R3 Hyponatremia and Hypernatremia

-serum sodium concentration less than the normal range of 135-145 mEq/L

**patient may have hyponatremia but have excess total body sodium and edema

-serum sodium concentration greater than the normal range of 135-145 mEq/L

**patient may have hypernatremia but have low total body sodium

• -"tonicity"
• -particles which can lead to water movement across cell membranes (ignore urea)
• -osmolality includes all particles

Posm = 2Na + glucose/18 + BUN/2.8

• -water compromises 50-70% of total weight
• -fat contains less water than muscle (TBW dependent on body habitus)

-most cell membranes are freely permeable to water (due to the presence of aquaporins)

-At equilibrium ECFosm = ICFosm

-we defend volume over tonicity (we will tolerate high or low electrolytes to maintain BP)

• 
• *** water only expands 1/12 into the intravascular compartment

• 1. Water ingestion
• 2. GI absorption
• 3. Distributed throughout TBW (0.6 body weight)
• 4. Small decrease in serum osmolality
• 5. Suppression of ADH and Thirst
• 6. Free water excreted by kidney

** serum Na⁺ concentration maintained within a normal range

• 
• -net result: temporary increase in urine flow and decrease in urine osmolality
• -serum osmolality pretty much stays the same
• -180 minutes after ingestion urine flow rate slows

= urinary dilution

• -major site: thick AL
• -minor site: cortical dilution

*ADH MUST BE SUPPRESSED to make collecting duct water impreameable

• 
• 1. Delivery of filtrate to medullary thick ascending limb

2. Intact function of medullary thick ascending limb (NKCC2)

3. ADH absent in CD

• Causes:
• -renal failure
• -volume depletion
• -low "effective circulating volume"

**enhance proximal reabsorption of NaCl and water (harder to dilute urine)

• Causes:
• -loop diuretics (inhibit NKCC2: decrease Na reabsorption/abolish medullary concentration gradient --> defects in concentrating and diluting urine)
• -thiazide diuretics (defect in urinary dilution only)

--> defects in urinary dilution

• Causes:
• -SIADH
• -Non-osmotic stimuli for ADH release:
•      -volume depletion
•      -pain
•      -anxiety
•      -fear

• --> impaired dilution of urine
• ***combinations of defects are common

-people ingest hypotonic fluids AND they cannot dilute their urine

OR

-water ingestion > water excretion

-based on assessment of volume status

• 1. Volume contracted or volume depleted
• -trauma
• -burns
• -bleeding

• 2. Volume overload (may have pitting edema)
• -nephrosis
• -cirrhosis
• -CHF-low "effective circulating volume"

3. Normal or "near normal" volume status

• 
• -all causes lead to decreased CO
• -this results in a low effective circulating volume

• Effects of Low ECV:
• 1. Thirst (ingest hypotonic fluids)
• 2. Decreased filtrate delivery to mTAL
• 3. Increased ADH (due to hyposomolality)

--> decreased water excretion

• Excess ADH due to:
• 1. Hypothalamic/pituitary synthesis of ADH
• -pulmonary disease (TB, HIV, pneumonia, ARDS)
• -drugs
• -CNS disease (trauma, infection, tumor, MS)

• 2. Ectopic synthesis of ADH
• -carcinoma (SIADH due to lung carcinoma)

• 3. Potentiation of ADH action
• -drugs (cyclophosphamide, NSAIDS, TCAs, antidepressants)

• BRAIN SWELLING!
• -in the setting of water overload and hyponatremia the brain swells (if there is no adaptation)

• Acute Adaptation
• -brain cells start exporting electrolytes to remove water

• Chronic Adaptation
• -other osmolytes like AAs are removed

• Sx correlate with:
• 1. severity
• 2. rapidity

**pts may be asymptomatic (especially with chronic hypotonic hyponatremia)

• Symptoms (due to CNS swelling):
• -HA
• -N/V
• -Confusion
• -Seizures
• -Coma

-function of the amount of water ingested, the rate of ingestion and solute load

-if minimal Uosm is 50 mOsm/L and the daily solute load is 600 mOsm then ingestion of > 12L of water could lead to hyponatremia

--> ACUTE WATER INTOXICATION

• 
• 1. Is it hypotonic hyponatremia
• -patients may have hypertonic hyponatremia
• -classic in patients with high blood sugar
• -glucose pulls water out of ICF compartment, diluting Na+

2. What is the volume status?

3. UNa+ and Uosm

• Low Volume:
• 1. UNa < 10 mEq/L = Volume contraction
• 2. UNa > 40 mEq/L = Diuretics

• High Volume:
• 1. UNa < 10 mEq/L = CHF, Nephrotic Syndrome, Cirrhosis (Great volume retaining states)

• Normal Volume:
• 1. Uosm > 300 mOsm, UNa > 40 mEq/L = SIADH, Adrenal insufficiency, hypothyroidism
• 2. Uosm < 100 mOsm = psychogenic polydipsia (water intoxication), low solute intake

• 1. Volume depleted states
• -restore volume status with isotonic fluids
• -water (hypotonic) will make them worse!

• 2. Volume overloaded states
• -water restriction
• -ACEIs (CHF)
• -ADH Antagonists

• 3. Euvolemic states
• -water restriction
• -hypertonic saline and loop diuretics (severe hyponatremia)
• -drugs producing a nephrogenic DI (demeclocyline)
• -ADH antagonists

-due to rapid and/or overcorrection of hyponatremia

-quadriparesis and pseudobulbar palsies

-onset of sx delayed: 24-48 hours

• To avoid rapid correction of hyponatremia:
• -manage asymptomatic patients conservatively
• -5-7 mEq/L increase (should reverse cerebral edema in those with sx)
• -correction rate no greater than 0.5-1.0 mEq/h
• -absolute correction no greater than 10-12 mEq/24hrs

-mortality is higher in patients with lower Na (both total death and cardiac death)

• Reasons for Association:
• 1. Directly enhances mortality
• 2. A disease process causes hyponatremia when it is more severe (mortality is a reflection of more severe disease)
• 3. Severe disease is associated with increased mortality and hyponatremia (hyponatremia is indepently associated with enhanced mortality)

• -gain of solute in excess of water
• -loss of water in excess of solute

• Defense against hypernatremia:
• 1. Thirst
• -more important mechanism
• -doesn't need a big increase in osm to increase thirst
• -stimuli: increase osms, decreased volume, decreased BP, Ang II
• 2. ADH
• Clinical Correlate:
• -pts who become hypernatremic typically cannot access water
• -absence of ADH can be compensated for by water ingestion
• -susceptible: very young, very old, mentally impaired, anesthetized

• 1. >800
• -impaired thirst

• 2. < 150
• -complete diabetes insipidus
• -no ADH action

• 3. ~300
• -osmotic agent (glucose, urea)
• -cause water loss in urine (lots of free water loss)

• 4. 150-800
• -partial diabetes insipidus
• -impaired CCM

• Features:
• -low circulating ADH
• -Uosm < 150
• -polyuria, polydipsia
• -responsive to ADH

• Major Causes:
• -neurosurgical procedures
• -head trauma
• -anoxic encephalopathy
• -cancers

• Features:
• -normal or high circulating ADH
• *ADH not working at the level of the kidney
• -Uosm < 150
• -polyuria, polydipsia
• -unresponsive to ADH

• Major Causes:
• -Li, democlocycline
• -HIV drugs
• -Hypercalcemia
• -TIN, CKD
• -Pregnancy

-urine output > 2.5 L/day

• Uosm <150 mOsm:
• -Complete DI
• -psychogenic polydipsia

• Uosm > 300 mOsm:
• 1. 2(Na + K) < Uosm
• =osmotic diuresis
• -glucose
• -urea
• -mannitol

• 2. 2(Na + K) = Uosm
• =Sodium diuresis
• -diuretic use
• -renal salt wasting
• -cerebral salt wasting
• -excessive Na intake

• 1. Assess and treat volume status
• 2. Then address the hypernatremia
• --> how much water will it take to correct the hypernatremia (be sure to address ongoing losses as well)

Current TBW x Current PNa = Normal TBW x Normal PNa

Replace no greater than 1/2 over 24 hours