Hyponatremia and Hypernatremia

What are the vaptan drugs?

Block V2 ADH receptor work as an aquaretic (water loss only) NOT A DIURETIC (Na and water loss)

How do you treat central and nephrongenic DI?

Central: give daily exogenous ADH Nephrogenic: no good treatment, just conservative care -water restriction, NSAIDS, thiazide diuretics

How do you see if it is central or nephrogenic diabetes insipidus?

Check response to Exogenous ADH: measure urine osmolarity to see if they were able to use the ADH to concentrate the urine

What is isosthenuria? Value?

Concentration of urine is the same as the plasma (neither concentrated or dilute) Specific gravity= 1.010 Osmolarity= 300 mosm/L

Describe the mechanism of action of ADH Where does it act?

Cortical and Medullary Collecting Ducts (principal cells): V2 receptor -on basolateral membrane -Gs protein coupled receptor (Guanidine) -activates cAMP----> increases production of AQP2 channels on luminal membrane -water diffuses through the principal cells down its gradient --the medullary intersitium is hypertonic with 50% NaCL and 50% urea

What are the drugs that can cause SIADH?

Drugs that increase ADH secretion: 1. Narcotics 2. Antipsychotics 3. Antidepressents Drugs that enhance ADH action: 1. NSAIDS Drugs that cause hyponatremia by unknown mechanisms -SSRI -Esctasy

If patient has Na 120-135 and asymptomatic, how should you treat

Free water restriction

What type of cells swell in the brain as a result of hyponatremia

Glial cells- such as ASTROCYTES (have aquaporin 4 channels) NOT NEURONS

How should you treat sodium under 120?

Hypertonic saline (3%) and Free water restriction *must be given in ICU setting and with freqent monitoring to avoid over correction*

When are Vaptan's indicated

Hypervolemic or Isovolemic Hyponatremia NOT Hypovolemic Hyponatremia -will make the fluid deficit greater

When is hyponatremia normal and what is the expected value?

Hyponatremis is normal and expected in pregnancy Normal value is Na= 130 a value of 140 is abnormal in prengancy

Only people who are _______ can develop Hyponatremic Encepalopathy (HE)

Hypotonic and hyponatremic

Describe the cellular response to hyponatremia

In order to prevent cells from swelling: -Immediate: K efllux from the cell -After 48 hours: extrusion of organic osmolytes -if you give NaCl infusion rapidly, the cells will shrink because they have degraded their intracellular osmolyltes!

IF you are hypotonic, what is the appropriate response of the body?

Inhibit ADH--- to produce dilute urine

What drug can cause nephrogenic diabetes insipidus? How is it absorbed? What can be used to block its absorbtion in the kidney

Lithium absorbed through ENAC blocked with Amiloride

3 classes of hyponatremia

Mild: Na= 130-134 Moderate: Na= 121-129 Severe: under 120 *high risk of seizures*

What is the value and causes of hypernatremia

Na> 145 Water deficiency (dehydration): most common 1. osmotic diuresis 2. water diuresis: primary polydipsia, central diabetes insipidus, nephrogenic diabetes insipidus OR Salt overload (almost impossible)

Formulas for osmolality and tonicity

Osmolality: (2 * Na) + (Glucose/18) + (BUN/3) Toniciity: (2 x Na) + (Glucose/18)

Osmolality vs Tonicity

Osmolality: number of particles that exist in the fluid environment -Na + glucose + urea Tonicity: number of particles that have effective osmolality (the potential to exert transmembrane water movement) -particles that can cause water to move -Na + glucose (urea is non an effective osmole) *for clinical complications to occur, have to be hypotonic and hyponatremic!!! (not just hypoosomolar)

Value of hyponatremia

Plasma Na < 135 (140 is normal)

What is the value for severe hyponatremia? main associated risk?

Plasma Na under 120 High risk of seizures

What do hyperglycemia, mannitol, sorbitol, and glycine cause?

They are hypertonic solutions that act by pulling free water out of the intracellular compartment: leads to dilutional hyponatremia (but the patients are hypertonic, so brain swelling!!!!) used to treat cerebral edema (mannitol) and prostate surgery

Which class of diurectics causes hyponatremia?

Thiazides: cause hyponatremia -because they do not disrupt the renal concentrating mechanism- so you can still absorb water and get hyponatremic Loop: can not cause hyponatremia -because interfere with generation of hyperosmolar medullary gradient- so you cant resorb water and concentrate urine

What determines if the brain swells or not?

Tonicity (only swells if hypotonic) -osmolarity doesn't matter (could be hyper, hypo, or iso-osmolar)

What do sodium disorders reflect

abnormal water balance (due to ADH)

What is cerebral salt wasting

after brain injury or surgery release of BNP causes significant urine Na losses *PRESENTATION: hypotension, signs of volume depletion* will also have increased urinary Na and osmolarity, but differentiate from SIADH by checking volume status of patient -SIADH: euvolemic or hypervolemic -cerebral salt wasting: hypovolemic (severe)

Signs of SIADH

inappropriate urine concentration elevated urinary sodium (over 30) -due to overfilled arterial circulation from water retention= decreased renin, AGII and increased ANP= increased urine Na

Pseudo-hyponatremia

machine error produced by elevated proteins (mulitple myeloma) or lipids (hypertriglyceridemia) *no hypotonicity and no treatment needed: complete artifact

What rate of correction of serum Na is the upper limit

never do more than 10 meq/24 hours ideal= 4-6 meq/L/day

What is SIADH

syndrome of inappropriate antidiuretic hormone

How can you tell if ADH is active?

urine osmolality urine specific gravity *reflects the removal of water from the urine by ADH* concentrated urine= increased ADH Dilute urine= suppressed ADH

What is the most powerful stimuli of ADH

when the change in volume is over 10%: ADH will protect VOLUME>>>>> osmolarity -decreased volume= exponential increase in ADH -increased osmolarity= only a linear increase in ADH

What causes osmotic demyelinating syndrome

**TREATMENT OF HYPONATREMIA** when the cells are recovering from hyponatremia, it takes time to regenerate the solutes that they destroyed so if the rate of solute addition from IV exceeds the rate of re-syntehesis of intracellular organic solutes --- cells will shrivel *acute volume contraction of the cell will cause it to stop making myelin and apoptosis

For hypernatremia caused by water diuresis (low urine osmolarity) what test should you order next and what are the possible causes?

*check serum sodium 1. Psychogenic Polydipsia -Hyponatremia or Normonatremia 2. Diabetes Insipidus -hypernatremia

2 types of diabetes insipidus

*dont actually have diabetes (blood sugar is not elevated) just dont have ADH or response to ADH 1. Central: deficient ADH secretion 2. Nephrogenic: kidney can't respond to ADH -LITHIUM

If it is a real hypotonic hyponatremia, what is the next question to ask?

-establish volume status -determine if ADH is overactive: appropriate elevation (decreased circulatory volume) or innapropriate elevation (normal circulating volume)

2 main consequences of hyponatremia

1. Direct CNS Neurotoxin 2. Increased Marker for mortality in CHF and Cirrhosis

2 main clinical sequale of hyponatremia

1. Due to the actual serum Na concentration: hyponatremic encephalopathy (HE) -swelling of brain 3. Due to the treatment of Na concentration: Osmotic Demyelinating Syndrome -shrinkage of brain

What are the 2 main causes of hypernatremia associated with osmotic diuresis

1. Glucose (sugar drags water into the urine) -diabetic ketoacidosis -severe hyperglycemia 2. Urea -high protein feedings -NH4+ gets peed out and drags water with it *no further workup needed for either

3 causes of nephrogenic diabetes insipidus

1. Lithium -absorbed through ENAC -use Amiloride to block ENAC so the lithium can't be absorbed 2. Hypercalcemia 3. Hypokalemia

What are the 2 main classifications of hypernatremia (caused by water deficiency)

1. Osmotic Diuresis -higher urine osmolarity 2. Water Diuresis -lower urine osmolarity

What 2 types of malignancies can cause SIADH

1. Small cell carcinoma of lung (oat cell) 2. Head and neck squamous cell carcinomas

3 main etiologies of hyponatremia -which is most common

1. Sodium loss -VERY RARE -in order to cause hyponatremia this way, you would have to excrete more Na than water -only happens in Cerebral Salt Wasting syndromes 2. Water retention (due to ADH excess) 3. Water retention and Na loss (thiazide diuretics) *most common= water retention with or without a lesser component of Na loss*

2 main classes of ADH stimuli

1. Volume: indirect stimulation from baroreceptor, stimulation of AGII and SNS 2. Tonicity: direct stimulation *usually volume and tonicity work together to maintain the osmolar balance and volume balance in the body: not in CHF* *body protects volume over tonicity if the change in volume is over 10%*

Non osmotic and non volumentric causes of SIADH

1. nausea/emesis pain surgery hypoxia drugs *very common for post-op people to get hyponatremic due to ADH release and hypotonic IV fluids (.45 NS) 2. malignancies -small cell lung carcinoma -head and neck squamous cell carcinomas 3. Drugs -narcotics -antipsychotics -antidepressants -NSAIDS -SSRI -ecstasy