Disorders of Sodium and Water Balance

Acute Hyponatremia

(< 48hrs) Main risk is *acute cerebral edema* secondary to water moving into brain cells (ICV) Primary diagnostic question: where did the excess EFW come from (e.g. IV fluids, polydipsia)? *Treatment must be aggressive!!*

Chronic Hyponatremia

(>48hrs) Main risk is *overly aggressive therapy producing major neurological consequences (central pontine myelinolysis)* Primary diagnostic question: why are the kidneys not able to excrete the excess EFW (why is ADH acting)? Treatment: Aim is to *increase serum Na slowly*

Water Deficit

(Serum Na-140)/140*TBW

Urine Sodium [Lab Tests to Asses Hyponatremia]

*Low urine Na* (< 20mmol/L) may suggest *volume depletion* which has already activated ADH in an attempt to compensate. - In heart or liver failure or nephrotic syndrome, Decreased EABV causes both activation of ADH and an impaired renal perfusion with a low urine Na

Diuretics and Hyponatremia

*Thiazide* diuretics commonly cause *hypovolaemic hyponatremia due to volume depletion mediated activation of ADH and ongoing EFW ingestion*. - Loop diuretics rarely cause this effect as the blockade of Na reabsorption in the loop of Henle interferes with the maintenance of medullary concentration gradient which impairs ADH action

Lab Tests for Hypernatremia

*Urine osmolality*: helps to differentiate between the 3 major causes of hypernatremia - Serum hypertonicity stimulates ADH and the urine osmolality should be markedly increased (800-1200mOsm/kg). *Low urine osmolality* suggests deficiency of ADH (central diabetes insipidus) or a diminished response to ADH (nephrogenic diabetes insipidus)

Hypernatremia (Basic Definition)

*Water Depletion* - in hypernatremia, *increase ADH levels* to produce a concentrated urine (maximal 1200 mosm/kg) and retain water

Hyponatremia (Basic Definition)

*Water Excess* Definition: *Serum Na < 135*mEq/L (relatively too much water) - normal response to hyponatremia is to inhibit thirst and *turn off ADH* allowing the passage of a dilute urine (minimal ~50mosm/kg) to correct the abnormality [volume takes priority over osmolality; ADH stimulated in volume depletion *despite hypo-osmolality*] - Typically found in settings of *volume depletion or a decreased EABV* (effective arterial blood volume) (e.g. heart failure, liver disease).

Question 4: Hyponatremia Case: Lab Interpretation 58yo woman presents with mild confusion,and hyponatremia. Exam: BP 138/72, no edema. Labs: Blood glucose 70 mg/dl Serum Osm 244 mOsm/kg Urine: UNa 46 Uosm 450 mOsm/kg *What is the most likely cause of her hyponatremia?* a.) SIADH b.) Volume depletion c.) Psychogenic polydipsia d.) Liver cirrhosis e.) Pseudohyponatremia

*a.) SIADH* - Pt was hyponatremic - Urine Osmolality was High (not Polydipsia) - Urine Na High (Not decreased EAFB)

What is the *source of the water loss*?

- Insensible loss (fever, ventilated, excess sweating) - Diarrhea - Renal loss (polyuria, glycosuria).

Question 5: Hypernatremia A 59yo man is admitted to hospital with diarrhea. He has a 3 month history of weight loss, fatigue, polyuria and nocturia. Exam: P98, BP 120/63, no edema. Labs: Blood glucose 70 mg/dl Serum Osm 309 mOsm/kg Urine: UNa 14 Uosm 58 mOsm/kg *What is the cause of his hypernatremia?* a.) Osmotic diuresis given his serum osmolality of 309 b.) Nephrogenic diabetes insipidus resulting in polyuria c.) Central diabetes insipidus resulting in polyuria d.) Diarrhea leading to excess stool water loss

............

Causes of Central Diabetes Insipidus

1.) *Genetic* - Autosomal dominant (mutations in vasopressin precursor) - Auto recessive (Wolfram syndrome) 2.) *Acquired* - Tumors (pituitary, metastases) - Post surgery, head trauma - Infiltration (sarcoid, histiocytosis) - CNS infections - idiopathic (50%)

Causes of Nephrogenic Diabetes Insipidus

1.) *Genetic*: -X-linked (mutations in V2 receptor) -Autosomal Recessive (mutations in aquaporin 2) 2.) *Acquired*: - Chronic renal failure - Renal interstitial disease (interstitial nephritis, obstructive uropathy, polycystic kidney disease, lithium therapy, sickle cell anemia) - Electrolyte disorders (hypokalemia, hypercalcemia) - Drugs (lithium, amphotericin, foscarnet)

Causes of Polyuria

1.) *Osmotic Diuresis* - Glucose - Urea/Mannitol 2.) *Water Diuresis* a.) Central Diabetes Insipidus - responds to ADH Therapy b.) Nephrogenic Diabetes Insipidus - poor response to ADH Therapy

Causes of SIADH

1.) *Pulmonary* 2.) *CNS* 3.) *Carcinoma* 4.) Drugs [See chart]

Other Drugs Associated with Hyponatremia

1.) ADH Analogs 2.) Drugs that Stimulate ADH Release 3.) Drugs that caused Enhanced ADH Renal Effect

2 Most Major Clinical Concerns for Hyponatremia

1.) Cerebral Edema 2.) Central Pontine Myelinolysis (from the Rx!)

Why is ADH turned on? Urine Na can help!

1.) Decreased EABV (most common) 2.) Physiological Stress, Pain, Nausea 3.) Syndrome of Inapporporiate ADH (SIADH) - Urine Na is HIGH (>20)

3 Major Causes of Hypernatremia

1.) Diabetes Insipidus 2.) Osmotic Diuresis (usually glucose) 3.) Inadequately replaced non-renal EFW loss

2 Causes of Decreased EABV

1.) ECV Depletion - vomiting, diarrhea - Urine Na LOW bc kidneys are retaining Na to try to expand ECV 2.) Edema (CHF, Cirrhosis, NS) - heart not pumping enough blood so baroreceptors detect underperfusion - Urine NA LOW

Angiotensin II Action on Volume Depletion

1.) Efferent arterial vasoconstriction preserves GFR 2.) Peripheral vasoconstriction preserves BP 3.) Stimulates proximal Na Reabsorption - stimulates Na-H Antiporter (NHE3) - Increased Filtration Fraction, Decreased Pcap, increased πcap in peritubular capillary, promoting Na/H2O reabsorption 4.) Increased Aldosterone --> increased Na/H2O reabsorption in cortical collecting duct (results in low urine Na<10) 5.) Stimulates thirst and ADH --> increased H2O balance and hyponatremia with high urine oslmolality (Uosm>300mOsm/kg)

Precautions when treating Hypernatremia

1.) Great care must be taken with polyuric patients as any changes in urine osmolality or urine volume can rapidly change the serum [Na] which needs frequent monitoring 2.) Correction of hypernatremia should not occur too rapidly as this may precipitate *cerebral edema* and seizures. In general the hypernatremia should be corrected over greater than 48hrs and no faster than 1-2 mOsm/hr.

Diagnostic criteria for SIADH

1.) Hyponatremia (<135mmol/L) 2.) Decreased serum osmolality (< 270mOsm/kg) 3.) Urine sodium > 20mmol/L (reflects daily sodium intake) 4.) Inappropriate urine concentration (Urine osmolality > 100mOsm/kg) = evidence of ADH acting 5.) Exclusion of renal failure and endocrine dysfunction [hypovolemia, edematous states, endocrine dysfunction (adrenal insufficiency and hypothyroidism), renal disease or drugs]

Urine Osmolality: If you have hyponatremia, what would you want the kidneys to do to correct this?

1.) Hyponatremia with LOW Urine osmolality is rare - seen in Primary Polydipsia 2.) Hyponatremia with HIGH Osmolality - ADH is working when it shouldn't be (Diluting problem)

Assessment of Hypernatremia

1.) Is the *ECF Volume Expanded* (edema, hypertension, heart failure, pulmonary edema), and what is the *change in patient's weight*? 2.) What is the *source of the water loss*? 3.) Why is *water intake not compensating*? 4.) Is the pt *polyuric*?

Assessment of the Patient for Hyponatremia

1.) Is this *Pseudohyponatremia*? 2.) Is the Hyponatremia *Acute or Chronic*? 3.) Is the pt having *acute neuro consequences* (seizures, confusion)? 4.) What is the *volume status* of the pt? 5.) What is the *source of the EFW* (check IV Fluids, TPN or tube feeds, oral intake)? (Determine underlying cause to determine therapy) 6.) *Why are the kidneys not able to excrete the excess EFW?*

Differential Diagnosis of Hypernatremia

1.) Non-Renal Water Loss 2.) Osmotic Diuresis 3.) Diabetes Insipidus

Two factors are required to develop hyponatremia

1.) Source of Electrolyte Free Water - usually requires #2 to cause hyponatremia 2.) Impaired Excretion of Dilute Urine by Kidneys (decreased ADH or Renal Failure --> low urine output)

Management of Hypernatremia

1.) Stop ongoing loss of EFW 2.) Replace EFW loss with *hypotonic fluids* (5% dextrose, oral H2O, half-normal saline) at an appropriate rate If the pt has significant *volume depletion* in addition, (osmotic diuresis, diarrhea) this should be *corrected first with normal saline*

Disorders of Total Body Na

1.) Volume Depletion (Hypovolemia) - Occurs when ECV is reduced, leading to low BP and decreased tissue perfusion 2.) Volume Expansion

Causes of ADH Release

ADH can be stimulated by factors other than hypertonicity - Volume depletion stimulates ADH synthesis - Hyponatremia is typically found in settings of volume depletion or a decreased effective arterial blood volume (e.g. heart failure, liver disease).

Drugs that Stimulate ADH Release

Carbamazepine Chlorpropamide Antidepressants Antipsychotic agents Vincristine/vinblastine Narrcotics Clofibrate Ifosfamide

Symptoms of Acute Hyponatremia

Clinical features related to CNS and relate to the degree of hyponatremia and the rate of decline. Acute hyponatremia leads to: - Swelling of the brain cells (ICV), cerebral oedema - Symptoms of confusion, seizure, coma and if severe, tonsillar herniation - Most patients w/ seizures and coma have serum Na <120mmol/L

Syndrome of Inappropriate ADH (SIADH)

Common cause of hyponatremia but is a *diagnosis of exclusion* *Disorder of osmoregulation where hypotonicity fails to adequately suppress the production of ADH*. Note: Mildly expanded ECF volume may lead to reduced serum urate levels

Urine Sodium in Edematous States (heart failure, liver failure, nephrotic syndrome)

Decreased effective arterial blood volume (EABV) causes both activation of ADH and an impaired renal perfusion with a low urine Na

Central DI

Deficiency of ADH caused by lesions on hypothalamus or pituitary - onset of polyuria often abrupt - Low Serum ADH - Low Urine Osmolality (~50-100mOsm/kg)

Treatment of Osmotic Diuresis

Direct therapy @ underlying cause (e.g. insulin for hyperglycemia) to reduce excess EFW loss - often significant volume depletion = correct wtih normal saline - Half normal saline used as source of EFW in hyperglycemia to correct hypernatremia (5% dextrose may exacerbate raised BG)

Central Pontine Myelinolysis

Dysarthria Dysphagia Paraplegia THIS IS PERMANENT!!!!

Polydipsia Caused Hyponatremia

Excess water intake is rarely sole cause of hyponatremia as normal kidneys can excrete close to 15-20L/day of EFW - Some psych patients may drink very large amounts --> *Urine osmolality will be very low* (<100mOsm/kg) - More commonly a *large water intake contributes* to the hyponatremia in the setting of *impaired free water excretion (ADH)*

For every 60mg/dl increase in BG, how much should Serum Na change?

Fall by 1mEq/L

Measuring Edema

Generalized edema not clinically apparent until interstitial volume expanded 2-3L Degree of Edema: measured on subjective qualitative scale of 1+ to 4+ - extent of edema measured along lower extremity (e,g, edema to ankle, knee, thigh, or hips): higher up it goes the worse it is

Is the *ECF Volume Expanded* (edema, hypertension, heart failure, pulmonary edema), and what is the *change in patient's weight*?

Hypernatremia is typically associated with a *decrease in body weight secondary to water loss*. - Rarely in the setting of Na gain the weight is increased with an expanded ECF volume.

Serum Osmolality

Hyponatremia typically associated with *low serum osmolality w/ 2 Exceptions* - Hyperglycemia - Pseudohyponatremia

Hyperglycemia as a Cause of Hyponatremia (Lecture Version)

In Hyperglycemia glucose cannot move from ECV into cells - relatively insulin deficient, BG is high Sugar is an osmole --> increased Osmolality --> Water moves from ICV to ECV - this water is Na deficient (very little Na in cells) and dilutes Na in the EVC and causes Hyponatremia ICV shrinks so no risk of cerebral edema --> *ONLY setting where ICV is decreased with hyponatremia*

Diabetes Insipidus (DI)

Inability of kidneys to concentrate urine --> *Polyuria* - Pt has intense thirst and polydipsia - If H2O intake lags behind polyurina, hypernatremia will develop, but normally pt can maintain normal serum Na by drinking lots of H2O (sometimes >10L/day) *Central DI* vs *Nephrogenic DI*

Acute Symptomatic Hyponatremia <48 hours: *Treatment Guidelines*

Include water restriction and: 1.) *IV administration of hypertonic 3% saline* (1-2mls/kg body weight per hour) which may be combined with frusemide to prevent sodium overload and increase EFW excretion 2.) If patients are severely obtunded or have seizures, the hypertonic saline may be administered at an increased rate (4-6mls/kg/hr) for 2-3 hours to improve symptoms. *Goal*: raise serum Na by 1-2mmol/hr over the first 3-4 hours but with a maximum increase of 8-12 mmol in 24hours. Vigilant monitoring (at least 2hrly) is clearly mandatory during this acute stage. - Note: *saline must be hypertonic to urine otherwise renal generation of EFW may occur, exacerbating hyponatremia*

Hyperglycemia

Increases the serum osmolality causing water to move from ICV to ECV to restore equilibrium. - Serum Na should fall by 1 mEq/L for every 60 mg/dl increase in blood glucose - This is the *ONLY setting where ICV is decreased with hyponatremia* - Although *urea and ethanol raise the serum osmolality*, they move rapidly across cell membranes and are *not effective osmoles*. They *do not alter the serum Na*.

Why is *water intake not compensating*?

Is the patient thirsty? - small increases in tonicity should lead to marked thirst *Absence of thirst suggests a CNS lesion or altered mental status*

Impaired Excretion of Dilute Urine by Kidneys

May be due to 1.) *ADH action* (most common cause) 2.) *Low urine output - severe renal failure (GFR < 10mls/min)*: - markedly decreased urine solute load [there is a min level to which the kidneys can dilute the urine (~50mOsm/kg) and if daily solute load is reduced (e.g. tea and toast diet in the elderly or beer potomania) the urine volume may be limited by the daily solute load]

Is the pt *polyuric*?

May be due to an *osmotic diuresis* (urine osmolality 400-500mOsm/kg) or a *water diuresis* (Uosm < 150mOsm/kg).

Artefactual Hyponatremia

May occur when the blood sample is taken from an arm with an infusion of 5% dextrose running.

Symptoms and Signs of EVC Depletion

Mild: Dizziness, weakness, fatigue Severe: orthostatic dizziness, syncope, circulatory collapse Exam *Cardinal Signs*: Tachycardia, hypotension (or orthostatic hypotention if BP is preserved when seated) - Cold peripheries, dry mucous membranes, and loss of skin turgor may also occur

Treatment of Non-Renal EFW Loss

Most common cause in hospitals (insensible loss can be large, esp if pt is ventilated) Key: accurately estimate all EFW losses (resp, sweat, GI) and match with appropriate IV fluids to prevent worsening of hypernatremia - Additional EFW must then be given to correct it ~1/2 water deficit may be replaced w/in first 24 hours

Osmotic Diuresis Causes

Most common cause: *Glycosuria secondary to hyperglycemia* - Occasionally a high excretion rate for urea (catabolism, high protein feeding, recovery from ARF) may cause urine H2O loss in excess of Na+

Drugs that caused Enhanced ADH Renal Effect

NSAIDs Chlorporpamide Cyclophsophamid

Volume Expansion (Edematous States)

Na excess results in increased ECV, if ECF expansion is significant, Pt will develop edema

Pseudohyponatremia

Na is distributed in the aqueous phase of plasma (~ 93% of plasma volume), but [Na+] is expressed based upon the Total volume of plasma analysed - Rarely, a marked *hypertriglyceridaemia* (> 10-15mmol/L) or *severe paraproteinaemia* ( > 100g/L), may *increase the non-aqueous phase* of the plasma = Pseudohyponatremia In this setting the *serum osmolality is normal*

Na+ Loss and Hyponatremia

Na+ loss could cause hyponatremia but this rarely happens in excess of water loss and therefore does not cause hyponatremia directly. Instead, Na+ loss causes *ECV depletion with subsequent volume-mediated activation of ADH* leading to an *impairment of electrolyte free water (EFW) excretion*

Development of Central Pontine Myelinolysis

Occurs in *Chronic* Hyponatremia with over-rapid correction In Chronic Hyponatremia (3-4 days), the brain is stuffed inside the skull and compensates by shrinking - cannot get rid of water, so instead it exports osmoles into the ECV (taurine, myoinosotol, aa's) --> decreased ICV With over-rapid correction 3% Saline is given to raise serum Na --> increases osmolality of ECV (relative to ICV) --> Water enters ECV --> brain shrinks FURTHER

Symptoms of Chronic Hyponatremia

Often asymptomatic or present with *mild confusion or nausea*. Cerebral adaptation has occurred as the brain cells have excreted intracellular osmoles (taurine, myoinositol, aminoacids) to limit cell swelling Over-rapid correction of chronic hyponatremia may produce profound neurological abnormalities (*central pontine myelinolysis*)

Cerebral Edema (expansion of ICV)

Osmolality drops, H2O moves into ICV, ICV expands - if ICV is in muscles, not a big deal - if ICV is in brain this is a PROBLEM! --> Cerebral edema, compression of brainstem

Solute Diuresis

Polyuria due to excess solute excretion: - Glycosuria - High Na Intake (IV saline, diet) - High Urea Excretion (catabolism, high protein feeds, recovery from ARF) Correcting source of excess volume will treat Polyuria; hypotonic fluids will correct Hypernatremia

Water Diuresis

Polyuria due to excess urine water loss - Diabetes insipidus - Psychogenic polydipsia 24hr osmole excretion rate normal (~10mOsm/kg/day) (diluted urine, but more of it for same total osmole excretion) - Water deprivation test and measurement of plasma Vasopressin (ADH) may help distinguish DI vs polydipsia

Hypernatremia Symptoms and Signs

Predominant symptom: *Thirst* - Serum hypertonicity promotes water movement from ICF to ECF with shrinking of cells - CNS symptoms may occur (confusion, coma) if severe (typically approaching 160mmol/L). Marked brain cell shrinkage increases the risk of cerebral haemorrhage

Volume Depletion Treatment

Pts w/ hyponatremia secondary to volume depletion typically respond to *isotonic normal saline* - correction of volume depletion will remove the stimulus for ADH and permit renal excretion of a maximally dilute urine - Careful: rapid renal excretion of the excess water may correct the serum Na level too quickly

Assessment of Polyuria

Pts with abnormal H2O balance can maintain normal Na by matching EFW loss with water intake --> presents as *Polyuria (rather than hypernatremia)*. Measure at least *two 24/hr urine tests*. Polyuria *>3L/day*. *Labs*: serum Na, Ca, Glucose, and Plasma Osmolality *UA*: Osmolality, urine electrolytes (Na, K, Cl, Urea), and urine glucose

Treatment of ECV Depletion

Re-expansion of ECV with normal Saline - careful to ensure Hypokalemia is not worsened (nay need additional K supplement) and that Hyponatremia is not corrected too quickly by the increasing dilute urine output Address underlying cause!

Hypernatremia

Represents a decrease in water relative to Na - Almost always due to a problem with water balance - Rarely caused by excess Na intake (e.g. iatrogenic, drinking seawater) when it is associated with a marked increase in ECF volume. Will Not develop unless there is impaired thirst mechanism or difficulties with access to water (hospitalized patient, infants, elderly)!

Treatment of Central Diabetes Insipidus

Responds to ADH replacement therapy given as *intranasal desmopressin acetate* (10-20ug BID) - Ensure pt cuts down oral water intake or hyponatremia will develop

Depletion of Volume vs Osmolality Imbalance

Restoration of plasma volume takes precedence over osmolality and ADH is stimulated in volume depletion despite hypo-osmolality

Laboratory Tests to Asses Hyponatremia

Serum Osmolality Urine Osmolality Urine Na

Plasma (Serum) Osmolality [Lab Tests to Asses Hyponatremia]

Should be *Hypotonic (< 280 mOsm/kg)* - *Isotonic* (280-295 mOsm/kg) suggests *pseudohyponatremia* - *Hypertonic* (> 295 mOsm/kg) suggests *hyperglycemia* or rarely mannitol treatment

Chronic Hyponatremia (>48 hours)

Some cerebral adaptation has occurred and pts are at risk of central pontine myelinolysis if Na is corrected too quickly - correction rate should be less than 1mmol/L/hr with a maximum of 10-12 mmol/L over a 24hr period Treatment: 1.) *Water restriction* 2.)* Increased salt intake* with frusemide to promote renal EFW excretion 3.) Administration of *drugs to antagonize ADH* (aquaretics, e.g. conivaptan) --> IF pt is symptomatic (seizures, decreased level of consciousness), even with chronic hyponatremia, initial treatment should be rapid, raising serum Na by 1-2mmol/L/hr over the first 3-4 hours

Hyponatremia - the patient having acute neurological consequences (seizures, confusion)

Symptomatic hyponatremia needs *rapid treatment usually with hypertonic saline*

Differential Diagnosis of Hyponatremia

This can be determined from the algorithm (Pic!!) - Note: Several factors are often present in the same patient 1.) Hyperglycemia 2.) Pseudohyponatremia and Artefactual 3.) Iatrogenic 4.) Polydipsia 5.) Diuretics and other Drugs 6.) Syndrome of Inappropriate ADH (SIADH)

Desmopressin (DDAVP) Challenge

To determine if a patient has Central vs Nephrogenic DI, administer ADH in the form of *Desmopressin* If Pt responds (increased urine osmolality due to increased water retrnetion), DI is Central

Treatment of Nephrogenic Diabetes Insipidus

Treat underlying cause and discontinue any contributing drugs - Nephrogenic DI often due to chronic interstitial disease: may not be reversible Maintenance of high oral water intake will maintain serum Na in normal range at expense of Polyuria - treat polyuria with dietary changes (low Na intake, protein restriction) and drugs that interfere with urine dilution (thiazide diuretics)

Treatment of Hyponatremia

Treatment of acute symptomatic hyponatremia = medical emergency. Treatment of chronic asymptomatic hyponatremia must be cautious as over-aggressive therapy can have serious consequences. Treatment related both to the underlying cause and the clinical severity. *If symptoms are present (seizures, coma), this is a medical emergency*. Note: It's NOT sufficient to successfully correct the hyponatremia without treating the underlying cause (e.g. bronchial carcinoma)! *Never treat a sodium concentration in isolation. Clinically important consequences often depend on the rate of change of serum Na levels and not the absolute value.*

Acute Symptomatic Hyponatremia <48 hours

Typically arises in *post-op patients who have received excessive hypotonic IV fluids* May also be seen in *acute water intoxication* (e.g. ecstasy use, psychogenic polydipsia). Main risk: *cerebral edema* with potentially devastating neuro injury. - For unclear reasons, the neuro complications appear more common in women

Why are the kidneys not able to excrete the excess EFW?

Typically due to ADH Secretion

Non-Renal Water Loss

Typically occurs in hospitalized/nursing home pt. - Insensible loss (respiratory tract and sweat) is relatively hypotonic and if not replaced with adequate H2O will lead to hypernatremia. - GI losses (diarrhea) also typically hypotonic (80-200mOsm/kg); may exacerbate EFW loss. Pts w/ diarrhea often have a significant Na loss in addition to the relatively greater water loss, reflected by additional evidence of volume depletion on examination. - With non-renal water loss, the normal kidneys are able to produce a *low volume, high osmolality urine*

Question 3: Rx of Hyponatremia A 27yo female is found unconscious and taken to the ER. Exam: Awake, eyes open, but incoherent speech. Evidence of urinary incontinence. P88, BP 104/60. No edema. Labs: BG: 85 __109_|_75_|_15__ __3.2_|_24_|_0.5__ *Which is the best therapy?* a.) Water restriction for a slow correction of hyponatremia b.) 5% Dextrose to prevent hypoglycemia c.) Normal (0.9%) saline (Na 154mEq/L) to avoid over-rapid correction of the hyponatremia d.) 3% Hypertonic saline (500 mEq/L) to rapidly raise Na

Urinary incontinence plus altered mental status = possible seizure Serum Na 109 = Emergency Low! Seems Acute, needs 3% saline *Answer: d.) 3% Hypertonic saline (500 mEq/L) to rapidly raise Na*

Osmotic Diuresis

Urine osmolality is typically ~ 500mOsm/kg and the urine contains close to 50mmol/L Na+ and 25-50mmol/L K+. Dx should be suspected in Pts w/ a *high urine volume and a high urine osmolality*. --> results in a *high osmole excretion rate* (normal 600-900mOsm per day).

Source of Electrolyte Free Water (EFW)

Usually oral or IV fluids Rarely EFW generation from hypertonic urine Note: excess free water alone (psychogenic polydipsia) rarely causes hyponatremia in the absence of impaired urinary dilution

Causes of Volume Depletion (Hypovolemia)

VD occurs due to loss of Na (and H2O) from body --> shrinks ECV - water loss alone has less effect on ECV as 2/3 of water loss will be from ICV 1.) GI Losses (diarrhea vomiting) 2.) Excess sweating (sweat [Na] ~30mmol/L) 3.) Renal Na Loss (e.g. excess diuretics)

ADH Analogs

Vasopressin Desmopressin (DDAVP) Oxytocin

Iatrogenic Hyponatremia

Very common cause of hyponatremia in hospitalized patients due to inappropriate IV fluids - Post-op, there is often *ADH release secondary to pain and stress, and excess 5% dextrose may result in hyponatremia* - should be remembered that hospitalized patients often have *additional sources of EFW* including oral fluids, parenteral nutrition or ice chips

Question 2 60yo man develops gastritis and vomits for 3 days. He can only keep down water. Exam: Weight 65kg (down 5kg), BP 90/54, pulse 96, no edema. Labs: Serum Na 130 *What has happened to the volume of his intracellular fluid (ICV)?* a.) Decreased b.) Unchanged c.) Increased

Volume Depleted Serum Sodium Low (normal 140) = ECV Osmolality Low, water moves into ICV, ICV Expands *Answer*: ICV Increased bc the Serum Na is Low

Body's Response to Volume Depletion

Volume Depletion sensed by *arterial baroreceptors* --> Activation of *RAAS and SNS*

Question 1 A 60yo man with a history of coronary artery disease presents with SOB. Exam: Wt 75kg (up 5kg), BP 110/70; P88; 2+ peripheral edema, JVP raised, chest bibasal crackles. Labs: serum Na 130 *What has happened to the volume of his intracellular fluid (ICV)?* a.) Decreased b.) Unchanged c.) Increased

Volume Expanded Serum Sodium Low (normal 140) = ECV Osmolality Low, water moves into ICV, ICV Expands *Answer*: ICV Increased bc the Serum Na is Low

Edema

abnormal accumulation of fluid (salt and water) in the interstitial compartment. Can describe: - Micoscopic Fluid (edema in renal interstitium viewed on biopsy) - Fluid in an entire organ (plumonary edema seen on CXR) - Overall Volume Status (gross edema on exam) *Localized*: - limited to specific region of body *Generalized*: - reflects disturbance in overall Na balance

Loop Diuretics rarely cause Hypovolaemic Hyponatremia because....

blockade of Na reabsorption in the loop of Henle interferes with the maintenance of medullary concentration gradient which impairs ADH action

SNS Action on Volume Depletion

causes tachycardia, peripheral vasoconstriction, dry mouth, and activates RAAS and *Na-H Antiporter in Proximal Tubule*, increasing proximal Na absorption

Primary Polydipsia

drinking more water than kidneys can excrete

Dependent Edema

edema that increases in an area bc of gravity - in upright pts typically found in lower extremities and ankles worsening through day and improving after laying all night - bed-bound pts, found in Sacrum, buttocks, and hips

Pitting Edema

indentation left by finger after compressing a body region (usually lower extremity)

Anasarca

massive generalized edema

Serum Na in Diabetes Insipidus

may be normal due to marked polydipsia compensating for the polyuria.

Urine Osmolality [Lab Tests to Asses Hyponatremia]

typically >100mOsm/kg *high* confirming *impaired urine dilution* (renal excretion of EFW). - Rarely the *urine osmolality is low* (<100mOsm/kg) implying *excess water intake*

Pseudohyponatremia

very rare detected by a *normal serum osmolality despite hyponatremia*