Another Salt Problem: Hypernatremia

We often talk about Hyponatremia, but Hypernatremia primarily occurs in patients who do not experience and/or respond to thirst normally, often due to impaired mental status (i.e. elderly, critically ill patients). It occurs in patients with impaired access to water, those with loss of hypotonic fluid and infrequently, due to infusion of a hypertonic fluid. It is defined as a serum Na>145 mmol/L. It constitutes a deficit of water relative to salt. 

·       Hypernatremia is a powerful stimuli for thirst! Salt intake and water loss seldom result in hypernatremia, because the ensuing rise in plasma osmolality stimulates both the release of ADH and thirst. Note that older adults experience a change in their thirst stimulus (it is not as robust as people get older)!

Symptoms: intense thirst (+/-), muscle weakness, confusion, coma; brain shrinkage could potentially cause vascular rupture, leading to cerebral bleeding, SAH, permanent neurological deficit and death

ETIOLOGY- 3 Major mechanisms: Un-replaced water loss (*common), water loss into cells, Na+ overload

1.Hypovolemic Hypernatremia

·       Renal water loss (Urine Osmol 300-600): loop diuretics, osmotic diuresis (i.e. mannitol, urea, glucose)

o   Osmotic diuresis: due to non-reabsorbed, non-electrolyte solutes (i.e. glucose, mannitol, urea)àincrease urine output

§  Initially: Mannitol in serum causes osmotic water movement out of cellsàlowering [Na]; in absence of impaired renal functionà mannitol is excreted in the urineà associated osmotic diuresisà raise [Na]

§  Urea: an inefficient osmoleàas urea is excreted in the urine, the loss of water will raise the serum [Na]

·       Extra-renal water loss (Uosm>600): diarrhea, insensible loss (fever, exercise)

·       Decreased access to water

·       Decreased thirst stimuli

o   Hypothalamic lesions affecting thirst or osmoRC functionàhypodipsia!

o   i.e. in children +/- DI, if congenital or acquired structural lesion (i.e. dysplasia of midline structures); older adults have a reduced thirst response with normal aging processes

2.Euvolemic Hypernatremia (Diabetes Insipidus)

·       Nephrogenic DI: renal resistance to the effect of ADH à cause excretion of dilute urine

o   i.e. renal disorders (PCKD, infiltration, infection, ischemia), meds (Lithium, demeclocycline, amphotericin B), idiopathic, hypercalcemia, amyloid

·       Central DI: impaired ADH release

o   i.e. trauma, tumors, infections (TB, meningitis, encephalitis), infiltrative disease of hypothalamus or PP (sarcoidosis), vascular, idiopathic

·       Most: have a normal thirst mechanism, thus present with polydipsia AND polyuria, high serum [Na]

·       Water loss into cells/Transientà serum [Na] rises by 10-15 mmol/L within minutes

o   i.e. severe exercise, electro-shock induced seizures

o   due to breakdown of large complex organic molecules into numerous small componentsè increases cell osmolality

3.Hypervolemic Hypernatremia

·       Hypertonic saline administration (IVF)- i.e. NaHCO3 during resuscitation

·       Drink seawater!

·       Primary Hyperaldosteronism (mineralocorticoid excess)

Work-Up

Physical: VS (orthostatic VS), CDV, JVP, skin turgor, MM, peripheral edema

Investigations: CBC, Cr, Urea, Lytes, Extended lytes, glucose, UA, Serum & Urine osmolality, Urine lytes

Hypovolemic Hypernatremia	Euvolemic Hypernatremia	Hypervolemic Hypernatremia
Urine Osm>300-600 & UNa>20: Renal loss Urine Osm>600, UNa<20: Extra-renal losses	Urine Osm<300: Complete DI Urine Osm 300-600: ? Partial DI Urine Osm>600: intracellular osmole generation	Exogenous Hypertonic Saline Mineralcorticoid excess
Urine Osmolality- Patterns to Consider
Uosm: LOW (<300)à DI	Uosm: INTERMEDIATE (300-600)à DI or Osmotic Diuresis	Uosm: HIGH (>600)à endogenous ADH is intact…both the response and the secretion!

·       If the urine osmolality is <600 mosmol/kg, observe the change in urine osmolality after administration of exogenous ADH

o   If both renal and hypothalamic function are intact, Urine Osmol in the presence of hypernatremia should be >600

§  If given exogenous ADH: should NOT produce a further rise in urine osmol

o   If urine osmolality is low (<300), less than serum osmolality, the patient has DI (central or nephrogenic)

§  Distinguish: administer exogenous ADH, followed by monitoring urine osmolality and volume q30 minutes over the next 2 hours

o   If urine osmolality is intermediate (300-600): hypernatremia is d/t an osmotic diuresis or to DI

§  Osmotic Diuresis: confirm by measuring total solute excretion (= urine osmol x daily urine volume); normal 600-900 mosmol/d (Na, K, Ammonium, Urea)

·       Value >1000: suggests a contribution from increased solute excretion

·       Do NOT respond to exogenous ADH (since endogenous effect is max)

§  If NO osmotic diuresis, consider DI

o   If urine osmolality is high (>600): both secretion and response to endogenous ADH are intact!

Treatment

·       Restore access to water (>1L/day), replace free water deficits and losses

1.Calculate TBW (0.6 x kg, men; 0.5 x kg for women)= i.e. 0.6 x 100 kg= 60 L

2. Water deficit: TBW x [(Na current/Na goal) -1]

3.Choose Fluid (i.e. D5W—0 Na)

4. Na infusate – Na serum/ (TBW-1)= (0-160)/(60-1)= 2.7= each 1 L of D5 lowers Na by 2.7 mmol/L

5. Correction Rate: maximum decrease of 10 mmol/L over 24 h

NOTE: study by Linder et al., found that the predictive potential of the above formula (and other formulas) are not perfect. The formulae correlated significantly with measured changes in serum Na in the patient cohort as a total. However; the individual variations were extreme! Thus, these formulas ONLY GUIDE therapy. Serial measurements are prudent!!

NOTE: 1.35 ml/h x patients wt in kg (for chronic, >48h hypernatremia)

CAUTION

·       D5 IVF can lead to hyperglycemia (especially if DM or physiologically stressed)à risk of osmotic diuresis à electrolyte and free fluid loss, limiting tx of hypernatremia (can use a 2.5% Dextrose!)

·       Rate of correction: 10 mmol in 24 h= max. Otherwise, risk cerebral edema!

Polyuria with Water Diuresis

·       DDx: DI (Na>140) versus Primary Polydipsia (Na<140)

o   DI work-up: Uosm<300 suggests complete DI while 300-600 may be a Partial DI

o   Water Deprivation test: deprive until serum osmol <295 and Urine osmol <300, then administer vasopressin (5U SC) or DDAVP (10 mcg intranasal)

§  Urine Osmol increases by >50%: central DI

§  Urine Osmol unchanged: Nephrogenic DI


Interesting Read: Clinical presentation of hypernatremia in elderly patients: a case control study. Journal Am Geriatric Soc. 2006 Aug;54(8): 1225-30. Chassagne, P. et al. 

http://www.ncbi.nlm.nih.gov/pubmed/16913989

Hypoxemia!

Approach to Hypoxemia

Recap on a few things...

A-a oxygen gradient — a common measure of oxygenation (“A” denotes alveolar and “a” denotes arterial oxygenation). It is the difference between the amount of the oxygen in the alveoli (ie [PAO₂]) and the amount of oxygen dissolved in the plasma (PaO₂)

 A-a oxygen gradient = PAO₂ - PaO_2. 

PaO₂ is measured by ABG and the PAO₂ is calculated using the alveolar gas equation:

 PAO₂  =  (FiO₂  x  [Patm  -  PH₂O])  -  (PaCO₂  ÷  R)

·       FiO₂ is the fraction of inspired oxygen (0.21 at room air), Patm is the atmospheric pressure (760 mmHg at sea level),  PH₂O is the partial pressure of water (47 mmHg at 37 degrees C), PaCO₂ is the arterial carbon dioxide tension (obtain from the ABG) and R is the respiratory quotient (~0.8 at steady state), but varies according to the relative utilization of carbohydrate, protein, and fat.

NOTE: The normal A-a gradient varies with age and can be estimated, assuming the patient is breathing room air

A-a gradient = 4 + age/4

PaO2/FiO2 ratio — The PaO₂/FiO₂ ratio is another common measure of oxygenation. A normal PaO₂/FiO₂ ratio is 300 to 500 mmHg, with values <300 mmHg indicating abnormal gas exchange

MECHANISMS OF HYPOXEMIA — Hypoxemia is defined as a decrease in the partial pressure of oxygen in the blood. 

Causes: Hypoventilation, ventilation-perfusion mismatch, right-to-left shunt, diffusion impairment, or reduced inspired oxygen tension

1.Hypoventilation — arterial (PaCO₂) and alveolar (PACO₂) carbon dioxide tension increase during hypoventilation, which causes the alveolar oxygen tension (PAO₂) to decrease. As a result, diffusion of oxygen from the alveolus to the pulmonary capillary declines. The net effect is hypoxemia.

Hypoxemia due to pure hypoventilation can be identified by 2 clues:

·       A) It readily corrects with a small increase in FiO₂

·       B) The A-a gradient is usually normal, EXCEPT, when the hypoventilation is prolonged because atelectasis can occur, which will increase the A-a gradient. Examples that can cause hypoventilation:

o   CNS depression (i.e. drug overdose- narcotics, structural CNS lesions, ischemic CNS lesions affecting the respiratory centre)

o   Obesity hypoventilation (Pickwickian) Syndrome

o   Impaired neural conditions (i.e. ALS, GBS, high C-spine injury, phrenic nerve paralysis)

o   Muscular weakness (i.e. myasthenia gravis, muscular dystrophy, polymyositis, severe hypothyroidism)

o   Poor chest wall elasticity (i.e. flail chest or kyphoscoliosis)

2.V/Q mismatch — an imbalance of blood flow and ventilationà composition of alveolar gas varies among lung regions:

Lung regions with low ventilation compared to perfusion will have a low alveolar oxygen content and high CO₂ content

 Lung regions with high ventilation compared to perfusion will have a low CO₂ content and high oxygen content

NOTE: In the normal lung, there is V/Q mismatch because perfusion and ventilation are heterogeneous. Both ventilation and perfusion are greater in the bases than in the apices. However, the difference between apical and basilar ventilation is smaller than the difference between apical and basilar perfusion. This causes the V/Q ratio to actually be higher in the apices compared to the bases. This V/Q mismatch is responsible for the normal A-a gradient.

In the diseased lung, V/Q mismatch increases because heterogeneity of both ventilation and perfusion worsen. This results in hypoxemia.

Clues for V/Q mismatch: correction with low to moderate flow supplemental oxygen and characterized by an increased A-a gradient.

o   i.e. obstructive lung diseases (asthma, COPD), pulmonary vascular diseases (PE), alveolar (CHF), interstitial diseases.

3.Right-to-left shunt —exists when blood passes from the right to the left side of the heart without being oxygenated. There are 2 types to keep in mind

·       Anatomic shunts, where alveoli are bypassed!

o   i.e. intra-cardiac shunts, pulmonary AVMs, hepato-pulmonary syndrome

·       Physiologic shunts: where non-ventilated alveoli are perfused.

o   i.e. atelectasis and diseases with alveolar filling (i.e. pneumonia, ARDS).

NOTE: Right-to-left shunts cause very extreme V/Q mismatch, with a V/Q ratio of zero in some lung regions. The net effect is hypoxemia, which is difficult to correct with supplemental oxygen. True anatomical shunts DO NOT correct with supplemental oxygen!!!!

4.Diffusion limitation — where the movement of oxygen from the alveolus to the pulmonary capillary is impaired, often as a result of alveolar and/or interstitial inflammation and fibrosis (i.e. interstitial lung diseases). In such diseases, diffusion limitation usually coexists with V/Q mismatch.

o       Clues: characterized by exercise-induced or -exacerbated hypoxemia.

o   During rest, blood traverses the lung relatively slowly allowing for sufficient time for oxygenation to occur even if diffusion limitation exists.

o   During exercise, cardiac output increases and blood traverses the lung more quickly. As a result, there is less time for oxygenation.

o   In healthy pts, compensatory mechanisms occur

o   Pulmonary capillary dilatation (increase in surface area available for gas exchange)

o   PAO₂ increasesàpromotes oxygen diffusion by increasing the oxygen gradient from the alveolus to the artery

o   In diffusion limitation (i.e. IPF, anemia): there is insufficient time for oxygenation to occur & most have parenchymal destruction (impossible to even recruit additional surface area!!!)

5.Reduced inspired oxygen tension 

Reduction of the PiO₂ will decrease the PAO₂. This impairs oxygen diffusion by decreasing the oxygen gradient from the alveolus to the artery. The net effect is hypoxemia. A common example is living at high altitude.

Complications of Hypoxemia: Dyspnea, reduction in exercise tolerance and functional capacity. Over time,  Pulmonary HTN can arise in the setting of chronic alveolar hypoxemia

PRES- Posterior Reversible Encephalopathy Syndrome

We had an excellent presentation today during team rounds on PRES. If anyone is interested, here is an article discussing the associated clinical and radiographic findings:

Posterior Reversible Encephalopathy Syndrome: Associated Clinical and Radiologic Findings

Jennifer E. Fugate et al.

Posterior Reversible Encephalopathy Syndrome: Associated Clinical and Radiographic Findings