GC068 Indigestion And ‘heartburn’
Indigestion (dyspepsia) and heartburn are upper gastrointestinal symptoms characterized by epigastric discomfort, bloating, and a retrosternal burning sensation typically caused by gastric acid reflux or impaired digestion.
This lecture, delivered by Dr. Mak Lung-Yi (QMH / HKU), covers four interconnected topics spanning the upper GI tract, from the most common presentations to the rarest [1]:
- Approach to indigestion (dyspepsia) and heartburn (GERD)
- Approach to nausea and vomiting
- Overview of gastric motility problems — focusing on gastroparesis
- Overview of benign esophageal lesions
The unifying clinical thread: a patient walks in saying "I have heartburn" or "I keep vomiting." Your job is to distinguish physiological from pathological, organic from functional, and benign from sinister — all while being cost-effective. The exam loves testing the definitions, the diagnostic approach (especially the PPI test, 24-hr pH monitoring, and when to scope), the pharmacology of anti-emetics and prokinetics, and the classification of benign esophageal lesions.
How This Fits into Exams
- MCQs: PPI side-effect causation vs. association (directly tested in 2022 MCQ Q40 [18]), Los Angeles classification, refractory GERD workup, anti-emetic pharmacology, gastroparesis diagnostic thresholds.
- SAQs: Dyspepsia algorithm (test-and-treat vs. endoscopy), Barrett's esophagus predisposing factors (2016 SAQ Q6 [17]).
- Minicases: Vomiting workup, electrolyte complications of vomiting, perforated PUD with preceding dyspepsia history (2018 Minicase [19]).
- OSCE: History taking for GERD, counselling on lifestyle modifications, interpreting OGD findings.
Part 1: Approach to Indigestion and Heartburn
Heartburn typically refers to GERD: a burning feeling rising from the stomach or lower chest up towards the neck. May include acid regurgitation, sour stomach, bitter belching, waterbrash. [1]
Indigestion / Dyspepsia is pain or discomfort centered in the upper abdomen. May include epigastric pain/burning, postprandial fullness, early satiety, epigastric bloating. Sometimes patients confusingly refer to heartburn or regurgitation as "indigestion." [1]
Why this matters from first principles: Heartburn implies an esophageal problem (acid going up through an incompetent barrier). Dyspepsia implies a gastroduodenal problem (the stomach or duodenum is irritated, obstructed, or dysmotile). But there is significant symptom overlap — this is explicitly stated on the slides as an "area of controversy" [1].
| Feature | Heartburn (GERD) | Dyspepsia |
|---|---|---|
| Direction | Rising from stomach → neck | Centred in upper abdomen |
| Key symptom | Burning, acid regurgitation, waterbrash | Epigastric pain, fullness, early satiety |
| Timing | Within 1 hr of eating; supine; ↑ intra-abdominal pressure | Variable; postprandial or fasting |
| Overlap | GERD patients can have dyspepsia | Dyspepsia patients can describe "heartburn" |
Regurgitation is defined as the effortless return of gastric contents upward — key word is "effortless" — distinguishing it from vomiting which is forceful [1].
High Yield
The lecture explicitly notes the overlap between GERD (32%), dyspepsia (14%), and NCCP (16%), with 8% having all three (Wong WM, AP&T 2003). Exam questions may present mixed symptoms and ask you to identify the predominant syndrome.
1.2 Gastro-Esophageal Reflux Disease (GERD)
GERD is the condition in which the reflux of gastric contents into the esophagus results in symptoms and/or complications. Gastroesophageal reflux (GER) itself is physiological — it becomes a disease only when it causes symptoms or mucosal damage. [1]
This is a crucial conceptual point: everyone refluxes to some degree after meals. The threshold at which it becomes GERD is when the reflux is frequent/severe enough to produce symptoms (heartburn ≥ 2x/week is a common clinical benchmark) or complications (esophagitis, stricture, Barrett's).
GERD is a spectrum of disease resulting from imbalance between anti-reflux barriers vs. aggravating factors. [1]
Anti-reflux barriers (why they prevent reflux):
| Barrier | Mechanism |
|---|---|
| LES (resting pressure ~10 mmHg) | Tonic contraction creates a high-pressure zone; intra-abdominal location means abdominal pressure compresses it shut [1] |
| Diaphragmatic hiatus (crural muscle + phrenoesophageal ligaments) | External "pinch" on the esophagus during inspiration reinforces LES [1] |
| Angle of His (oblique entry of esophagus into stomach) | Creates a flap valve: when gastric pressure rises, the sharp angle on the greater curvature side compresses the esophageal opening shut [1] |
Aggravating factors (why reflux increases):
| Factor | Explanation |
|---|---|
| tLESR (transient LES relaxation) | The single most important mechanism in most GERD patients. Stimulated by proximal gastric distension (large meal, swallowed air). The LES relaxes inappropriately for 10-60 seconds, allowing reflux [1] |
| Hiatus hernia | Proximal stomach herniates above the diaphragm → LES loses its intra-abdominal location → loses the reinforcing "pinch" of the crural muscle → ↑ reflux episodes and ↓ acid clearance [1] [4] |
| Impaired esophageal emptying/peristalsis | Normally, secondary peristalsis clears refluxed acid. If peristalsis is weak (e.g., scleroderma), acid dwell time ↑ → more mucosal damage [1] |
| Hypotensive LES (post-POEM) | POEM (per-oral endoscopic myotomy for achalasia) deliberately disrupts LES → high rate of post-procedure GERD [1] |
| Acid pocket | Post-meal, an area of unbuffered acid sits on top of the food bolus near the cardia; if LES opens, this acid preferentially refluxes [1] |
| Excessive gastric acid | Hypergastrinaemia from Hp-positive antral gastritis (G-cells spared), post-Hp eradication in corpus-predominant gastritis (parietal cells recover but G-cell drive persists temporarily), Zollinger-Ellison syndrome (gastrinoma), or delayed gastric emptying [1] |
Exam Trap
Hiatus hernia is an exacerbating factor, NOT a cause of GERD. Not all patients with hiatus hernia have GERD, and not all GERD patients have hiatus hernia [4]. The lecture lists it under "aggravating factors" — never say it "causes" GERD in an exam answer.
Typical GERD symptoms: post-prandial (especially after large meals); triggered by spicy food, citrus, fat, chocolates, alcohol; worsened in supine or right decubitus posture. [1]
Why right decubitus worsens GERD: lying on the right side positions the gastric fundus (acid pocket) above the GEJ, facilitating reflux. Left lateral decubitus keeps the acid pool below the GEJ.
Atypical chest pain — this is NCCP (non-cardiac chest pain). Important to exclude cardiac causes first [1].
Extra-esophageal symptoms: asthma, chronic cough, sleep disturbance, laryngo-pharyngeal reflux, hoarseness of voice, throat tightness, dental erosion. [1]
Why extra-esophageal symptoms occur: Acid can microaspirate into the larynx/tracheobronchial tree (direct contact theory), or vagal reflex from acid in the distal esophagus triggers bronchospasm (reflex theory). This explains why some GERD patients present first to ENT or Respiratory.
Endoscopic classification: erosive vs. non-erosive [1]
Complications: esophagitis, esophageal ulcer and stricture, Barrett's esophagus, adenocarcinoma of esophagus [1]
The cascade: chronic acid exposure → inflammation (esophagitis) → ulceration → scarring and stricture → intestinal metaplasia (Barrett's) → dysplasia → adenocarcinoma. This is the dreaded long-term complication that drives surveillance programmes.
| Associated Conditions | DDx of GERD |
|---|---|
| Pregnancy (30-80%) — progesterone relaxes LES + growing uterus ↑ intra-abdominal pressure [1] | Achalasia — failure of LES relaxation (opposite mechanism!) but can mimic with regurgitation |
| NG tube — splints the LES open [1] | Zenker's diverticulum — regurgitation of undigested food, halitosis |
| Scleroderma (38% erosive disease) — fibrosis of esophageal smooth muscle → ↓ peristalsis + ↓ LES tone [1] | Gastroparesis — nausea, vomiting, early satiety |
| MEN — associated with Zollinger-Ellison (MEN1) [1] | Angina pectoris — must always exclude cardiac chest pain |
| Obesity [1] | Other causes of esophagitis: pill-induced, infective (Candida, HSV, CMV in immunosuppressed), radiation, eosinophilic |
1.3 Diagnosis of GERD
The lecture presents a hierarchy from subjective to objective, emphasizing cost-effectiveness [1]:
PPI empirical trial can be considered as initial diagnostic step. Try standard PPI for 8 weeks. Accurate and cost-effective in patients with symptoms suggestive of GERD and NCCP. [1]
Why this works: If symptoms resolve with acid suppression, the diagnosis of acid-related disease is supported. It is both diagnostic and therapeutic. The 8-week duration matters because some patients with erosive esophagitis need the full course for healing.
Why to take PPI 30-60 min before meals: PPIs are prodrugs that require an acidic environment to be activated. They irreversibly bind to H+/K+ ATPase (proton pumps) that are actively secreting acid. Meals stimulate proton pump activity via gastrin/vagal/histamine pathways. If you take PPI with an empty stomach and no meal follows, fewer pumps are active → less drug effect [1].
Chinese (Cantonese) GERDQ — validated 7-question questionnaire assessing frequency and severity of heartburn, acidity in stomach, acid regurgitation, and use of antacids. [1]
Often referred to as the 'gold standard' in diagnosing GERD. A study is abnormal if the total percentage of time with pH < 4.0 is ≥ 4.2% in the distal esophagus (DeMeester score). [1]
| Parameter | Detail |
|---|---|
| Sensitivity for erosive GERD | ~90% [1] |
| Sensitivity for NERD | Much lower [1] |
| Catheter type | 2 antimony pH electrodes [1] |
| Newer technology | BRAVO™ catheter-free capsule — transmits pH via radio frequency; more comfortable [1] |
| Combined impedance-pH | Can detect non-acid reflux (bile, food bolus, liquid, air) in addition to acid reflux [1] |
Why pH 4.0 threshold? Below pH 4, pepsin is activated and causes mucosal injury. This is the physiological basis for the DeMeester threshold.
Role of endoscopy in GERD: [1]
- Diagnosing erosive GERD (~30% of all GERD; i.e. 70% GERD is NERD) — Normal endoscopy does NOT exclude GERD
- Look for cause — hiatus hernia, EoE, antral gastritis, associated PUD
- Look for complications — strictures, Barrett's, adenocarcinoma
- Alarm symptoms: weight loss, dysphagia, odynophagia, GI bleeding
Key Exam Fact
~70% of GERD is NERD (non-erosive reflux disease). A normal endoscopy does NOT exclude GERD. This is a very commonly tested concept. Only 20-60% of patients with abnormal esophageal pH have visible esophagitis on endoscopy [1].
| Grade | Description |
|---|---|
| A | ≥1 mucosal break confined to folds, ≤5 mm long [1] |
| B | ≥1 mucosal break confined to folds, >5 mm long [1] |
| C | ≥1 mucosal break continuous between tops of ≥2 folds, < 75% circumference [1] |
| D | ≥1 mucosal break continuous between tops of ≥2 folds, ≥75% circumference [1] |
Why this classification matters: LA grade C/D = severe erosive esophagitis → requires long-term maintenance PPI therapy [1]. LA A/B may be managed with on-demand or intermittent therapy.
1.4 Management of GERD
Confirm diagnosis, relieve symptoms, reassure patients, heal esophagitis, improve quality of life, prevent long-term complications. [1]
This is the first-line approach. The lecture lists it but the details come from associated materials [1] [4]:
- Weight loss (if obese)
- Elevate head of bed (gravity assists acid clearance)
- Avoid late meals / lying down within 2-3 hours of eating
- Avoid trigger foods: spicy, citrus, fat, chocolate, alcohol, caffeine
- Smoking cessation
- Avoid right lateral decubitus sleeping position
| Drug Class | Role | Key Points |
|---|---|---|
| Antacids | On-demand symptom relief | Little evidence for sustained benefit [1] |
| H2 Receptor Antagonists (H2RA) | Main role: add-on therapy for bedtime breakthrough GERD despite PPI | Tachyphylaxis develops — effect wanes with chronic use [1] |
| Proton Pump Inhibitors (PPI) | Superior relief of heartburn/regurgitation + healing of esophagitis cf. H2RA | Take 30-60 min before meal; try to discontinue long-term therapy if possible [1] |
PPI Maintenance Therapy Indications: [1]
- Long-term: Erosive esophagitis LA grade C/D, peptic stricture, Barrett's esophagus
- On-demand/intermittent: NERD patients with severe symptoms responsive to PPI
No role: Baclofen, prokinetics, sucralfate (except sucralfate during pregnancy). [1]
High Yield - PPI Side Effects (Directly Tested in 2022 MCQ Q40)
Known effects: fundic gland polyps (mostly benign), acute interstitial nephritis [1].
Association studies (many, but NO cause-and-effect confirmed): intestinal infections, pneumonia, gastric cancer, osteoporosis-related fractures, CKD, stroke, dementia, hepatic encephalopathy, hypomagnesemia [1].
The ONLY association with established causation: enteric infections other than C. difficile (OR 1.33, 95% CI 1.01-1.75) [1].
Bottom line from the lecture: PPIs are the most effective medical treatment for GERD. Benefits > theoretical risks for indicated patients. Guidelines do NOT recommend routine additional calcium/vitamin D, DEXA, or monitoring serum B12/Cr [1].
Exam answer for 2022 MCQ Q40: The answer is C. Enteric infections — the only complication with established causation [18].
Possible actions for refractory GERD: [1]
- Optimize PPI dose, timing, compliance
- Try switching class of PPI (different CYP2C19 metabolism profiles)
- Add nocturnal H2RA for night-time symptoms
- Add Alginate (e.g. Gaviscon) for post-dinner symptoms
- 24-hour pH monitoring ± impedance study
- Anti-reflux surgery (only after confirmed with objective testing)
- Esophageal manometry
- Repeat OGD after OFF PPI for 2-4 weeks (drug holiday) to look for erosive esophagitis and obtain esophageal biopsies for EoE — 1-8% of refractory GERD [1]
Why switch PPI class? PPIs are metabolized by CYP2C19 (and to a lesser extent CYP3A4). Genetic polymorphisms in CYP2C19 mean some patients are "rapid metabolizers" who break down certain PPIs too quickly → inadequate acid suppression. Switching to a PPI less dependent on CYP2C19 (e.g., rabeprazole) may improve response.
Why biopsy for EoE? Eosinophilic esophagitis mimics GERD with heartburn and dysphagia but does not respond to PPI (or only partially responds). Diagnosis requires ≥15 eosinophils/HPF on esophageal biopsy. Must take PPI holiday before biopsy to avoid PPI-responsive esophageal eosinophilia being mistaken for EoE.
Anti-reflux surgery options: [1]
- Laparoscopic fundoplication (Nissen) — wraps gastric fundus around distal esophagus to augment LES
- Magnetic sphincter augmentation (MSA) - LINX — ring of magnetic beads placed around LES
- Trans-oral incisionless fundoplication (TIF)
Pre-op evaluation: [1]
- Confirm GERD diagnosis
- Confirm symptoms are at least partially PPI-responsive
- Exclude contraindications (e.g., achalasia — you would make achalasia worse by adding a fundoplication)
Drawbacks: [1]
- Surgical risks (~4%)
- Recurrence of GERD post-op (~20% long-term)
- Post-operative dysphagia / gas bloat / inability to belch (Nissen-specific complications [5])
1.5 Uninvestigated Dyspepsia — The Algorithm
Most prevalent causes: peptic ulcer disease, Hp infection, functional dyspepsia [1] Significant organic causes to exclude: malignancy of upper GIT, hepato-pancreatic-biliary causes [1]
Two approaches (may be sequential): [1]
- Test (for Hp) and Treat — non-invasive Hp testing (urea breath test or stool antigen), if positive → eradication therapy
- Empirical anti-secretory drug (PPI trial)
If no response or recurrence → may eventually need upper endoscopy [1]
Laboratory tests (CBC, LRFT, TFT): cost-effectiveness not established [1]
Dyspepsia with normal endoscopy [1]
Note: presence of H. pylori does NOT exclude FD. Eradication of Hp CAN relieve symptoms in some FD patients. [1]
ROME IV criteria divide FD into: [1]
- Post-prandial distress syndrome (PDS) — bothersome postprandial fullness or early satiety
- Epigastric pain syndrome (EPS) — bothersome epigastric pain or burning
The two subtypes have different pathophysiological mechanisms: PDS relates more to gastric motor dysfunction (impaired accommodation, delayed emptying), while EPS relates more to visceral hypersensitivity. This distinction guides therapy: PDS → prokinetics; EPS → acid suppression.
Part 2: Approach to Nausea and Vomiting
Nausea → retching → vomiting: a progression leading to the emetic reflex, but they may occur separately. [1]
| Term | Definition |
|---|---|
| Nausea | An unpleasant subjective sensation as a feeling of impending vomiting in the epigastrium or throat [1] |
| Retching | Spasmodic abortive respiratory movement with glottis closed [1] |
| Vomiting | Partially voluntary act of forcefully expelling gastric/intestinal content through the mouth; requires central neurologic coordination [1] |
| Regurgitation | Effortless reflux of gastric contents into esophagus; NOT associated with forceful ejection [1] |
Exam Trap: Vomiting vs. Regurgitation
If an exam question describes "effortless" return of food — that is regurgitation (think GERD, achalasia, Zenker's diverticulum). If it describes "forceful" ejection with retching — that is vomiting (think mechanical obstruction, raised ICP, metabolic causes). This distinction is tested in history-taking scenarios.
Emetic center: located in the medulla (dorsal portion of the lateral reticular formation) — the solitary nucleus [1]
Afferent pathways (what triggers vomiting):
| Source | Examples |
|---|---|
| GI tract | Pharynx, stomach, small intestine, bile duct, peritoneum [1] |
| Non-digestive organs | Heart (AMI), testicles [1] |
| CNS | Cerebellum, vestibular system, brainstem, chemoreceptor trigger zone (CTZ) [1] |
The CTZ (area postrema) lies outside the blood-brain barrier, allowing it to detect circulating emetogenic substances (drugs, toxins, metabolites like urea).
Efferent pathway (what happens during vomiting): [1]
- Cerebral cortex activation (you become aware)
- Stomach: antral relaxation + inhibition of intestinal peristalsis
- Intercostal muscles and diaphragm: spasmodic contraction + closure of glottis
- Brisk muscular contraction, relaxation of LES, forceful retrograde peristalsis of jejunum
- ± Hypersalivation, cardiac arrhythmia
The lecture divides causes into GIT and Non-GIT, with a brilliant clinical pearl: bowel sounds help you differentiate [1].
| Category | Causes | Bowel Sounds |
|---|---|---|
| Mechanical obstruction | GOO, SBIO, SMA syndrome | ↑ |
| Motility disorder | Paralytic ileus, gastroparesis, colonic pseudo-obstruction, achalasia | ↓ / Normal |
| Hepato-biliary-pancreatic | Acute hepatitis, acute cholecystitis, acute pancreatitis | ↓ / Normal |
| Bowel inflammation | Acute mesenteric ischemia, gastroenteritis | ↓ |
| Pharyngeal irritation | — | Normal |
| Eating disorder | Bulimia, anorexia nervosa | ↓ / Normal |
| Peritoneal irritation | Peritonitis, carcinomatosis | — |
| CNS/PNS | Raised ICP, CNS infection, acute stroke, vestibular, migraine | — |
| Cardiac | AMI, heart failure | — |
| Systemic/Metabolic | DKA, Addisonian crisis, hypoNa, uraemia | — |
| Drugs | Chemotherapy, metformin, colchicine, levodopa, anticonvulsants, antibiotics, narcotics, digoxin | — |
| Hormonal | Hyperestrogenemia (pregnancy, OCPs) | — |
| Other | Alcohol abuse | — |
Key history elements: [1]
- Onset: acute (< 1 week) vs. chronic
- Timing: empty stomach vs. post-prandial
- Nature of vomitus: total undigested vs. acidic vs. bilious
- Preceding nausea: if absent → projectile vomiting → suggestive of direct stimulation of emetic center (e.g., raised ICP)
- Constitutional symptoms
- Associated GI symptoms: abdominal pain, jaundice, diarrhea, hematemesis
- Associated CNS/vestibular/cardiac symptoms
- LMP for females (always!)
- PMH: DM (medication? DKA? Gastroparesis?), stroke, MI, psychiatric history
- Drug history
- Surgical history: abdominal surgery → adhesive SBIO
Why "nature of vomitus" matters:
- Undigested food → esophageal cause (Zenker's, achalasia) or very proximal obstruction
- Acidic (partially digested) → gastric cause
- Bilious (green/yellow) → obstruction DISTAL to ampulla of Vater (i.e., beyond D2)
- Feculent → distal small bowel or colonic obstruction
General exam: [1]
- Vitals: hypovolaemic shock?
- Hydration status: capillary refill, mucous membrane, skin turgor, body weight, urine output
- Acidotic breathing (Kussmaul — metabolic acidosis)
- Jaundice? Uraemic complexion?
- Russell's sign (callused knuckles — self-induced vomiting in eating disorders)
Abdominal exam: [1]
- Inspection: distension, surgical scars, hernia
- Palpation: peritoneal signs, Murphy's sign, mass
- Percussion: characterize mass, shifting dullness
- Auscultation: bowel sounds!!! (critical discriminator as shown in the causes table)
Targeted exam based on history: [1]
- Cardiovascular exam (if cardiac cause suspected)
- Neurological + fundoscopy (if CNS cause suspected — papilloedema in raised ICP)
Investigations (underlined = complications OF vomiting; not underlined = causes): [1]
| Investigation | Looking For |
|---|---|
| Urinary pregnancy test | Pregnancy (always in women of childbearing age) |
| CBC | Leukocytosis, reactive thrombocytosis, anaemia |
| LFT, GGT | Hepato-biliary causes, hypoalbuminaemia |
| Amylase ± lipase | Acute pancreatitis, IO, bowel ischemia, perforated gut |
| RFT, CaPO4 | Cr↑, Ca↑, electrolyte disturbances (K↓, Na↓ or Na↑), AKI |
| Random glucose | DKA |
| Ketone | DKA |
| Venous blood gas | Metabolic acidosis OR metabolic alkalosis (from vomiting: loss of HCl → hypochloraemic hypokalaemic metabolic alkalosis) |
| Serum ethanol | Alcohol intoxication |
| ECG | U wave, flat T wave, long QTc (from hypokalaemia), myocardial ischemia |
| Cardiac enzymes | AMI |
| CXR | Aspiration pneumonia (complication), perforated viscus (free air), Boerhaave's syndrome (pneumomediastinum) |
| AXR | Dilated small/large bowel, gastric distension |
| Imaging | USG/CT abdomen; CT brain |
Boerhaave's Syndrome
Boerhaave's syndrome = spontaneous esophageal perforation from forceful vomiting. Look for Mackler's triad: vomiting + lower thoracic pain + subcutaneous emphysema. CXR shows pneumomediastinum. This is a surgical emergency.
Detailed history + physical examination → narrow DDx → then: [1]
- Upper GI endoscopy
- Contrast studies
- Gastric emptying study
- CT/MR enterography
- Referrals (neurology, psychiatry)
5 steps: [1]
- Fluid rehydration (chart I/O)
- Correction of electrolyte disturbance
- Nutritional support (enteral preferred over parenteral)
- Pharmacological therapy
- Look for and treat underlying cause
Anti-emetic Pharmacology (High Yield)
| Drug Class | Examples | Mechanism | Side Effects |
|---|---|---|---|
| Dopamine D2 antagonist | Metoclopramide (Maxolon) 10 mg q8h IV/PO | Central anti-emetic + peripheral prokinetic (5HT4 agonist) | Somnolence, extrapyramidal effects [1] |
| Domperidone 10 mg TDS PO only | Peripheral D2 antagonist (crosses BBB poorly) | Less extrapyramidal S/E, risk of ↑QTc [1] | |
| Both can increase prolactin [1] | |||
| Antihistamines / Antimuscarinics | Diphenhydramine | H1 antagonism at vomiting center | Drowsiness; C/I in glaucoma, asthma [1] |
| Serotonin 5HT3 antagonist | Ondansetron | Blocks 5HT3 at CTZ and vagal afferents | Well tolerated; may cause constipation, headache |
| NK1 receptor antagonist | Aprepitant | Blocks substance P at emetic center | Used mainly for chemotherapy-induced N/V |
| Motilin receptor agonist | Erythromycin IV (3 mg/kg q8h) | Mimics motilin → stimulates gastric motility | Long QTc; more specific for gastroparesis [1] |
Exam Pearls: Metoclopramide vs. Domperidone
Metoclopramide has DUAL action: central anti-emetic (D2 antagonist) + peripheral prokinetic (5HT4 agonist). It crosses the BBB → more extrapyramidal side effects. Domperidone crosses BBB poorly → fewer CNS side effects but still raises prolactin (acts on pituitary, which is outside BBB). Both prolong QTc. Domperidone is oral only [1].
Part 3: Gastroparesis
Gastroparesis is a syndrome of: [1]
- Delayed gastric emptying
- In the absence of mechanical obstruction
- Cardinal symptoms: early satiety, postprandial fullness, nausea, vomiting, PPI-refractory GERD
- Less specific: bloating, upper abdominal pain
Prevalence: [1]
- Type 1 DM: 5-40%
- Type 2 DM: 1-20%
- Non-diabetic controls: 0.2% → 'Idiopathic gastroparesis'
Interstitial Cells of Cajal (ICC) = pacemaker cells derived from c-Kit positive mesenchymal cell precursors. Located on the greater curvature between fundus and proximal corpus. Generate slow waves at ~3 cycles per minute.* [1]
Depletion of ICCs in the corpus-antrum is the key pathological finding in gastroparesis [1].
Why diabetes causes gastroparesis: Chronic hyperglycaemia → autonomic neuropathy (vagal nerve damage) → loss of excitatory neural input to ICC + smooth muscle → impaired gastric accommodation and antral contractions. Additionally, hyperglycaemia itself acutely slows gastric emptying (reversible component).
| Causes | Triggering Factors | DDx |
|---|---|---|
| DM, Idiopathic, Thyroid dysfunction, Neurological (Parkinsonism, amyloidosis, paraneoplastic), Post-surgical (vagotomy, fundoplication, bariatric), Autoimmune (scleroderma), Medications (GLP-1 agonist, narcotics, anticholinergics, cyclosporine) [1] | Infection (post-viral), Hyperglycaemia, Ischemia, Electrolyte disturbance [1] | Cyclic vomiting syndrome, Rumination syndrome, Eating disorders, Cannabinoid misuse [1] |
GLP-1 Agonists and Gastroparesis
GLP-1 receptor agonists (e.g., semaglutide, liraglutide — increasingly used for DM and obesity) slow gastric emptying as part of their mechanism. This can cause or worsen gastroparesis. Very relevant in current clinical practice and increasingly tested.
Step 1: Exclude gastric outlet obstruction → endoscopy ± cross-sectional imaging [1] Step 2: Scintigraphy → gastric emptying study (solid meal) [1] Step 3: Look for secondary causes → review history, CBC, RG, LRFT, CaPO4, TFT, blood gas [1] Step 4: Prepare for pharmacological treatment → ECG (baseline QTc before prokinetics) [1] Step 5: Nutritional support → enteral route preferred (post-pyloric feeding) over parenteral [1]
Gastric Emptying Study (Scintigraphy) — Key Details:
Precautions: [1]
- Withhold drugs affecting gastric motility for 48-72 hours: narcotic opioids, anticholinergics, metoclopramide, macrolides, domperidone
- Control glucose to < 15 mmol/L (hyperglycaemia slows emptying and invalidates test)
- Solid phase meal: 99mTc sulfur colloid-labeled egg sandwich (or EggBeaters with jam + toast + water)
- Standard imaging at 0, 1, 2, and 4 hours
- Normal: < 10% retention at 4 hours [1]
| Agent | Dose | Mechanism | Key Side Effects / Notes |
|---|---|---|---|
| Metoclopramide | 10 mg TDS PO or q8h IV | D2 antagonist (central + peripheral) + 5HT4 agonist | < 1% tardive dyskinesia; prolongs QTc [1] |
| Domperidone | 10 mg TDS PO | D2 antagonist (peripheral predominant) | Less CNS S/E; hyperprolactinaemia; prolongs QTc — avoid if QTc > 470 ms (male) or > 450 ms (female) [1] |
| Erythromycin | 3 mg/kg q8h IV | Motilin receptor agonist | Prolongs QTc; tachyphylaxis (motilin receptor downregulation) [1] |
| Gastric electrical stimulation | Device implant | Electrical pacing | Marginal benefit — mainly in diabetic gastroparesis [1] |
| G-POEM | Endoscopic procedure | Pyloromyotomy | Modest benefit [1] |
No use: intra-pyloric botulinum toxin injection [1]
Nutritional support hierarchy: [1]
- NG tube for decompression; NJ tube for temporary feeding (post-pyloric preferred)
- PEG-J (percutaneous endoscopic gastrostomy with jejunal extension)
- Jejunostomy ± gastrostomy for venting
Part 4: Benign Esophageal Lesions
Mostly asymptomatic, incidentally found during endoscopy for other reasons. Rare, prevalence ≤ 0.5%. [1]
Epithelial lesions vs. sub-epithelial lesions. Endoscopic ultrasound (EUS) is helpful for sub-epithelial lesions. Biopsies may be helpful sometimes. [1]
EUS layer anatomy (exam favourite):
- A (mucosa/interface with lumen) — hyperechoic
- B (muscularis mucosae) — hypoechoic
- C (submucosa) — hyperechoic
- D (muscularis propria) — hypoechoic
- E (adventitia) — hyperechoic
Mnemonic: alternate echogenicity starting with hyperechoic at the luminal surface.
| Condition | Incidence | Key Points |
|---|---|---|
| Heterotopic gastric mucosa | 0.1-10% | Must differentiate from Barrett's esophagus (heterotopic = congenital island of gastric mucosa, usually in cervical esophagus; Barrett's = metaplasia at distal esophagus from chronic acid exposure) [1] |
| Squamous cell papilloma | 0.01-0.45% | Hypothesis: chronic mucosal irritation, HPV infection [1] |
| Xanthoma | Unknown | Ectopic xanthoma in GIT (stomach 75%, esophagus 12%, duodenum 12%). NOT necessarily associated with hypercholesterolaemia. Hypothesis: focal mucosal damage → lipids from broken-down cell membranes captured by interstitial histiocytes [1] |
| Acanthosis glycogenes | Unknown | Glycogen accumulation in squamous epithelium; no clinical significance [1] |
| Condition | Frequency | Layer of Origin | Key Points |
|---|---|---|---|
| Leiomyoma | Most common benign esophageal neoplasm (2/3 of all tumors) | Muscularis propria | Can cause dysphagia; malignant transformation rare [1] |
| Granular cell tumor | 2nd most common | Submucosa (Schwann cell origin) | 1-3% can be malignant [1] |
| Hemangioma | 0.04% | — | Differentiate from esophageal varices [1] |
| Carcinoid tumor | Rare (more common in small bowel, stomach) | Mucosa | Chromogranin and synaptophysin positive; may be hormone-secreting [1] |
| GIST | Extremely rare in esophagus (most common in stomach/SI) | ICC origin (muscle layer) | KIT mutation; positive for c-KIT (CD117); ALL GISTs have malignant potential; difficult to differentiate from leiomyoma [1] |
Leiomyoma vs. GIST
Both arise from the muscle layer and look similar on endoscopy. GIST has a KIT mutation and is positive for CD117 (c-KIT). Crucially, all GISTs have malignant potential while leiomyoma malignant transformation is rare. EUS can help but sometimes biopsy/immunohistochemistry is needed for definitive differentiation [1].
Appear as tortuous, dilated blue veins running along the long axis of the esophagus [1]. Must differentiate from hemangioma. Clinically significant in portal hypertension / cirrhosis.
| Condition | Key Features |
|---|---|
| Zenker's diverticulum | Pharyngeal pouch; posterior herniation of esophageal mucosa into Killian's triangle (area of least resistance above cricopharyngeal muscle). Incidence 0.01-0.11%, increases with age (esp. male > 70). DDx for recurrent vomiting / aspiration pneumonia / dysphagia. Treatable by surgical/endoscopic diverticulotomy [1] |
| Paterson-Brown Kelly syndrome (= Plummer-Vinson syndrome) | Triad: dysphagia + iron deficiency anaemia + esophageal webs. Females 40-70, rare in Asian populations. Can be associated with Zenker's diverticulum. Increases risk of esophageal cancer [1] |
Exam Intelligence
| Year/Paper | Relevant Question | Key Concept |
|---|---|---|
| 2022 MCQ Q40 [18] | Long-term PPI side effects | Enteric infections = only proven causal association |
| 2016 SAQ Q6 [17] | Barrett's esophagus from chronic GERD | Predisposing factors, staging investigations, standard treatment |
| 2018 Minicase [19] | Epigastric pain → perforation | Background of chronic dyspepsia + NSAIDs/migraine meds → perforated PUD workup |
| Trap | Correct Answer |
|---|---|
| "GERD is caused by hiatus hernia" | Hiatus hernia is an aggravating factor, not a cause |
| "Normal OGD excludes GERD" | 70% of GERD is NERD — normal OGD does NOT exclude GERD |
| "PPI causes osteoporosis/dementia" | Association only; no cause-and-effect established (except enteric infections) |
| "Botulinum toxin injection is useful for gastroparesis" | No — intra-pyloric botulinum toxin injection has NO demonstrated benefit |
| "Domperidone can be given IV" | Domperidone is oral only |
| "Metoclopramide is only a prokinetic" | It is ALSO a central anti-emetic (D2 antagonist at CTZ) |
Q: Name the anti-reflux barriers. → "LES (resting pressure ~10 mmHg, intra-abdominal location); diaphragmatic hiatus (crural muscle + phrenoesophageal ligaments); angle of His (oblique esophago-gastric junction creating flap valve effect)."
Q: What is the gold standard for diagnosing GERD? → "24-hour esophageal pH monitoring. Abnormal if total time pH < 4.0 ≥ 4.2% (DeMeester score)."
Q: Describe the management algorithm for uninvestigated dyspepsia in a 45-year-old. → "No alarm symptoms and age < 60: test for H. pylori (UBT or stool antigen). If positive → eradicate. If negative or persistent symptoms post-eradication → empirical PPI trial. If still symptomatic → OGD."
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MCQ: A 45-year-old man with GERD symptoms does not respond to 8 weeks of PPI. What is the MOST appropriate next step?
- Answer: Optimize PPI timing/compliance, consider switching PPI class, add nocturnal H2RA. If still refractory → 24-hr pH monitoring ± impedance, repeat OGD off PPI with biopsies for EoE.
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SAQ: List 3 anti-reflux barriers and explain how each prevents reflux.
- Answer: LES (tonic contraction creates high-pressure zone), diaphragmatic hiatus (crural pinch reinforces LES), angle of His (flap valve effect from oblique esophago-gastric junction).
-
MCQ: Which complication of long-term PPI has established causation?
- Answer: Enteric infections (other than C. difficile).
-
SAQ: A patient has delayed gastric emptying. Describe the gastric emptying study protocol and normal threshold.
- Answer: Withhold affecting drugs 48-72 hr, control glucose < 15 mmol/L, 99mTc-labeled solid meal, imaging at 0/1/2/4 hr. Normal = < 10% retention at 4 hours.
-
OSCE: Differentiate regurgitation from vomiting.
- Answer: Regurgitation = effortless reflux without retching or forceful contraction. Vomiting = forceful ejection requiring coordinated diaphragmatic/abdominal contraction with glottis closure.
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MCQ: The most common benign esophageal neoplasm is:
- Answer: Leiomyoma (2/3 of all benign esophageal tumors).
-
SAQ: A 65-year-old woman with chronic dysphagia and iron deficiency anaemia. Name the syndrome and its triad.
- Answer: Plummer-Vinson (Paterson-Brown Kelly) syndrome. Triad: dysphagia + iron deficiency anaemia + esophageal webs. Increases risk of esophageal cancer.
High Yield Summary
GERD = reflux causing symptoms/complications. Anti-reflux barriers: LES, diaphragmatic hiatus, angle of His. Aggravating: tLESR, hiatus hernia, impaired peristalsis, acid pocket. 70% of GERD is NERD (normal OGD). Diagnosis: PPI trial (8 wk, cost-effective) → GERDQ → 24-hr pH (gold standard, abnormal ≥4.2% time pH < 4) → OGD (for alarm symptoms, age ≥60, complications). LA classification A-D. Treatment: lifestyle → PPI (30-60 min pre-meal) → H2RA add-on → surgery. Long-term PPI: only proven harm = enteric infections. Maintenance PPI for LA C/D, Barrett's, stricture.
Dyspepsia: if age < 60, no alarms → test-and-treat Hp → empirical PPI → OGD if refractory. Functional dyspepsia = normal OGD; ROME IV PDS vs EPS.
Vomiting: emetic centre in medulla. Always check pregnancy test, electrolytes (hypoK, metabolic alkalosis), ECG. Anti-emetics: metoclopramide (D2 + 5HT4), domperidone (oral only, less CNS), ondansetron (5HT3), erythromycin (motilin agonist, for gastroparesis).
Gastroparesis: delayed emptying + no obstruction. ICC depletion. Scintigraphy: < 10% retention at 4 hr = normal. Treat: metoclopramide, domperidone, erythromycin. No botulinum toxin.
Benign esophageal lesions: Leiomyoma (most common, muscularis propria). GIST (c-KIT/CD117+, ALL malignant potential). Zenker's diverticulum (Killian's triangle). Plummer-Vinson (dysphagia + IDA + webs → ↑ esophageal cancer risk).
Active Recall - Lecture Notes
[1] Lecture slides: GC 068. Indigestion and 'heartburn'.pdf (all pages) [2] Senior notes: Block A - Indigestion and 'heartburn': nausea and vomiting; gastric motility problems; benign esophageal lesions.pdf [3] Senior notes: Ryan Ho GI.pdf (pages 57, 63, 75, 94) [4] Senior notes: Maksim Medicine Notes.pdf (page 122) [5] Senior notes: Maksim Surgery Notes.pdf (page 57) [6] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (page 676) [7] Senior notes: Block A - Introduction to GI_Hepatology investigations (LFT, Endoscopy).pdf (pages 19, 21) [8] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (pages 5, 30) [9] Senior notes: Block A - Gastroenterology Interactive Tutorial.pdf (page 1) [10] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (page 2) [11] Senior notes: Adrian Lui Pediatrics Notes.pdf (page 253) [12] Senior notes: Ryan Ho Cardiology.pdf (pages 54, 56) [13] Senior notes: Ryan Ho Fundamentals.pdf (page 268) [14] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (page 1) [15] Senior notes: Block A - I am overweight, doctor_ obesity; Hyperlipidaemia.pdf (page 6) [16] Senior notes: Block A - Pallor_ diagnosis of anaemia; nutritional anaemia; anaemia of systemic diseases.pdf (page 10) [17] Past papers: 2016 Fourth Summative SAQ.pdf (page 3, Q6) [18] Past papers: 2022 Fourth Summative MCQ.pdf (page 15, Q40) [19] Past papers: 2018 Fourth Summative Minicase.pdf (page 9) [20] Medicine Lecture Slides: Gastroenterology - Two cases of dyspepsia.pdf (page 13)
GC067 I Keep On Bumping Into People On My Side
Homonymous hemianopia is the loss of vision in the same half of the visual field in both eyes, typically caused by a lesion in the contralateral optic tract, lateral geniculate nucleus, optic radiation, or occipital cortex, leading patients to collide with objects or people on their blind side.
GC069 Inherited Cardiac Conditions
Inherited cardiac conditions are a group of genetically determined disorders affecting the heart's structure, rhythm, or function—including cardiomyopathies, channelopathies, and familial aortopathies—that predispose affected individuals to arrhythmias, heart failure, and sudden cardiac death.