergic drugs). CI: concurrent MAOIs.
Simeticone	Anti-foaming agent	↓ Surface tension of gas bubbles → coalescence → easier passage	Belching, bloating — commonly used in GOPC ^[2]	Essentially no side effects. OTC.

Complication	Immediate Management	Definitive Management
Bleeding PUD	Resuscitation (IV fluids, blood products); Post-OGD PPI infusion: pantoprazole/esomeprazole 80mg stat, then 8mg/h for 72h ^[15] (high pH stabilises clot — platelet aggregation is pH-dependent, optimal at pH > 6). Endoscopic therapy: dual therapy: adrenaline 1:10,000 injection + heater probe or clips ^[15].	HP eradication; stop NSAIDs; long-term PPI if ongoing risk factors. Surgery: indicated if failed endoscopic haemostasis, rebleeding failing re-scope, ongoing transfusion requirement ^[14]^[15].
Perforated PUD	Resuscitation, IV antibiotics, erect CXR (pneumoperitoneum).	Emergency surgery: omental patch repair (Graham patch) for DU; partial gastrectomy for GU (malignancy risk).
GOO	NGT decompression, IV fluids, correct metabolic alkalosis (hypokalaemic hypochloraemic from vomiting).	OGD for diagnosis and balloon dilatation (benign); surgical bypass or resection (malignant).

These apply to all causes of dyspepsia and should be part of every management plan:

Modification	Rationale
Smoking cessation ^[3]	Smoking ↓ mucosal blood flow, ↓ bicarbonate secretion, ↑ acid output, delays ulcer healing
Limit alcohol intake ^[3]	Alcohol is a direct mucosal irritant and ↓ LES tone (promoting reflux)
Avoid known dietary triggers	Fat → ↓ LES tone + ↓ gastric emptying; coffee, chocolate, spicy food — all can worsen symptoms
Weight loss (if overweight)	↓ Intra-abdominal pressure → ↓ reflux
Avoid late-night eating	Allows gastric emptying before lying down → ↓ nocturnal reflux
Head-of-bed elevation	Gravity assists oesophageal clearance of refluxed material
Stress management	Brain–gut axis: stress → ↑ visceral hypersensitivity, altered motility

High Yield Summary

Management is diagnosis-driven: Drug-induced → stop drug. HP +ve → eradicate. PUD → HP eradication + PPI (4–8w). GERD → PPI (4–8w). FD → stepwise empirical therapy.

FD stepwise approach: (1) Reassurance + dietary changes. (2a) HP eradication if +ve. (2b) Empirical low-dose PPI × 4w. (3) Prokinetics (metoclopramide/domperidone). (4) TCA (amitriptyline 10–25mg) or SSRI. (5) Psychological therapy (CBT). (6) Re-scope if refractory.

NICE guideline table: Know the treatment protocols for uninvestigated dyspepsia, FD, PUD, and GERD — they differ in PPI dose and duration.

HP eradication: 14-day regimens. First-line in HK: bismuth quadruple (due to high clarithromycin resistance). Confirm eradication with UBT ≥ 4 weeks post-therapy.

PPIs: Take 30 min before meals. Use lowest dose for shortest duration. Long-term risks: fractures, hypoMg, C. difficile, B12 deficiency.

Prokinetics: Metoclopramide (EPSEs — limit duration), domperidone (QT prolongation). Best for PDS subtype.

TCAs: Amitriptyline 10–25mg nocte for EPS/pain-dominant FD. Works via visceral pain modulation, not antidepressant effect.

Gastric ulcer follow-up: ALWAYS re-scope at 6–8 weeks to confirm healing and exclude malignancy. Non-healing at 12 weeks → surgery.

Aspirin rule: Resume with PPI cover once haemostasis achieved (bleeding PUD) or continue with PPI (non-bleeding PUD).

Active Recall - Management of Dyspepsia

References

Complications of Dyspepsia and Its Underlying Causes

Dyspepsia itself is a symptom complex — it does not cause complications per se. The complications arise from the underlying organic conditions that present as dyspepsia, from the treatments we use, and from the functional condition when it becomes chronic and refractory. Let's go through each systematically.

1. Complications of Peptic Ulcer Disease

PUD is the most common organic cause of dyspepsia with serious complications. The classic teaching is 'bleed', 'burst', 'block' and 'burrow' — haemorrhage, perforation, gastric outlet obstruction, and penetration/fistulisation ^[6].

This is the leading cause of death from peptic ulcer ^[14].

Pathophysiology: The ulcer erodes through the mucosa into the submucosa and muscularis, reaching blood vessels. A posterior duodenal ulcer classically erodes into the gastroduodenal artery (GDA — a branch of the common hepatic artery running behind D1). A lesser curvature gastric ulcer can erode into the left gastric artery. When the vessel wall is breached, arterial (or venous) haemorrhage occurs into the GI lumen.

Clinical presentation ^[3]:

Haematemesis: vomiting of red blood or coffee-ground material — the "coffee ground" appearance is blood that has been partially digested by gastric acid (acid converts haemoglobin to acid haematin, which is dark/brown)
Melaena: black, tarry stools — blood that has transited through the entire GI tract; the dark colour comes from bacterial degradation of haemoglobin in the colon (requires ≥ 50–100 mL of blood and transit time of ≥ 14 hours)
Haematochezia: fresh red blood per rectum — occurs in massive upper GI bleeding when transit is too rapid for bacterial degradation
Postural hypotension, tachycardia, shock — signs of hypovolaemia
Iron-deficiency anaemia — from chronic occult bleeding (the patient may not notice visible blood loss)

Endoscopic assessment — Forrest Classification ^[15]:

This classification grades the endoscopic stigmata of recent haemorrhage (ESRH) and predicts the risk of rebleeding, which determines management:

Forrest Class	Description	Risk of Rebleeding (if untreated)	Management
Ia	Active spurting	~100%	Endoscopic therapy + IV PPI bolus + infusion × 72h ^[15]
Ib	Active oozing	10–27%	As above
IIa	Non-bleeding visible vessel	50%	As above
IIb	Non-bleeding adherent clot	30–35%	As above (remove clot by vigorous flushing to reveal underlying vessel)
IIc	Flat pigmented spot	5–8%	Oral PPI only
III	Clean base	< 3%	Oral PPI only

Endoscopic therapy ^[15]:

Dual therapy: adrenaline injection + heater probe or clips ^[15]
- Adrenaline 1:10,000 — works via tamponade (volume compression of vessel) + vasoconstriction (α₁-adrenergic) + platelet aggregation ^[15]
- Heater probe — coaptive effect: pressure + heat ^[15] — compresses the vessel while thermal energy coagulates it
- Haemospray — mechanical barrier + absorbent ^[15] — useful for large-area ulcers where clips cannot cover the entire surface
- Clips — mechanical closure of the bleeding vessel — more durable than injection alone

Post-endoscopy management ^[15]:

PPI infusion: pantoprazole/esomeprazole 80mg stat, then 8mg/h for 72h ^[15]
- Why? Higher pH stabilises clot formation because platelet function depends on normal pH — platelet aggregation is optimal at pH > 6; at pH < 5.4, pepsin is activated and dissolves clots ^[15]
- Indicated for Forrest Class Ia, Ib, IIa, IIb ulcer bleeding ^[15]
- NOT efficacious for variceal bleeding ^[15]

When endoscopy fails ^[14]:

Surgery: indicated if failed endoscopic haemostasis, rebleeding failing re-scope, ongoing transfusion requirement ^[14]
- DU: suture ligation of bleeding vessels → ± partial gastrectomy ^[14]
- GU: partial gastrectomy (risk of malignant ulcer — need histology) ^[14]
Interventional radiology: transcatheter arterial embolisation (TAE) if unfit for surgery ^[14]

Pathophysiology: The ulcer erodes through the full thickness of the bowel wall (serosa) → gastric or duodenal contents leak into the peritoneal cavity → chemical peritonitis (initially from acid, bile, enzymes) → secondary bacterial peritonitis (from gut flora colonisation).

Anterior duodenal/gastric ulcers are more likely to perforate freely into the peritoneal cavity (no protective structures anteriorly)
Posterior ulcers tend to penetrate into adjacent organs (pancreas, lesser omentum) rather than perforate freely (because the pancreas and omentum provide a "wall")

Clinical presentation ^[3]:

Acute onset of severe diffuse abdominal pain — sudden, dramatic ("thunderclap")
Fever, tachycardia, hypotension — signs of systemic sepsis
Board-like rigidity on examination — peritonitis causes reflex abdominal muscle spasm
Erect CXR: free gas under diaphragm (pneumoperitoneum) — sensitivity ~75%; absence does NOT exclude perforation ^[10]

Management ^[14]^[17]:

Resuscitation + IV antibiotics + IV PPI
Small DU/GU ( < 2cm): laparoscopic/open omental patch repair (Graham patch) ^[17] — the greater omentum is mobilised and sutured over the perforation, sealing it
Large DU: distal gastrectomy + Billroth II reconstruction ^[17]
Large GU: wedge excision / partial gastrectomy + Billroth II reconstruction ^[17] — resection is necessary because GU may be malignant
Biopsy ulcer edge for ALL gastric ulcers to rule out malignancy ^[17]

Prognosis — Boey's Score ^[17]:

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

Pathophysiology ^[3]: Chronic peptic ulceration at or near the pylorus/duodenal bulb causes a cycle of:

Inflammation → oedema and duodenal spasm (reversible)
Fibrosis and scarring from repeated ulceration and healing (irreversible — pyloric stenosis)
Gastric atony develops after prolonged obstruction (the chronically distended stomach loses its contractile ability)

Clinical presentation ^[3]^[6]:

Epigastric pain after eating
Early satiety, bloating, indigestion
Non-bilious projectile vomiting of undigested food (obstruction is proximal to the ampulla of Vater → bile cannot enter the stomach)
Nausea, anorexia, weight loss
Succussion splash on examination ( > 4 hours post-meal) — retained fluid sloshing in a dilated stomach

Metabolic consequences ^[3]:

Prolonged vomiting → hyponatraemia, hypokalaemia, hypochloraemic metabolic alkalosis — loss of HCl (H⁺ and Cl⁻) in vomitus → kidneys compensate by retaining H⁺ and excreting K⁺ and HCO₃⁻ (but initially H⁺ retention is insufficient → alkalosis). The kidneys also paradoxically excrete acid urine ("paradoxical aciduria") because K⁺ depletion forces the distal tubule to exchange H⁺ instead of K⁺ for Na⁺ reabsorption.
Risk of aspiration pneumonia — vomiting of retained gastric contents
Dehydration

Management ^[3]:

NPO + nasogastric (NG) tube — decompresses stomach, stops vomiting cycle
Fluid resuscitation + correction of electrolyte abnormalities — normal saline and KCl ^[3]
IV PPI — reduces ongoing acid damage, ↓ oedema around ulcer ^[3]
Endoscopic balloon dilatation — for benign pyloric stenosis ^[3]
Surgery if medical/endoscopic management fails ^[3]:
- GU: antrectomy with Billroth I/II reconstruction
- DU: truncal vagotomy + antrectomy with Billroth I/II reconstruction

GOO: Malignant Until Proven Otherwise

In clinical practice, always remember that GOO is malignant in 80% of cases (gastric cancer being the most common cause). PUD-related pyloric stenosis is the second most common cause but accounts for only ~20% of cases. Always biopsy during endoscopy.

GERD is the second most common organic cause of dyspepsia. Its complications follow a cascade of progressive mucosal injury:

Oesophagitis → ulcer → stricture → Barrett's oesophagus (10%) → metaplasia → adenocarcinoma (7% of Barrett's) ^[15]

Complication	Pathophysiology	Clinical Features
Reflux oesophagitis	Chronic acid/pepsin/bile exposure → inflammation → mucosal erosions (LA grade A–D)	Heartburn, odynophagia (painful swallowing due to inflamed mucosa)
Oesophageal ulceration	Deep erosion extending beyond epithelium	Odynophagia, haematemesis, chest pain
Oesophageal stricture ^[18]	Chronic inflammation → fibrosis → luminal narrowing (typically distal oesophagus)	Progressive dysphagia (solids first, then liquids) — the gradual onset distinguishes it from malignant dysphagia (which is also progressive but usually in an older patient with weight loss).
Barrett's oesophagus ^[18]	Chronic acid exposure → intestinal metaplasia of distal oesophageal squamous epithelium to specialised columnar epithelium with goblet cells. This is an adaptive response — columnar epithelium is more resistant to acid than squamous epithelium — but it comes at a cost.	Often asymptomatic (because the metaplastic epithelium is LESS sensitive to acid → patients may actually feel BETTER as Barrett's develops). Diagnosed on OGD: salmon-pink mucosa extending above GOJ.
Adenocarcinoma of oesophagus ^[18]	Barrett's → low-grade dysplasia → high-grade dysplasia → invasive adenocarcinoma. Risk of developing cancer is 30–100× compared with normal population ^[18]. The annual risk is ~0.5%/year for non-dysplastic Barrett's, ~1%/year for low-grade dysplasia.	Progressive dysphagia, weight loss, GI bleeding, chest pain. Occurs at distal oesophagus/GOJ — the classic "adenocarcinoma at the GOJ" in a patient with long-standing GERD.
Oesophageal haemorrhage ^[18]	Erosion of oesophageal ulcer into submucosal vessels	Haematemesis, melaena, IDA
Aspiration	Nocturnal reflux reaching the larynx/pharynx → trickle aspiration	Recurrent pneumonia, chronic cough, laryngeal inflammation

Barrett's Oesophagus Surveillance ^[18]:

ALL patients with Barrett's oesophagus should receive PPI whether they are symptomatic or not ^[18]
Non-dysplasia → surveillance OGD every 3–5 years
Low-grade dysplasia → surveillance every 6 months for 1 year, then annually; OR endoscopic mucosal resection (EMR) + radiofrequency ablation (RFA)
High-grade dysplasia → EMR + RFA; esophagectomy if unable to achieve complete eradication

When dyspepsia is the presenting symptom of gastric cancer, the cancer itself brings its own set of complications [18b]:

Complication	Pathophysiology
Bleeding — IDA, haematemesis, melaena [18b]	Tumour erodes into mucosal vessels; malignant tissue is friable and bleeds with minimal trauma
Gastric outlet obstruction (GOO) [18b] — abdominal distension, vomiting	Distal (antral/pyloric) tumours cause mechanical obstruction
Perforation → peritonitis [18b]	Tumour necrosis creates a full-thickness defect
Metastatic disease	Virchow's node (left supraclavicular LN), Sister Mary Joseph nodule (periumbilical), Krukenberg tumour (ovarian metastasis), peritoneal carcinomatosis (ascites), liver metastases (jaundice, hepatomegaly) ^[6]

4. Complications of Treatment

PPIs are the mainstay of dyspepsia management, but long-term use carries risks (all related to chronic acid suppression):

Complication	Mechanism
Osteoporotic fractures	Gastric acid enhances calcium absorption (dissolves Ca²⁺ salts). ↓ Acid → ↓ Ca²⁺ absorption → ↓ BMD → ↑ fracture risk (hip, vertebral, wrist). 20–35% ↑ risk with > 1 year PPI use.
Hypomagnesaemia	Chronic PPI use impairs intestinal Mg²⁺ absorption (mechanism unclear, possibly via altered TRPM6/7 channels). Can cause muscle cramps, arrhythmia, seizures.
C. difficile infection	Gastric acid is a natural barrier against ingested bacteria. ↓ Acid → ↑ survival of C. difficile spores → ↑ colonisation risk.
Vitamin B₁₂ deficiency	Acid and pepsin are required to release B₁₂ from food proteins. ↓ Acid → ↓ B₁₂ release → ↓ absorption.
Iron deficiency	Non-haem iron (Fe³⁺) requires acid for reduction to Fe²⁺ (absorbable form). ↓ Acid → ↓ Fe absorption.
Rebound acid hypersecretion	Chronic acid suppression → compensatory ↑ gastrin (from G-cells, due to loss of negative feedback) → ECL cell hyperplasia → trophic effect on parietal cells. When PPI is abruptly stopped → massive acid output (even higher than baseline). This is why PPIs should be tapered gradually, not stopped abruptly.
Small intestinal bacterial overgrowth (SIBO)	↓ Acid → loss of bactericidal barrier → ↑ bacterial colonisation of upper GI tract → bloating, flatulence, diarrhoea
Community-acquired pneumonia	↓ Acid → ↑ bacterial colonisation of stomach → aspiration of colonised gastric contents → pneumonia. Risk is greatest in the first month of PPI use.
Possible ↑ CKD risk	Mechanism unclear; may relate to interstitial nephritis or altered gut microbiome. Evidence is observational and debated.

The 'Lowest Dose, Shortest Duration' Principle

Given these risks, the key management principle is: use the lowest dose possible PPI for the shortest duration needed ^[2]. Step down to H2RA or on-demand PPI when able. Long-term PPI is justified for Barrett's oesophagus, severe oesophagitis (LA grade C/D), and high-risk patients on dual antiplatelet/anticoagulant therapy.

Drug	Key Complication	Mechanism
Metoclopramide	Extrapyramidal side effects (acute dystonia, akathisia, tardive dyskinesia)	Crosses BBB → blocks D₂ receptors in basal ganglia → loss of dopaminergic inhibition of cholinergic interneurons → excessive cholinergic drive → involuntary movements. Risk highest in young women. Tardive dyskinesia (chronic involuntary orofacial movements) is potentially irreversible.
Domperidone	QT prolongation → ventricular arrhythmia (Torsades de Pointes)	Blocks cardiac hERG K⁺ channels → delayed ventricular repolarisation → prolonged QT interval → increased susceptibility to triggered ventricular arrhythmias. Risk highest in elderly and those on concurrent QT-prolonging drugs.

When PUD is severe enough to require surgery (gastrectomy, vagotomy), a distinct set of complications can arise. These are high-yield for exams ^[14]^[19]^[20]:

Complication	Mechanism	Clinical Features	Management
Dumping syndrome (20%) ^[19]	Loss of pylorus → rapid gastric emptying of hyperosmolar carbohydrates → draw fluid into intestinal lumen (osmotic shift) and release vasoactive gut hormones ^[19]	Early (15–30 min): abdominal pain, N/V/D, vasomotor symptoms (sweating, flushing, palpitations) ^[19]. Late (1–3h): post-prandial hyperinsulinaemic hypoglycaemia ^[19] — rapid glucose absorption → exaggerated insulin spike → rebound hypoglycaemia.	Small frequent meals, avoid simple carbohydrates, separate fluids from solids, octreotide ^[19]
Afferent loop syndrome ^[19]^[20]	Mechanical obstruction of afferent limb (in Billroth II) due to kinking, anastomotic narrowing, adhesions, volvulus ^[20] → accumulation of biliary and pancreatic secretions → risk of duodenal stump blowout	Post-prandial severe epigastric pain, non-bilious vomiting ^[20]. Risk of obstructive jaundice, ascending cholangitis, pancreatitis (high pressure transmitted back to biliopancreatic ductal system) ^[20].	Conversion to Roux-en-Y gastrojejunostomy ^[20]
Efferent loop syndrome ^[20]	Intermittent obstruction of efferent limb → GOO symptoms	Abdominal pain, bilious vomiting months to years after surgery ^[20]	Surgical correction
Roux stasis syndrome ^[20]	Disruption of normal propagation in Roux limb → ectopic pacemakers → net propulsive activity proximal (towards stomach) rather than distal ^[20]	Chronic abdominal pain, nausea, vomiting aggravated by eating ^[20]	Prokinetics; surgical revision if refractory
Alkaline reflux gastritis	Bile reflux into gastric remnant (loss of pyloric barrier) → chemical gastritis	Epigastric burning, bilious vomiting, not relieved by antacids	Prokinetics; surgical conversion to Roux-en-Y (diverts bile away from remnant)
Small stomach syndrome ^[19]	Inadequate reservoir function after partial gastrectomy	Early satiety ^[19] → weight loss	Small frequent meals ^[19]
Post-vagotomy diarrhoea ^[20]	Alteration in gastric emptying and vagal denervation of small bowel and biliary tree ^[20]. Occurs in 20% after truncal vagotomy.	Watery, episodic diarrhoea ^[20]	Antidiarrhoeal medications; ↓ lactose intake ^[20]
Nutritional deficiencies ^[19]	Loss of gastric acid, intrinsic factor, and duodenal absorptive surface	B₁₂ deficiency anaemia (↓ intrinsic factor + ↓ acid → requires IM B₁₂ every 3 months). Iron deficiency (↓ acid to reduce Fe³⁺ → Fe²⁺). Calcium deficiency → osteoporosis. Fat-soluble vitamin deficiency (loss of duodenal continuity). Steatorrhoea ^[19].	B₁₂ supplementation, iron tablets, calcium + vitamin D ^[20]
Gastric stump carcinoma	Chronic bile reflux → chronic atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma (similar to HP-driven Correa cascade). Typically develops 15–20 years post-gastrectomy.	Dyspepsia, weight loss, anaemia in a patient with remote history of gastrectomy	Surveillance OGD; surgical resection if detected

Functional dyspepsia does not cause direct structural complications (by definition, there is no organic disease). However, the chronic nature of FD leads to significant indirect complications:

Complication	Mechanism
Impaired quality of life	Chronic symptoms (pain, fullness, nausea) → ↓ ability to eat normally → ↓ social functioning, ↓ work productivity. Studies show FD reduces quality of life comparable to moderate-severe chronic diseases.
Weight loss / nutritional deficiency	Severe early satiety and food avoidance → inadequate caloric intake. Some patients develop restrictive eating patterns (fear of eating → "sitophobia").
Psychiatric comorbidity	Anxiety, depression, somatisation — may be bidirectional (brain-gut axis). Chronic unexplained symptoms → frustration → doctor-shopping → iatrogenic harm from unnecessary investigations and medications.
Iatrogenic complications	Over-investigation (repeated endoscopies, unnecessary CT scans), polypharmacy (long-term PPI, multiple drug trials), unnecessary surgery. Do not overinvestigate ^[1].
Opioid dependence	In severe chronic pain, some patients are inappropriately prescribed opioids → central sensitisation → narcotic bowel syndrome (paradoxical worsening of pain). This should be avoided at all costs.

The Biggest Complication of FD is Mismanagement

The real danger with functional dyspepsia is not the disease itself but what we do to the patient: unnecessary repeated endoscopies, long-term unsupervised PPI use, and failure to address the psychological component. Reassurance after ruling out organic pathologies ^[2] is therapeutic. Conversely, the clinician who fails to investigate appropriately may miss a cancer. The balance is: thorough initial evaluation → targeted treatment → avoid escalating interventions without new clinical information.

Since OGD is the primary investigative tool for dyspepsia, its complications are relevant [3b]:

Timing	Complication	Mechanism / Explanation
Sedation-related	Hypoxaemia, respiratory depression, aspiration pneumonia [3b]	Midazolam (benzodiazepine) → CNS depression → ↓ respiratory drive, ↓ protective airway reflexes. Manage with monitoring (pulse oximetry) and reversal (IV flumazenil for midazolam).
	Hypotension, cardiac arrhythmia, AMI [3b]	Vagal stimulation during scope insertion → bradycardia; pre-existing cardiac disease + stress → ischaemia
Intraoperative	Perforation [3b]	Risk increased with therapeutic manoeuvres (dilatation, polypectomy, EMR/ESD) and in patients with oesophageal diverticula or thin-walled strictures. Incidence ~0.03% for diagnostic OGD, up to 1–2% for therapeutic.
	Bleeding [3b]	Biopsy sites, polypectomy sites. Usually self-limiting; occasionally requires endoscopic haemostasis. Incidence ~3 per 10,000.
Post-procedural	Nausea, abdominal distension, sore throat	Air insufflation → gastric distension; scope trauma to pharynx → soreness (self-limiting)
	Transient dysphagia	Due to local anaesthetic spray (LA) → temporary → resolves when LA effect wears off

High Yield Summary

PUD complications ("Bleed, Burst, Block, Burrow"): (1) Haemorrhage — leading cause of PUD death; Forrest classification guides endoscopic therapy; post-OGD PPI infusion 80mg stat then 8mg/h × 72h stabilises clot. (2) Perforation — anterior ulcers perforate freely; erect CXR for pneumoperitoneum; Graham omental patch for small perforations; Boey's score predicts mortality. (3) GOO — vomiting → hypokalaemic hypochloraemic metabolic alkalosis; decompress (NGT), correct electrolytes, endoscopic dilatation or surgery. (4) Penetration — posterior ulcers into pancreas (back pain); fistulisation → feculent vomiting.

GERD complications: Oesophagitis → stricture → Barrett's → adenocarcinoma (30–100× ↑ risk). All Barrett's patients need PPI regardless of symptoms.

Long-term PPI risks: Osteoporotic fractures, hypoMg, C. difficile, B₁₂/Fe deficiency, rebound acid hypersecretion, SIBO, CAP. Use lowest dose for shortest duration.

Post-gastrectomy syndromes: Dumping syndrome (early = osmotic fluid shift + hormones; late = hyperinsulinaemic hypoglycaemia), afferent/efferent loop syndrome, Roux stasis, alkaline reflux gastritis, nutritional deficiencies (B₁₂, Fe, Ca, fat-soluble vitamins), gastric stump carcinoma.

FD complications: Mainly indirect — impaired QoL, psychiatric comorbidity, iatrogenic harm from over-investigation/polypharmacy. The biggest risk is mismanagement.

Active Recall - Complications of Dyspepsia and Underlying Causes

References

^[1] Lecture slides: murtagh merge.pdf (Dyspepsia, pp. 38–39) ^[2] Senior notes: Ryan Ho GI.pdf (pp. 54–55, Section 2.1.4) and Ryan Ho Fundamentals.pdf (pp. 264–265, Section 3.3.4) ^[3] Senior notes: felixlai.md (PUD section, pp. 567–579; Dyspepsia section, pp. 490–492) [3b] Senior notes: felixlai.md (OGD complications, pp. 124–127) ^[6] Senior notes: Ryan Ho GI.pdf (pp. 76–78, Section 2.3.2 — PUD) ^[7] Senior notes: Ryan Ho Endocrine.pdf (p. 102, Section 4.2.3 — Gastrinoma/ZES) ^[10] Senior notes: Ryan Ho GI.pdf (p. 105) and Ryan Ho Fundamentals.pdf (p. 279 — Investigations) ^[14] Senior notes: maxim.md (PUD surgical management, pp. 127–129) ^[15] Senior notes: maxim.md (OGD therapeutic / Forrest classification, pp. 101–103; GERD, p. 107) ^[17] Senior notes: maxim.md (Perforated PUD, p. 129) ^[18] Senior notes: felixlai.md (Barrett's oesophagus, pp. 541–542) [18b] Senior notes: felixlai.md (Gastric cancer complications, p. 610) ^[19] Senior notes: maxim.md (Post-gastrectomy complications, pp. 143–144) ^[20] Senior notes: felixlai.md (Post-gastrectomy syndromes, pp. 609–610)