• HG complicates approximately 0.3–3.6% of all pregnancies (varies by population and definition used)
• In Hong Kong, the incidence is broadly in line with East Asian data (~0.3–1.5%)

• NVP affects 50–80% of pregnant women
• Typically begins by 4–7 weeks of gestation, peaks at 9–12 weeks (correlating with the hCG peak), and resolves by 16–20 weeks in most
• Despite the name "morning sickness," symptoms occur at any time of day

• More common in:
  • Younger women
  • Primigravidae (first pregnancy)
  • Women with a prior history of HG (recurrence risk ~15–20%, some studies up to 80%)
  • Non-smokers (paradoxically, smoking is "protective" — likely due to decreased placental mass/hCG levels)
  • Obesity (BMI > 30)
  • Family history of HG (suggesting a genetic component)

• Gestational trophoblastic disease (GTD), particularly hydatidiform mole, is relatively more common in Southeast/East Asian populations. GTD causes massively elevated hCG, which can produce very severe HG — this is a critical DDx in the HK setting.

The vomiting centre is not a discrete nucleus but a functional network in the medulla oblongata. Key structures:

1. Chemoreceptor Trigger Zone (CTZ)

   • Located in the area postrema (floor of the 4th ventricle)
   • This is outside the blood-brain barrier — meaning it can directly sample blood-borne emetic stimuli (hCG, GDF15, oestrogen metabolites, uraemia, drugs)
   • Receives input from circulating emetogens and relays to the vomiting centre

2. Nucleus of the Solitary Tract (NTS)

   • Receives afferent input from vagal nerve (CN X) carrying signals from the GI tract (stretch, inflammation, noxious stimuli)
   • Integrates peripheral and central signals

3. GFRAL (Glial-derived neurotrophic factor Family Receptor Alpha-Like) ^[1]

   • A receptor expressed specifically in the area postrema and NTS
   • The ligand for GFRAL is GDF15 (Growth/Differentiation Factor 15) ^[1]
   • GDF15 binds GFRAL → activates downstream signalling → nausea, vomiting, nutrient deprivation

4. Vomiting centre (medullary reticular formation)

   • Coordinates the motor act of vomiting via vagus (oesophageal relaxation, gastric retroperistalsis), phrenic nerve (diaphragmatic contraction), and spinal nerves (abdominal wall contraction)

5. Higher cortical centres

   • Psychological stimuli (anxiety, anticipatory nausea), olfactory input, visual stimuli — all can trigger vomiting via cortico-medullary connections

In early pregnancy, the trophoblast (and later the placenta) produces:

• hCG — peaks at 10–12 weeks, declines thereafter
• Oestrogen (mainly oestradiol) — rises progressively
• Progesterone — rises progressively; relaxes smooth muscle (including the lower oesophageal sphincter and gastric motility)
• GDF15 — a stress-response cytokine produced by trophoblast; levels rise dramatically in pregnancy ^[1]

This is the most exciting recent discovery and is highlighted on the lecture slides ^[1]:

GDF15 (Growth/Differentiation Factor 15) is a member of the TGF-β superfamily. It is a stress-response cytokine produced by many tissues under stress, but in pregnancy, the trophoblast/placenta is the major source.

• GDF15 binds to GFRAL (Glial-derived neurotrophic factor Family Receptor Alpha-Like), which is expressed almost exclusively in the area postrema and nucleus of the solitary tract ^[1]
• This binding triggers a downstream signalling cascade → nausea, vomiting, anorexia ("nutrient deprivation") ^[1]
• The relationship is summarised on the lecture slide as: "Pregnancy → GDF15 → GFRAL (area postrema and NTS) → Nausea, Vomiting → Nutrient deprivation → Maternal and fetal adverse events" ^[1]

Why do some women get HG while others don't?

• Women with low pre-pregnancy circulating GDF15 levels who then experience a large relative increase in GDF15 during pregnancy appear most susceptible — their brainstem receptors are not "desensitised"
• Genetic variants in the GDF15 gene (on chromosome 19p13) influence baseline GDF15 levels and susceptibility to HG
• This explains the familial clustering and ethnic variation in HG incidence

The temporal correlation between hCG levels and NVP/HG is well established ^[1]:

• hCG peaks at 10–12 weeks — exactly when HG is worst ^[1]
• Conditions with higher hCG levels (multiple pregnancy, GTD) have worse NVP/HG ^[1][3]
• The beta-subunit of hCG shares homology with the beta-subunit of TSH ^[3] → hCG can stimulate the TSH receptor on thyroid follicular cells → gestational thyrotoxicosis (see below)

Mechanism of emetogenesis:

• hCG may directly stimulate the CTZ (area postrema)
• hCG-induced thyroid hormone excess may contribute (thyroid hormones are emetogenic)
• hCG stimulates ovarian production of oestradiol, which is itself emetogenic

This is a critical concept linking hCG to HG:

• Beta-subunit of hCG shares structural homology with beta-subunit of TSH ^[3]
• Physiological rise of hCG (peak at 10–12 weeks of pregnancy) stimulates TSH-R on thyroid follicular cells → increased T4 release, suppressed TSH ^[3]
• Risk factors for gestational thyrotoxicosis: markedly elevated hCG (e.g., twin pregnancy, HG, molar pregnancy) ^[3]
• Biochemically indistinguishable from other causes of thyrotoxicosis (e.g., Graves' disease); distinguished by: past history of thyroid disease, any thyrotoxic symptoms pre-conception, any goitre, autoantibody profile ^[3]
• Closely monitor fT4: expect to decline after 1st trimester ^[3]
• Anti-thyroid drugs are NOT indicated ^[3][1]
• Transient biochemical hyperthyroidism with no clinical features of thyrotoxicosis can occur in early pregnancy, especially in women with HG ^[5]

"In a patient who has no prior history of thyroid disease, no evidence of Graves' disease such as goitre, and a self-limited disorder with symptoms of emesis, routine thyroid tests are not needed. The appropriate management of abnormal maternal thyroid tests attributable to gestational transient thyrotoxicosis, or HG, or both, includes supportive therapy, and antithyroid drugs are not recommended (Level A)" — ACOG Practice Bulletin No. 189 (2018) ^[1]

• Oestrogen levels rise rapidly in early pregnancy
• Oestrogen is known to be emetogenic (think of nausea as a side effect of the combined oral contraceptive pill)
• Acts on the CTZ and slows gastric emptying

• Progesterone causes smooth muscle relaxation → reduces lower oesophageal sphincter (LES) tone and slows gastric motility
• This leads to gastroparesis, gastro-oesophageal reflux, and delayed gastric emptying → worsening nausea
• Also contributes to constipation

• Helicobacter pylori infection has been associated with HG in some studies (serological positivity rates higher in HG vs. controls)
• Mechanism: H. pylori exacerbates gastric inflammation and dysmotility, lowering the threshold for nausea/vomiting on top of the hormonal milieu

• Older theories emphasised a psychogenic aetiology — this is now largely discredited as a primary cause
• However, there is clear bidirectional interaction: HG causes significant psychological distress (depression, anxiety, PTSD), and pre-existing anxiety may lower the vomiting threshold (cortical inputs to vomiting centre)
• Social isolation, poor support, and the under-recognition of HG severity contribute to suffering

• The fetus is a semi-allograft (half of its antigens are paternal)
• Some have proposed that HG represents an exaggerated maternal immune response to fetoplacental antigens
• This remains speculative but may explain the association with nulliparity and female fetus

NVP and HG exist on a continuum:

A validated scoring tool (modified PUQE-24) that quantifies NVP severity over 24 hours:

• Scores nausea (duration in hours), vomiting (number of episodes), retching (number of episodes)
• Mild: ≤ 6, Moderate: 7–12, Severe: ≥ 13
• Useful for monitoring response to treatment

• Early onset (before 9 weeks) — typical for HG
• Late onset (after 9 weeks) — should raise suspicion for alternative diagnoses

Since HG is a diagnosis of exclusion, always classify by whether:

• It is "primary" HG (idiopathic, hormonal-mediated)
• It is "secondary" to an identifiable cause (GTD, multiple pregnancy, hyperthyroidism, UTI, etc.)

• GTD is an important differential diagnosis of threatened miscarriage and of HG ^[1]
• Complete hydatidiform mole produces massively elevated hCG (often > 100,000 mIU/mL)
• In HK, the incidence of GTD is higher than in Western populations (~1 in 500 pregnancies vs. 1 in 1000 in the West)
• Always consider GTD when HG presents with:
  • Very early onset, very severe vomiting
  • Uterus large for dates
  • Extremely high hCG
  • "Snowstorm" appearance on pelvic ultrasound

• Pregnancy is the most common cause of megaloblastosis worldwide. It is more likely in twin pregnancies, multiparity, and hyperemesis gravidarum ^[6]
• HG → poor oral intake + vomiting → folate deficiency → megaloblastic anaemia
• Ensure folic acid supplementation

• Risk of thromboembolism is increased in pregnancy: Virchow's triad is fully present ^[5]
• Viscosity may be increased in hyperemesis ^[5]
• Dehydrated, immobilised, hospitalised pregnant women with HG are at particularly high VTE risk
• Thromboprophylaxis is part of HG management ^[1]

Key teaching point from lecture: "In a patient who has no prior history of thyroid disease, no evidence of Graves' disease such as goitre, and a self-limited disorder with symptoms of emesis, routine thyroid tests are not needed" ^[1]. However, if TFT is done and shows ↑fT4/↓TSH, antithyroid drugs are NOT indicated for gestational thyrotoxicosis ^[3][1].

In Hong Kong, chronic hepatitis B carriage is common (~7% prevalence). An acute flare of chronic HBV or superinfection (e.g., with hepatitis D or E) during pregnancy can present with nausea, vomiting, and jaundice. Hepatitis E in particular is dangerous in pregnancy (fulminant hepatic failure risk up to 20% in 3rd trimester).

UTI is one of the most commonly missed causes of vomiting in pregnancy. Always send a midstream urine in any pregnant woman with unexplained nausea/vomiting. Asymptomatic bacteriuria in pregnancy is itself an indication for treatment (risk of ascending pyelonephritis).

"How is HG diagnosed? Clinical triad" ^[1]:

The teaching notes explicitly emphasise this as "another triad" — "triad for hyperemesis gravidarum (5% prepregnancy weight loss, dehydration based on urine ketones, electrolyte imbalance)" ^[7]

The Windsor consensus definition requires ALL of the following ^[1]:

1. Symptom onset in early pregnancy, before a gestational age of 16 weeks
2. Characterized by severe nausea and/or vomiting
3. Inability to eat and/or drink normally
4. Strongly limits daily activities
5. Signs of dehydration were deemed contributory but not mandatory

Why was the Windsor definition created? Because the RCOG triad is very "hard endpoint" focused (weight, labs) and may miss patients who are functionally severely impaired but haven't yet lost 5% body weight or don't have lab derangements. The Windsor definition captures the patient experience earlier in the disease course.

For your exam OSCE or written answer, a good approach is:

A patient meets diagnostic criteria for HG when:

1. She is pregnant, with symptom onset < 16 weeks gestation
2. She has severe, persistent nausea and/or vomiting that prevents adequate oral intake
3. She has evidence of clinical consequence: weight loss > 5%, dehydration (ketonuria, clinical signs), and/or electrolyte imbalance
4. Other causes of vomiting have been excluded (this is non-negotiable)

This is a validated scoring system used to quantify NVP/HG severity over the preceding 24 hours:

Total score interpretation:

• ≤ 6: Mild NVP
• 7–12: Moderate NVP
• ≥ 13: Severe NVP / HG

This is useful for monitoring treatment response and guiding escalation of therapy, but it is not a diagnostic criterion per se — it is a clinical tool.

Urine dipstick ketones are a simple bedside marker of starvation severity:

Why ketones? When caloric intake is insufficient, the body switches from glucose-based metabolism to fat-based metabolism. Lipolysis releases free fatty acids → hepatic beta-oxidation → ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone). These spill into the urine. Ketonuria is therefore a direct marker of "your body is starving."

"hCG NOT useful" ^[1]

Why is hCG not useful?

• hCG levels are highly variable between individuals and across gestational ages
• A "high" hCG in one woman might be normal for her pregnancy stage
• There is no hCG threshold that distinguishes HG from normal NVP
• The one exception: if hCG is extremely elevated ( > 100,000 mIU/mL), this raises suspicion for GTD — but you would diagnose GTD by USS, not by hCG alone
• Therefore, do not order hCG to "diagnose" HG — it adds cost without diagnostic value

The lecture slide puts thyroid function in parentheses: "CBP, RFT, LFT, (thyroid function)" ^[1] — the parentheses suggest it is not universally required but ordered when clinically indicated.

When should you order TFT?

• When the patient has clinical features of thyrotoxicosis (tremor, resting tachycardia disproportionate to dehydration, lid lag, weight loss beyond what vomiting explains)
• When you need to distinguish gestational thyrotoxicosis from Graves' disease
• When vomiting persists beyond 16 weeks (gestational thyrotoxicosis should have resolved by then)

When can you omit TFT?

• "In a patient who has no prior history of thyroid disease, no evidence of Graves' disease such as goitre, and a self-limited disorder with symptoms of emesis, routine thyroid tests are not needed" ^[1]

The typical HG TFT pattern:

• TSH: suppressed (often < 0.1 mU/L) — because hCG is stimulating the TSH-R, the pituitary appropriately reduces TSH output (negative feedback)
• fT4: mildly elevated (usually < 1.5× ULN)
• This resolves spontaneously as hCG declines after the 1st trimester — if it doesn't, reconsider Graves' ^[3]

Up to 50% of women with HG have mildly elevated transaminases (ALT/AST up to ~200 U/L). Mechanisms:

• Hepatic ischaemia from dehydration/hypovolaemia → reduced hepatic perfusion
• Starvation-related hepatocyte stress → "starvation hepatitis"
• Thiamine deficiency can cause hepatic dysfunction

This is self-limiting and resolves with rehydration and nutritional support. Do not reflexively investigate for hepatitis unless transaminases are markedly elevated ( > 300) or there are other features (jaundice, fever, risk factors).

A dehydrated HG patient may have:

• ↑ Hb and ↑ Hct — this is haemoconcentration, not true polycythaemia. After rehydration, expect these to normalise (or even reveal underlying anaemia)
• ↑ MCV — if present, think folate deficiency. Pregnancy is the most common cause of megaloblastosis worldwide, and it is more likely in twin pregnancies, multiparity, and hyperemesis gravidarum ^[6]

When a patient has been starving for > 5 days (common in severe HG), check baseline phosphate, magnesium, potassium, and thiamine before refeeding. Why?

During starvation, intracellular stores of phosphate, K⁺, and Mg²⁺ are depleted. When you refeed (especially with carbohydrates), insulin surges drive these ions back into cells → precipitous falls in serum levels → cardiac arrhythmias, respiratory failure, rhabdomyolysis, seizures. This is refeeding syndrome.

→ Always correct electrolytes and give thiamine BEFORE restarting significant caloric intake.

• Bolus: if haemodynamically compromised (tachycardia > 100, systolic BP < 90), give 500 mL–1 L NS over 1–2 hours
• Maintenance: typically 125–150 mL/h of NS or Hartmann's, adjusted to clinical response (urine output, heart rate, postural BP)
• Target urine output: > 0.5 mL/kg/h (a reliable bedside marker of adequate renal perfusion)

Thiamine (vitamin B1) is the most critical micronutrient to replace in HG. The body stores only ~30 mg of thiamine, and the daily requirement is ~1.5 mg. In a patient who has been vomiting and unable to eat for > 2 weeks, stores can be completely depleted.

The consequences of thiamine deficiency are devastating and irreversible if not caught early:

• Wernicke's encephalopathy: ophthalmoplegia, ataxia, confusion (acute, reversible if treated immediately)
• Korsakoff syndrome: anterograde amnesia + confabulation (chronic, largely irreversible)
• Peripheral neuropathy: distal sensorimotor polyneuropathy

Pabrinex = a UK/HK-used combination of B vitamins (B1, B2, B3, B6) + vitamin C. Each pair of ampoules contains 250 mg thiamine.

Why do antihistamines work as antiemetics? H₁ receptors are expressed in the vomiting centre (medullary reticular formation), the NTS, and the vestibular nuclei. Blocking them reduces the excitatory input to the vomiting reflex arc. The anticholinergic properties of some H₁ blockers add further suppression by blocking muscarinic receptors on the same pathways.

Why do dopamine antagonists work? The CTZ (area postrema) is rich in D₂ receptors. Circulating emetogens (metabolites, drugs, hormones) activate these D₂ receptors → signal to vomiting centre. Blocking D₂ in the CTZ interrupts this pathway.

• Dose: 10–25 mg TDS (oral)
• Mechanism: not fully understood, but B6 is a cofactor for amino acid metabolism and neurotransmitter synthesis; deficiency may contribute to nausea
• Evidence: reduces nausea more than vomiting; most effective in mild-moderate NVP
• Safety: safe in pregnancy
• Key use: the doxylamine + pyridoxine combination is ACOG first-line for NVP/mild HG

As discussed in the pathophysiology section: HG patients fulfil all three components of Virchow's triad:

• Stasis: immobility from severe illness + hospitalisation + gravid uterus compressing IVC
• Hypercoagulability: pregnancy is a physiological prothrombotic state (↑ factors VII, VIII, X, fibrinogen; ↓ protein S)
• Endothelial injury/dehydration: viscosity may be increased in hyperemesis ^[5] → haemoconcentration from dehydration

LMWH is safe in pregnancy — it does not cross the placenta (large molecular weight) and is the anticoagulant of choice in pregnancy. Warfarin is teratogenic (crosses placenta) and is contraindicated.

"There is little published evidence regarding the efficacy of dietary changes for prevention or treatment of nausea and vomiting of pregnancy" (ACOG Practice Bulletin 189) ^[1]

"Eat whatever pregnancy-safe food appeals to them and lifestyle changes should be liberally encouraged" (SOGC 2016) ^[1]

So the evidence is limited, but these are consensus-based recommendations that make physiological sense and are low risk.

• Route: Nasogastric (NG) or nasojejunal (NJ) tube
• When: Patient cannot tolerate oral intake but has a functional GI tract distal to the site of pathology
• NJ feeding is preferred over NG in HG because:
  • Bypasses the stomach (where the vomiting reflex originates)
  • Post-pyloric feeding is less likely to trigger vomiting
  • Continuous pump feeding is better tolerated than bolus ^[10]
• Formula: polymeric feeds (e.g., Ensure) at 1 kcal/mL; start at a low rate (20–30 mL/h) and increase gradually ^[10]
• Always a first choice if the GI tract can be used safely ^[10]

• When: GI tract truly cannot be used (persistent vomiting despite NJ tube, or contraindication to enteral feeding)
• Route: central venous catheter (PICC line preferred in pregnancy — avoids repeated cannulation and thrombophlebitis) ^[10]
• Formulation: dextrose + lipid emulsion + amino acids + electrolytes + trace elements + vitamins ^[10]
• Complications: line sepsis, thrombosis, metabolic complications (hyperglycaemia, refeeding syndrome, liver dysfunction)
• Note: TPN is a last resort — it carries significant risks and should be managed jointly with a dietitian and nutrition team

What is it? A longitudinal mucosal tear at the gastro-oesophageal junction (GEJ) or the gastric cardia, caused by forceful retching or vomiting.

• "Mallory-Weiss" — named after the two pathologists who first described it (Kenneth Mallory and Soma Weiss, 1929)

Why does it happen in HG?

• Repeated, forceful retching generates a sudden, dramatic rise in intra-abdominal pressure and intragastric pressure
• The GEJ is a transition point between squamous oesophageal epithelium and columnar gastric epithelium — this junction is mechanically vulnerable
• The sudden pressure differential between the high-pressure stomach and the lower-pressure thoracic oesophagus tears the mucosa at this point

Clinical features:

• Haematemesis — typically bright red blood or "coffee-ground" vomitus after a particularly forceful retching episode
• Can range from streaks of blood in vomitus (minor) to significant upper GI bleeding (rare but serious)
• Usually self-limiting — ~90% of Mallory-Weiss tears stop bleeding spontaneously

Management:

• Minor: observation, IV PPI (e.g., pantoprazole 40 mg IV) to reduce gastric acid exposure to the tear, continue antiemetics to prevent further vomiting
• Significant bleeding: urgent OGD (oesophagogastroduodenoscopy) with endoscopic haemostasis (injection, clips, or thermocoagulation)
• Massive bleeding (very rare): angiographic embolisation or surgery

What is it? Mendelson syndrome = aspiration chemical pneumonitis ^[7] — an acute chemical injury to the lungs caused by aspiration of acidic gastric contents into the tracheobronchial tree.

• Named after Curtis Mendelson (1946), who described it in obstetric patients undergoing general anaesthesia

Why does it happen in HG?

• Repeated vomiting increases the risk of aspiration — especially if:
  • The patient is drowsy (sedating antiemetics, Wernicke's encephalopathy, severe electrolyte disturbance)
  • The lower oesophageal sphincter is relaxed (progesterone effect)
  • Vomiting occurs in the supine position
• Gastric acid (pH < 2.5) is highly caustic to pulmonary epithelium → chemical burn → acute inflammatory response

Pathophysiology of aspiration pneumonitis:

1. Acidic gastric contents contact alveolar epithelium
2. Direct chemical injury → destruction of surfactant, disruption of alveolar-capillary membrane
3. Massive inflammatory response → neutrophil infiltration → increased alveolar permeability
4. Non-cardiogenic pulmonary oedema → impaired gas exchange → hypoxaemia
5. If large volume: mechanical obstruction of airways by particulate matter

Clinical features:

• Acute onset dyspnoea, cough, wheeze, tachypnoea within hours of aspiration
• Hypoxaemia (SpO₂ drop)
• CXR: bilateral infiltrates, especially in dependent lung segments (right lower lobe most common — the right main bronchus is wider, shorter, and more vertical)
• Can progress to ARDS (acute respiratory distress syndrome) in severe cases
• Important distinction: aspiration pneumonitis (chemical, sterile initially) vs. aspiration pneumonia (bacterial infection superimposed, typically 24–72 hours later with fever, purulent sputum)

Prevention (this is the key!):

• Effective antiemetic therapy to reduce vomiting episodes
• Keep head of bed elevated at 30° during sleep
• Avoid sedating medications that suppress airway reflexes (or use with caution)
• If any procedure requiring sedation/anaesthesia is needed, treat as "full stomach" precautions (RSI — rapid sequence induction)

Management:

• Supportive: supplemental O₂, suction, bronchoscopy if particulate matter
• Respiratory support: CPAP or mechanical ventilation if progressing to ARDS
• Antibiotics: NOT routinely indicated for aspiration pneumonitis (sterile chemical injury); only if secondary bacterial pneumonia develops (fever, leucocytosis, purulent sputum after 48–72 hours)
• Steroids: no evidence of benefit; not recommended

This is the most feared neurological complication of HG and is entirely preventable.

What is it? An acute neuropsychiatric emergency caused by thiamine (vitamin B1) deficiency, characterised by the classic triad:

1. Ophthalmoplegia (paralysis of eye movements — especially lateral rectus, CN VI)
2. Ataxia (cerebellar gait ataxia — wide-based, unsteady)
3. Confusion (global confusional state, apathy, disorientation)

The full triad is present in only ~16% of cases. A high index of suspicion is essential — any one component in an at-risk patient should prompt treatment.

Why does it happen in HG?

• Thiamine (B1) is a critical co-factor for: ^[4]
  • Pyruvate dehydrogenase → links glycolysis to the TCA cycle
  • α-ketoglutarate dehydrogenase → key step in the TCA cycle
  • Transketolase → pentose phosphate pathway (DNA synthesis)
• Body stores of thiamine are small (~30 mg) and daily requirement is ~1.5 mg
• In HG: poor oral intake + persistent vomiting → thiamine stores depleted within 2–3 weeks
• Consequences: neuronal injury by decreased metabolism in brain regions with high energy requirements ^[4]
• Neuropathology: periventricular petechial haemorrhage — most classically affecting the mamillary bodies, medial thalamus, periaqueductal grey matter, and floor of the 4th ventricle ^[4]

Why these specific brain regions? These periventricular structures have exceptionally high metabolic rates and are exquisitely sensitive to energy failure. When thiamine is absent, the TCA cycle stalls → ATP depletion → failure of Na⁺/K⁺-ATPase → cellular swelling → cytotoxic oedema → petechial haemorrhages from capillary injury.

Hyperemesis gravidarum is explicitly listed as a cause of Wernicke-Korsakoff syndrome alongside chronic alcoholism, GI surgery, systemic malignancy, prolonged TPN, refeeding, anorexia nervosa, and dieting or starvation ^[4]

Management:

• IV thiamine immediately — do NOT wait for blood results
• Prophylactic: 100 mg IV daily in all admitted HG patients
• Treatment of suspected Wernicke's: high-dose IV Pabrinex (250 mg thiamine per pair of ampoules) 2–3 pairs TDS for 3–5 days
• NEVER give IV glucose/dextrose before thiamine — glucose loading drives glycolysis → pyruvate accumulates → cannot enter TCA cycle without B1 → worsens the energy crisis → precipitates or exacerbates Wernicke's

Prognosis:

• If treated promptly: ophthalmoplegia resolves within hours-days, confusion over days-weeks, ataxia may partially persist
• If untreated or delayed: progresses to Korsakoff syndrome (irreversible)

What is it? The chronic sequel of untreated Wernicke's encephalopathy — an amnestic syndrome characterised by:

• Anterograde amnesia: invariably impaired, information learned is forgotten a few minutes later ^[4]
• Retrograde amnesia: striking loss of autobiographical information and disorientation for time ^[4]
• Confabulation and lack of insight (the patient fills memory gaps with fabricated stories, without awareness) ^[4]
• Integrity of other cognitive functions, especially registration/working memory (normal digit span) ^[4]

Pathology: bilateral mamillary body atrophy and medial thalamic damage (neuronal loss, gliosis)

Prognosis: largely irreversible. Only ~20% show meaningful recovery. This is why prevention with prophylactic thiamine in HG is so critical.

What is it? Distal, symmetrical, sensorimotor polyneuropathy (glove-and-stocking distribution).

Why does it happen? Multiple vitamin deficiencies from prolonged malnutrition:

• Thiamine (B1) deficiency → axonal degeneration of peripheral nerves (similar to "dry beriberi")
• Pyridoxine (B6) deficiency → demyelination
• Cobalamin (B12) deficiency → subacute combined degeneration (posterior columns + corticospinal tracts)

Clinical features:

• Numbness, tingling, burning pain in feet > hands
• Distal weakness (foot drop in severe cases)
• Reduced ankle reflexes
• Teaching notes: "will require thiamine, B12 replacement" ^[7]

What is it? Demyelination of the central pons (and sometimes extrapontine structures) caused by over-rapid correction of hyponatraemia.

Why is it relevant to HG?

• HG causes hyponatraemia (ADH-mediated dilutional hyponatraemia + Na⁺ losses from vomiting)
• Overzealous correction with hypertonic saline or rapid NS infusion can raise serum Na⁺ too quickly
• Safe correction rate: ≤ 8–10 mmol/L per 24 hours

Clinical features (typically 2–6 days after correction):

• Quadriparesis, dysphagia, dysarthria
• "Locked-in syndrome" in severe cases
• MRI: characteristic pontine demyelination

Prevention: monitor Na⁺ closely; correct slowly; use hypotonic fluids if Na⁺ rising too fast; consider DDAVP to slow correction if overshooting.

Why? Vomiting → HCl loss → metabolic alkalosis → renal K⁺ wasting + RAAS activation → aldosterone-driven K⁺ excretion. Severe K⁺ < 2.5 mmol/L.

Cardiac consequences:

• Hypokalaemia → hyperpolarisation of myocardial cells → delayed repolarisation → prolonged QT interval → risk of Torsades de Pointes (polymorphic ventricular tachycardia) → cardiac arrest
• ECG changes: flattened T waves → ST depression → prominent U waves → widened QRS (progressive with worsening hypoK)

Management: IV KCl replacement with cardiac monitoring if K⁺ < 2.5 mmol/L; always check and correct Mg²⁺ first (hypoMg causes refractory hypoK).

Why? Loss of gastric HCl → H⁺ depletion → alkalosis; volume contraction → "contraction alkalosis" (enhanced proximal HCO₃⁻ reabsorption).

Consequences: leftward shift of the oxygen-haemoglobin dissociation curve (Bohr effect) → haemoglobin binds O₂ more tightly → reduced O₂ delivery to tissues. Also worsens hypokalaemia and hypocalcaemia (ionised Ca²⁺ binds to albumin more avidly at alkaline pH → functional hypocalcaemia → tetany, paraesthesiae).

Why? Severe dehydration → decreased renal perfusion → pre-renal AKI.

Lab pattern: ↑ urea disproportionate to creatinine (urea:creatinine ratio > 100:1), low fractional excretion of Na⁺ ( < 1%), concentrated urine (SG > 1.030).

Management: IV fluid resuscitation — most pre-renal AKI in HG reverses promptly with adequate rehydration.

Why? After prolonged starvation ( > 5 days), intracellular stores of phosphate, K⁺, and Mg²⁺ are depleted. When carbohydrate intake resumes, insulin release drives these ions into cells → precipitous drops in serum levels.

Consequences:

• Hypophosphataemia (most dangerous) → impaired ATP production → cardiac failure, respiratory failure, rhabdomyolysis
• Hypokalaemia → cardiac arrhythmias
• Hypomagnesaemia → seizures, arrhythmias
• Fluid shifts → acute heart failure from fluid overload

Prevention: check and correct electrolytes + give thiamine BEFORE refeeding; start calories at 50–75% of needs; increase over 3–5 days; monitor electrolytes daily for the first week.