Electrolytes — Sodium

101. Hyponatremia

low serum Na · the algorithm: osmolality → volume status → urine Na/osm · SIADH / hypovolemia / HF / cirrhosis / drugs · correct SLOWLY (ODS risk) · Super Compact

Sx: depends on severity + acuity — mild (Na 125–134): nausea, headache, malaise · moderate (115–125): confusion, lethargy, gait instability/falls · severe (<115 or acute): seizures, obtundation, coma, respiratory arrest (cerebral edema) (acute drops are far more dangerous than chronic at the same Na — the brain hasn't adapted)

Neg: denies hyperglycemia/mannitol (translocational — correct Na up ~2.4 per 100 glucose >100) · denies hyperlipidemia/paraproteinemia (pseudohyponatremia — normal measured osm) · denies acute/symptomatic status needing hypertonic (assess) · denies adrenal/thyroid cause unchecked (cortisol, TSH)

SHx: diuretics (esp thiazides) · medications (SSRIs, carbamazepine, etc.) · CHF/cirrhosis/CKD · low solute intake (beer potomania, "tea & toast") · psychiatric polydipsia · recent surgery/desmopressin · malignancy/lung/CNS disease (SIADH)

Etiology / framework: almost always impaired free-water excretion · hypovolemic (renal loss — diuretics, salt-wasting, adrenal insufficiency; or extrarenal — GI/third-space) · euvolemic (SIADH — malignancy/CNS/pulmonary/drugs; hypothyroid; glucocorticoid deficiency; low solute) · hypervolemic (heart failure, cirrhosis, nephrotic/CKD — ↓effective arterial volume → ADH on) · medication-induced (thiazides, SSRIs, carbamazepine, desmopressin)

RF: older age · thiazide/SSRI use · HF/cirrhosis/CKD · malignancy/CNS/pulmonary disease · low oral solute intake · post-op

Data — the stepwise workup: 1) serum osmolality (low = true hypotonic hyponatremia; normal = pseudo; high = hyperglycemia/mannitol) · 2) volume status (exam — JVP, edema, mucous membranes, orthostatics) · 3) urine osmolality (<100 = appropriate ADH suppression — primary polydipsia/low solute; >100 = ADH acting) · 4) urine sodium (<20–30 = hypovolemia/HF/cirrhosis — avid retention; >30 = SIADH/diuretic/salt-wasting/adrenal) · TSH, AM cortisol (exclude hypothyroid/adrenal) · BMP, glucose, uric acid (low in SIADH) · meds review

DDx: SIADH (euvolemic, U-osm>100, U-Na>30, low uric acid, normal TSH/cortisol) · hypovolemic (U-Na<20 extrarenal; responds to saline) · HF/cirrhosis (edema/ascites, U-Na<20) · pseudohyponatremia (normal osm) · hyperglycemic (high osm)

Home Meds: review/hold thiazides, SSRIs, carbamazepine, desmopressin, other ADH-promoting drugs · adjust diuretics per volume state · avoid hypotonic fluids

Plan

CONSULT: Nephrology (severe/refractory/unclear, SIADH management, correction concerns) · Endocrine (adrenal/thyroid cause) · ICU (severe symptomatic — seizures/coma needing hypertonic)

– FIRST triage by symptoms/acuity: severe symptoms (seizures, coma, severe confusion) or known acute (<48h) drop → hypertonic saline emergently: 3% NaCl 100–150 mL IV bolus over 10 min, may repeat ×1–2 to a target rise of ~4–6 mEq/L to stop symptoms (do NOT exceed the daily limit below); ICU/close monitoring
– RESPECT the correction-rate limit (ODS prevention): in chronic/uncertain-duration hyponatremia, limit rise to ≤8 mEq/L per 24h (more cautious ≤6 in high-risk: alcohol, malnutrition, hypokalemia, liver disease, Na<105); recheck Na q2–4h during active correction; overcorrection → re-lower with D5W ± desmopressin
– Then treat by category (after the acute triage):
  • Hypovolemic: isotonic saline (0.9% NaCl) to restore volume → turns off ADH → free water excretion (watch for autocorrection/overshoot once volume restored — be ready with D5W ± desmopressin)
  • SIADH (euvolemic): fluid restriction (often <800–1000 mL/day) first-line; treat the underlying cause (drug, malignancy, CNS); add oral salt tabs ± loop diuretic or urea if restriction insufficient; vaptans (tolvaptan) selectively per nephrology (caution: overcorrection, hepatotoxicity)
  • Hypervolemic (HF/cirrhosis): fluid + sodium restriction + loop diuretic (furosemide); treat underlying HF/cirrhosis; manage effective arterial volume; vaptans selectively
  • Medication-induced: stop the offending drug (thiazide, SSRI, etc.); supportive per resulting volume state
  • Low solute (beer potomania/tea & toast): restore solute/protein intake — corrects rapidly, high overcorrection risk → monitor closely
– Replete K if hypokalemic — giving K raises serum Na too (counts toward the correction limit)
– The single most dangerous error is overcorrection. In a chronic, asymptomatic hyponatremia, slow is safe and fast is dangerous — osmotic demyelination is iatrogenic and irreversible, so cap the rise, recheck often, and don't hesitate to give D5W/desmopressin to re-lower if you overshoot.
– PT/OT: fall precautions (gait instability); mobilize as safe
– Trend: serial Na q2–4h during active correction (then space out), volume status, urine output (a brisk water diuresis warns of impending overcorrection), K, mental status/symptoms
– Escalation triggers: seizures/coma → ICU + hypertonic saline; overcorrection (rise too fast) → D5W ± desmopressin to re-lower; refractory SIADH → nephrology (urea/vaptan); failure to identify cause → broaden workup (CNS/chest imaging, endocrine)
– Discharge checklist: cause identified + addressed; offending drugs stopped/substituted; Na stable + trending to baseline; fluid-restriction or solute plan documented (SIADH); diuretic/HF/cirrhosis optimization; outpatient Na recheck + nephrology/endocrine follow-up; return precautions (confusion, seizures, severe headache, falls)

101. Hyponatremia

complete reference · SIADH + hypovolemia + heart failure + cirrhosis + medication-induced · osmolality/volume/urine algorithm · ODS-safe correction · Full Card

Symptoms / Associated Sx

• Severity and acuity determine symptoms: mild (Na 125–134) causes nausea, headache, and malaise

• Moderate (115–125) causes confusion, lethargy, and gait instability with falls

• Severe (<115 or acute) causes seizures, obtundation, coma, and respiratory arrest from cerebral edema

• An acute drop is far more dangerous than a chronic one at the same sodium, because the brain has not had time to adapt by extruding osmoles

Neg

• Pt denies hyperglycemia or mannitol use — translocational hyponatremia, where the measured sodium should be corrected upward by ~2.4 mEq/L for each 100 mg/dL of glucose above 100

• Pt denies severe hyperlipidemia or paraproteinemia — pseudohyponatremia, in which the measured serum osmolality is normal

• Pt denies a severely symptomatic or acute presentation requiring immediate hypertonic saline; and denies an unexamined adrenal or thyroid cause (check cortisol and TSH)

Social History (SHx)

• Diuretics, especially thiazides

• Medications such as SSRIs and carbamazepine; recent desmopressin or surgery

• Heart failure, cirrhosis, or CKD

• Low solute intake (beer potomania, a "tea and toast" diet) and psychiatric polydipsia; malignancy or pulmonary/CNS disease (SIADH)

Main Etiology

• Nearly always reflects impaired renal free-water excretion (excess ADH activity), categorized by volume status

• Hypovolemic: renal losses (diuretics, salt-wasting, adrenal insufficiency) or extrarenal losses (GI, third-spacing) — volume depletion stimulates ADH

• Euvolemic: SIADH (from malignancy, CNS or pulmonary disease, or drugs), hypothyroidism, glucocorticoid deficiency, and low solute intake

• Hypervolemic: heart failure, cirrhosis, and nephrotic syndrome/CKD — a reduced effective arterial blood volume drives ADH despite total-body fluid excess

• Medication-induced: thiazides, SSRIs, carbamazepine, and desmopressin

RF

• Modifiable: thiazide/SSRI use, fluid and solute intake patterns, management of HF/cirrhosis

• Non-modifiable: older age, malignancy, and CNS/pulmonary disease

Data — the stepwise workup

• 1) Serum osmolality (low confirms true hypotonic hyponatremia; normal indicates pseudohyponatremia; high indicates a translocational cause such as hyperglycemia or mannitol)

• 2) Volume status (clinical exam — JVP, edema, mucous membranes, skin turgor, and orthostatic vital signs)

• 3) Urine osmolality (<100 mOsm/kg indicates appropriately suppressed ADH — primary polydipsia or low solute intake; >100 indicates ADH is acting)

• 4) Urine sodium (<20–30 mEq/L indicates avid sodium retention — hypovolemia, heart failure, or cirrhosis; >30 suggests SIADH, a diuretic effect, salt-wasting, or adrenal insufficiency)

• TSH and AM cortisol (exclude hypothyroidism and adrenal insufficiency)

• BMP, glucose, and uric acid (uric acid is characteristically low in SIADH)

• Medication review (identify ADH-promoting drugs)

DDx

SIADH (euvolemic, urine osmolality >100, urine sodium >30, low uric acid, normal TSH/cortisol) · hypovolemic hyponatremia (urine sodium <20 if extrarenal; corrects with saline) · heart failure or cirrhosis (edema/ascites, urine sodium <20) · pseudohyponatremia (normal serum osmolality) · hyperglycemic (translocational) hyponatremia (high serum osmolality)

Home Meds

• Review/hold: thiazides, SSRIs, carbamazepine, desmopressin, and other ADH-promoting drugs

• Adjust: diuretics according to the volume state

• Avoid: hypotonic IV fluids

Plan

CONSULT: Nephrology (severe, refractory, or unclear cases; SIADH management; correction concerns) · Endocrinology (adrenal or thyroid cause) · ICU (severe symptoms — seizures or coma requiring hypertonic saline)

• Triage first by symptoms and acuity: for severe symptoms (seizures, coma, severe confusion) or a known acute (<48h) drop, give hypertonic saline emergently — 3% NaCl 100–150 mL IV over 10 minutes, repeated once or twice as needed to achieve a rise of about 4–6 mEq/L to stop symptoms, without exceeding the daily limit below — with ICU-level monitoring

• Respect the correction-rate limit to prevent osmotic demyelination syndrome: in chronic or uncertain-duration hyponatremia, limit the rise to ≤8 mEq/L per 24 hours (and more conservatively ≤6 in high-risk patients — alcohol use, malnutrition, hypokalemia, advanced liver disease, or sodium <105); recheck the sodium every 2–4 hours during active correction; and re-lower an overcorrection with D5W with or without desmopressin

• Then treat by category once the acute issue is addressed:

• • Hypovolemic: isotonic saline (0.9% NaCl) restores volume and switches off ADH, allowing free-water excretion — watch for autocorrection and overshoot once volume is restored, and be prepared with D5W and desmopressin

• • SIADH (euvolemic): fluid restriction (often <800–1000 mL/day) is first-line, alongside treating the underlying cause; add oral salt tablets with a loop diuretic, or urea, if restriction is insufficient; reserve vaptans (tolvaptan) for selected cases per nephrology, with caution for overcorrection and hepatotoxicity

• • Hypervolemic (heart failure, cirrhosis): fluid and sodium restriction with a loop diuretic (furosemide), treatment of the underlying disease, and optimization of effective arterial volume; vaptans selectively

• • Medication-induced: stop the offending drug (thiazide, SSRI) and provide supportive care according to the resulting volume state

• • Low solute (beer potomania, tea-and-toast): restore solute and protein intake; this corrects rapidly and carries a high overcorrection risk, so monitor closely

• Replete potassium if hypokalemic — administered potassium also raises the serum sodium and counts toward the correction limit

• PT/OT: fall precautions for gait instability; mobilize as safe

• Trend: serial sodium every 2–4 hours during active correction (spacing out once stable), volume status, urine output (a brisk water diuresis warns of impending overcorrection), potassium, and mental status

• Escalation triggers: seizures or coma → ICU and hypertonic saline; an overly rapid rise → D5W with desmopressin to re-lower; refractory SIADH → nephrology for urea or a vaptan; failure to identify the cause → broaden the workup (CNS and chest imaging, endocrine testing)

• Discharge checklist: the cause identified and addressed; offending drugs stopped or substituted; a stable sodium trending toward baseline; a documented fluid-restriction or solute plan for SIADH; optimization of diuretics and HF/cirrhosis therapy; an outpatient sodium recheck with nephrology/endocrine follow-up; return precautions for confusion, seizures, severe headache, or falls

Red Flags

• Seizures, coma, or obtundation, or a known acute drop → cerebral edema → emergent hypertonic saline and ICU care

• Overcorrection (sodium rising faster than the limit) → osmotic demyelination risk → re-lower with D5W and desmopressin

• High-risk patient for ODS (alcohol, malnutrition, hypokalemia, liver disease, Na <105) → use the most conservative correction targets

• Sudden brisk water diuresis during treatment → impending overcorrection → intervene early

• Hyponatremia with hypotension and hyperkalemia → consider adrenal insufficiency

Senior IM Resident Pearls

• Run the algorithm in order: osmolality → volume status → urine osmolality → urine sodium. Skipping steps is how SIADH gets treated with saline (which can worsen it) and hypovolemia gets fluid-restricted.

• Overcorrection is the iatrogenic catastrophe. In chronic hyponatremia, cap the 24-hour rise, recheck the sodium often, and treat an overshoot promptly with D5W and desmopressin — osmotic demyelination is preventable and irreversible.

• Saline can paradoxically worsen SIADH. If the urine osmolality exceeds the infusate osmolality, the kidney retains the water and excretes the salt — fluid restriction, not saline, is the treatment.

• A low uric acid quietly points to SIADH, while a high one fits a volume-depleted state — a cheap discriminator people overlook.

• Watch for autocorrection in hypovolemia. Once you restore volume, ADH switches off and a water diuresis can overshoot the target — anticipate it rather than react late.

• Always check cortisol and TSH in euvolemic hyponatremia before labeling it SIADH — adrenal insufficiency and hypothyroidism are reversible mimics.

• Common mistake: giving hypotonic maintenance fluids to a hyponatremic inpatient — it deepens the problem; match the fluid to the diagnosis and the volume state.

Electrolytes — Potassium

102. Hyperkalemia

high serum K · the ECG + the cocktail · AKI / CKD-ESRD / ACEi-ARB / K-sparing diuretics · stabilize → shift → remove · exclude pseudohyperkalemia · Super Compact

Sx: often asymptomatic until dangerous · weakness, fatigue, paresthesias, palpitations · the real danger is cardiac: arrhythmia, bradycardia, cardiac arrest (symptoms are a poor guide — the ECG and the absolute K drive urgency; a "normal feeling" patient can arrest)

Neg: denies hemolyzed/difficult draw, marked thrombocytosis/leukocytosis, fist-clenching (pseudohyperkalemia — repeat sample, confirm before treating) · denies missed AKI/obstruction · denies adrenal insufficiency (hypoNa + hyperK + hypotension) · denies massive cell lysis (rhabdo/TLS)

SHx: CKD/ESRD + dialysis status/missed sessions · ACEi/ARB, MRA (spironolactone/eplerenone), K-sparing diuretics, TMP-SMX, NSAIDs · K supplements/salt substitutes · diabetes (type 4 RTA) · tissue breakdown (crush, tumor lysis)

Etiology: impaired excretion and/or transcellular shift · impaired renal excretion (AKI, CKD/ESRD, hypoaldosteronism/type 4 RTA) · drugs reducing excretion (ACEi/ARB, MRA, K-sparing diuretics, TMP, calcineurin inhibitors, NSAIDs) · transcellular shift (acidosis, insulin deficiency/hyperglycemia, beta-blockers, cell lysis — rhabdomyolysis, tumor lysis, hemolysis) · increased intake (usually only with impaired excretion)

RF: CKD/ESRD · RAAS-inhibitor + MRA combinations · diabetes · metabolic acidosis · tissue breakdown states · K supplements/salt substitutes

Data: ECG FIRST (the urgency driver) (peaked T waves → PR prolongation/flattened P → widened QRS → sine wave → arrest; ECG changes = emergency regardless of number) · repeat/confirm K (exclude pseudohyperkalemia — hemolysis, plt/WBC, draw technique) · BMP (renal function, bicarbonate) · glucose · CK (rhabdo) · uric acid/phosphate/Ca (tumor lysis) · consider digoxin level, aldosterone/renin (type 4), VBG (acidosis)

DDx: true vs pseudohyperkalemia (repeat sample, plasma vs serum) · impaired excretion vs shift vs lysis (renal fxn, CK, glucose, acid-base) · drug-induced (med review) · adrenal insufficiency (hypoNa, hypotension)

Home Meds: STOP/hold ACEi/ARB, MRA, K-sparing diuretics, TMP-SMX, NSAIDs, K supplements, salt substitutes · review/adjust beta-blockers (shift) · renally dose

Plan

CONSULT: Nephrology (dialysis need, ESRD, refractory) · ICU (ECG changes/instability) · Cardiology (arrhythmia)

– STEP 1 — STABILIZE the myocardium (if ECG changes OR K markedly elevated): calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 min (or calcium chloride via central line) — onset minutes, lasts ~30–60 min, repeat if ECG changes persist; does NOT lower K — buys time (use cautiously in digoxin toxicity)
– STEP 2 — SHIFT K intracellularly (rapid, temporary):
  • Insulin 10 units regular IV + dextrose (D50 25 g IV) — onset ~15 min, lasts hours; recheck glucose (delayed hypoglycemia, esp ESRD/low weight — consider 5 units or extra dextrose)
  • Albuterol 10–20 mg nebulized (high dose — 4–8× the asthma dose) — additive shift
  • Sodium bicarbonate only if significant metabolic acidosis (not a reliable acute lowering agent alone)
– STEP 3 — REMOVE K from the body (definitive):
  • Loop diuretic (furosemide IV) if making urine + ensure volume
  • GI cation binder: patiromer or sodium zirconium cyclosilicate (SZC/Lokelma) (preferred for onset/tolerability over old SPS/Kayexalate, which has colonic-necrosis risk — avoid in ileus/post-op bowel)
  • Hemodialysis — definitive for refractory/severe hyperK, ESRD/anuric, or ongoing release (rhabdo/TLS); arrange urgently
– STEP 4 — stop the source + treat the cause: stop all K-raising drugs and supplements/salt substitutes; treat AKI/relieve obstruction, treat acidosis, treat cell-lysis cause (rhabdo hydration, tumor lysis management), dialyze if ESRD/refractory
– Continuous cardiac monitoring throughout for any significant hyperkalemia
– The classic teaching: "stabilize, shift, remove." Calcium protects the heart but doesn't lower the K; insulin/albuterol shift it temporarily; only diuresis, binders, or dialysis actually remove it — so a patient "treated" with calcium and insulin still needs a removal plan or the K rebounds.
– PT/OT: as tolerated
– Trend: serial K + ECG, glucose (post-insulin, repeatedly), renal function/UOP, source markers (CK, etc.), response to therapy
– Escalation triggers: ECG changes/arrhythmia → emergent calcium + cocktail + cardiac monitoring + dialysis; refractory or anuric/ESRD → urgent hemodialysis; ongoing lysis → treat cause + dialysis; recurrent rebound → reassess removal adequacy
– Discharge checklist: K normalized + stable off offending drugs (RAAS/MRA reconciled — restart cautiously with monitoring if indicated); cause addressed (renal, drug, lysis); dietary K counseling + avoid salt substitutes; binder prescription if needed; outpatient K recheck + nephrology follow-up; return precautions (weakness, palpitations, fainting)

102. Hyperkalemia

complete reference · AKI + CKD/ESRD + ACEi/ARB + K-sparing diuretics · stabilize–shift–remove · Full Card

Symptoms / Associated Sx

• Frequently asymptomatic until dangerous levels are reached

• Weakness, fatigue, paresthesias, and palpitations

• The principal danger is cardiac: arrhythmias, bradycardia, and cardiac arrest

• Symptoms are an unreliable guide — the ECG and the absolute potassium drive urgency, and a comfortable-appearing patient can still arrest

Neg

• Pt denies a hemolyzed or difficult draw, marked thrombocytosis or leukocytosis, or fist-clenching during phlebotomy — causes of pseudohyperkalemia that warrant a repeat sample before treatment

• Pt denies missed AKI or obstruction

• Pt denies adrenal insufficiency (hyponatremia with hyperkalemia and hypotension) and denies massive cell lysis (rhabdomyolysis, tumor lysis)

Social History (SHx)

• CKD/ESRD with dialysis status and any missed sessions

• ACE inhibitors/ARBs, mineralocorticoid receptor antagonists (spironolactone, eplerenone), potassium-sparing diuretics, TMP-SMX, and NSAIDs

• Potassium supplements and salt substitutes

• Diabetes (type 4 RTA) and tissue-breakdown states (crush injury, tumor lysis)

Main Etiology

• Impaired excretion and/or a transcellular shift of potassium

• Impaired renal excretion: AKI, CKD/ESRD, and hypoaldosteronism/type 4 RTA

• Drugs reducing excretion: ACE inhibitors/ARBs, MRAs, potassium-sparing diuretics, TMP, calcineurin inhibitors, and NSAIDs

• Transcellular shift: metabolic acidosis, insulin deficiency/hyperglycemia, beta-blockers, and cell lysis (rhabdomyolysis, tumor lysis, hemolysis)

• Increased intake (which usually causes hyperkalemia only when excretion is already impaired)

RF

• Modifiable: combinations of RAAS inhibitors with MRAs, potassium supplements and salt substitutes, and NSAID use

• Non-modifiable: CKD/ESRD, diabetes, and tissue-breakdown states

Data

• ECG first (the urgency driver) (peaked T waves → PR prolongation and flattened P waves → widened QRS → sine wave → arrest; any ECG change is an emergency regardless of the number)

• Repeat/confirm the potassium (exclude pseudohyperkalemia — hemolysis, high platelet or white cell counts, draw technique)

• BMP (renal function, bicarbonate); glucose

• CK (rhabdomyolysis); uric acid, phosphate, and calcium (tumor lysis)

• Consider a digoxin level, aldosterone/renin (type 4 RTA), and a VBG (acidosis)

DDx

True versus pseudohyperkalemia (repeat sample, plasma versus serum) · impaired excretion vs transcellular shift vs cell lysis (renal function, CK, glucose, acid-base) · drug-induced (medication review) · adrenal insufficiency (hyponatremia, hypotension)

Home Meds

• Stop/hold: ACE inhibitors/ARBs, MRAs, potassium-sparing diuretics, TMP-SMX, NSAIDs, potassium supplements, and salt substitutes

• Review/adjust: beta-blockers (impair potassium shift)

• Renally dose medications

Plan

CONSULT: Nephrology (dialysis need, ESRD, refractory cases) · ICU (ECG changes or instability) · Cardiology (arrhythmia)

• Step 1 — stabilize the myocardium (for ECG changes or a markedly elevated potassium): calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 minutes (or calcium chloride through a central line), which acts within minutes and lasts ~30–60 minutes and should be repeated if ECG changes persist; it does not lower potassium but buys time, and is used cautiously in digoxin toxicity

• Step 2 — shift potassium intracellularly (rapid but temporary): insulin 10 units regular IV with dextrose (D50 25 g IV), which acts within ~15 minutes and lasts hours — recheck the glucose for delayed hypoglycemia, especially in ESRD or low body weight (consider 5 units or extra dextrose); high-dose albuterol 10–20 mg nebulized (4–8 times the asthma dose) for an additive shift; and sodium bicarbonate only when there is significant metabolic acidosis (it is not a reliable acute lowering agent alone)

• Step 3 — remove potassium from the body (definitive): a loop diuretic (IV furosemide) if the patient is making urine, ensuring adequate volume; a GI cation binder — patiromer or sodium zirconium cyclosilicate (preferred over older sodium polystyrene sulfonate, which carries a colonic-necrosis risk and should be avoided in ileus or postoperative bowel); and hemodialysis, which is definitive for refractory or severe hyperkalemia, anuric/ESRD patients, or ongoing potassium release (rhabdomyolysis, tumor lysis)

• Step 4 — stop the source and treat the cause: discontinue all potassium-raising drugs and supplements/salt substitutes; treat AKI and relieve obstruction; correct acidosis; treat the cell-lysis cause (hydration for rhabdomyolysis, tumor lysis management); and dialyze for ESRD or refractory cases

• Maintain continuous cardiac monitoring throughout for any significant hyperkalemia

• PT/OT: as tolerated

• Trend: serial potassium with ECGs, glucose repeatedly after insulin, renal function and urine output, source markers (CK, etc.), and the response to therapy

• Escalation triggers: ECG changes or arrhythmia → emergent calcium, the full cocktail, cardiac monitoring, and dialysis; refractory, anuric, or ESRD cases → urgent hemodialysis; ongoing cell lysis → treat the cause and dialyze; recurrent rebound → reassess the adequacy of removal

• Discharge checklist: potassium normalized and stable off offending drugs (RAAS/MRA reconciled and restarted cautiously with monitoring if indicated); the cause addressed (renal, drug, or lysis); dietary potassium counseling with avoidance of salt substitutes; a binder prescription if needed; an outpatient potassium recheck with nephrology follow-up; return precautions for weakness, palpitations, or fainting

Red Flags

• Any ECG change (peaked T waves, widened QRS, bradyarrhythmia, sine wave) → emergent calcium and the full cocktail; can progress to arrest

• Anuric or ESRD hyperkalemia → urgent hemodialysis, since shifting agents only buy time

• Ongoing cell lysis (rhabdomyolysis, tumor lysis) → recurrent rebound → treat the cause and dialyze

• Hyperkalemia with bradycardia and hypotension → impending cardiovascular collapse

• Pseudohyperkalemia → avoid overtreating a spurious value; confirm with a clean repeat sample if the clinical picture doesn't fit

Senior IM Resident Pearls

• Stabilize, shift, remove — in that order. Calcium protects the heart but doesn't lower the potassium; insulin and albuterol shift it temporarily; only diuresis, binders, or dialysis actually remove it — so every "treated" patient still needs a removal plan.

• The ECG, not the number, sets the urgency. Get a 12-lead immediately, and treat ECG changes emergently even before the repeat potassium returns.

• Recheck the glucose after insulin — more than once. Delayed hypoglycemia is common, especially in ESRD and low-weight patients; consider a reduced insulin dose or extra dextrose.

• Calcium doesn't lower potassium — a recurring misconception; it only stabilizes the membrane, so don't mistake it for definitive therapy.

• If the kidneys can't excrete, dialysis is the answer. In anuric or ESRD patients, shifting agents are a bridge to dialysis, not a treatment.

• Hunt for the silent contributors — salt substitutes (potassium chloride), the ACEi-plus-spironolactone combination, and TMP-SMX are classic, easily missed culprits.

• Common mistake: treating a single elevated value without an ECG or a confirmatory sample — either under-treating a true emergency or over-treating hemolyzed pseudohyperkalemia.

Electrolytes — Potassium

103. Hypokalemia

low serum K · diuretics / GI losses / poor intake / alcohol · replete K AND magnesium · watch the ECG (U waves, arrhythmia) · IV rate limits matter · Super Compact

Sx: often asymptomatic if mild · weakness, fatigue, cramps, constipation/ileus · severe (<2.5–3): muscle paralysis, rhabdomyolysis, arrhythmias (esp with digoxin or QT-prolonging drugs), respiratory muscle weakness · palpitations (arrhythmia risk is the danger — magnified by digoxin, ischemia, and concurrent hypomagnesemia)

Neg: denies transcellular shift cause masking total-body status (insulin, beta-agonists, alkalosis, refeeding — K low but body stores ok) · denies untreated hypomagnesemia (refractory hypoK until Mg replaced) · denies spurious (very high WBC) · denies periodic paralysis

SHx: diuretics (loop/thiazide) · vomiting/NG suction or diarrhea/laxatives · alcohol use disorder (poor intake + Mg loss + shifts) · poor intake/malnutrition · refeeding · primary hyperaldosteronism (HTN + hypoK) · amphotericin

Etiology: renal loss (diuretics — commonest; hyperaldosteronism; type 1/2 RTA; hypomagnesemia; amphotericin) · GI loss (diarrhea — direct K loss; vomiting/NG — mostly renal K wasting from the metabolic alkalosis + volume depletion) · transcellular shift (insulin, beta-agonists, alkalosis, refeeding, periodic paralysis) · poor intake (rare alone — usually with another mechanism; alcohol use disorder combines several)

RF: diuretic use · GI losses · alcohol use disorder/malnutrition · hypomagnesemia · digoxin therapy (synergy) · hyperaldosteronism

Data: BMP (K low; bicarbonate — alkalosis common with vomiting/diuretics) · magnesium (ALWAYS check & replace) (hypomagnesemia causes renal K wasting → refractory hypoK) · ECG (flattened T, U waves, ST depression, ↑QT/arrhythmia; PVCs) · urine K (or spot K/Cr) (low <20 = extrarenal/GI/intake; high = renal wasting) · acid-base + urine Cl (if alkalosis — vomiting vs diuretic vs Bartter) · consider aldosterone/renin (HTN + hypoK), digoxin level

DDx: renal vs extrarenal loss (urine K) · shift vs true depletion (clinical context — insulin/alkalosis/refeeding) · hypomagnesemia-driven refractory hypoK (check Mg) · hyperaldosteronism (HTN + hypoK + alkalosis)

Home Meds: review/adjust diuretics (loop/thiazide) · stop laxative misuse · review beta-agonists, insulin regimen, amphotericin · caution with digoxin (hypoK potentiates toxicity)

Plan

CONSULT: Nephrology (refractory/renal-wasting/unclear, RTA) · Cardiology (arrhythmia, digoxin toxicity) · Endocrine (hyperaldosteronism) · ICU (severe — paralysis/arrhythmia)

– Assess severity + symptoms + ECG — severe (<2.5–3), symptomatic, on digoxin, or with arrhythmia/ECG changes → urgent aggressive repletion + cardiac monitoring
– CHECK AND REPLACE MAGNESIUM (critical co-step): hypomagnesemia causes ongoing renal potassium wasting and makes hypokalemia refractory — you cannot fix the K without fixing the Mg; give magnesium sulfate 1–2 g IV (more if low) when repleting K
– Potassium replacement:
  • Oral (preferred when able): potassium chloride (KCl) PO — e.g. 40–80 mEq/day in divided doses for mild–moderate; ~10 mEq raises serum K by roughly 0.1 mEq/L (deficit is often large — total-body depletion exceeds the serum drop)
  • IV (severe, symptomatic, or NPO): KCl IV — peripheral rate generally ≤10 mEq/h (up to 20 mEq/h via central line with continuous cardiac monitoring in critical hypoK); concentration limits per line; never IV push; use saline (not dextrose — dextrose→insulin→drives K intracellularly)
– Treat the cause: adjust/stop diuretics or add K-sparing agent (spironolactone/amiloride) if ongoing renal wasting; treat GI losses; correct alkalosis; manage hyperaldosteronism; nutrition in alcohol/malnutrition (also watch refeeding — repletion needs intensify)
– Recheck K frequently during aggressive repletion to avoid overshoot into hyperkalemia (esp if renal impairment)
– If the potassium won't come up despite repletion, check the magnesium — magnesium depletion drives renal potassium wasting, and the hypokalemia stays refractory until the magnesium is corrected. Always replace them together.
– PT/OT: as tolerated; monitor for weakness
– Trend: serial K (frequent during IV repletion), magnesium, ECG, renal function, symptoms, urine K if renal wasting
– Escalation triggers: arrhythmia/severe weakness/paralysis → ICU + aggressive monitored IV repletion; digoxin toxicity → cardiology + correct K/Mg; refractory despite Mg → reassess (renal wasting, hyperaldo); overshoot hyperK → hold repletion
– Discharge checklist: K + Mg normalized + stable; cause addressed (diuretic adjusted ± K-sparing, GI losses treated, nutrition); oral K/Mg maintenance if ongoing losses; dietary K counseling; outpatient recheck + relevant follow-up (nephrology/endocrine/cardiology); return precautions (weakness, palpitations, muscle cramps)

103. Hypokalemia

complete reference · diuretics + GI losses + poor intake + alcohol use disorder · replete K with Mg · ECG-guided urgency · Full Card

Symptoms / Associated Sx

• Often asymptomatic when mild

• Weakness, fatigue, muscle cramps, and constipation or ileus

• Severe hypokalemia (<2.5–3) causes muscle paralysis, rhabdomyolysis, arrhythmias (especially with digoxin or QT-prolonging drugs), and respiratory muscle weakness

• The arrhythmia risk is the central danger and is magnified by digoxin, myocardial ischemia, and concurrent hypomagnesemia

Neg

• Pt denies a transcellular shift (insulin, beta-agonists, alkalosis, refeeding) that would lower the serum potassium without true total-body depletion

• Pt denies untreated hypomagnesemia, which renders hypokalemia refractory until the magnesium is replaced

• Pt denies a spuriously low value (very high white cell count) and denies periodic paralysis

Social History (SHx)

• Diuretics (loop or thiazide)

• Vomiting or NG suction, and diarrhea or laxative use

• Alcohol use disorder (poor intake combined with magnesium loss and shifts)

• Poor intake/malnutrition, refeeding, primary hyperaldosteronism (hypertension with hypokalemia), and amphotericin

Main Etiology

• Renal loss: diuretics (the most common cause), hyperaldosteronism, type 1 and 2 RTA, hypomagnesemia, and amphotericin

• GI loss: diarrhea (direct potassium loss) and vomiting/NG suction (mostly renal potassium wasting driven by the resulting metabolic alkalosis and volume depletion)

• Transcellular shift: insulin, beta-agonists, alkalosis, refeeding, and periodic paralysis

• Poor intake: rarely a cause alone, usually combined with another mechanism, as in alcohol use disorder which combines several

RF

• Modifiable: diuretic use, laxative misuse, alcohol use, and correction of magnesium

• Non-modifiable: GI-loss states, hyperaldosteronism, and concurrent digoxin therapy (arrhythmic synergy)

Data

• BMP (low potassium; bicarbonate, as metabolic alkalosis is common with vomiting and diuretics)

• Magnesium — always check and replace (hypomagnesemia causes renal potassium wasting and makes hypokalemia refractory)

• ECG (flattened T waves, U waves, ST depression, QT prolongation, PVCs, and arrhythmia)

• Urine potassium (or spot K/Cr ratio) (low, <20, indicates extrarenal/GI loss or poor intake; high indicates renal wasting)

• Acid-base status with urine chloride (in alkalosis, to separate vomiting, diuretics, and Bartter/Gitelman syndromes)

• Aldosterone/renin (hypertension with hypokalemia) and a digoxin level when relevant

DDx

Renal versus extrarenal loss (urine potassium) · transcellular shift versus true depletion (clinical context — insulin, alkalosis, refeeding) · hypomagnesemia-driven refractory hypokalemia (check magnesium) · hyperaldosteronism (hypertension with hypokalemia and alkalosis)

Home Meds

• Review/adjust: diuretics (loop/thiazide)

• Stop: laxative misuse; review beta-agonists, the insulin regimen, and amphotericin

• Caution with digoxin — hypokalemia potentiates digoxin toxicity

Plan

CONSULT: Nephrology (refractory, renal-wasting, or unclear cases; RTA) · Cardiology (arrhythmia, digoxin toxicity) · Endocrinology (hyperaldosteronism) · ICU (severe — paralysis or arrhythmia)

• Assess severity, symptoms, and the ECG: severe (<2.5–3), symptomatic, on digoxin, or with arrhythmia/ECG changes warrants urgent aggressive repletion with cardiac monitoring

• Check and replace magnesium (a critical co-step): hypomagnesemia causes ongoing renal potassium wasting and makes hypokalemia refractory, so the potassium cannot be corrected without correcting the magnesium — give magnesium sulfate 1–2 g IV (more if markedly low) alongside potassium repletion

• Potassium replacement — oral when possible: potassium chloride (KCl) PO, for example 40–80 mEq/day in divided doses for mild-to-moderate deficits; roughly 10 mEq raises the serum potassium by about 0.1 mEq/L, and the total-body deficit usually exceeds what the serum value suggests

• Potassium replacement — IV for severe, symptomatic, or NPO patients: IV KCl at a peripheral rate generally ≤10 mEq/h (up to 20 mEq/h through a central line with continuous cardiac monitoring in critical hypokalemia), respecting concentration limits per line, never given as an IV push, and mixed in saline rather than dextrose (dextrose stimulates insulin, which drives potassium intracellularly)

• Treat the cause: adjust or stop diuretics or add a potassium-sparing agent (spironolactone, amiloride) for ongoing renal wasting; treat GI losses; correct alkalosis; manage hyperaldosteronism; and provide nutrition in alcohol use disorder/malnutrition (watching for refeeding, which intensifies repletion needs)

• Recheck the potassium frequently during aggressive repletion to avoid overshoot into hyperkalemia, especially with renal impairment

• PT/OT: as tolerated, monitoring for weakness

• Trend: serial potassium (frequently during IV repletion), magnesium, the ECG, renal function, symptoms, and urine potassium if there is renal wasting

• Escalation triggers: arrhythmia, severe weakness, or paralysis → ICU with aggressive monitored IV repletion; digoxin toxicity → cardiology and correction of potassium and magnesium; refractory despite magnesium → reassess for renal wasting or hyperaldosteronism; overshoot into hyperkalemia → hold repletion

• Discharge checklist: potassium and magnesium normalized and stable; the cause addressed (diuretic adjusted with a potassium-sparing agent if needed, GI losses treated, nutrition optimized); oral potassium/magnesium maintenance if losses continue; dietary potassium counseling; an outpatient recheck with the relevant follow-up (nephrology, endocrinology, cardiology); return precautions for weakness, palpitations, or muscle cramps

Red Flags

• Ventricular arrhythmia or severe weakness/paralysis → ICU and aggressive monitored repletion

• Hypokalemia on digoxin → potentiated digoxin toxicity → correct potassium and magnesium urgently

• Refractory hypokalemia despite repletion → unrecognized hypomagnesemia until proven otherwise

• Rhabdomyolysis from severe hypokalemia → adds an AKI and ongoing electrolyte derangement

• Overshoot into hyperkalemia during repletion → particularly with renal impairment

Senior IM Resident Pearls

• Always replace magnesium with potassium. Magnesium depletion drives renal potassium wasting, so hypokalemia stays refractory until the magnesium is corrected — this is the single most common reason a potassium "won't come up."

• The serum value understates the deficit. Total-body potassium depletion is large relative to the serum drop, so the replacement dose is usually bigger than the number suggests — but recheck to avoid overshoot.

• Mix IV potassium in saline, not dextrose. Dextrose triggers insulin release that drives potassium into cells and can transiently worsen the hypokalemia.

• Respect the IV rate limits. Peripheral KCl is irritating and fast infusion is arrhythmogenic — keep peripheral rates low and reserve faster, central, monitored infusions for critical hypokalemia.

• Vomiting causes a renal potassium leak. The potassium is lost in the urine (driven by the alkalosis and volume depletion), not in the vomitus — which is why restoring volume and chloride is part of the fix.

• Hypertension with hypokalemia and alkalosis should prompt a thought of primary hyperaldosteronism rather than just repleting and moving on.

• Common mistake: repleting potassium alone in an alcoholic or malnourished patient and ignoring the magnesium — the level barely budges, and the underlying driver goes untreated.

Electrolytes — Sodium

104. Hypernatremia

high serum Na = free-water deficit · dehydration / poor PO intake / dementia / diabetes insipidus · almost always impaired access to water · replace free water, correct slowly · Super Compact

Sx: thirst (key defense — absent/unmet if impaired access), lethargy, weakness, irritability, confusion · severe: seizures, coma (brain cell shrinkage/dehydration; risk of intracranial hemorrhage from bridging-vein tearing) · in DI: polyuria + polydipsia · signs of volume depletion (dry mucosa, tachycardia, hypotension) (hypernatremia in a hospitalized patient usually means they can't get to water — infants, elderly, dementia, intubated, restrained)

Neg: denies normal thirst + free water access (would self-correct — implies a barrier or massive loss) · denies sodium overload cause (hypertonic saline/bicarb, salt ingestion — rarer) · denies osmotic diuresis missed (glucose, mannitol, high urea) · denies DI undiagnosed (dilute urine despite hypernatremia)

SHx: dementia/impaired access to water, bedbound, tube-fed · poor PO intake/NPO · GI losses (diarrhea/vomiting) · osmotic diuresis (hyperglycemia, mannitol, tube feeds) · lithium/DI history · CNS disease/pituitary surgery (central DI) · diuretics

Etiology: a water problem (deficit of water relative to sodium), almost always impaired water access or intake plus a loss · pure water loss (insensible, fever; diabetes insipidus — central [↓ADH] or nephrogenic [ADH-resistant — lithium, hypercalcemia, hypokalemia]) · hypotonic fluid loss (GI — diarrhea/vomiting; renal — osmotic diuresis, diuretics) · sodium gain (hypertonic saline/bicarb, salt ingestion — less common) · the common thread: can't drink enough to keep up (dementia, NPO, restrained, infants)

RF: dementia/altered mental status · advanced age · NPO/tube-fed · ICU/intubated · osmotic diuresis · DI · uncontrolled diabetes

Data: BMP (↑Na; glucose — osmotic diuresis) · volume status assessment (hypovolemic — most common — vs euvolemic vs hypervolemic/Na gain) · urine osmolality (high >600–800 = appropriate renal water conservation [extrarenal loss/poor intake]; low/inappropriately dilute = renal water loss / diabetes insipidus) · urine Na · if DI suspected: response to desmopressin (DDAVP) (urine osm rises with DDAVP = central DI; no response = nephrogenic) · Ca, K (nephrogenic DI causes), calculate free water deficit

DDx: hypovolemic (water + some Na loss) (GI/renal losses, hypotension) · pure water loss / DI (dilute urine, polyuria) · poor intake/dementia (concentrated urine, access barrier) · Na overload (iatrogenic, euvolemic/hypervolemic)

Home Meds: review lithium (nephrogenic DI), diuretics, lactulose/osmotic agents · ensure water access/free-water in tube feeds · renally dose · address hyperglycemia

Plan

CONSULT: Nephrology (severe/refractory, DI management, correction) · Endocrine (central DI, pituitary) · ICU (severe symptomatic — seizures/coma)

– Restore circulation first if hypovolemic/hypotensive: resuscitate with isotonic saline (0.9% NaCl) until hemodynamically stable (perfusion before free-water correction), then switch to free-water replacement
– Calculate the free water deficit and replace it: free water deficit ≈ 0.6 (♂) or 0.5 (♀) × weight(kg) × [(Na/140) − 1]; also account for ongoing losses + insensible
– Replace free water — oral/enteral water (preferred if gut works — via NG/PO, the safest route) or IV D5W (or hypotonic ¼–½ NS) for the calculated deficit plus ongoing losses
– CORRECT SLOWLY (cerebral edema risk): lower Na by ≤10–12 mEq/L per 24h (≤0.5 mEq/L/h) — too-rapid correction causes cerebral edema/seizures; recheck Na q4–6h and adjust the rate
– Treat the cause:
  • Impaired access/poor intake/dementia: ensure ongoing water (scheduled free-water via tube feeds, assisted hydration), treat the barrier; this is the most common and most preventable scenario
  • Central DI: desmopressin (DDAVP) + free water; find cause (pituitary/CNS imaging, endocrine)
  • Nephrogenic DI: remove offending cause (stop lithium if possible, correct hyperCa/hypoK); low-solute diet, thiazide ± amiloride, NSAID (selected) to reduce urine output; free water
  • Osmotic diuresis: control hyperglycemia, address the osmotic load; replace water + electrolytes
  • Sodium overload: stop the sodium source; D5W ± loop diuretic (remove excess Na)
– Most inpatient hypernatremia is a "no-water-access" problem in a patient who can't ask for or reach a glass of water — the fix is as much ensuring ongoing free water (and removing the access barrier) as it is the IV calculation. And correct slowly: the dehydrated brain is vulnerable to edema if you drop the sodium too fast.
– PT/OT: aspiration/fall precautions; assist with hydration/feeding
– Trend: Na q4–6h during correction, volume status, urine output (huge in DI), glucose, ongoing losses, mental status
– Escalation triggers: seizures/coma → ICU; massive polyuria/DI → endocrine/nephrology + DDAVP trial; correcting too fast → slow the rate; refractory despite water → reassess (ongoing loss, DI, Na source)
– Discharge checklist: Na corrected to baseline + cause addressed; sustainable hydration plan (free-water orders, assisted intake, tube-feed water flushes) — critical to prevent recurrence; DI regimen (DDAVP) if applicable; offending drugs reviewed (lithium); caregiver education on hydration; outpatient Na recheck + follow-up; return precautions (confusion, lethargy, decreased intake, excessive urination)

104. Hypernatremia

complete reference · dehydration + poor PO intake + dementia + diabetes insipidus · free-water deficit + slow correction · Full Card

Symptoms / Associated Sx

• Thirst is the key defense and is absent or unmet when water access is impaired; lethargy, weakness, irritability, and confusion develop

• Severe hypernatremia causes seizures and coma from brain cell dehydration, with a risk of intracranial hemorrhage as bridging veins are torn by the shrinking brain

• In diabetes insipidus, polyuria and polydipsia are prominent

• Signs of volume depletion (dry mucous membranes, tachycardia, hypotension) accompany hypovolemic cases

• Hospitalized hypernatremia usually means the patient cannot access water — infants, the elderly, those with dementia, and intubated or restrained patients

Neg

• Pt denies normal thirst with free access to water — which would self-correct, implying either a barrier to drinking or a large ongoing loss

• Pt denies a sodium-overload source (hypertonic saline/bicarbonate, salt ingestion) and denies a missed osmotic diuresis (glucose, mannitol, high urea)

• Pt denies an undiagnosed diabetes insipidus (inappropriately dilute urine despite hypernatremia)

Social History (SHx)

• Dementia or impaired access to water, bedbound or tube-fed status

• Poor oral intake or NPO status

• GI losses (diarrhea, vomiting) and osmotic diuresis (hyperglycemia, mannitol, high-protein tube feeds)

• Lithium use or a history of DI; CNS disease or pituitary surgery (central DI); diuretics

Main Etiology

• A water problem — a deficit of water relative to sodium — almost always involving impaired water access or intake combined with a loss

• Pure water loss: insensible losses and fever; diabetes insipidus, either central (deficient ADH) or nephrogenic (ADH resistance from lithium, hypercalcemia, or hypokalemia)

• Hypotonic fluid loss: GI (diarrhea, vomiting) and renal (osmotic diuresis, diuretics)

• Sodium gain: hypertonic saline/bicarbonate or salt ingestion (less common)

• The common thread is an inability to drink enough to keep pace (dementia, NPO, restraint, infancy)

RF

• Modifiable: water access, glycemic control, review of osmotic and lithium exposures

• Non-modifiable: dementia/altered mental status, advanced age, critical illness with intubation, and diabetes insipidus

Data

• BMP (elevated sodium; glucose for osmotic diuresis)

• Volume status assessment (hypovolemic, the most common, versus euvolemic versus hypervolemic/sodium gain)

• Urine osmolality (high, >600–800, indicates appropriate renal water conservation from extrarenal loss or poor intake; low or inappropriately dilute indicates renal water loss or diabetes insipidus)

• Urine sodium (helps characterize the loss)

• Response to desmopressin (DDAVP) if DI is suspected (a rise in urine osmolality indicates central DI; no response indicates nephrogenic DI)

• Calcium and potassium (causes of nephrogenic DI); calculate the free water deficit

DDx

Hypovolemic hypernatremia (water plus some sodium loss — GI/renal losses, hypotension) · pure water loss / diabetes insipidus (dilute urine, polyuria) · poor intake/dementia (concentrated urine with an access barrier) · sodium overload (iatrogenic, euvolemic or hypervolemic)

Home Meds

• Review: lithium (nephrogenic DI), diuretics, and osmotic agents such as lactulose

• Ensure: water access and free-water content in tube feeds

• Address: hyperglycemia; renally dose medications

Plan

CONSULT: Nephrology (severe or refractory cases, DI management, correction concerns) · Endocrinology (central DI, pituitary disease) · ICU (severe symptoms — seizures or coma)

• Restore circulation first if hypovolemic or hypotensive: resuscitate with isotonic saline (0.9% NaCl) until hemodynamically stable (perfusion takes priority over free-water correction), then transition to free-water replacement

• Calculate the free water deficit and replace it: free water deficit ≈ 0.6 (men) or 0.5 (women) × weight in kg × [(Na/140) − 1], also accounting for ongoing and insensible losses

• Replace free water: oral or enteral water (preferred when the gut works, via NG or PO — the safest route) or IV D5W (or hypotonic ¼–½ normal saline) for the calculated deficit plus ongoing losses

• Correct slowly to avoid cerebral edema: lower the sodium by ≤10–12 mEq/L per 24 hours (≤0.5 mEq/L/h), since too-rapid correction causes cerebral edema and seizures; recheck the sodium every 4–6 hours and adjust the rate

• Treat the cause:

• • Impaired access, poor intake, or dementia: ensure ongoing water (scheduled free-water flushes with tube feeds, assisted hydration) and address the barrier — the most common and most preventable scenario

• • Central DI: desmopressin (DDAVP) with free water, and identify the cause with pituitary/CNS imaging and endocrine evaluation

• • Nephrogenic DI: remove the offending cause (stop lithium if possible, correct hypercalcemia or hypokalemia); use a low-solute diet, a thiazide with or without amiloride, and a selected NSAID to reduce urine output, with free water

• • Osmotic diuresis: control hyperglycemia, address the osmotic load, and replace water and electrolytes

• • Sodium overload: stop the sodium source and use D5W with a loop diuretic to remove the excess sodium

• PT/OT: aspiration and fall precautions; assist with hydration and feeding

• Trend: sodium every 4–6 hours during correction, volume status, urine output (large in DI), glucose, ongoing losses, and mental status

• Escalation triggers: seizures or coma → ICU; massive polyuria or suspected DI → endocrine/nephrology and a DDAVP trial; correction proceeding too fast → slow the rate; refractory despite water → reassess for ongoing losses, DI, or a sodium source

• Discharge checklist: sodium corrected to baseline with the cause addressed; a sustainable hydration plan (free-water orders, assisted intake, tube-feed water flushes) — critical to prevent recurrence; a DI regimen (DDAVP) if applicable; offending drugs reviewed (lithium); caregiver education on hydration; an outpatient sodium recheck with follow-up; return precautions for confusion, lethargy, decreased intake, or excessive urination

Red Flags

• Seizures or coma → severe cerebral dehydration → ICU care with carefully paced correction

• Correcting too rapidly → cerebral edema → slow the rate and recheck the sodium

• Massive polyuria with dilute urine → diabetes insipidus → DDAVP trial and endocrine/nephrology input

• Hypovolemic shock → resuscitate with isotonic saline before free-water correction

• Recurrent hypernatremia after discharge → an unaddressed water-access problem

Senior IM Resident Pearls

• Inpatient hypernatremia is usually a water-access problem. The patient can't ask for or reach water — the cure is as much an ongoing free-water plan and removing the barrier as it is the IV calculation.

• Correct slowly. The brain has adapted to the high sodium, so dropping it too fast causes cerebral edema — cap the fall at ≤10–12 mEq/L/24h and recheck.

• Resuscitate the circulation first. In a hypotensive patient, give isotonic saline for perfusion before switching to free water — fixing the volume comes before fixing the tonicity.

• The urine tells you the mechanism. Concentrated urine means the kidney is conserving water appropriately (intake/extrarenal loss); inappropriately dilute urine in the face of hypernatremia means DI or a renal water leak.

• DDAVP separates the DI types. A urine that concentrates after desmopressin is central DI; no response is nephrogenic — and the treatments diverge completely.

• Don't forget the enteral route. Free water down an NG tube is safe, effective, and often faster to start than titrating IV D5W.

• Common mistake: fixing the number in the hospital and discharging without a hydration plan — the same patient bounces back hypernatremic because the access problem was never solved.

Electrolytes — Magnesium

105. Hypomagnesemia

low serum Mg · alcohol / malnutrition / diuretics / chronic diarrhea / PPIs · drags K and Ca down with it · the "refractory hypokalemia/hypocalcemia" culprit · Super Compact

Sx: often asymptomatic · neuromuscular — tremor, hyperreflexia, tetany, Chvostek/Trousseau (often via accompanying hypocalcemia), cramps, weakness · cardiac — arrhythmias including torsades de pointes, ↑QT, atrial/ventricular ectopy · CNS — irritability, seizures · (suspect when hypoK or hypoCa won't correct, or with unexplained QT prolongation/arrhythmia)

Neg: denies that this is isolated (almost always co-travels with hypoK and/or hypoCa — check all three) · denies massive transfusion/citrate alone · denies redistribution (refeeding, acute pancreatitis) without depletion · denies other QT causes overlooked

SHx: alcohol use disorder (poor intake + renal wasting + GI loss — the classic) · malnutrition/refeeding · diuretics (loop/thiazide) · chronic diarrhea/malabsorption, PPI use (chronic — impairs absorption) · meds — aminoglycosides, amphotericin, cisplatin, calcineurin inhibitors · uncontrolled diabetes

Etiology: GI loss (chronic diarrhea, malabsorption, chronic PPI use → reduced absorption) · renal wasting (loop/thiazide diuretics, alcohol, hypercalcemia, drugs — aminoglycosides/amphotericin/cisplatin/calcineurin inhibitors, osmotic diuresis/uncontrolled DM, tubular disorders — Gitelman/Bartter) · poor intake (alcohol, malnutrition, refeeding) · redistribution (refeeding, acute pancreatitis — saponification)

RF: alcohol use disorder · diuretic use · chronic PPI use · malabsorption/chronic diarrhea · nephrotoxic drugs · diabetes · critical illness

Data: serum magnesium (low; note serum reflects only ~1% of total body Mg — can underestimate depletion) · BMP + K + Ca + phosphate (check the whole panel — hypoK and hypoCa commonly coexist and are caused/perpetuated by the low Mg) · ECG (↑QT, T-wave changes, arrhythmia/torsades risk) · consider urine Mg / FE-Mg (renal wasting [high] vs GI/intake [low/conserving] if cause unclear)

DDx: renal wasting vs GI/poor intake (urine Mg, history) · accompanying hypoK/hypoCa (check & co-treat) · drug-induced (diuretics, PPI, nephrotoxins) · redistribution (refeeding, pancreatitis)

Home Meds: review diuretics, PPI (chronic — consider deprescribe/switch), nephrotoxins (aminoglycosides, amphotericin, cisplatin, calcineurin inhibitors) · alcohol cessation support · renally dose

Plan

CONSULT: Cardiology (torsades/arrhythmia) · Nephrology (renal wasting/refractory, tubular disorders) · GI/Nutrition (malabsorption, alcohol/malnutrition) · ICU (torsades, severe symptomatic)

– Assess severity + ECG + symptoms: torsades, arrhythmia, seizures, or severe symptomatic hypomagnesemia → IV magnesium urgently + cardiac monitoring
– Magnesium replacement:
  • Severe/symptomatic or torsades: magnesium sulfate 1–2 g IV over 5–60 min (give 2 g IV over 1–2 min in torsades/arrest), then continued repletion (e.g. infusion); cardiac monitoring
  • Moderate (asymptomatic, IV): magnesium sulfate 1–2 g IV, repeat to target; give slowly (rapid infusion → flushing, hypotension, and renal Mg loss — a fast bolus is partly excreted)
  • Mild/chronic (oral): oral magnesium (e.g. magnesium oxide/glycinate) — limited by diarrhea at higher doses
  • Caution in renal impairment: reduce dose + monitor (risk of hypermagnesemia)
– CO-REPLETE potassium and calcium: you often can't correct hypoK or hypoCa until the Mg is replaced — magnesium depletion causes renal K wasting and impairs PTH secretion/action; replace all three together
– Treat/remove the cause: alcohol cessation + nutrition (thiamine, watch refeeding), adjust/stop diuretics (or add K/Mg-sparing amiloride for renal wasting), deprescribe or switch chronic PPI, treat diarrhea/malabsorption, review nephrotoxic drugs, control diabetes
– Give magnesium slowly — much of a rapid IV bolus is excreted in the urine before tissues replete, so slower infusion (or oral maintenance) is more effective for true repletion
– Magnesium is the hidden driver behind refractory hypokalemia and hypocalcemia — if either won't budge with replacement, the magnesium is usually low and untreated. And in alcohol use disorder, the whole panel (K, Mg, Phos, Ca) is typically depleted at once.
– PT/OT: as tolerated; fall precautions if weak
– Trend: Mg, K, Ca, phosphate, ECG/QT, renal function (esp during IV repletion), symptoms
– Escalation triggers: torsades/arrhythmia → ICU + IV magnesium + cardiology; seizures → treat + replete; refractory despite repletion → renal wasting workup (urine Mg, Gitelman) or ongoing loss; renal impairment → watch for hypermagnesemia
– Discharge checklist: Mg (and K/Ca/Phos) normalized; cause addressed (diuretic/PPI reviewed, alcohol/nutrition support, diarrhea treated); oral Mg maintenance if ongoing losses; outpatient electrolyte recheck + relevant follow-up; return precautions (palpitations, cramps/tremor, weakness, seizures)

105. Hypomagnesemia

complete reference · alcohol use disorder + malnutrition + diuretics + chronic diarrhea · co-repletion of K and Ca · Full Card

Symptoms / Associated Sx

• Often asymptomatic

• Neuromuscular: tremor, hyperreflexia, tetany, Chvostek and Trousseau signs (frequently mediated by accompanying hypocalcemia), cramps, and weakness

• Cardiac: arrhythmias including torsades de pointes, QT prolongation, and atrial/ventricular ectopy

• CNS: irritability and seizures

• Suspect it when hypokalemia or hypocalcemia will not correct, or with unexplained QT prolongation or arrhythmia

Neg

• Pt denies that the abnormality is isolated — it almost always co-travels with hypokalemia and/or hypocalcemia, so check all three

• Pt denies massive transfusion/citrate as the sole cause

• Pt denies pure redistribution (refeeding, acute pancreatitis) without true depletion, and denies other overlooked causes of QT prolongation

Social History (SHx)

• Alcohol use disorder (poor intake combined with renal wasting and GI loss — the classic cause)

• Malnutrition and refeeding

• Diuretics (loop and thiazide)

• Chronic diarrhea/malabsorption and chronic PPI use (which impairs magnesium absorption); nephrotoxic drugs (aminoglycosides, amphotericin, cisplatin, calcineurin inhibitors); uncontrolled diabetes

Main Etiology

• GI loss: chronic diarrhea, malabsorption, and chronic PPI use (reduced absorption)

• Renal wasting: loop and thiazide diuretics, alcohol, hypercalcemia, nephrotoxic drugs (aminoglycosides, amphotericin, cisplatin, calcineurin inhibitors), osmotic diuresis/uncontrolled diabetes, and tubular disorders (Gitelman, Bartter)

• Poor intake: alcohol use disorder, malnutrition, and refeeding

• Redistribution: refeeding and acute pancreatitis (saponification)

RF

• Modifiable: alcohol use, diuretic and chronic PPI use, treatment of malabsorption, glycemic control

• Non-modifiable: nephrotoxic drug requirements, tubular disorders, and critical illness

Data

• Serum magnesium (low; note that serum reflects only ~1% of total-body magnesium and can underestimate depletion)

• BMP with potassium, calcium, and phosphate (check the whole panel — hypokalemia and hypocalcemia commonly coexist and are caused or perpetuated by the low magnesium)

• ECG (QT prolongation, T-wave changes, and a risk of arrhythmia including torsades)

• Urine magnesium or fractional excretion of magnesium (to separate renal wasting from GI/poor intake when the cause is unclear)

DDx

Renal wasting versus GI loss or poor intake (urine magnesium, history) · accompanying hypokalemia/hypocalcemia (check and co-treat) · drug-induced (diuretics, PPI, nephrotoxins) · redistribution (refeeding, pancreatitis)

Home Meds

• Review: diuretics, chronic PPIs (consider deprescribing or switching), and nephrotoxins (aminoglycosides, amphotericin, cisplatin, calcineurin inhibitors)

• Support: alcohol cessation

• Renally dose medications

Plan

CONSULT: Cardiology (torsades, arrhythmia) · Nephrology (renal wasting, refractory cases, tubular disorders) · GI/Nutrition (malabsorption, alcohol/malnutrition) · ICU (torsades or severe symptoms)

• Assess severity, the ECG, and symptoms: torsades, arrhythmia, seizures, or severe symptomatic hypomagnesemia warrant urgent IV magnesium with cardiac monitoring

• Magnesium replacement:

• • Severe/symptomatic or torsades: magnesium sulfate 1–2 g IV over 5–60 minutes (2 g IV over 1–2 minutes for torsades or arrest), followed by continued repletion (often an infusion), with cardiac monitoring

• • Moderate (asymptomatic, IV): magnesium sulfate 1–2 g IV, repeated to target and given slowly, since rapid infusion causes flushing and hypotension and increases renal magnesium loss (a fast bolus is partly excreted)

• • Mild/chronic (oral): oral magnesium (such as magnesium oxide or glycinate), limited by diarrhea at higher doses

• • Renal impairment: reduce the dose and monitor closely for hypermagnesemia

• Co-replete potassium and calcium: hypokalemia and hypocalcemia often cannot be corrected until the magnesium is replaced, because magnesium depletion causes renal potassium wasting and impairs PTH secretion and action — replace all three together

• Treat or remove the cause: alcohol cessation with nutritional support (thiamine, watching for refeeding), adjusting or stopping diuretics (or adding a magnesium-sparing agent such as amiloride for renal wasting), deprescribing or switching a chronic PPI, treating diarrhea/malabsorption, reviewing nephrotoxic drugs, and controlling diabetes

• Give magnesium slowly: much of a rapid IV bolus is excreted before tissues replete, so a slower infusion (or oral maintenance) achieves more effective true repletion

• PT/OT: as tolerated, with fall precautions if weak

• Trend: magnesium, potassium, calcium, and phosphate; the ECG/QT; renal function (especially during IV repletion); and symptoms

• Escalation triggers: torsades or arrhythmia → ICU, IV magnesium, and cardiology; seizures → treat and replete; refractory despite repletion → a renal-wasting workup (urine magnesium, Gitelman syndrome) or ongoing loss; renal impairment → watch for hypermagnesemia

• Discharge checklist: magnesium (and potassium, calcium, phosphate) normalized; the cause addressed (diuretic/PPI reviewed, alcohol and nutrition support, diarrhea treated); oral magnesium maintenance for ongoing losses; an outpatient electrolyte recheck with relevant follow-up; return precautions for palpitations, cramps or tremor, weakness, or seizures

Red Flags

• Torsades de pointes or ventricular arrhythmia → IV magnesium and ICU care

• Seizures from severe hypomagnesemia → treat and replete aggressively

• Refractory hypokalemia or hypocalcemia → unrecognized hypomagnesemia driving both

• Renal impairment during repletion → risk of overshoot into hypermagnesemia

• Profound depletion in alcohol use disorder → the entire electrolyte panel (K, Mg, phosphate, Ca) is typically low at once

Senior IM Resident Pearls

• Magnesium is the hidden driver of refractory hypokalemia and hypocalcemia. If either won't correct with replacement, the magnesium is almost always low and untreated — replace all three together.

• The serum level understates the deficit. Only about 1% of body magnesium is in the serum, so a "low-normal" value in a depleted patient still warrants repletion.

• Give it slowly. A rapid IV bolus is largely peed out before tissues take it up — slower infusions (or oral maintenance) achieve genuine repletion.

• The alcoholic patient is depleted across the board. Anticipate low magnesium, potassium, phosphate, and calcium together — and give thiamine before glucose.

• Chronic PPIs cause hypomagnesemia that's easy to miss — consider it in unexplained, recurrent low magnesium and review the indication.

• Magnesium is the drug for torsades regardless of the magnesium level — give it empirically in polymorphic VT with a long QT.

• Common mistake: repleting potassium and calcium while ignoring the magnesium — the levels barely move and the patient stays at arrhythmic risk.

Electrolytes — Calcium

106. Hypercalcemia

high calcium · "stones, bones, groans, psychiatric moans" · malignancy / primary hyperparathyroidism / vitamin D excess · PTH splits the differential · saline → calcitonin → bisphosphonate · Super Compact

Sx: "stones, bones, groans, psychiatric moans" — renal (polyuria/polydipsia → dehydration, nephrolithiasis, nephrogenic DI), GI (nausea, constipation, anorexia, pancreatitis), neuro/psych (fatigue, confusion, lethargy → coma), cardiac (short QT, arrhythmia, ↑digoxin sensitivity) · bone pain · (severity tracks the level + rate of rise; acute/malignant rises are more symptomatic)

Neg: denies that this is just ↓albumin artifact (correct Ca: add 0.8 per 1 g/dL albumin below 4; or check ionized Ca) · denies thiazide/lithium contributing (med review) · denies immobilization-only cause · denies factitious (tourniquet/stasis)

SHx: known/suspected malignancy (breast, lung, myeloma, renal, squamous) · thiazides, lithium, vitamin D/A supplements, calcium/antacids (milk-alkali) · family history (MEN, FHH) · sarcoidosis/granulomatous disease · immobilization · prior stones/fractures

Etiology: PTH-mediated (primary hyperparathyroidism — commonest in outpatients; tertiary; familial hypocalciuric hypercalcemia [FHH]) · PTH-independent (malignancy — commonest in inpatients: PTHrP [squamous/renal], osteolytic mets/myeloma, 1,25-vit D from lymphoma; vitamin D excess; granulomatous disease [sarcoid → ↑1,25-vit D]; thiazides; milk-alkali; immobilization; thyrotoxicosis)

RF: malignancy · primary hyperparathyroidism · vitamin D/calcium supplement excess · thiazide/lithium use · granulomatous disease · immobilization

Data: calcium (albumin-corrected or ionized) (confirm true hypercalcemia) · PTH — the key splitter (high/inappropriately normal = PTH-mediated/primary hyperparathyroidism; suppressed/low = PTH-independent → malignancy/vit D/other) · if PTH low: PTHrP, 1,25- and 25-OH vitamin D, SPEP/UPEP/free light chains, imaging for malignancy · phosphate (low in hyperparathyroidism/PTHrP; variable) · BMP/renal function · ECG (short QT) · 24h urine Ca (FHH — low urine Ca) · TSH

DDx: primary hyperparathyroidism (↑PTH, ↑Ca, ↓phos) · malignancy (↓PTH, ↑PTHrP or lytic mets/myeloma) · vitamin D excess/granulomatous (↑1,25-vit D) · FHH (↑PTH-ish, low urine Ca, family hx) · thiazide/milk-alkali (meds/supplements)

Home Meds: STOP thiazides, lithium, calcium/vitamin D/vitamin A supplements, calcium-containing antacids · caution digoxin (hypercalcemia potentiates toxicity) · renally dose · avoid further calcium loads

Plan

CONSULT: Endocrine (hyperparathyroidism, workup) · Oncology (malignancy-related) · Nephrology (severe/refractory, renal failure, dialysis) · ICU (severe symptomatic — >14, coma/arrhythmia)

– Severity-based urgency: mild (<12, asymptomatic) → treat cause + hydrate; moderate (12–14) → treat per symptoms; severe (>14 or symptomatic) → aggressive emergent treatment
– STEP 1 — Volume repletion (cornerstone): IV isotonic saline (0.9% NaCl) 200–300 mL/h (titrate to euvolemia + urine output ~100–150 mL/h) — corrects the dehydration (hypercalcemia causes a nephrogenic DI) and promotes calciuresis; monitor volume (caution in CHF/CKD)
– STEP 2 — Calcitonin (rapid, short-lived): calcitonin 4 units/kg SC/IM q12h — onset ~4–6h, lowers Ca ~1–2 mg/dL but tachyphylaxis in 48h; bridges until bisphosphonate works
– STEP 3 — Bisphosphonate (definitive for malignancy/high turnover, delayed onset): zoledronic acid 4 mg IV (or pamidronate 60–90 mg IV) — onset 2–4 days, peak ~4–7 days, durable; renally dose/adjust; preferred for malignancy hypercalcemia
– Alternatives/adjuncts: denosumab (bisphosphonate-refractory or renal failure where bisphosphonate contraindicated); glucocorticoids (prednisone) for vitamin D–mediated/granulomatous/lymphoma hypercalcemia (reduce 1,25-vit D); hemodialysis (with low-Ca bath) for severe, refractory, or renal-failure cases; loop diuretics only after euvolemia + for volume overload — not routine
– Treat the underlying cause: parathyroidectomy for symptomatic/severe primary hyperparathyroidism; treat the malignancy; stop offending supplements/drugs; treat granulomatous disease
– Saline first, always — these patients are profoundly dehydrated from the calcium-induced nephrogenic DI, and rehydration alone meaningfully lowers calcium and restores renal calcium excretion. Calcitonin buys time; the bisphosphonate is the durable fix but takes days. And don't reach for furosemide until the patient is volume-repleted.
– PT/OT: mobilize (immobilization worsens hypercalcemia); fall/confusion precautions
– Trend: calcium (serial), renal function, volume status/UOP, ECG, mental status, phosphate; PTH/workup results
– Escalation triggers: Ca >14/coma/arrhythmia → ICU + aggressive therapy ± dialysis; renal failure → dialysis/denosumab; refractory → escalate agents; underlying malignancy → oncology
– Discharge checklist: calcium controlled + cause identified (PTH-directed workup completed); offending drugs/supplements stopped; definitive plan (parathyroidectomy referral, oncology treatment, bisphosphonate/denosumab schedule); hydration counseling; outpatient calcium recheck + endocrine/oncology follow-up; return precautions (confusion, severe constipation/vomiting, excessive urination, weakness)

106. Hypercalcemia

complete reference · malignancy + primary hyperparathyroidism + vitamin D excess · PTH-based workup · saline/calcitonin/bisphosphonate · Full Card

Symptoms / Associated Sx

• The classic mnemonic "stones, bones, groans, and psychiatric moans": renal (polyuria/polydipsia leading to dehydration, nephrolithiasis, nephrogenic DI), gastrointestinal (nausea, constipation, anorexia, pancreatitis), neuropsychiatric (fatigue, confusion, lethargy, coma), and cardiac (short QT, arrhythmia, increased digoxin sensitivity)

• Bone pain

• Severity tracks both the level and the rate of rise; acute, malignancy-related rises are typically more symptomatic

Neg

• Pt denies that the value is an artifact of low albumin — correct the calcium (add 0.8 mg/dL per 1 g/dL of albumin below 4) or measure ionized calcium

• Pt denies a contributing thiazide or lithium (review medications)

• Pt denies immobilization as the sole cause and denies a factitious value from tourniquet/venous stasis

Social History (SHx)

• Known or suspected malignancy (breast, lung, myeloma, renal, squamous cell)

• Thiazides, lithium, vitamin D or A supplements, and calcium-containing antacids (milk-alkali syndrome)

• Family history (MEN syndromes, familial hypocalciuric hypercalcemia)

• Sarcoidosis or other granulomatous disease; immobilization; prior stones or fractures

Main Etiology

• PTH-mediated: primary hyperparathyroidism (the most common outpatient cause), tertiary hyperparathyroidism, and familial hypocalciuric hypercalcemia

• PTH-independent: malignancy (the most common inpatient cause — PTHrP from squamous and renal tumors, osteolytic metastases and myeloma, and 1,25-vitamin D production by lymphoma), vitamin D excess, granulomatous disease (sarcoidosis, via increased 1,25-vitamin D), thiazides, milk-alkali syndrome, immobilization, and thyrotoxicosis

RF

• Modifiable: vitamin D/calcium supplement excess, thiazide and lithium use, immobilization

• Non-modifiable: malignancy, primary hyperparathyroidism, and granulomatous disease

Data

• Calcium (albumin-corrected or ionized) (confirm true hypercalcemia)

• PTH — the key splitter (high or inappropriately normal indicates a PTH-mediated process such as primary hyperparathyroidism; suppressed/low indicates a PTH-independent cause — malignancy, vitamin D, or other)

• When PTH is low: PTHrP, 1,25- and 25-OH vitamin D, SPEP/UPEP with serum free light chains, and imaging for malignancy

• Phosphate (low in hyperparathyroidism and PTHrP-mediated hypercalcemia; otherwise variable)

• BMP/renal function

• ECG (short QT interval)

• 24-hour urine calcium (low in familial hypocalciuric hypercalcemia); TSH

DDx

Primary hyperparathyroidism (elevated PTH, elevated calcium, low phosphate) · malignancy (suppressed PTH with elevated PTHrP or lytic metastases/myeloma) · vitamin D excess or granulomatous disease (elevated 1,25-vitamin D) · familial hypocalciuric hypercalcemia (mildly elevated PTH, low urine calcium, family history) · thiazide or milk-alkali (medications/supplements)

Home Meds

• Stop: thiazides, lithium, calcium/vitamin D/vitamin A supplements, and calcium-containing antacids

• Caution with digoxin — hypercalcemia potentiates digoxin toxicity

• Avoid further calcium loads; renally dose medications

Plan

CONSULT: Endocrinology (hyperparathyroidism and workup) · Oncology (malignancy-related hypercalcemia) · Nephrology (severe/refractory cases, renal failure, dialysis) · ICU (severe symptoms — calcium >14, coma, arrhythmia)

• Match urgency to severity: mild (<12, asymptomatic) — treat the cause and hydrate; moderate (12–14) — treat according to symptoms; severe (>14 or symptomatic) — aggressive emergent treatment

• Step 1 — volume repletion (the cornerstone): IV isotonic saline (0.9% NaCl) at 200–300 mL/h, titrated to euvolemia with a urine output of ~100–150 mL/h — this corrects the dehydration (hypercalcemia causes a nephrogenic DI) and promotes calciuresis; monitor volume, with caution in heart failure or CKD

• Step 2 — calcitonin (rapid but short-lived): calcitonin 4 units/kg SC/IM every 12 hours, which acts within ~4–6 hours and lowers calcium by ~1–2 mg/dL but develops tachyphylaxis within 48 hours, bridging until the bisphosphonate takes effect

• Step 3 — bisphosphonate (the durable treatment for malignancy/high turnover, with delayed onset): zoledronic acid 4 mg IV (or pamidronate 60–90 mg IV), with onset over 2–4 days and a peak at ~4–7 days, dose-adjusted for renal function and preferred for malignancy-related hypercalcemia

• Alternatives/adjuncts: denosumab (for bisphosphonate-refractory cases or renal failure where bisphosphonates are contraindicated); glucocorticoids (prednisone) for vitamin D–mediated, granulomatous, or lymphoma hypercalcemia (reducing 1,25-vitamin D); and hemodialysis with a low-calcium bath for severe, refractory, or renal-failure cases — loop diuretics only after euvolemia is achieved and for volume overload, not routinely

• Treat the underlying cause: parathyroidectomy for symptomatic or severe primary hyperparathyroidism, treatment of the malignancy, discontinuation of offending supplements/drugs, and treatment of granulomatous disease

• PT/OT: mobilize (immobilization worsens hypercalcemia); fall and confusion precautions

• Trend: serial calcium, renal function, volume status and urine output, the ECG, mental status, phosphate, and the PTH/workup results

• Escalation triggers: calcium >14, coma, or arrhythmia → ICU with aggressive therapy and possible dialysis; renal failure → dialysis or denosumab; refractory disease → escalate agents; an underlying malignancy → oncology

• Discharge checklist: calcium controlled with the cause identified (a completed PTH-directed workup); offending drugs/supplements stopped; a definitive plan (parathyroidectomy referral, oncologic treatment, a bisphosphonate/denosumab schedule); hydration counseling; an outpatient calcium recheck with endocrine/oncology follow-up; return precautions for confusion, severe constipation or vomiting, excessive urination, or weakness

Red Flags

• Calcium >14 mg/dL or coma/arrhythmia → hypercalcemic crisis → aggressive saline, calcitonin, bisphosphonate, and ICU care

• Renal failure precluding bisphosphonates → denosumab or dialysis with a low-calcium bath

• New hypercalcemia with suppressed PTH → search for malignancy

• Hypercalcemia on digoxin → potentiated toxicity

• Pancreatitis or severe AKI complicating the picture → escalate care

Senior IM Resident Pearls

• Saline first, always. These patients are volume-depleted from the calcium-induced nephrogenic DI, and rehydration alone lowers the calcium meaningfully while restoring renal calcium excretion.

• PTH splits the entire differential. A high or inappropriately normal PTH points to hyperparathyroidism; a suppressed PTH sends you hunting for malignancy and vitamin D causes.

• Calcitonin bridges, the bisphosphonate fixes. Calcitonin works in hours but fades by 48; zoledronic acid is durable but takes days — use them in sequence, not as substitutes.

• Hold the furosemide. Loop diuretics are not first-line and only have a role once the patient is volume-repleted and overloaded — giving them to a dehydrated patient worsens the hypercalcemia.

• Steroids are the answer for vitamin D–driven hypercalcemia (granulomatous disease, lymphoma) — they cut 1,25-vitamin D production, where bisphosphonates are less effective.

• Always correct for albumin or check an ionized calcium — a low albumin can mask or mimic abnormalities.

• Common mistake: giving a bisphosphonate and waiting — without aggressive saline up front, the calcium stays dangerously high for the days it takes the bisphosphonate to work.

Electrolytes — Calcium

107. Hypocalcemia

low calcium · CKD / hypoparathyroidism / vitamin D deficiency / acute pancreatitis · Chvostek & Trousseau, ↑QT · check Mg + albumin · IV calcium for symptomatic/severe · Super Compact

Sx: neuromuscular irritability — perioral/distal paresthesias, cramps, tetany, carpopedal spasm, Chvostek sign (facial tap) & Trousseau sign (carpal spasm w/ BP cuff) · severe: laryngospasm, seizures, ↑QT → arrhythmia, hypotension/↓cardiac contractility · chronic: cataracts, basal ganglia calcification, papilledema (severity tracks the level + rate of fall; acute drops are far more symptomatic)

Neg: denies ↓albumin artifact (correct: add 0.8 per 1 g/dL albumin below 4, or check ionized Ca — true ionized may be normal) · denies untreated hypomagnesemia (causes/worsens hypoCa — must replace Mg) · denies alkalosis/citrate (massive transfusion) lowering ionized Ca · denies that this is just dilutional

SHx: CKD/ESRD · neck/thyroid/parathyroid surgery (post-op hypoparathyroidism — classic) or radiation · vitamin D deficiency (malabsorption, poor intake, sunlight) · acute pancreatitis · alcohol use (↓Mg) · meds — bisphosphonates, denosumab, cinacalcet, foscarnet, PPIs (↓Mg)

Etiology: ↓PTH (hypoparathyroidism — post-surgical [thyroid/parathyroid], autoimmune; hypomagnesemia impairs PTH) · ↓ or resistance to vitamin D (deficiency — poor intake/malabsorption/sunlight; CKD — ↓1,25-vit D + hyperphosphatemia) · calcium sequestration/chelation (acute pancreatitis — saponification; tumor lysis — hyperphosphatemia; citrate from massive transfusion; rhabdomyolysis) · ↑phosphate · drugs (bisphosphonates, denosumab)

RF: CKD/ESRD · recent neck surgery · vitamin D deficiency/malabsorption · pancreatitis · hypomagnesemia · massive transfusion · antiresorptive drugs

Data: calcium (ionized, or albumin-corrected) (confirm true hypocalcemia) · magnesium (ALWAYS — low Mg causes refractory hypoCa) · PTH (low/inappropriately normal = hypoparathyroidism; high = appropriate response to vit D deficiency/CKD/chelation) · phosphate (high in CKD/hypoPTH/tumor lysis; low in vit D deficiency) · 25-OH (and 1,25-) vitamin D · BMP/renal function · ECG (↑QT) · lipase if pancreatitis

DDx: hypoparathyroidism (↓PTH, ↑phos — post-surgical) · vitamin D deficiency (↑PTH, ↓phos, ↓25-OH vit D) · CKD (↑PTH, ↑phos, ↓1,25) · chelation/sequestration (pancreatitis, tumor lysis, transfusion) · hypomagnesemia-driven (low Mg)

Home Meds: review bisphosphonates/denosumab, cinacalcet, PPIs (↓Mg), foscarnet · continue/adjust calcium + active vitamin D (calcitriol) in CKD/hypoPTH · renally dose

Plan

CONSULT: Endocrine (hypoparathyroidism, vitamin D, chronic management) · Nephrology (CKD-MBD) · ICU (severe — laryngospasm/seizure/arrhythmia) · Surgery (if post-thyroidectomy)

– Triage by symptoms/severity/ECG: symptomatic (tetany, laryngospasm, seizure), severe (ionized very low), or ↑QT/arrhythmia → IV calcium emergently + cardiac monitoring
– IV calcium (symptomatic/severe): calcium gluconate 1–2 g IV (10–20 mL of 10%) over 10–20 min (preferred peripherally — less sclerosing than calcium chloride; CaCl₂ via central line in arrest/severe), then a calcium gluconate infusion for ongoing/severe (e.g. ~0.5–1.5 mg/kg/h elemental calcium, titrated) — bolus effect is short-lived, so an infusion bridges to oral; continuous monitoring
– CHECK AND REPLACE MAGNESIUM: hypomagnesemia impairs PTH secretion/action and makes hypocalcemia refractory — give magnesium sulfate 1–2 g IV; the calcium won't correct until Mg is repleted
– Oral calcium + vitamin D (mild/chronic/maintenance): oral calcium carbonate/citrate + active vitamin D (calcitriol) — especially in hypoparathyroidism and CKD (where 1-α-hydroxylation is impaired, so calcitriol, not plain vitamin D, is needed); plain vitamin D (ergo-/cholecalciferol) for simple deficiency
– Treat by cause:
  • Post-surgical hypoparathyroidism: calcium + calcitriol; monitor (can be transient or permanent)
  • Vitamin D deficiency: repletion (cholecalciferol/ergocalciferol) + calcium; treat malabsorption
  • CKD: calcitriol/active vit D analog, phosphate binders (control the hyperphosphatemia), manage CKD-MBD
  • Acute pancreatitis / tumor lysis / chelation: treat the underlying process; replace calcium for symptoms (in hyperphosphatemia, correcting phosphate is also key — don't give large calcium into very high phosphate → precipitation)
– Always check magnesium and albumin first. Low magnesium makes hypocalcemia refractory until corrected, and a low albumin can make the total calcium look falsely low when the physiologically active ionized calcium is fine — an ionized calcium settles it.
– PT/OT: fall precautions; monitor for tetany
– Trend: ionized/corrected calcium, magnesium, phosphate, PTH, ECG/QT, symptoms, renal function
– Escalation triggers: laryngospasm/seizure/arrhythmia → ICU + IV calcium; refractory despite calcium → check/replace Mg; post-thyroidectomy falling Ca → aggressive replacement + surgery aware; very high phosphate → correct phosphate before large calcium loads
– Discharge checklist: calcium corrected + cause identified; magnesium normalized; maintenance regimen defined (calcium + appropriate vitamin D form — calcitriol for hypoPTH/CKD); offending drugs reviewed; outpatient Ca/Mg/phos recheck + endocrine/nephrology follow-up; return precautions (tingling, cramps/spasm, seizures, palpitations)

107. Hypocalcemia

complete reference · CKD + hypoparathyroidism + vitamin D deficiency + acute pancreatitis · check Mg/albumin · IV calcium + appropriate vitamin D · Full Card

Symptoms / Associated Sx

• Neuromuscular irritability: perioral and distal paresthesias, cramps, tetany, and carpopedal spasm, with Chvostek sign (facial twitch on tapping) and Trousseau sign (carpal spasm with blood pressure cuff inflation)

• Severe hypocalcemia causes laryngospasm, seizures, QT prolongation with arrhythmia, and hypotension from reduced cardiac contractility

• Chronic hypocalcemia causes cataracts, basal ganglia calcification, and papilledema

• Severity tracks the level and the rate of fall, with acute drops far more symptomatic

Neg

• Pt denies a low-albumin artifact — correct the calcium (add 0.8 mg/dL per 1 g/dL of albumin below 4) or measure ionized calcium, which may be normal

• Pt denies untreated hypomagnesemia, which causes and perpetuates hypocalcemia and must be replaced

• Pt denies an alkalosis or citrate effect (massive transfusion) lowering the ionized calcium, and denies a purely dilutional value

Social History (SHx)

• CKD/ESRD

• Neck, thyroid, or parathyroid surgery (post-surgical hypoparathyroidism — the classic cause) or radiation

• Vitamin D deficiency (malabsorption, poor intake, limited sun exposure)

• Acute pancreatitis; alcohol use (low magnesium); and drugs (bisphosphonates, denosumab, cinacalcet, foscarnet, and PPIs that lower magnesium)

Main Etiology

• Reduced PTH: hypoparathyroidism (post-surgical after thyroid/parathyroid surgery, or autoimmune), and hypomagnesemia (which impairs PTH secretion and action)

• Reduced or resistance to vitamin D: deficiency (poor intake, malabsorption, limited sunlight) and CKD (reduced 1,25-vitamin D with hyperphosphatemia)

• Calcium sequestration/chelation: acute pancreatitis (saponification), tumor lysis (hyperphosphatemia), citrate from massive transfusion, and rhabdomyolysis

• Hyperphosphatemia and antiresorptive drugs (bisphosphonates, denosumab)

RF

• Modifiable: vitamin D status, magnesium status, antiresorptive drug use

• Non-modifiable: CKD/ESRD, recent neck surgery, pancreatitis, and massive transfusion

Data

• Calcium (ionized, or albumin-corrected) (confirm true hypocalcemia)

• Magnesium — always check (low magnesium causes refractory hypocalcemia)

• PTH (low or inappropriately normal indicates hypoparathyroidism; high is an appropriate response to vitamin D deficiency, CKD, or chelation)

• Phosphate (high in CKD, hypoparathyroidism, and tumor lysis; low in vitamin D deficiency)

• 25-OH (and 1,25-) vitamin D

• BMP/renal function

• ECG (QT prolongation); lipase if pancreatitis is suspected

DDx

Hypoparathyroidism (low PTH, high phosphate — post-surgical) · vitamin D deficiency (high PTH, low phosphate, low 25-OH vitamin D) · CKD (high PTH, high phosphate, low 1,25-vitamin D) · chelation/sequestration (pancreatitis, tumor lysis, transfusion) · hypomagnesemia-driven (low magnesium)

Home Meds

• Review: bisphosphonates/denosumab, cinacalcet, PPIs (lower magnesium), and foscarnet

• Continue/adjust: calcium and active vitamin D (calcitriol) in CKD and hypoparathyroidism

• Renally dose medications

Plan

CONSULT: Endocrinology (hypoparathyroidism, vitamin D, chronic management) · Nephrology (CKD–mineral bone disease) · ICU (severe — laryngospasm, seizure, arrhythmia) · Surgery (post-thyroidectomy)

• Triage by symptoms, severity, and ECG: symptomatic (tetany, laryngospasm, seizure), severe (very low ionized calcium), or QT prolongation/arrhythmia warrants emergent IV calcium with cardiac monitoring

• IV calcium for symptomatic/severe hypocalcemia: calcium gluconate 1–2 g IV (10–20 mL of 10%) over 10–20 minutes (preferred peripherally, being less sclerosing than calcium chloride, which is reserved for central access in arrest or severe cases), followed by a calcium gluconate infusion for ongoing or severe hypocalcemia (e.g. ~0.5–1.5 mg/kg/h of elemental calcium, titrated), since the bolus effect is short-lived and an infusion bridges to oral therapy, with continuous monitoring

• Check and replace magnesium: hypomagnesemia impairs PTH secretion and action and makes hypocalcemia refractory — give magnesium sulfate 1–2 g IV, as the calcium will not correct until the magnesium is replaced

• Oral calcium and vitamin D for mild/chronic/maintenance: oral calcium carbonate or citrate with active vitamin D (calcitriol), especially in hypoparathyroidism and CKD (where renal 1-α-hydroxylation is impaired, so calcitriol rather than plain vitamin D is required); use plain vitamin D (ergocalciferol or cholecalciferol) for simple deficiency

• Treat by cause:

• • Post-surgical hypoparathyroidism: calcium and calcitriol, with monitoring (it may be transient or permanent)

• • Vitamin D deficiency: repletion (cholecalciferol/ergocalciferol) with calcium, and treatment of any malabsorption

• • CKD: calcitriol or an active vitamin D analog, phosphate binders to control the hyperphosphatemia, and management of CKD–mineral bone disease

• • Acute pancreatitis, tumor lysis, or chelation: treat the underlying process and replace calcium for symptoms — in hyperphosphatemia, correcting the phosphate is also key, and large calcium loads given into a very high phosphate can cause calcium-phosphate precipitation

• PT/OT: fall precautions; monitor for tetany

• Trend: ionized/corrected calcium, magnesium, phosphate, PTH, the ECG/QT, symptoms, and renal function

• Escalation triggers: laryngospasm, seizure, or arrhythmia → ICU and IV calcium; refractory despite calcium → check and replace magnesium; a falling calcium after thyroidectomy → aggressive replacement with surgery aware; a very high phosphate → correct the phosphate before large calcium loads

• Discharge checklist: calcium corrected with the cause identified; magnesium normalized; a defined maintenance regimen (calcium plus the appropriate vitamin D form — calcitriol for hypoparathyroidism/CKD); offending drugs reviewed; an outpatient calcium/magnesium/phosphate recheck with endocrine/nephrology follow-up; return precautions for tingling, cramps or spasm, seizures, or palpitations

Red Flags

• Laryngospasm, seizures, or arrhythmia with QT prolongation → emergent IV calcium and ICU care

• Refractory hypocalcemia despite calcium → unrecognized hypomagnesemia until proven otherwise

• Rapidly falling calcium after thyroid/parathyroid surgery → aggressive replacement and surgical awareness

• Hyperphosphatemia with hypocalcemia → avoid large calcium loads (precipitation); correct phosphate

• Acute symptomatic hypocalcemia → treat without waiting for the full workup

Senior IM Resident Pearls

• Check magnesium and albumin before anything else. Low magnesium makes hypocalcemia refractory, and a low albumin makes the total calcium look falsely low while the active ionized calcium is normal — an ionized calcium resolves the ambiguity.

• CKD needs calcitriol, not plain vitamin D. The failing kidney can't perform the 1-α-hydroxylation step, so plain vitamin D won't raise the calcium — give the active form.

• The bolus wears off — bridge with an infusion. A single calcium gluconate push corrects briefly; symptomatic or severe patients need a continuous infusion until oral therapy takes hold.

• Post-thyroidectomy calcium is a predictable pitfall. Watch the trend closely in the first days; transient (or permanent) hypoparathyroidism is common and can drop the calcium fast.

• Don't dump calcium into a high phosphate. In tumor lysis or renal failure, large calcium loads precipitate with phosphate — correct the phosphate and treat calcium conservatively for symptoms.

• Use calcium gluconate peripherally. Calcium chloride is more sclerosing and tissue-toxic on extravasation — reserve it for central access in arrest or severe cases.

• Common mistake: repleting calcium while ignoring a low magnesium — the calcium won't budge, and the underlying driver goes untreated.

Acid-Base — Metabolic Acidosis

108. Metabolic Acidosis

low bicarb + low pH · AKI / CKD / sepsis / DKA / lactic · the anion gap splits it (HAGMA vs NAGMA) · check gap, delta-delta, compensation · treat the cause · Super Compact

Sx: underlying illness often dominates · Kussmaul (deep, rapid) breathing (respiratory compensation), tachypnea · nausea/vomiting, abdominal pain, confusion/lethargy · signs of cause (DKA — polyuria/dehydration; sepsis/shock — hypotension; uremia — AKI/CKD) (severe acidemia → ↓cardiac contractility, arrhythmia, vasodilation/hypotension)

Neg: denies vomiting/NG loss/diuretics (suggests metabolic alkalosis — may coexist) · denies pure respiratory cause (check pCO2/compensation) · denies missed mixed disorder (delta-delta + compensation) · denies toxic alcohol unexamined if unexplained HAGMA (osmolar gap)

SHx: diabetes (DKA) · sepsis/critical illness · CKD/ESRD · alcohol (AKA, toxic alcohols, lactic) · toxic ingestion (methanol/ethylene glycol/salicylate) · diarrhea (NAGMA) · metformin (lactic)

Etiology / framework: HAGMA (↑unmeasured anions) — "GOLD MARK": Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin/salicylate, Renal failure (uremic acids), Ketoacidosis · NAGMA (↑Cl⁻) — "HARDASS": Hyperalimentation, Acetazolamide, RTA, Diarrhea (#1), Ammonium chloride, Spironolactone, Saline · key drivers per request — AKI/CKD (impaired acid excretion — gap or non-gap), sepsis (lactic — hypoperfusion), DKA (ketoacids — HAGMA), lactic acidosis (shock/ischemia/metformin — HAGMA)

RF: diabetes · sepsis/shock/hypoperfusion · CKD/ESRD · toxic ingestion · diarrhea · metformin (esp with AKI)

Data: ABG/VBG + BMP (low HCO3, low pH) · anion gap = Na − (Cl + HCO3) (normal ~8–12; correct for albumin: +2.5 per 1 g/dL below 4) · delta-delta (ΔAG/ΔHCO3) (~1–2 pure HAGMA; <1 concurrent NAGMA; >2 concurrent metabolic alkalosis) · Winter's formula (expected pCO2 = 1.5×HCO3 + 8 ±2) (adequate respiratory compensation vs added respiratory disorder) · lactate · glucose + ketones (β-hydroxybutyrate) · osmolar gap (↑ → toxic alcohols) · salicylate level · BUN/Cr · urine pH/anion gap (NAGMA — RTA vs diarrhea) · K

DDx: HAGMA causes (lactate, ketones, uremia, toxins — GOLD MARK) · NAGMA causes (diarrhea vs RTA — urine anion gap) · respiratory/mixed (compensation formulas) · coexisting metabolic alkalosis (delta-delta >2)

Home Meds: hold metformin (lactic, esp with AKI) · hold SGLT2i (euglycemic DKA) · review acetazolamide/spironolactone/TPN (NAGMA) · renally dose if AKI/CKD

Plan

CONSULT: Nephrology (RTA, severe/refractory, dialysis, toxic ingestion) · Toxicology/Poison control (methanol/ethylene glycol/salicylate) · ICU (severe acidemia/shock) · Endocrine (refractory DKA)

– Step 1 — confirm + classify: ABG/VBG + BMP; calculate the albumin-corrected anion gap — HAGMA vs NAGMA organizes the whole differential
– Step 2 — check for mixed disorders: delta-delta (concurrent NAGMA or metabolic alkalosis) and Winter's formula (appropriate respiratory compensation vs added respiratory disorder)
– Step 3 — treat the cause (this is the therapy):
  • Sepsis / lactic acidosis: restore perfusion — IV fluids, source control, broad-spectrum antibiotics, vasopressors to a MAP target; correct hypoxia/ischemia; stop metformin; bicarbonate generally not helpful unless pH very low
  • DKA: IV isotonic fluids, IV insulin infusion (0.1 units/kg/h after fluids; do not start insulin if K <3.3 until repleted), aggressive potassium repletion (total-body deplete despite normal/high serum), find/treat trigger, close glucose/K/gap monitoring; transition to SC insulin when gap closed
  • AKI/CKD (uremic) acidosis: treat the kidney injury; oral sodium bicarbonate for chronic CKD acidosis (target HCO3 ≥22); dialysis if severe/refractory or other indication (AEIOU)
  • NAGMA (diarrhea/RTA): treat losses, oral bicarbonate/citrate; type-specific RTA care
  • Toxic alcohols: fomepizole + dialysis ± bicarbonate; salicylate: urine alkalinization + dialysis if severe
– Bicarbonate therapy — selective: consider IV sodium bicarbonate for severe acidemia (pH <7.1, or per cause); routine bicarbonate for lactic/ketoacidosis is generally not beneficial and can harm (watch Na, volume, ionized Ca, paradoxical intracellular acidosis)
– Monitor K closely — acidosis shifts K out (serum may mask total-body depletion, esp DKA); treatment shifts it back in
– Always run three calculations, not one: the albumin-corrected gap, the delta-delta, and Winter's. A "simple" low bicarbonate frequently hides a second or third acid-base disorder — and in sepsis/DKA the fix is perfusion and insulin, not bicarbonate.
– PT/OT: per underlying illness
– Trend: serial ABG/VBG + bicarbonate + gap, lactate, glucose/ketones (DKA), K + electrolytes, mental status, hemodynamics
– Escalation triggers: pH <7.1 with instability, refractory acidosis, toxic ingestion, or AEIOU → ICU + dialysis/toxicology; worsening despite cause-directed therapy → reassess for mixed/missed cause
– Discharge checklist: cause treated + acid-base normalized/trending; offending drugs addressed (metformin/SGLT2i decision); chronic bicarbonate if CKD; diabetes sick-day plan if DKA; nephrology/endocrine follow-up; return precautions (rapid breathing, confusion, vomiting, recurrent symptoms)

108. Metabolic Acidosis

complete reference · AKI + CKD + sepsis + DKA + lactic acidosis · HAGMA vs NAGMA · gap + delta-delta + compensation · Full Card

Symptoms / Associated Sx

• The underlying illness often dominates; Kussmaul respirations (deep, rapid breathing) reflect respiratory compensation

• Nausea, vomiting, abdominal pain, confusion, and lethargy

• Features of the specific cause: polyuria and dehydration in DKA; hypotension and hypoperfusion in sepsis/lactic acidosis; uremic features with AKI/CKD

• Severe acidemia depresses cardiac contractility, predisposes to arrhythmia, and causes vasodilation and hypotension

Neg

• Pt denies vomiting, NG suction, or diuretic use — which generate a metabolic alkalosis that may coexist as a mixed disorder

• Pt denies a pure respiratory cause — verify with the pCO2 and expected compensation

• Pt denies a missed mixed disorder (apply the delta-delta and compensation formulas) and denies an unexamined toxic alcohol exposure when a high-gap acidosis is otherwise unexplained (check the osmolar gap)

Social History (SHx)

• Diabetes (DKA)

• Sepsis or critical illness; CKD/ESRD

• Alcohol use (alcoholic ketoacidosis, toxic alcohols, lactic acidosis)

• Toxic ingestions (methanol, ethylene glycol, salicylate); diarrhea (NAGMA); metformin use (lactic acidosis, especially with AKI)

Main Etiology / Framework

• High anion gap (HAGMA) — "GOLD MARK": Glycols (ethylene/propylene glycol), Oxoproline, L-lactate, D-lactate, Methanol, Aspirin (salicylates), Renal failure (retained uremic acids), Ketoacidosis (diabetic, alcoholic, starvation)

• Normal anion gap (hyperchloremic, NAGMA) — "HARDASS": Hyperalimentation, Acetazolamide, Renal tubular acidosis, Diarrhea (the most common), Ammonium chloride, Spironolactone, Saline

• The drivers emphasized here: AKI/CKD impair acid excretion (gap or non-gap); sepsis causes lactic acidosis from hypoperfusion; DKA produces ketoacids (HAGMA); and lactic acidosis arises from shock, ischemia, or metformin (HAGMA)

RF

• Modifiable: metformin use with AKI, glycemic control, perfusion optimization

• Non-modifiable: diabetes, CKD/ESRD, and predisposition to sepsis/shock

Data

• ABG/VBG with BMP (low bicarbonate and low pH confirm a primary metabolic acidosis)

• Anion gap = Na − (Cl + HCO3) (normal ~8–12; correct upward by ~2.5 for each 1 g/dL the albumin falls below 4)

• Delta-delta ratio (ΔAnion gap / ΔHCO3) (~1–2 in a pure HAGMA; <1 suggests a concurrent NAGMA; >2 suggests a concurrent metabolic alkalosis)

• Winter's formula (expected pCO2 = 1.5 × HCO3 + 8 ± 2) (assesses respiratory compensation; a pCO2 outside the range indicates an added respiratory disorder)

• Lactate (lactic acidosis); glucose and ketones (β-hydroxybutyrate) (ketoacidosis)

• Osmolar gap (elevated with toxic alcohols); salicylate level

• BUN/creatinine (uremic acidosis); urine pH and urine anion gap (separate RTA from diarrhea in NAGMA); potassium (shifts with acidosis)

DDx

HAGMA causes (lactate, ketones, uremia, toxins — the GOLD MARK list) · NAGMA causes (diarrhea vs renal tubular acidosis — by the urine anion gap) · respiratory or mixed acid-base disorder (compensation formulas) · coexisting metabolic alkalosis (delta-delta >2)

Home Meds

• Hold: metformin (lactic acidosis risk, especially with AKI)

• Hold: SGLT2 inhibitors (euglycemic DKA risk during acute illness)

• Review: acetazolamide, spironolactone, and TPN as NAGMA contributors; renally dose if AKI/CKD

Plan

CONSULT: Nephrology (renal tubular acidosis, severe/refractory acidosis, dialysis, toxic ingestion) · Toxicology/Poison Control (methanol, ethylene glycol, salicylate) · ICU (severe acidemia or shock) · Endocrinology (refractory DKA)

• Step 1 — confirm and classify: obtain an ABG/VBG with a BMP and calculate the albumin-corrected anion gap; the HAGMA-versus-NAGMA split organizes the entire differential

• Step 2 — check for mixed disorders: apply the delta-delta ratio (concurrent NAGMA or metabolic alkalosis) and Winter's formula (appropriate respiratory compensation versus an added respiratory disorder)

• Step 3 — treat the underlying cause, the definitive therapy:

• • Sepsis/lactic acidosis: restore perfusion — IV fluids, source control, broad-spectrum antibiotics, and vasopressors to a MAP target; correct hypoxia and ischemia; stop metformin; bicarbonate is generally unhelpful unless the pH is very low

• • DKA: IV isotonic fluids, an IV insulin infusion (0.1 units/kg/h after initial fluids; do not start insulin if potassium is <3.3 mmol/L until repleted), aggressive potassium repletion (total-body potassium is depleted despite a normal or high serum value), identification and treatment of the trigger, and close monitoring of glucose, potassium, and the anion gap, transitioning to subcutaneous insulin once the gap closes

• • AKI/CKD (uremic) acidosis: treat the kidney injury; for chronic CKD acidosis use oral sodium bicarbonate targeting a serum bicarbonate ≥22 mmol/L; dialyze for severe or refractory acidosis or other indications

• • NAGMA (diarrhea or RTA): address losses and replace base with oral sodium bicarbonate or citrate, with type-specific management for renal tubular acidosis

• • Toxic alcohols: fomepizole and dialysis (with bicarbonate as adjunct); for salicylate toxicity, urine alkalinization and hemodialysis for severe poisoning

• Bicarbonate therapy is selective: consider IV sodium bicarbonate for severe acidemia (pH <7.1, or as dictated by the cause); routine bicarbonate for lactic acidosis or ketoacidosis is generally not beneficial and may harm (watch sodium, volume, ionized calcium, and paradoxical intracellular acidosis)

• Monitor potassium closely: acidosis shifts potassium out of cells so the serum value can mask total-body depletion (notably in DKA), and treatment shifts it back intracellularly

• PT/OT: guided by the underlying illness

• Trend: serial ABG/VBG with bicarbonate and the anion gap, lactate, glucose and ketones (in DKA), potassium and other electrolytes, mental status, and hemodynamics

• Escalation triggers: pH <7.1 with instability, refractory acidosis, a toxic ingestion, or any dialysis indication → ICU with dialysis/toxicology; worsening despite cause-directed therapy → reassess for a mixed or missed cause

• Discharge checklist: the cause treated and the acid-base status normalized or trending toward normal; offending drugs addressed (metformin/SGLT2 inhibitor decisions); chronic oral bicarbonate for CKD acidosis; a diabetes sick-day plan if DKA; nephrology or endocrinology follow-up; return precautions for rapid breathing, confusion, vomiting, or recurrent symptoms

Red Flags

• Severe acidemia (pH <7.1) with hemodynamic instability → ICU; consider bicarbonate and dialysis

• Elevated osmolar gap with a high anion gap → toxic alcohol ingestion → fomepizole and dialysis emergently

• DKA with potassium <3.3 → replete potassium before insulin to avoid fatal hypokalemia

• Lactic acidosis from sepsis/ischemia → the lactate marks a perfusion emergency, not a number to buffer

• Mixed disorder masking severity → always run the delta-delta and compensation checks

Senior IM Resident Pearls

• Three calculations, not one: the albumin-corrected anion gap, the delta-delta, and Winter's formula. A "simple" low bicarbonate frequently hides a second or third acid-base disorder.

• Correct the gap for albumin. Each 1 g/dL drop lowers the measured gap by ~2.5 — an uncorrected gap can hide a real HAGMA in a hypoalbuminemic patient.

• The treatment is the cause, not the bicarbonate. In sepsis the fix is perfusion and antibiotics; in DKA it's fluids and insulin — routine bicarbonate doesn't help and can harm.

• Watch the potassium in DKA like a hawk. The serum value overstates total-body stores; insulin and fluids drop it fast, and a low-normal potassium before insulin is a trap.

• An unexplained high-gap acidosis with an osmolar gap is a toxic alcohol until proven otherwise — start fomepizole and call toxicology rather than waiting for levels.

• Urine anion gap separates diarrhea from RTA in a non-gap acidosis — negative (appropriate ammonium excretion) points to GI loss, positive points to renal acidification failure.

• Common mistake: chasing the bicarbonate number with IV bicarbonate in lactic acidosis — it can worsen intracellular pH and distracts from the real fix, which is restoring perfusion.