MEDICINE 2 – [MODULE]: GENERAL LECTURE AY 21-22

SODIUM DISORDERS
Porshia B. Comes-Natividad, MD
1.14 09 SEPT 21

TABLE OF CONTENTS ● Solutes restricted to the ICF or ECF compartment determine

I. INTRODUCTION .................................................................... 1
the tonicity
A. OSMOLALITY ................................................................... 1 ● Osmolar state determining the volume behavior of cells in a
B. MAINTENANCE OF NORMAL PLASMA OSMOLALITY .... 2 solution; regulated by water balance | 
C. SODIUM DISORDERS ...................................................... 2 Table 1. Effective vs Ineffective Osmoles
II. HYPONATREMIA................................................................... 2 Effective Osmoles Ineffective osmoles
A. HYPONATREMIA & PLASMA OSMOLALITY .................... 3 Sodium, Glucose Urea, Ethanol
B. VOLUME STATUS IN TRUE HYPONATREMIA ..................... 3 • An increase in sodium and/or • Do NOT contribute to the
C. ACUTE HYPONATREMIA (<48h) ........................................... 5 glucose in the ECF causes water shift across the ICF and
D. CHRONIC HYPONATREMIA (>48h) ................................. 5 water to move into the ECF. ECF membrane.
E. DIAGNOSTIC EVALUATION OF HYPONATREMIA .......... 5 • Wherever sodium or glucose
F. SIADH or Syndrome of Inappropriate ADH Secretion ........ 6 go, water follows
G. MANAGEMENT OF HYPONATREMIA .............................. 6 • Sodium and water are always
H. ADMINISTRATION OF INTRAVENOUS FLUIDS .............. 7 interrelated
III. HYPERNATREMIA ................................................................ 7
A. VOLUME STATUS IN HYPERNATREMIA ........................ 8 Plasma Osmolality
B. CLINICAL MANIFESTATIONS OF HYPERNATREMIA ..... 8 ● Solute concentration of plasma
C. DIAGNOSTIC EVALUATION OF HYPERNATREMIA ........ 9 → Components that determine plasma osmolality are the
D. RESPONSE TO HYPERNATREMIA & concentration of sodium, which is the major component of
HYPEROSMOLALITY ................................................................. 9 plasma PLUS the concentration of glucose and urea.
E. MANAGEMENT OF HYPERNATREMIA............................ 9 ● Calculated plasma osmolality
F. CORRECTION OF HYPERNATREMIA ........................... 10
IV. FLIPPED CASE 1................................................................. 10  | CALCULATED PLASMA OSMOLALITY (pOSM)
A. PLASMA OSMOLALITY .................................................. 10 ● N.V. 280 – 295 mOsm/kg
B. VOLUME STATUS .......................................................... 10 ● pOSM = (2 x Na in mmol/L) + glucose [mg/dL] + BUN [mg/dL]
C. ADDITIONAL DIAGNOSITIC TESTS ............................... 11 18 2.8
D. MANAGEMENT............................................................... 11 ● Effective pOSM = (2 x plasma Na) + plasma glucose [mg/dL]
V. FLIPPED CASE 2................................................................. 12 18
A. DEVELOPMENT OF HYPERNATREMIA ........................ 12
B. MANAGEMENT OF THE PATIENT ................................. 12 → Effective plasma osmolality or plasma tonicity is computed by
REFERENCES .............................................................................. 12 subtracting the measured concentration of ineffective osmole,
urea (BUN), to the computed plasma osmolality
MUST KNOW BOOK PREVIOUS TRANS ● Plasma osmolality is within narrow limits | 
   → A 1-2% variation initiate the defense mechanisms to return the
plasma osmolality to normal
I. INTRODUCTION ● ↑ in calculated osmolality by >10–15 mmol/kg H2O | 
→ Serum sodium may be spuriously low (in hyperlipidemia or
● Total Body Water comprises: hyperproteinemia/pseudohyponatremia)
→ Females: 50% of BW |  → Osmolytes other than sodium salts, glucose, or urea may have
→ Males: 60% of BW |  accumulated in plasma
● 2 major compartments of TBW ■ Osmolytes: mannitol, radiocontrast media, ethanol,
→ Intracellular fluid: 55-75% of TBW isopropyl alcohol, EG, propylene glycol, methanol, and
→ Extracellular fluid: 25-45% of TBW acetone
■ Intravascular (plasma): ⅓ ● Effectors in the defense of plasma osmolality: | 
■ Extravascular (interstitial spaces): ⅔ → Arginine vasopressin (AVP) secretion
● Major solutes |  → Water ingestion (via thirst mechanism)
→ ECF: sodium, chloride and bicarbonate → Renal water transport | 
■ Also found are small amounts of Ca 2+, K+
→ ICF: potassium and organic phosphate esters (ATP, creatine Vasopressin (ADH, AVP)
phosphate, and phospholipids)
■ Also found are small amounts of Mg2+, Na+, protein
● Water diffuses freely via a semipermeable membrane between
the ICF and ECF compartment in response to gradients produced
by effective osmolality.
A. OSMOLALITY
● Solute concentration of a fluid
● mOsm/kg
● ATP pumps, transporters, and channels affect the amount of
solutes (ions) in a particular compartment
Effective Osmolality Figure 1. Formation and Mechanism of AVP/ADH
● aka Tonicity ● Arginine Vasopressin (AVP) aka Antidiuretic Hormone (ADH)
● Equal to the sum of the concentration of the solutes which have ● Synthesized in the hypothalamus and stored in the posterior
the capacity to determine the movement of water across the ICF pituitary gland
and ECF

TG3 GAMENG | DUNGO, FLORES, GUANZON, IRINCO, ISON Page 1 of 12

TG8
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021)
● From the posterior pituitary, AVP is subsequently released into
the circulation after an appropriate stimuli | 
→ ↑ plasma osmolality
→ ↓ effective circulating volume
● AVP then acts on the vasopressin renal vasoreceptors (V2
receptors in the TAL, and principal cells of the collecting duct)
→ ↑ permeability of the collecting tubules
■ Promoting renal water reabsorption
■ Impairing renal water excretion
Figure 2. Renal Concentration of Urine
● Increased AVP secretion in response to an increase plasma
osmolality and/or a decrease in effective circulating volume,
forms a hypertonic, “concentrated” urine | 
→ Osmolality up to 1200 mOsm/kg
● A concentrated urine is produced by equilibration of the fluid in
the collecting tubules with hyperosmotic medullary interstitium
● Medullary interstitium becomes hyperosmotic → collecting
tubules become permeable to water in the presence of ADH →
increase water reabsorption, decrease renal water excretion
→ Final product: concentrated urine
Thirst Mechanism
● Loss of dilute fluid through excessive sweating → net effect of
increased plasma osmolality and possibly a decrease in ECF
volume
→ Presence of ADH would increase renal water reabsorption and
decrease renal water excretion
→ Intact thirst mechanism: an increase in plasma osmolality
stimulates the osmoreceptors in the hypothalamic thirst center
resulting in the desire to drink water
B. MAINTENANCE OF NORMAL PLASMA OSMOLALITY
Figure 3. Normalized Plasma Osmolality
● Increase in plasma osmolality >295 mOsm/kgH2O
→ Stimulation of thirst: increase water ingestion
→ Increase AVP release: increase renal water reabsorption,
decrease renal water excretion and formation of a
concentrated urine
→ Net effect: Concentrated urine to normalize pOsm
● Decrease in plasma osmolality <280 mOsm/kgH2O
→ Suppression of thirst: decrease water intake
→ Decrease AVP release: decrease renal water reabsorption,
increase renal water excretion and formation of a dilute urine
→ Net effect: Diluted urine to normalize pOsm
Page 2 of 12
● Changes in blood volume and blood pressure also stimulate AVP
release and thirst | 
→ ECF volumes strongly modulates AVP release, such that
hypovolemia reduces the osmotic threshold and increases
the response of AVP to plasma osmolality
→ Hypervolemia increases the osmotic threshold and
decreases the response of AVP to plasma osmolality
● Non-osmotic stimuli with potent activating effects on
osmosensitive neurons and AVP release: nausea, intracerebral
angiotensin II, and multiple drugs | 
C. SODIUM DISORDERS
● Any problem in the thirst mechanism and/or ADH secretion, renal
water reabsorption and excretion will result in disorders involving
urine dilution or concentration.
Figure 4. Sodium Disorders. When plasma osmolality fails to normalize.
● Disorders of serum Na concentration are caused by
abnormalities in water homeostasis, leading to changes in the
relative ratio of Na to body water. | 
● Water intake & circulating AVP constitute the two key effectors
in the defense of serum osmolality; defects in one or both of these
two mechanisms cause most cases of hyponatremia and
hypernatremia
 | SODIUM DISORDERS (Serum Na)
● HYPOnatremia = <135 mmol/L
● HYPERnatremia = >145 mmol/L
II. HYPONATREMIA
● Plasma Na concentration <135 mmol/L
● Very common disorder occurring in up to 22% of hospitalized
patients
● Almost always the result of an increase in AVP secretion and/or
increased renal sensitivity to AVP PLUS intake of free water
→ Result in excess water relative to sodium | 
Figure 5. Hyponatremia in the setting of high intake of free water
● Low solute intake also causes hyponatremia
→ Very low urine osmolality (<100-200 mOsm/kg)
→ Urine Na <10-20 Mm
→ e.g. in vegans, low-sodium diets
→ Alcoholics with beer potomania (beer is very low in protein and
salt)
→ Non-alcoholic patients with highly restricted solute intake due
to nutrient-restricted diets (e.g. extreme vegetarian diets)
→ Treatment | 
■ Resume normal salt intake in the diet
■ IV hydration with saline
■ Stop drinking beer for potomaniacs
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 3 of 12

A. HYPONATREMIA & PLASMA OSMOLALITY B. VOLUME STATUS IN TRUE HYPONATREMIA

Figure 6. Hyponatremia and Plasma Osmolality

With NORMAL pOsm
● Pseudohyponatremia | 
● Causes: Figure 8. Volume Status in Hyponatremia
→ Severe hyperlipidemia ● Assessment of volume status will help us determine the
→ Hyperproteinemia conditions causing hyponatremia
● There is a reduction in the fraction of plasma that is composed of Hypovolemic Hyponatremia
plasma water
● Plasma sodium concentration is artifactually reduced ● Has both total body sodium and water deficit
→ Sodium deficit > water deficit
With HIGH pOsm ● Causes hyponatremia by appropriately stimulating thirst and
● Seen in cases of: increasing secretion of AVP
→ Hyperglycemia ● Due to renal or extrarenal losses
■ Hyperglycemia will create a transcellular osmotic gradient ● Extrarenal Losses (Urine Na <20 mmol/L, usually <10 mmol/L,
resulting in water movement out of the cells into the ECF due to avid tubular reabsorption of Na)
compartment and a reduction in plasma sodium → Vomiting
concentration by dilution. → Diarrhea
■ Due to the glucose-induced water efflux from cells, the → Burns
plasma Na+ concentration falls by 1.6 mmol/L for every → Trauma
100mg/dL increase in plasma glucose. |  → Sequestration of fluids in third spaces
■ Results from increases in vascular permeability and/or a
reduction in oncotic pressure that alter Starling forces | 
■ e.g. Peritoneal cavity with peritonitis or pancreatitis
● Renal Losses (Urine Na excretion is high, >20 mmol/L)
→ Diuretic excess | 
■ Most common cause of hypovolemic hyponatremia
■ Pharmacologic diuretics selectively impair NaCl
reabsorption at specific sites along the nephron | 
→ Mineralocorticoid deficiency
■ Can reduce NaCl reabsorption by the aldosterone-sensitive
Figure 7. Hyperglycemia induced hyponatremia distal nephron | 
→ Administration of Mannitol → Salt losing deficiency
→ Bicarbonaturia (RTA, metabolic alkalosis)
With LOW pOsm
→ Ketonuria
● True hyponatremia |  → Osmotic diuresis
● Present only if the effective pOSM: <275 mOsm/kg water → Cerebral salt wasting
● Once true hyponatremia is ascertained, assess the volume status
of the patient!  | Effect of THIAZIDE DIURETICS on Renal Urine
→ Hypovolemic hyponatremia Concentration
→ Euvolemic hyponatremia
→ Hypervolemic hyponatremia

Figure 9. Effects of Thiazide Diuretics on Renal Urine Concentration

● Reasons that thiazides cause hypovolemic hyponatremia:
→ Thiazides block NaCl cotransporter in the distal tubule
inhibiting sodium chloride reabsorption and increasing
excretion of sodium and chloride in the urine.
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 4 of 12

→ Thiazides do not interfere with the ability of ADH to promote Table 2. Causes of SIADH. Adapted from Dr. Natividad’s lecture.
water retention because the medullary hypertonicity in the Carcinomas Pulmonary Nervous System Others
interstitium is intact. Disorders Disorders
● Thiazide diuretics COMMONLY cause hyponatremia due to ▪ Bronchogenic ▪ Viral/Bacterial ▪ Viral/Bacterial ▪ HIV
CA pneumonia encephalitis ▪ AIDS
renal water retention plus renal excretion of effective solutes.
▪ CA of the ▪ Pulmonary ▪ Viral/Bacterial or ▪ Idiopathic
 | Effect of LOOP DIURETICS on Renal Urine Concentration duodenum, abscess Tuberculous/Fungal (elderly)
stomach, or ▪ Tuberculosis meningitis ▪ Prolonged
pancreas ▪ Aspergillosis ▪ Head trauma exercise
▪ Thymoma ▪ Positive- ▪ Brain abscess
▪ Lymphoma pressure ▪ Brain tumors
▪ Ewing sarcoma ventilation ▪ Guillain-Barre
▪ CA of the ▪ Asthma syndrome
bladder, ▪ Pneumothorax ▪ Acute intermittent
prostate, ureter ▪ Mesothelioma porphyria
▪ Oropharyngeal ▪ Cystic fibrosis ▪ Subarachnoid
tumor hemorrhage or
subdural hematoma
▪ Cerebellar and
cerebral atrophy
→ Drugs
Figure 10. Effects of Loop Diuretics on Renal Urine Concentration
Table 3. Drugs associated with Hyponatremia
● Mechanism of loop diuretics:
→ Loop diuretics inhibit NaCl reabsorption in the medullary Vasopressin Analogues Drugs that Potentiate Renal
thick ascending loop of Henle thereby diminishing the Action of Vasopressin
medullary interstitial tonicity Desmopressin (DDAVP) Chlorpropamide
→ Diminished medullary interstitial tonicity interferes with the Oxytocin Cyclophosphamide
ability of ADH to promote water retention NSAIDs
Acetaminophen
● Loop diuretics DO NOT cause hyponatremia as much as
thiazides because water retention with loop diuretics is limited by Drugs that Enhance Drugs that Cause
the lack of medullary hypertonicity. Vasopressin Release Hyponatremia by Unknown
Mechanisms
Euvolemic Hyponatremia Chlorpropamide Haloperidol
● Most common cause of hyponatremia in hospitalized Clofibrate Fluphenazine
patients Carbamazepine-Oxcarbazepine Amitriptyline
● These patients have no physical signs of ↑ or ↓ in total body Vincristine Thioridazine
sodium Nicotine Fluoxetine
● Since volume status is normal, the renal tubules do not avidly Narcotics Methamphetamine (MDMA,
SSRIs “Ecstasy”)
reabsorb sodium, thus urine sodium excretion is high.
(Antipsychotics/Antidepresssants) Intravenous immune globulin
● Urine Na >20 mmol/L Ifosfamide (IVIG)
→ Glucocorticoid deficiency
■ Drugs that commonly cause hyponatremia:
■ ↑ ADH release due partly to effective volume depletion
− Selective Serotonin Receptor Inhibitors (SSRIs)
from:
− Carbamazepine
− diarrhea, vomiting, or renal loss from marked lack of
− Haloperidol
aldosterone
− Other additional drugs like
■ ADH is co-secreted with corticotropin releasing hormone
Methylenedioxymethamphetamine or ecstasy
(CRH) so when there is cortisol insufficiency, there will be
→ Primary Polydipsia (only added under hyponatremia)
↑ CRH secretion by the pituitary cells and enhanced co-
■ The only hyponatremia where water excretion is not
secretion of ADH
impaired (hence, not a true hyponatremia)
→ Severe Hypothyroidism
■ Not included in the diagnostic algorithm in Harrison’s
■ Exact mechanisms for hyponatremia are not well
■ There is a primary increase in water intake and typically
understood
complains of polyuria or excessive thirst
■ ↓ CO leads to non-osmotic release of AVP
■ Presumed to be a central defect in thirst regulation
■ ↓ GFR → diminished free water excretion through ■ Plasma sodium concentration is usually normal or only
decreased distal delivery to the distal nephron slightly reduced in this disorder since excessive water can
■ Hyponatremia is readily reversed by Hormone readily be excreted
Replacement Treatment ■ Rarely, their water intake reaches 10-15 L/day which may
→ Stress overwhelm the renal excretory capacity → FATAL
→ SIADH (Dx will be further explained in section F. SIADH) hyponatremia
■ ↑ ADH secretion even in the absence of ■ Particularly prevalent in psychosis (7% of patients with
hyperosmolality or effective circulating volume schizophrenia)
depletion
■ Most frequent cause of euvolemic hyponatremia |  Hypervolemic Hyponatremia
■ Seen in a wide variety of clinical states ● In hypervolemia, if the total body water is increased more than
■ Common causes of SIADH: the total body sodium → Hyponatremia
− Bronchogenic carcinoma ● High Urine Na >20 mmol/L
− Lung infection such as viral and bacterial pneumonia → Acute Renal Failure
− Pulmonary abscess → Chronic Renal Failure
→ There is an impaired renal water excretion especially when
− Tuberculosis
GFR falls to very low levels
− Brain infections/tumors
● Low Urine Na <20 mmol/L (typically very low: <10, even after
− HIV infection & AIDS
hydration with normal saline)
→ Congestive Heart Failure (↓ cardiac output)
→ Hepatic Cirrhosis (splanchnic vasodilatation)
→ Nephrotic Syndrome (severe hypoalbuminemia)
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021)
■ All mechanisms per condition will ↓ ECV
■ ↓ effective circulating volume (ECV) stimulates AVP
secretion and release → impaired renal water excretion
and hyponatremia
C. ACUTE HYPONATREMIA (<48h)
● <48 hours
● Symptoms are primarily neurologic due to cerebral edema! |
 ■ DDAVP (AVP agonist desmopressin acetate)
● ↓ pOsm → osmolal gradient is created across BBB → water
movement into the brain
● Degree of cerebral edema correlates to the severity of
symptoms
→ Mild: headache, nausea and vomiting
→ Severe: drowsiness, seizures, coma and death
● Acute symptomatic hyponatremia is a medical emergency!
→ Changes induced by acute hyponatremia may result to
permanent neurologic damage
● RBCs become turgid because water goes inside the cell (the
higher osmolality inside the cell, as compared to the extra-
cellular compartment, draws water inside) | 
● Normocapneic or hypercapneic respiratory failure due to
noncardiogenic, “neurogenic” pulmonary edema, with a normal
pulmonary capillary wedge pressure | 
Adaptive Responses of the Brain to Hyponatremia | 
Figure 11. Effects of hyponatremia on the Brain and its Adaptive Responses
1. Rapid Adaptation
● Within 1-3h after the development of hyponatremia, the initial
cerebral edema elevates the hydrostatic pressure in the
cerebral interstitial fluid
● A favorable gradient for fluid movement from the cerebral
interstitium into the cerebrospinal fluid is created
● Thereby, ↓ cerebral swelling
● This movement of fluid is accompanied by efflux of solutes
such as sodium, potassium and chloride out of the brain
cells. This is followed by slow adaptation.
2. Slow adaptation
● Characterized by loss of organic osmolytes over a period of
hours to days, greatly ↓ cerebral swelling
→ Myoinositol, amino acids (glutamine, glutamate and
taurine)
● As a result of these adaptations, some patients may have
minimal symptoms despite severe hyponatremia or plasma
sodium concentration of <125 mmol/L.
● Acute elevation in plasma sodium concentration because of
overly aggressive correction can lead to osmotic demyelination
or osmotic shrinkage of axons.
→ Important to keep in mind these cerebral adaptations when
correcting a patient’s hyponatremia
Osmotic Demyelination Syndrome | 
● Complication of overly aggressive treatment/rapid correction
of hyponatremia
● Increase in water → low osmolality → brain swelling
→ Brain cannot expand in the rigid skull
→ The brain needs to excrete electrolytes to maintain its volume
resulting to low organic osmolyte concentration
● End stage: osmotic demyelination (brain will shrink)
Page 5 of 12
● Characterized by paraparesis or quadriparesis, dysarthria,
dysphagia and coma
● Diagnosis is confirmed by CT scan or MRI
● Therapy: Prevention is best!
● Do slow correction; if done too fast, ODS is aggravated
● Treatment for ODS (Sodium Overcorrection) | 
→ If plasma Na+ overcorrects following therapy
→ Hyponatremia can be safely reinduced or stabilized by:
■ IV D5W (a form of free water)
→ Goal: to prevent or reverse the development of ODS
D. CHRONIC HYPONATREMIA (>48h)
● Results in an efflux of organic osmolytes (creatine, betaine,
glutamate, myoinositol, taurine) from brain cells | 
● Symptoms: vomiting, nausea, confusion and seizures
→ Seizure may be a manifestation if the plasma sodium
concentration is <125 mmol/L
● Most patients are “asymptomatic” but can still manifest
subtle gait and cognitive defects
● Chronic asymptomatic hyponatremia increases the risks of
falls and bony fractures
● You usually cannot distinguish acute from chronic, so treat
patients as chronic while you request for a serum Na+ level.
E. DIAGNOSTIC EVALUATION OF HYPONATREMIA
History
● Provides important clues to the correct diagnosis
● History should be directed at finding the underlying cause
because it is frequently multifactorial
● Ask or look for the following: | 
→ Conditions that ↑ AVP secretion combined with free water
intake
■ Ask for history of vomiting, diarrhea, symptoms of
heart failure, hepatic cirrhosis, nephrotic syndrome.
→ Consider all the possible causes for excessive circulating
AVP/ADH
■ Ask for history of malignancy, infection, neurologic
diseases
→ Detailed drug history which can cause hyponatremia
Physical Examination
● Assessment of the patient’s volume status | 
→ Very important in the evaluation of patients with true
hyponatremia
Laboratory Investigation
● Plasma osmolality
→ To exclude pseudohyponatremia
● Plasma Na, Glucose, BUN
→ Needed in the computation of plasma osmolality
→ Serum glucose is taken to “rule out” hyponatremia
secondary to hyperglycemia | 
● Urine Na and Osmolality
→ Done in confirmed hyponatremia
→ To determine whether water excretion is impaired or
not
 | CALCULATED PLASMA OSMOLALITY
pOSM = (2 x plasma Na) + plasma glucose [mg/dL] + BUN [mg/dL]
18 2.8
 | EFFECTIVE PLASMA OSMOLALITY
Effective pOSM = (2 x plasma Na) + plasma glucose [mg/dL]
18
Where, plasma Na is in mmol/L and plasma glucose is in mg/dL
Plasma glucose and BUN is divided into 18 and 28 respectively to convert to
mmol/L
N.V. 280 – 295 mOsm/kg
● Effective pOsm is normal: check for severe hyperproteinemia
or hyperlipidemia
● Effective pOsm is elevated: check for hyperglycemia or use of
mannitol
● Effective pOsm is below 275 mOsm/kg H2O: evaluate for
causes of true hyponatremia
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021)
● Urine Osmolality
→ Urine Na determination is useful in distinguishing causes of
hypovolemic and hypervolemic hyponatremia
→ Requested once patient has been confirmed to have true
hyponatremia
→ Can be used to determine whether water excretion is normal
or impaired
Table 4. Urine Osmolality
<100 mOsm/kg Primary Polydipsia
(water excretion is normal)
100-400mOsm/kg AVP excess with increase water
intake
>400 mOsm/kg AVP excess is playing a
(impaired, concentrated) dominant role
● Serum Creatinine, Potassium, ABG
→ SCr and BUN – check patient’s renal function
■ Acute/Chronic renal failure are potential causes of
hyponatremia
→ Abnormalities in acid-base and K homeostasis are
occasionally associated with hyponatremic disorders
■ e.g. hyponatremic patient + metabolic alkalosis +
hypokalemia: consider vomiting or diuretic therapy as
possible causes of hyponatremia
■ e.g. hyponatremic patient + hyperkalemia + metabolic
acidosis: undergo evaluation for adrenal insufficiency
F. SIADH or Syndrome of Inappropriate ADH Secretion
● Main problem: increased ADH | 
● A primary defect in osmoregulation caused by another disorder
such as malignancy, stroke or pneumonia that cannot be easily
or quickly corrected
→ Neoplasms: carcinomas (lung, duodenum, pancreas, ovar,
bladder, ureter) or other neoplasms (thymoma, mesothelioma,
bronchial adenoma, carcinoid, gangliocytoma, Ewing’s
sarcoma)
→ May also be caused by head trauma, infections, etc.
Essential Diagnostic Criteria of SIADH
● Decreased extracellular fluid (plasma) effective osmolality
(≤270 mOsm/kg H2O)
● Inappropriately elevated urine concentration (>100
mOsm/kg H2O)
→ In the presence of true hypotonicity
● Clinical euvolemia
● Elevated urine Na+ concentration under conditions of normal
salt and water intake
→ Since the volume status of patients with SIADH is normal,
there is no need for the renal tubules to avidly reabsorb Na
and so the urine Na excretion is high
● Absence of adrenal, thyroid, pituitary, or renal insufficiency
or diuretic use
→ Rule these out first for SIADH is a diagnosis of exclusion!
Supplemental Criteria of SIADH
● Abnormal water-load test result (inability to excrete at least 90%
of a 20-ml/kg water load in 4 hours and/or failure to dilute urine
osmolality to <100 mOsm/kg)
● Serum vasopressin level inappropriately elevated relative to the
serum osmolality
● No significant correction of serum Na level with volume
expansion, but improvement after fluid restriction
● Hyperuricemia and elevated fractional excretion of uric acid
Page 6 of 12
G. MANAGEMENT OF HYPONATREMIA
Figure 12. Management of Hyponatremia
Acute Symptomatic Hyponatremia (<48h)
● EMERGENCY CORRECTION
→ Necessary if presenting with neurologic symptoms
● INITIAL: Hypertonic saline (3% NaCl) at 1-2 ml/kg/hr over 60
minutes
→ For patients presenting with seizures, obtundation, or
coma, 3% NaCl at higher rates of 4-6 ml/kg/hr
● GOAL: Increase the plasma sodium concentration by 1-2
mmol/L/hr to a total of 4-6 mmol/L for 3-4 hours or until severe
neurologic symptoms have abated
● Coadministration of furosemide (loop diuretic)
→ Loop diuretic enhances free water excretion and hastens
normalization of sodium
→ DO NOT give furosemide in patients with hypovolemia
Chronic Symptomatic Hyponatremia (>48h)
● SOME IMMEDIATE CORRECTION NEEDED
● INITIAL: Hypertonic saline (3% NaCl) at 1-2 ml/kg/hr if with
seizures
→ Otherwise, isotonic saline solution
● Coadministration of furosemide
→ 20 mg IV to enhance water excretion
● Change to water restriction upon 10% increase of sodium, or if
symptoms resolve
● Perform frequent measurement of serum and urine
electrolytes
→ In patients who are being given therapeutic interventions such
as hypertonic solution
→ Serum sodium concentration monitored every 2-4 hours
during treatment because there is a highly unpredictable
response to therapy
→ Patient should be monitored for changes in neurologic and
pulmonary status during correction
→ Once the severe neurologic symptoms have subsided or
resolved, follow the guide for sodium correction for chronic
hyponatremia
■ Correct serum sodium <8-10 mmol/L/24 hour or <18
mmol/L within 48 hours
− To decrease the risk of development of ODS (Osmotic
Demyelination Syndrome)
Chronic Asymptomatic Hyponatremia (Rarely <48h)
● NO IMMEDIATE CORRECTION
● Chronic hyponatremia is usually asymptomatic as the body is
usually compensating | 
Long Term Management in Both Asymptomatic and
Symptomatic Chronic Hyponatremia
● Identification and treatment of reversible causes
● Water restriction
→ Cornerstone of therapy in chronic hyponatremia
→ [(urinary Na + urinary K) / plasma Na] can be quick indicator
of electrolyte-free water excretion | | 
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 7 of 12

■ Ratio of >1: more aggressively restricted water intake → Totilac = 504 mmol of Na and 504 mmol of lactate in 1L of
(<500mL/24h) water
■ Ratio of ~1: restricted to 500-700mL/day ■ Hypertonic sodium lactate IV fluid
■ Ratio of <1: restricted to 1L/day ■ May also be given to symptomatic patients, but its use
● Urea should be avoided in cases of lactic acidosis or in
● If unresponsive: give oral loop diuretics and advise to increase conditions which increase lactate
salt intake → Severe symptomatic hyponatremia: hypertonic solution
● Patients whose serum sodium levels do not increase with (such as 3% NaCl in water) is the IVF of choice! | 
therapy (furosemides, sodium chloride tablets), give: ● ISOTONIC (yellow)
→ Demeclocycline → 0.9% NaCl (plain normal saline solution/plain NSS) = 154
■ Inhibits adenyl cyclase activation after AVP binds to mmol Na + 154 mmol Cl in 1L of water
vasopressin receptor in kidneys → Ringer’s lactate solution = 130 mmol Na + 109 mmol Cl +
■ Directly affects AVP’s effect on the collecting tubules 28 mmol lactate in 1L of water
■ Effective, but not popular due to many side effects ■ Isotonic sodium lactate solution
→ Vaptans (Tolvaptan): Vasopressin 2 receptor antagonists → Solute concentrations similar to plasma
■ Counteract actions of vasopressin by blocking receptors → No movement of water into or out of the cell
thereby decreasing expression of aquaporin channels → → Solutes and water remain in the intravascular space
aquaresis/renal excretion of free water → Should be given to patients with hypovolemic
■ Highly effective in treating patients with SIADH or hyponatremia | 
hypervolemic hyponatremia due to heart failure ● HYPOTONIC (red)
■ Do not use for hypovolemic hyponatremia and acute → 0.45% NaCl in water = 77 mmol Na in 1L of water
hyponatremia as it may aggravate the volume depletion! → 0.3% NaCl in 5% dextrose in water
→ 5% dextrose in water (D5W) = does not contain electrolytes,
only 50g of dextrose in 1L of fluids
→ Have lower solute concentrations than plasma
→ Will cause water to shift from EC → IC compartment (cell
swelling)
→ Contraindicated in treatment of hyponatremia! | 
● Treatment
→ It is a must to know the required rate of IV fluid.
 | STEPS IN ESTIMATING THE REQUIRED RATE OF IV fluid
FOR HYPONATREMIC PATIENTS
● Calculate the sodium deficit
Na deficit = TBW x (target plasma Na - actual plasma Na)
→ Amount of Na required to raise plasma Na concentration to
a desired value
→ Males: TBW = 0.6 x body weight in kg
→ Females: TBW = 0.5 x body weight in kg
● Determine the rate of infusion (mL/hr)
Infusion rate (in L) = Na deficit / 513 mmol/L
mL per hr = Convert infusion rate to mL / 24 hrs
Figure 13. Treatment of Chronic Asymptomatic Hyponatremia
Where, 513 mmol/L is the Na content of hypertonic saline (3%) and desired
Correct concomitant electrolyte disorders |  rate per hour should not exceed 1-2 mmol/hr in symptomatic hyponatremia
For SIADH patients excreting minimal electrolyte-free III. HYPERNATREMIA
water: | 
● Plasma Na >145 mmol/L
→ Aggressive fluid restriction <500-1000 mL/day
● Less common than hyponatremia, but it is associated with
→ Combined oral furosemide 20 mg twice a day and oral salt
mortality rates as high as 40-60%
tablets
→ Mostly due to the severity of the associated underlying
→ Furosemide inhibits the renal countercurrent mechanism and
disease processes.
blunts urinary concentration
● Produced by any disorder or condition that decreases formation
→ Salt tablets counteract diuretic-associated natriuresis
of a concentrated urine, combined with inadequate water intake
H. ADMINISTRATION OF INTRAVENOUS FLUIDS
Table 5. Sodium Content in commercially available IV Fluids. Green: Hypertonic;
Yellow: Isotonic; Red: Hypotonic
Common Infusate Na content (mmol/L)
Figure 14. Hypernatremia in the setting of low intake of free water
3% NaCl in water 513
Totilac 504 ● In most cases, there is less water relative to sodium.
0.9% NaCl in water or PNSS 154 ● The ingestion or iatrogenic administration of excess sodium can
Ringer’s lactate solution 130 be a cause of hypernatremia.
0.45% NaCl in water 77
0.3% NaCl in 5% dextrose in water 34
5% dextrose in water 0
● HYPERTONIC (green)
→ Na concentration of plasma fluid is normally between 135
mmol/L to 145 mmol/L
→ Cause water to shift from IC → EC compartment, thereby
decreasing cell swelling
→ 3% NaCl (aka 3% saline) = 513 mmol of Na+ and 513 mmol
of Cl- in 1L of water
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021)
A. VOLUME STATUS IN HYPERNATREMIA
Figure 15. Volume Status in Hypernatremia
Hypovolemic Hypernatremia
● Sustain losses of both sodium and water, but with relatively
greater loss of water
● Renal Losses (Urine Na excretion: High ≥20 mmol/L; inc. urine
osmolality)
→ Osmotic diuresis secondary to hyperglycemia
→ Use of loop diuretics
→ Post-obstructive diuresis
→ Intrinsic renal disease
● Extrarenal losses (Urine Na excretion: <20 mmol/L)
→ Increase insensible water loss from excessive sweating
→ Severe burns
→ Diarrhea (most common GI cause of hypernatremia)
■ Osmotic diarrhea
■ Viral gastroenteritis
− Both generate stools with sodium and potassium
<100mmol/L, leading to more water loss and
hypernatremia
→ Fistulas
Euvolemic Hypernatremia
● Normal total body sodium
● Loss of water without sodium does not lead to overt volume
contraction unless severe
● Renal Losses
→ Diabetes Insipidus (note: in both forms of DI, the thirst
mechanism is intact)
■ Central DI
− Defect in the AVP production or release
− 30% idiopathic
− 70% due to neurosurgery, head trauma, hypoxic or
ischemic encephalopathy, malignancy such as
craniopharyngioma
■ Nephrogenic DI
− Failure of the collecting ducts to respond to AVP
− Congenital or acquired disorder
− Genetic causes: loss-of-function mutations in the X-
linked vasopressin 2 receptor, mutation in the ADH
responsive aquaporin 2 water channel
− Major causes of acquired nephrogenic DI: lithium
toxicity, hypercalcemia, hyperkalemia (hypokalemia
based from the lecture)
→ Hypodipsia
■ Uncommon cause
■ Usually develops in those with no access to water and in
very young children and old persons with altered perception
of thirst
● Extrarenal Losses
→ High urine osmolality; osmoreceptor ADH renal response is
intact; urine sodium concentration varies with intake
→ Increase insensible losses from:
■ Skin – sweating during high fever
■ Respiratory tract – during mechanical ventilation
Page 8 of 12
Hypervolemic Hypernatremia
● Increased total body sodium
● Least common form
● Results from:
→ Administration of hypertonic solutions (3% NaCl and NaHCO3)
→ Consumption of too much salt tablets
→ Using a dialysate with high sodium concentration during
dialysis
B. CLINICAL MANIFESTATIONS OF HYPERNATREMIA
● Symptoms are predominantly neurologic like hyponatremia | 
● Altered mental status | 
→ Most frequent manifestation
→ Ranging from mild confusion and lethargy to deep coma
→ Neurologic symptoms are due to the immediate effect of
hypernatremia on the brain which is cell shrinkage because of
water loss
● Osmotic damage to muscle membrane
→ Hypernatremic rhabdomyolysis
→ Patient manifests with cramps
● Hypernatremic patients with Diabetes Insipidus usually
complain of these rather than neurologic symptoms!
→ Polyuria
→ Nocturia
→ Polydipsia
→ Doc mentioned: Hypernatremia is uncommon in either form of
DI because the thirst mechanism is intact!
● From previous trans:
→ RBCs become crenated because water goes out of the cell
(the higher osmolality outside the cell, as compared to the
intracellular compartment, draws water outside)
→ Hyperventilation
→ Restlessness
→ Disturbed glucose utilization
→ Impaired gluconeogenesis
→ Decreased left ventricular contractility
Adaptive Responses of the Brain to Hypernatremia
Figure 16. Effects of hypernatremia on the brain and adaptive responses
● The immediate effect of hypernatremia on the brain is cell
shrinkage because of water loss.
● The brain cells rapidly adapt to this situation by taking up sodium
and potassium, leading to an elevation of intracellular osmolality
that pulls water into the cells, thereby returning the brain cell
volume towards normal.
● If the uptake of electrolytes were the only cell adaptation, the
associated elevation in cell cation concentration could have
deleterious effects on the activity of the cell proteins.
→ This is minimized by accumulation of organic solutes called
osmolytes, which do not interfere with protein function as
their concentration rises.
→ These osmolytes are creatine, betaine, glutamate,
myoinositol, and taurine.
● The accumulation of electrolytes as the brain cells’ rapid
adaptation and accumulation of osmolytes as the brain cells’ slow
adaptation to hypernatremia = leads to near normalization of
brain volume.
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 9 of 12

● In consequence, patients with chronic hypernatremia are less Partial NDI -

likely to develop severe neurologic symptoms. Osmotic Diuresis -
● However, remember that an overly rapid correction of ● Hypernatremia due to insensible or GI water loss, primary
hypernatremia can lead to cerebral edema and possible polydipsia, and sodium overload
neurologic deterioration. → uOsm = >800 mOsm/kg
C. DIAGNOSTIC EVALUATION OF HYPERNATREMIA → Renal concentrating mechanisms are intact
History ● Hypernatremia due to central DI or Nephrogenic DI intact
→ Dilute urine, uOsm = <300 mOsm/kg
● Presence or absence of thirst → Renal concentrating mechanisms NOT intact
● Polyuria (>3 L/day) → Due to absence of AVP secretion, decrease in AVP secretion
→ Diuretics, mannitol (osmotic diuresis) or unresponsiveness of kidneys to AVP despite kidney
● Extrarenal source of water loss secretion
→ Fever, diarrhea ■ Central DI vs Nephrogenic DI – differentiated by
→ Sweating (>2 L), vomiting, bleeding, burns administration of exogenous vasopressin
● Accurate documentation of daily fluid intake and daily urine ■ Central DI – at least an ↑ 50% osmolality and a marked fall
output in urine volume (responsive to AVP)
→ Critical in the diagnosis and management → Exogenous AVP is only effective in central DI | 
Physical Examination ● Hypernatremia due to volume depletion in CDI, Partial CDI,
● Detailed neurologic exam Partial ND or osmotic diuresis
● Assessment of effective circulatory fluid volume (ECFV) or → Intermediate uOsm between 300-800 mOsm/kg
volume status → Many patients fall under this category

E. MANAGEMENT OF HYPERNATREMIA

Figure 18. Management of Hypernatremia

Figure 17. Diagnostic Approach to Hypernatremia
Hypovolemic Hypernatremia
→ Large water deficit and/or combined deficit in electrolytes and
water may be hypovolemic, with decreased JVP and ● Correction of volume deficit (restoration of tonicity)
orthostatic hypotension → Administer isotonic saline until volume improves until
→ Hypervolemia may be due to administration of hypertonic euvolemia is achieved
solution or sodium bicarbonate → Treat causes of losses
● Correction of water deficit after volume has been restored
Laboratory Evaluation → Calculate water deficit to achieve gradual correction of serum
● Plasma osmolality Na concentration
● Urine osmolality ■ Replace over 48-72h
● Plasma Na and Urine Na ■ Correct serum Na by not more than >10mmol/L/day to
D. RESPONSE TO HYPERNATREMIA & HYPEROSMOLALITY minimize risk of cerebral edema
→ Administer 0.45% saline D5W or oral water to replace deficit
Normal Response (see Figure 2) and oral losses
● ↑ AVP → ↑ renal water reabsorption, ↓ renal water excretion Euvolemic Hypernatremia
● Formation of a concentrated urine with urine osmolality (uOsm) ● Correction of water deficit
800-1400 mOsm/kg = urine SG of 1.023 to 1.035 → Calculate water deficit
→ A hypernatremic patient with a normal renal concentrating → Administer 0.45% saline D5W or oral water to replace deficit
ability should have a urine osmolality >800mOsm/kg of water and oral losses
Patients with Hypernatremia → Central DI with severe losses – aqueous vasopressin 5 units
SC q 6hrs
Table 5. uOsm and Response to AVP in Hypernatremia Patients
uOsm (mOsm/kg) Response to AVP
→ Monitor serum Na frequently, every 2-4 hours during
Greater than 800 correction to avoid water intoxication
Insensible or GI water loss - ● Long term therapy
Primary hypodipsia - → Central DI – Intranasal or oral DDAVP (desmopressin)
Sodium overload - → Nephrogenic DI – Remove offending drugs (like lithium), low
Less than 300 sodium diet, correction of K and Ca
Central DI (CDI) + ■ If lithium cannot be discontinued, treat with amyloride for
Nephrogenic DI (NDI) - lithium-induced polyuria
300 to 800 ■ Thiazides – may help by inducing hypovolemia and
Volume depletion in CDI + increasing proximal water reabsorption
Partial CDI +
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 10 of 12

Hypervolemic Hypernatremia → PR 105 bpm

● Removal of sodium ● RR 26 cpm
→ Discontinue offending agents ● T 38.5°C
→ Furosemide ● Moist buccal mucosa \
→ Hemodialysis as needed for renal failure ● JVP: 3 cm at 30° angle
● Discontinuation of hypertonic saline or sodium tablets is a ● Decreased breath sounds, R lung base
must! ● (-) edema
● Neurologic exam: cranial nerves and MMT not assessed, DTRs
 | TREATMENT OF HYPERNATREMIA (SUMMARY) (++), (-) Babinski
● Stop culprit medications (diuretics), if possible
● Correct hyperglycemia, hyperCa, hypoK, or diarrhea Laboratory Examination
● Correct gradually to avoid cerebral edema! ● CBC
● Calculate and replace the calculated free water deficit over 48-72 → Hgb 130 g/L, Hct 0.37, WBC 20.1 x10 9/L, Neutrophils 0.80,
hours Lymphocytes 0.20, Platelet count 257
● Give water by mouth or by NGT (most direct way) ● Urinalysis
● Give ONLY water, NOT water with electrolytes (Gatorade or → Yellow, clear, specific gravity 1.0105, pH 5.0
juice) → Trace protein, (-) sugar, RBC 2-4/hpf, WBC 2-4/hpf, few
● May also given by IV using D5W, but monitor blood glucose squamous cells, few bacteria, (-) casts, (-) crystals
● Other IVF: hypotonic saline solutions (1/4 or 1/2 normal saline) ● CXR
● Plasma Na+ concentration should be corrected by no more than → Ill-defined homogenous opacity in the right lower lobe, (+) air
10 mmol/L per day! bronchogram, right
● RT-PCR NPS/OPS swab for COVID 19: Negative
F. CORRECTION OF HYPERNATREMIA Table 6. Blood Chemistry Results
● Should be gradual to avoid the risk of cerebral edema Blood Chemistry Results Normal Values
● Goal: Lower plasma Na by not more than 10 mmol/L per day |  Sodium 118 136-146 mmol/L
Potassium 3.6 3.5-5.3 mmol/L
Water Deficit (mentioned by Doc) BUN 20 7-22 mg/dL
● Administer deficit over 48-72 h Creatinine 1.2 0.7-1.5 mg/dL
 | FREE WATER DEFICIT Glucose 200 70-110
[(Actual Na – 140)] x TBW A. PLASMA OSMOLALITY
[140]
● TBW Males: 0.6 x body weight kg 1 | CALCULATED PLASMA OSMOLALITY
● TBW Females: 0.5 x body weight kg NV: 280-295 mOsm/kg
● Estimates the amount of positive water balance require to return pOSM = (2 x Na) + glucose + BUN
the plasma Na concentration to 140mmol/L 18 2.8
● Aside from replacing the calculated free water deficit, replace Effective pOSM = (2 x Na) + glucose
daily water losses (ongoing and insensible water loss) 18
● Insensible water loss is approximately 10mmol/kg/day (lecture: 2 | DOES THE PATIENT HAVE TRUE HYPONATREMIA?
10mL/kg/day), more if febrile
pOSM = (2 x Na) + glucose + BUN
Ongoing Water Losses |  18 2.8
● Calculate free-water clearance, CeH2O: pOSM = (2 x 118) + 200/18 + 20/2.8
pOSM = 236 + 11 + 7
 | FREE-WATER CLEARANCE pOSM = 254 mOsm/kg
CeH2O = V x [(1) – (UNa + UK)]
PNa Effective pOSM = (2 x Na) + glucose
Where V is urinary volume, UNa is urinary Na, UK is urinary K, and PNa 18
is plasma Na Effective pOSM = (2 x 118) + 200/18
Insensible losses |  Effective pOSM = 236 + 11
Effective pOSM = 247 mOsm/kg
● ~10 mL/kg per day: less if ventilated, more if febrile
Total |  YES, the patient has true hyponatremia. (NV 280 – 295 mOsm/kg)
● Add components to determine water deficit and ongoing water B. VOLUME STATUS
loss ● Patient has no orthostatic hypotension
● Correct the water deficit over 48-72h and replace daily water loss.
→ Orthostatic hypotension: ↓20/↓10 (SBP/DBP) and 15 bpm
● Avoid correction of plasma Na+ by >10mmol/L per day.
● Moist buccal mucosa and axillae, JVP 3 cm at 30°, (-) edema,
IV. FLIPPED CASE 1 and continued water intake point to a euvolemic patient
● Possible cause of patient’s euvolemic hyponatremia (U Na >20):
History → SIADH
● 55 y/o female, 50 kg, diabetic, hypertensive ■ Secondary to pulmonary infection
● CC: altered level of sensorium
● 5 days PTA – headache, sore throat, non-productive cough
● 3 days PTA – fever, cough, productive (yellowish sputum),
diarrhea, with water intake despite loss of appetite
● Few hrs PTA – headache, vomiting, drowsiness
Physical Examination
● Drowsy but easily arousable by verbal stimuli
● Supine
→ BP 140/80
→ PR 110 bpm
● Sitting
→ BP 130/80
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 11 of 12

● Impaired renal water excretion

→ 100-400 mOsm/kg
■ Excess AVP with high water intake
→ >400 mOsm/kg
■ AVP excess is dominant
Disclosure
Table 8. Disclosure
Diagnostic test Results Normal values
Urine sodium 60 mmol/L
Urine osmolality 500 mmol/L
TSH 3.0 0.35-4.25 mlU/L
fT4 12 9-16 pmol/L
Final Diagnosis
● Euvolemic Hyponatremia secondary to SIADH secondary to
Community Acquired Pneumonia (CAP), COVID 19 negative
D. MANAGEMENT
Figure 19. Volume status of the patient
Table 7. Causes of SIADH. Adapted from Dr. Natividad’s lecture
Carcinomas Pulmonary Nervous System Others
Disorders Disorders
■ Bronchogenic ■ Viral/Bacterial ■ Viral/Bacterial ■ HIV
CA pneumonia encephalitis ■ AIDS
■ CA of the ■ Pulmonary ■ Viral/Bacterial or ■ Idiopathic
duodenum, abscess tuberculous/fung (elderly)
stomach or ■ Tuberculosis al meningitis ■ Prolonged
pancreas ■ Aspergillosis ■ Head trauma exercise
■ Thymoma ■ Positive- ■ Brain abscess
■ Lymphoma pressure ■ Brain tumors
■ Ewing ventilation ■ Guillain-Barre
sarcoma ■ Asthma syndrome
■ CA of the ■ Pneumothorax ■ Acute
bladder, ■ Mesothelioma intermittent
prostate, ■ Cystic fibrosis porphyria
Figure 20. Management of the patient
ureter ■ Subarachnoid
Appropriate IV Fluid
■ Oropharyngea hemorrhage or
l tumor subdural ● Use hypertonic (3%) saline at 1-2 mL/kg/hr
hematoma IVF Rate
■ Cerebellar and
cerebral atrophy | CORRECTION OF HYPONATREMIA
● Calculate the sodium deficit
Essential Diagnostic Criteria of SIADH Na deficit = TBW x (target plasma Na – actual plasma Na)
→ Males: TBW = 0.6 x body weight in kg
● Decreased extracellular fluid effective osmolality (<270 mOsm/kg
→ Females: TBW = 0.5 x body weight in kg
H2O)
● Determine the rate of infusion (mL/hr)
● Inappropriate urine concentration (>100 mOsm/kg H2O) Infusion rate (in L ) = Na deficit/513 mmol/L
● Clinical euvolemia mL per hr = convert infusion rate to mL/24 hrs
● Elevated urine Na+ concentration under conditions of normal salt Where 513 mmol/L is the Na content of hypertonic saline (3%) and desired rate per
and water intake hour should not exceed 1-2 mmol/hr in symptomatic hyponatremia
→ Since the volume status of patients with SIADH is normal, | RATE OF HYPERTONIC SALINE SOLUTION
there is no need for the renal tubules to avidly reabsorb Na With the goal of raising the plasma Na from 118 mmol/L to 126
and so, the urine Na excretion is high mmol/L in the first 24 hrs, what is the sodium deficit (in mmol) of this
● Absence of adrenal, thyroid, pituitary, or renal insufficiency or patient?
diuretic use Na deficit = TBW x (target plasma Na – actual plasma Na)
→ Rule these out first for SIADH is a diagnosis of exclusion! → Females: TBW = 0.5 x body weight in kg
Supplemental Criteria of SIADH Na deficit = (0.5 x 50 kg) x (126 mmol/L -118 mmol/L)
Na deficit = 25 L x 8mmol/L
● Abnormal water-load test result (inability to excrete at least 90% Na deficit = 200 mmol
of a 20-mL/kg water load in 4 hours and/or failure to dilute urine
osmolality to <100 mOsm/kg) ● Determine the rate of infusion (mL/hr)
● Serum vasopressin level inappropriately elevated relative to the Infusion rate (in L ) = Na deficit/513 mmol/L
serum osmolality Infusion rate (in L) = 200 mmol/513 mmol/L
● No significant correction of serum Na level with volume Infusion rate (in L) = 0.39 → 390 mL
Long method (from Doc)
expansion, but improvement after fluid restriction 200 mmol = 513 mmol
● Hyperuricemia and elevated fractional excretion of uric acid X liter 1L
(X liter)(513 mmol) = (200 mmol)(1L)
X liter = 200 mmol
C. ADDITIONAL DIAGNOSITIC TESTS 513 mmol
X liter = 0.390 L → 390 mL
● Urine sodium, urine osmolality, TSH, fT4
390 mL of 3% NaCl should be given to the patient in 24 hours
→ Once true hyponatremia is established, urine Na and uOsm
are used to determine whether water excretion is impaired or mL per hr = convert infusion rate to mL/24 hrs
not mL per hr = 390 mL/24 hrs
mL per hr = 16.72 mL/hr
 | URINE SODIUM OSMOLALITY
● Normal: <100 mOsm/kg (in 1° polydipsia)
 MED 2-NEPHRO 1.14 – Sodium Disorders (09 SEPTEMBER 2021) Page 12 of 12

Final Management Final Diagnosis

● 3% NaCl 390 mL to infuse for 24 hr Euvolemic Hypernatremia secondary to Central Diabetes Insipidus
● Treat cause of SIADH (Pneumonia) with antibiotics secondary to Traumatic brain injury
● Free water restriction
B. MANAGEMENT OF THE PATIENT
● IV furosemide (40 mg, OD) or Oral furosemide (20 mg, NGT BID)
→ Do not give to hypovolemic patients! ● Correction of Hypernatremia
● Monitor plasma Na frequently (every 2-4 hours) → Plasma Na should be corrected by no more than 10 mmol/L
per day
V. FLIPPED CASE 2 → Calculate and replace the free water deficit over 48-72 hours.
History and Physical Examination FREE WATER DEFICIT IN HYPERNATREMIA
[(Actual Na-130)] x TBW
● 50 y/o male alcoholic brought into the hospital in a comatose 140
state TBW Males: 0.6 x body weight in kg
● Found to have a skull fracture TBW Females: 0.5 x body weight in kg
● Patient is known diabetic and hypertensive with irregular intake FREE WATER DEFICIT
of metformin and sitagliptin, and losartan plus HCTZ FWD=[(Actual Na-130)] x TBW
● Weight: 50 kg 140
● VS FWD=[(166-140)] x (0.6 x 50kg)
→ BP 140/90, pr 80 BPM, RR 20 cpm, T 36.5° [140]
● Pupils 2-3mm, PERLA FWD= 0.186 x 30L
● Dry buccal mucosa FWD= 5.6L to be replaced over 72h
● JVP 3 cm at 30° ● Aside from replacing the calculated FWD, replace also the daily
● Unremarkable pulmonary, cardiac, and abdominal exam insensible water losses
● Most appropriate fluid: Plain 0.45% NaCl
findings
● Neurologic exam: cranial nerves and MMT not assessed, (-) Final Management
Babinski ● Treat underlying cause- refer to neurosurgery
● Plain 0.45% sodium chloride
Laboratory Examination
● Aqueous vasopressin 5U/SC q6hrs (long-term mgmt.)
● Urinalysis ● Give attention to co-morbid conditions-refer to endocrinologist
→ Yellow, clear, SG 1.020, ph 5.0 ● Monitor plasma Na frequently (every 2-4 hours)
→ (+) protein, (-) sugar, RBC 0-1/hpf, WBC 2-5/hpf, few
squamous cells, few bacteria END OF TRANSCRIPT

REFERENCES
Natividad, P.C., (2021), Disorders of Water Metabolism: Hyponatremia and
Table 8. Blood Chemistry Results Hypernatremia [PowerPoint Presentation]. Manila, Philippines: Faculty of
Medicine and Surgery, University of Santo Tomas, MED 2
Blood Chemistry Results Normal Values
Sodium 166 136-146 mmol/L Jameson J.L, Kasper, D.L., Longo, D.L., Fauci, A.S., Hauser, S.L.,
Loscalzo, J. (2018). Harrison’s Principles of Internal Medicine. USA:
Potassium 4 3.5-5.3 mmol/L McGraw-Hill Education. (Chapter 63, pp. 296-304)
Cl 130 102-109 mmol/L
HCO3 25 22-26
Glucose 180 70-110
BUN 20 7-22 g/dL
Serum Creatinine 0.8 0.6-1.2 mg/dL
Plasma Osm 349 280-295 mOsm/kg
Urine Na 20
Urine Osm 80
A. DEVELOPMENT OF HYPERNATREMIA
Possible Factors
● Skull fracture -> Central Diabetes Insipidus
● Uncontrolled Diabetes (irregular intake of metformin and
sitagliptin) -< osmotic diuresis secondary to hyperglycemia
● Alcoholic already comatose, probably no access to water ->
hypodipsia
Table 9. uOSM and Response to AVP in Patients with Hypernatremia
uOsm (mOsm/kg) Response to AVP
Greater than 800
Insensible or GI losses -
Primary Hypodipsia -
Sodium Overload -
Less than 300
Central DI +
Nephrogenic DI -
300-800
Volume Depletion in CDI -
Partial CDI -
Partial NDI -
Osmotic Diuresis -