1. Hyponatremia
Rivere, Robosa, Rodas, Rodriguez, Rogelio, Roque, Ruanto, Sabalvaro, Salac, Salazar J, Salazar R, Salcedo

2. 51 y/o, female CC : vomiting
1 week PTA
fever, dysuria, urgency
took Paracetamol and antibiotic which relieved fever
2 days PTA
headache, body malaise, nausea, vomited 3x (50 cc/episode)
Admission
Persistence of symptoms

3. (-) for smoking and alcohol history
ROS unremarkable
(-) for smoking and alcohol history
Hypertensive for 10 yrs, taking Telmisartan and HCTZ daily for the past month
Discontinued Amlodipine due to bipedal edema

4. Weighed 50 kg but usual weight was 53 kgPE
weak looking and wheelchair borne, poor skin turgor, dry mouth, tongue and axilla
BP supine-120/80
sitting-90/60
usual-130/80
HR supine-90/min
sitting-105/min
Weighed 50 kg but usual weight was 53 kg
JVP <5cm H20 at 45 degrees
Orthostatic hypotension (also known as postural hypotension,[1], orthostasis, and, colloquially, as head rush or a dizzy spell and to some people "the elevator effect") is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up. The decrease is typically greater than 20/10 mm Hg,[2] and may be most pronounced after resting.
The incidence increases with age.[3]
Orthostatic hypotension is primarily caused by gravity-induced blood pooling in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequently lowering of arterial pressure. For example, if a person changes from a lying position to standing, he or she will lose about 700 ml of blood from the thorax. It can also be noted that there is a decreased systolic (contracting) blood pressure and a decreased diastolic (resting) blood pressure. The overall effect is an insufficient blood perfusion in the upper part of the body.
Still, the blood pressure does not normally fall very much, because it immediately triggers a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. Therefore, a secondary factor that causes a greater than normal fall in blood pressure is often required. Such factors include hypovolemia, diseases, and medications.
Orthostatic hypotension may be caused by hypovolemia (a decreased amount of blood in the body), resulting from bleeding, the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or prolonged bed rest. It also occurs in people with anemia.

5. RBC 2-5/hpf (not dysmorphic)
Laboratory tests
Hb=132 mg/dL
Hct=0.35
WBC=12.5
Neutrophils=0.88
Lymphocytes=0.12
P Na=123 mEq/L
P K=3.7 mEq/L (N)
Cl=71 mEq/L
BUN=22 mg/dL
S Crea=0.9 mg/dL
Glucose=98 mg/dL
ABG:
pH=7.3
CO2=35
HCO3=18
U Na=100 mmol/L
U Osm=540 mosm/L
Urinalysis:
Yellow, sl.turbid
pH 6.0, SG 1.020
albumin and sugar (-)
hyaline casts 5/hpf
pus cells 10-15/hpf
RBC 2-5/hpf (not dysmorphic)
ARTERIAL VALUES pH
PaCO mm Hg
HCO mEq/L
O2 saturation %
PaO mm Hg
URINE
color Straw
specific gravity pH
Na mEq/L
K Less than 8 mEq/L
Cl Less than 8 mEq/L
protein mg/dL
osmolality mOsm/L
BLOOD CHEM
BUN mg/dL
Chloride mEq/L
Creatinine mg/dL
Glucose mg/dL
potassium mEq/L
sodium mEq/L

6. Salient Features 51 year old, female Vomiting Fever, dysuria, urgency
Headache, body malaise, nausea
Vomiting: 50cc/episode
Known hypertensive
Telmisartan (40 mg)
Hydrochlorthiazide (12.5 daily)
Weak looking, wheelchair-borne
BP: 120/80 (supine), 90/60 (sitting), 130/80 (usual)
HR: 90/min (supine), 105/min (sitting)
Lost weight, poor skin turgor, dry mouth, tongue and axillae
Normal JVP

7. What is the diagnosis? Hypoosmolal hyponatremia secondary to thiazide intake
Plasma osmolality = 2(plasma [Na+])+[glucose]/18 + [urea]/2.8
= 2(123) + 98/ /2.8 =
= mOsm/kg H2O (low)
Normal plasma osmolality = mOsm/kg H2O
Plasma Na+ concentration < 135 mEq/L, and is considered severe when the level is below 125 mEq/L
Most causes of hyponatremia are associated with a low plasma osmolality
HYPOTONIC hyponatremia is due either to a primary water gain (secondary Na loss) or a primary Na loss (and secondary water gain)
Contraction of the ECF volume stimulates thirst and AVP secretion. The increased water ingestion and impaired renal excretion result in hyponatremia

8. Basis?

9. Signs of ECF volume contraction
Body malaise
Weakness
Poor skin turgor
Dry mouth and tongue
Dry axillae
Postural hypotension
Postural tachycardia
Clinical Features:
Patients may be asymptomatic or complain of nausea and malaise. As the plasma Na+ concentration falls, the symptoms progress to include headache, lethargy, confusion, and obtundation. Stupor, seizures, and coma do not usually occur unless the plasma Na+ concentration falls acutely below 120 mmol/L or decreases rapidly.
The clinical manifestations of hyponatremia are related to osmotic water shift leading to increased ICF volume, specifically cerebral edema.
Sodium
125-nausea and malaise
120-headache,lethargy,obtundation
115-seizure,coma
A careful history is often helpful in determining the etiology of ECF volume contraction (e.g., vomiting, diarrhea, polyuria, diaphoresis). Most symptoms are nonspecific and secondary to electrolyte imbalances and tissue hypoperfusion and include fatigue, weakness, muscle cramps, thirst, and postural dizziness. More severe degrees of volume contraction can lead to end-organ ischemia manifest as oliguria, cyanosis, abdominal and chest pain, and confusion or obtundation. Diminished skin turgor and dry oral mucous membranes are poor markers of decreased interstitial fluid. Signs of intravascular volume contraction include decreased jugular venous pressure, postural hypotension, and postural tachycardia. Larger and more acute fluid losses lead to hypovolemic shock, manifest as hypotension, tachycardia, peripheral vasoconstriction, and hypoperfusion—cyanosis, cold and clammy extremities, oliguria, and altered mental status.

10. Factors that contributed to the development of hyponatremia in the patient
Vomited 3x (50 cc/episode)
Primary Sodium Loss (Secondary water gain): GastointestinaI Losses
due to vomiting predisposes the patient to hyponatremia since there is a corresponding sodium loss associated with water loss

11. Intake of hydrochlorothiazide
Primary Sodium Loss (Secondary water gain): Renal Losses
It is important to note that diuretic-induced hyponatremia is almost always due to thiazide diuretics  lead to Na+ and K+ depletion and AVP-mediated water retention
Inhibits reabsorption of sodium and chloride in the distal convoluted tubule  promoting water loss

12. Intake of telmisartan ARB
Inhibits tubular Na and Cl reabsorption, K excretion, water retention  promotes water loss

13. Computation of the plasma osmolality and the effective plasma osmolality
Osmolality (calc) = 2 x Na + glucose + urea **if all measurements in mmol/L Osmolality (calc) = 2 x Na + glucose/18 + urea/2.8 **if measurements are in mg/dL Given: Plasma Na = 123 mEq/L Glucose = 98 mg/dL Urea = 22 mg/dL Osmolality = 2(123) + (98/18) + (22/2.8) Osmolality =
N = 275 – 295 milli-osmoles per kilogram
Becker, K. (2001)Principles and Practice of Endocrinology and Metabolism 3rd Ed.

14. Effective Osmolality (calc) = 2 x Na + glucose
Effective Osmolality (calc) = 2 x Na + glucose **if all measurements in mmol/L Osmolality (calc) = 2 x Na + glucose/18 **if measurements are in mg/dL Given: Plasma Na = 123 mEq/L Glucose = 98 mg/dL Urea = 22 mg/dL Osmolality = 2(123) + (98/18) Osmolality =
< 275 = Hyponatremia
Becker, K. (2001)Principles and Practice of Endocrinology and Metabolism 3rd Ed.

15. Importance of computing for the plasma osmolality and the effective plasma osmolality
ECF tonicity is determined primarily by the Na+ concentration and patients who have hyponatremia have a decreased plasma osmolality
Becker, K. (2001)Principles and Practice of Endocrinology and Metabolism 3rd Ed.

16. Significance of Urine Osmolality (Uosm)
A more exact measurement of urine concentration than specific gravity
Patient with Uosm below 100 mOsm/kg are able to appropriately suppress ADH release, leading to a maximally dilute urine
Patients with a higher urine osmolality have an impairment in water excretion due to the presence of ADH
Indicated to evaluate the concentrating and diluting ability of the kidney
- accurate test for decreased kidney function
- monitor course of renal disease/ electrolyte therapy
Rennke H., Denker, B. (2007). Renal Pathophysiology: The Essentials

17. Significance of Urine Sodium (UNa)
Helps distinguish renal from non- renal causes of hyponatremia
Urine sodium exceeding 20 mEq/L is consistent with renal salt wasting
Diuretics, ACE inhibitors, mineralocorticoid deficiency, salt losing nephropathy
Urine sodium less than 10 mEq/L implies avid sodium retention by the kidney
Compensation for extra-renal fluid loss (vomiting, diarrhea, sweating or third space wasting)
Rennke H., Denker, B. (2007). Renal Pathophysiology: The Essentials

18. Effective circulating volume depletion and SIADH are the two major causes of true hyponatremia (with an inappropriately high urine osmolality) and these disordes can be distinguished by measuring the Una.
Patients with hypovolemia are sodium avid in an attempt to limit further losses
Urine sodium is generally below 25 mEq/L
In comparison, patients with SIADH are normovolemic and sodium excretion is in a steady state equal to intake
Urine sodium concentration is typically above 40 mEq/L
Rennke H., Denker, B. (2007). Renal Pathophysiology: The Essentials

19. Computation of Na deficit
Sodium Deficit = Total Body Water * Normal Wt in kg * (Pt's Na - Desired Na)
(TBW = 0.6 if male and 0.5 if female)

20. Computation of Na deficit
Sodium Deficit = (0.5)* (53kg)* (135mEq/L-123mEq/L)
Sodium Deficit= 318mmol/L

21. Principles of Therapy
Raise plasma sodium concentration by restricting water intake and promoting water loss
Correct underlying disorder

22. Principles of Therapy Asymptomatic hyponatremia
Sodium repletion (isotonic saline)
Restoration of euvolemia removes the hemodynamic stimulus for AVP release
Restriction of sodium and water intake, correction of hypokalemia, and promotion of water loss in excess of sodium.
Dietary water restriction should be less than urine output

23. Principles of Therapy Asymptomatic Hyponatremia
Sodium concentration should be raised by no more than 0.5 – 1.0mmol/L over the first 24hours
Acute or severe Hyponatremia
Plasma sodium conc: < mmol/L
Rapid correction
Severe symptomatic
Hypertonic saline
1-2 mmol/l per hour for the first 3-4 hours
Raised by no more than 12mmol/L during the first 24 hours

24. Complication of Rapid Correction of Hyponatremia
Rate of correction: Depends on the absence or presence of neurologic dysfunction
Related to the rapidity of onset and magnitude of fall in plasma Na+ concentration
Rapid correction of hyponatremia leads to osmotic demyelination syndrome (ODS)
Fauci et al. Harrison’s Principles of Internal Medicine, 17th ed.

25. Osmotic Demyelination Syndrome
Neurologic disorder characterized by flaccid paralysis, dysarthria and dysphagia
Mechanism:
Patients with chronic hyponatremia
(brain cell volume has returned to near normal)
Malnutrition secondary to alcoholism
Prior cerebral anoxic injury
Hypokalemia
Administration of hypertonic saline
Sudden osmotic shrinkage of brain cells
Fauci et al. Harrison’s Principles of Internal Medicine, 17th ed.
Vellaichamy M. Hyponatremia <

26. Central Pontine Myelinolysis
Subtype of osmotic demyelination syndrome occurring in the pons
Occurs when hypertonic saline is given too rapidly in a patient in whom hyponatremia has been present for >24-48 hours
Potentially fatal neurologic syndrome characterized by quadriparesis, ataxia, abnormal extraocular movements
May result in brain damage and death
Schwartz’s Principles of Surgery, 8th ed.
Fauci et al. Harrison’s Principles of Internal Medicine, 17th ed.
Vellaichamy M. Hyponatremia <

27. Central Pontine Myelinolysis
Predilection for pons:
During hyponatremia, these cells can adapt only by losing ions instead of swelling. This limitation makes them prone to damage when Na is replaced.
Grid arrangement of the oligodendrocytes in the base of pons
Limits their mechanical flexibility, thus capacity to swell
The predilection for myelinolysis in the pons is thought to be a result of the grid arrangement of the oligodendrocytes in the base of pons, which limits their mechanical flexibility and, therefore, their capacity to swell. During hyponatremia, these cells can adapt only by losing ions instead of swelling. This limitation makes them prone to damage when Na is replaced.
Vellaichamy M. Hyponatremia <

28. Central pontine myelinolysis, MRI FLAIR
T2 weighted magnetic resonance scan image showing bilaterally symmetrical hyperintensities in caudate nucleus (small, thin arrow), putamen (long arrow), with sparing of globus pallidus (broad arrow), suggestive of extrapontine myelinolysis.

29. Intravenous fluid to use and Rate of infusion
3% saline infused at a rate of ≤ 0.05 mL/kg body weight per minute
Effect should be monitored continuously by STAT measurements of serum sodium at least once every 2 hours
Fauci et al. Harrison’s Principles of Internal Medicine, 17th ed.

30. Intravenous fluid to use and Rate of infusion
Infusion should be stopped as soon as serum sodium increases by 12 mmol/L or to 130 mmol/L, whichever comes first
Urine output should be monitored continuously
SIAD can remit spontaneously at any time, resulting in an acute water diuresis that greatly accelerates the rate of rise in serum sodium produced by fluid restriction and 3% saline
Fauci et al. Harrison’s Principles of Internal Medicine, 17th ed.

31. Most cases of hyponatremia can be treated by free water restriction and, if severe, the administration of sodium. In patients with normal renal function, symptomatic hyponatremia does not occur until the serum sodium level is greater than or equal to 120 mEq/L. If neurologic symptoms are present, then 3% normal saline should be used to increase the sodium by no more than 1 mEq/L per hour until the serum sodium level reaches 130 mEq/L or neurologic symptoms are improved. Correction of asymptomatic hyponatremia should increase the sodium level by no more than 0.5 mEq/L to a maximum increase of 12 mEq/L per day, and even slower in chronic hyponatremia. The rapid correction of hyponatremia can lead to pontine myelinolysis, 42 with seizures, weakness/paresis, akinetic movements, and unresponsiveness, and may result in permanent brain damage and death. Magnetic resonance imaging (MRI) may assist in the diagnosis. 43

32. References
Becker, K. (2001)Principles and Practice of Endocrinology and Metabolism 3rd Ed.
Harrison’s Principle of Internal Medicine, 17th ed.
Rennke H., Denker, B. (2007). Renal Pathophysiology: The Essentials
Schwartz’s Principles of Surgery, 8th ed.
Vellaichamy M. Hyponatremia <