Info
🌱 來自: Huppert’s Notes
Sodium🚧 施工中
Sodium
Sodium homeostasis (Na**+** 135 to 145 mmol/L)
• Extracellular Na+ concentration reflects water homeostasis: Hyponatremia and hypernatremia are caused by too much/too little water. Total Na+ content reflects Na+ homeostasis
• Sodium is actively pumped out of cells: Na+ is the main cation in the extracellular fluid (ECF); most sodium reabsorption occurs at the proximal tubule
• Sodium homeostasis (RAAS):
- Decreased ECF volume → Decreased renal perfusion → ↑Renin by juxtaglomerular (JGA) cells → ACE activates angiotensin II
- Angiotensin II then increases ADH and aldosterone secretion, which increases net Na+ reabsorption and water is absorbed with the Na+
- Aldosterone is secreted by the adrenal gland: Na+/H2O reabsorbed, H+/K+ secreted
• Water homeostasis (ADH):
- Increased plasma osmolarity → Osmoregulators in the hypothalamus stimulate thirst and secretion of ADH
- ADH increases H2O permeability at the principal cells → Promotes water absorption (and also stimulates thirst!)
Hyponatremia (Na**+** <135 mEq/L)
• Etiologies: See Figure 6.4. History is key!
- Acuity: Has the hyponatremia occurred within the last 48 hours (e.g., postoperatively with a normal preoperative baseline)?
- Volume: Fluid intake, diet, urinary changes, extrarenal losses (e.g., diarrhea or hemorrhage)
- PMH: Active renal, endocrine, pulmonary or neurologic disease
- Medications: Especially diuretics and recent medication changes
- Social history: Use of alcohol, MDMA, other illicit substances
• Clinical features: Signs/symptoms predominantly neurologic: Headache, delirium, hyperactive deep tendon reflexes, seizures, coma
• Diagnosis: See Figure 6.4 and the steps below
Step 1: Is sodium the problem (e.g., is the blood hypotonic)? Check serum osms.
Sodium is the major solute in the blood, so if sodium is low then the serum osms should also be low unless another process is contributing to the serum mOsms. Test = serum osms.
- High serum osms (>295 mOsm/kg):
• Hypertonic hyponatremia: Low sodium is an appropriate response to the presence of excess osmotic substrate, e.g., glucose, mannitol, maltose/sucrose (IVIG)
• Correct for hyperglycemia: If glucose >100 mg/dL, for every additional 100 mg/dL, add 1.6 to Na+ (e.g., if glucose 300 mg/dL and Na+ 132 mEq/L then add 1.6(2) = approximately 135 mEq/L corrected)
- Normal serum osms (280–295 mOsm/kg):
• Pseudohyponatremia (normal amount of Na+ in water; however, there is a higher-than-normal amount of another non-aqueous substance, e.g., paraprotein, lipids, or bilirubin, causing underestimation of the Na+ concentration). May also be due to a mixed hypotonic and hypertonic process
- Low serum osms (<280 mOsm/kg): True hyponatremia. Proceed to step 2.
• If the measured serum osms are normal but the calculated osms are low, it is because a solute not included in the calculated estimate is present and being measured, e.g., ethanol or toxic alcohol
Step 2: Is the kidney responding appropriately (e.g., is ADH off)? Check urine osms.
ADH causes increased reabsorption of free water at the collecting ducts. In hyponatremia, ADH should be repressed if the kidneys are responding appropriately to get rid of excess free water. Test = urine osms.
- If urine osms <100 mOsm/kg: This indicates that the problem is not in the kidney, and instead it relates to how much water or salt the patient is consuming.
• Too much water = Primary polydipsia (12 to 20 L/day): Psychosis, ecstasy, marathon running. Will produce copious urine in the absence of extrarenal fluid loss.
• Too little solute = “Beer potomania”/“tea and toast diet” deficient in solute. In this case, the kidney cannot produce as much dilute urine to remove excess free water as someone with normal solute intake. This will often be a contributor in patients with concomitant hypovolemia.
- If urine osms ≥100 mOsm/kg: Proceed to Step 3
• Pearl: If intermediate urine osms, or even if low, think about tubular dysfunction due to diuretics, AKI or CKD. In severe renal disease, the kidney can’t concentrate urine appropriately, and this may cause hyponatremia. Isosthenuria, or a urine specific gravity similar to serum concentration (1.006 to 1.012), may be an early clue.
Step 3: Is ADH “on” for a hemodynamic reason (e.g., low effective arterial blood volume)? Check volume status and UNa.
- Hypovolemia: Hypovolemia → RAAS activation → ADH “on” and increases renal free H2O absorption. Signs: Orthostatic hypotension, dry mucous membranes, decreased skin turgor.
• Typically urine Na+ <20 mEq/L if extrarenal losses (e.g., vomiting, diarrhea, third-spacing)
• Urine Na+ may be higher if patient on diuretics or if tubular dysfunction is present (e.g., ATN advanced CKD)
- Hypervolemic: ADH “on” due to perceived low volume at the JGA (e.g., heart failure, cirrhosis, nephrotic syndrome)
• Typically urine Na+ <20 mEq/L with heart failure, cirrhosis, nephrotic syndrome, hypoalbuminemia
• Urine Na+ may be higher in advanced CKD or while taking diuretics
Step 4: Is ADH “on” for a non-hemodynamic reason? Consider euvolemic etiologies of hyponatremia.
- “Inappropriate” causes of ADH activity:
• Syndrome of inappropriate ADH (SIADH)
- Diseases: CNS, pulmonary, malignancy (especially SCLC)
- Medications: SSRIs, antiepileptic drugs, chemotherapy
- Cortical stimulation: Pain, nausea, psychosis
• Endocrine: Hypothyroidism, mineralocorticoid deficiency, glucocorticoid deficiency
FIGURE 6.4: Workup of hyponatremia. This diagram depicts one strategy to work up hyponatremia. See the text for additional details.
• Treatment of hyponatremia:
- General principles:
• Don’t correct too quickly! Unless acute (confirmed duration <48 hr, usually postoperatively) or presenting with severe symptoms (seizure, coma). Overcorrection can cause central pontine demyelination (see below).
• Goal for correction is 6–8 mEq/24 hr. Do not correct sodium more than 8 mEq/24 hr if hyponatremia has been present for >48 hours or an unknown duration of time.
• If Na+ <120 mEq/L: Consider nephrology consult, check Na+ q2–4 hours when beginning correction
• If severe symptoms or Na+ <115 mEq/L: Nephrology consult, check q1-2 hours when beginning correction
• Electrolyte-free water clearance (EFWC) can be used to estimate urinary free water excretion (and effective concentrating activity of ADH)
- EFWC = Urine output × [1 – (Urine Na+ + Urine K+ / P)/Plasma Na+]
- Gives volume of water free of osmotically active electrolytes “cleared” from plasma. If negative, kidneys are concentrating urine and hypertonic saline will likely be needed. If positive, kidney is correcting and hyponatremia may improve with isotonic fluids or salt tabs
- Assumes consistent urine concentration (usually true in SIADH, usually not true in hypovolemia or heart failure)
• Pearl: Giving potassium will increase serum sodium because the potassium is an exchangeable ion and will be transported intracellularly in exchange for sodium, so account for this when calculating fluids for sodium correction to avoid overcorrection
- Treatment of non-acute hyponatremia by volume status:
• Hypovolemia
- If mild, trial IV fluids and recheck
- Monitor urine free water output and recheck serum sodium frequently to avoid sodium overcorrection
- May need to give DDAVP to slow correction after volume repletion if patient is overcorrecting; hypertonic saline will likely be needed for subsequent correction
- If hyponatremia is severe (due to magnitude or symptoms) and hemodynamics are stable, volume resuscitation can be done gently with hypertonic saline and DDAVP, especially if SIADH is still on differential diagnosis, but do this in consultation with nephrology
• Euvolemia (often due to diuretics or SIADH)
- Address underlying cause
- Free water restriction
- Sodium tabs with loop diuretics or oral urea
- Consider demeclocycline or vasopressin antagonists (tolvaptan and conivaptan) if refractory to conservative measures
• Hypervolemic
- Free water restriction
- Diuresis with loop diuretics may be helpful and is often necessary to treat hypervolemia
- Vasopressin antagonists may be useful in heart failure but can cause liver injury in patients with cirrhosis
• Complication of hyponatremia correction that is too rapid: Central pontine demyelination
- Pathophysiology: Caused by osmotic shift due to sodium correction in the brain that has adapted to hypotonic environment over 1–2 days. Usually clinical effects occur days after sodium overcorrection.
- High-risk populations:
• Very low sodium <110 mEq/L (in most cases)
• Concurrent hypokalemia
• Liver disease
• Malnourished patients
• Patients with heavy alcohol use
Hypernatremia (Na**+** >145 mEq/L)
• Etiologies:
- Extra-renal water imbalance μOsm >600 mOsm/kg
• Inadequate free water intake (e.g., due to altered mental status, inadequate fluid replacement)
• Increased sodium intake (e.g., IV sodium bicarb, tube feeds, or TPN administration)
• Extrarenal free water loss (e.g., vomiting, diarrhea)
- Renal free water loss
• Diuresis due to medications (usually loop diuretics) or osmotic diuresis (hyperglycemia, azotemia, mannitol)
• Diabetes insipidus (DI): Inadequate ADH activity, μOsm <600 mOsm/kg.
- Two causes:
• Nephrogenic DI: Kidney is ADH-resistant. μOsm <300 mOsm/kg. Does not respond to water deprivation and decreased response to desmopressin. Differential diagnosis: Lithium, hypercalcemia, hypokalemia, tubulointerstitial disease
• Central DI: Pituitary is not secreting endogenous ADH. Urine remains dilute with water deprivation, responds to desmopressin. Differential diagnosis: Brain trauma, neurosurgery, tumor, CNS infection
- Diagnosis: Water deprivation test: Patient is deprived of water for 12–16 hours with serum sodium and serum Osm ideally achieving upper limit of normal. Normally ADH should be maximally released and urine osmolality should rise above 600 mOsm/kg. If not increased, DI is present. Desmopressin can be administered to further differentiate between nephrogenic and central DI; >50% increase in urine osms after desmopressin administration is consistent with central DI.
• Symptoms: Neurologic: altered mental status, restlessness, weakness, confusion, seizures, coma
• Diagnosis: Assess volume status, careful review of fluid intake and output, urine osms
• Treatment:
- Address the underlying cause
- Replace free water deficit
• Most easily done with IV D5W. Goal correction rate is no more than 10 mEq/24 hr. Less data about overcorrection than in hyponatremia
• Free water deficit can be estimated by multiplying total body water (TBW) × [(serum Na+/goal Na+) – 1]. TBW: 0.6 × body weight in kg; varies depending on age, sex, and muscle mass.
• Accounting for urinary free water loss using electrolyte free water clearance will help prevent under-replacement [EFWC = Urine output × (1 – (Urine Na+ Urine K+) / Plasma Na+)]
- Address volume depletion if present
• Can do this with separate isotonic fluid administration or “mixing” isotonic fluid with free water (e.g., D5 ¼ normal saline is roughly 25% isotonic fluid and 75% electrolyte-free water)