WORKSHOP CASE FOR FLUID AND ELECTROLYTE DISORDERS M I WORKSHOP CASE FOR FLUID AND ELECTROLYTE DISORDERS Saldana, E. * Sales, S. * Salonga, C. * San Diego, P. San Pedro, R. * Sanez, E. * Sanidad, E. * Santos, E. Santos, J. * Santos, J. * Santos, K. * Santos, E.

51 year old, female CHIEF COMPLAINT: Vomiting

H I S T O R Y CONSULTATION Persistence of vomiting 1 week PTC Fever, dysuria and urgency Paracetamol and an antibiotic (relieved the fever) 2 days PTC Headache, body malaise and nausea Vomited thrice, 50cc per episode H I S T O R Y Persistence of vomiting CONSULTATION

PAST MEDICAL HISTORY Hypertensive for 10 years Medications: Telmisartan, 40mg Hydrochlorthiazide 12.5 daily Amlodipine was discontinued due to bipedal edema

PERSONAL HISTORY REVIEW OF SYSTEMS No smoking No alcohol intake REVIEW OF SYSTEMS Unremarkable

P H Y S I C A L E X M Weak looking Wheelchair-borne Blood pressure Supine: 120/80 Sitting: 90/60 Usual BP: 130/80 Heart rate Supine: 90 bpm Sitting: 105 bpm Weight 50 kg Usual weight: 53 kg Poor skin turgor Dry mouth and tongue Dry axillae JVP: < 5cm H2O at 45o Supine: pre-hypertensive Sitting: hypotensive Usual: pre-hypertensive A form of hypotension in which a person's blood pressure suddenly falls when the person changes position, such as from supine to standing or sitting. The decrease is typically greater than 20/10 mm Hg, and may be most pronounced after resting. Incidence increases w/ age. 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.[4] 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. Possible causes of hypotension: Hypovolemia Electrolyte disorders Diuretics Dehydration due to vomiting HEART RATE: postural tachycardia

Yellow, slightly turbid A B O R T Y Patient’s Normal Hgb 132 mg/dL 12 – 16 g/dL Hct 0.35 0.36 – 0.46 WBC Neut. Lymph. 12.5 0.88 0.12 3.8 – 11 x 103 0.54 – 0.62 0.25 – 0.33 ARTERIAL BLOOD GAS Patient’s Normal pH 7.3 7.35 – 7.45 CO2 35 33 – 35 HCO3 18 22 - 26 URINALYSIS Patient’s Normal Urine Yellow, slightly turbid Straw colored, clear pH 6.0 4.6 – 8 S.G. 1.020 1.003 – 1.040 Albumin (-) Sugar Hyaline casts 5/hpf Pus cells 10-15/hpf RBC 2-5/hpf (not dysmorphic) Patient’s Normal Plasma Na 123 mEq/L 135 – 147 Plasma K 3.7 meq/L 3.5 - 5 Chloride 71meq/L 95 - 105 BUN 22mg/dl 6 – 23 Serum creatinine 0.9 mg/dl 0.6 – 1.2 Glucose 98 mg/dl 65 - 99 Urine Na 100 mmol/L 30 – 280 Uosm 540 mosm/L 450 – 900 The presence of dysmorphic RBC's in urine suggests a glomerular disease such as a glomerulonephritis. Dysmorphic RBC's have odd shapes as a consequence of being distorted via passage through the abnormal glomerular structure.

SALIENT FEATURES 51 year old, female (vomiting) Fever, dysuria, urgency Intake of paracetamol and antibiotic 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 bpm (supine), 105 bpm (sitting) Lost weight (53 kg  50 kg) Poor skin turgor Dry mouth, tongue and axillae Normal JVP

HYPOVOLEMIC HYPONATREMIA SECONDARY TO THIAZIDE DIURETIC INTAKE

In the average 70-kilogram adult human, the total body water is about 60 per cent of the body weight, or about 42 liters.This percentage can change, depending on age, gender, and degree of obesity. As a person grows older, the percentage of total body weight that is fluid gradually decreases. This is due in part to the fact that aging is usually associated with an increased percentage of the body weight being fat, which decreases the percentage of water in the body.

Source: Guyton and Hall. Textbook of Medical Physiology

20% of total body weight 40% of total body weight The total body fluid is distributed mainly between two compartments: the extracellular fluid and the intracellular fluid (Figure 25–1). The extracellular fluid is divided into the interstitial fluid and the blood plasma. There is another small compartment of fluid that is referred to as transcellular fluid. This compartment includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the cerebrospinal fluid; it is usually considered to be a specialized type of extracellular fluid, although in some cases, its composition may differ markedly from that of the plasma or interstitial fluid. All the transcellular fluids together constitute about 1 to 2 liters. The plasma is the noncellular part of the blood; it exchanges substances continuously with the interstitial fluid through the pores of the capillary membranes. These pores are highly permeable to almost all solutes in the extracellular fluid except the proteins. Therefore, the extracellular fluids are constantly mixing, so that the plasma and interstitial fluids have about the same composition except for proteins, which have a higher concentration in the plasma. 40% of total body weight Source: Guyton and Hall. Textbook of Medical Physiology

Source: Guyton and Hall. Textbook of Medical Physiology Because the plasma and interstitial fluid are separated only by highly permeable capillary membranes, their ionic composition is similar. The most important difference between these two compartments is the higher concentration of protein in the plasma; because the capillaries have a low permeability to the plasma proteins, only small amounts of proteins are leaked into the interstitial spaces in most tissues. Because of the Donnan effect, the concentration of positively charged ions (cations) is slightly greater (about 2 per cent) in the plasma than in the interstitial fluid. The plasma proteins have a net negative charge and, therefore, tend to bind cations, such as sodium and potassium ions, thus holding extra amounts of these cations in the plasma along with the plasma proteins. Conversely, negatively charged ions (anions) tend to have a slightly higher concentration in the interstitial fluid compared with the plasma, because the negative charges of the plasma proteins repel the negatively charged anions. Referring again to Figure 25–2, one can see that the extracellular fluid, including the plasma and the interstitial fluid, contains large amounts of sodium and chloride ions, reasonably large amounts of bicarbonate ions, but only small quantities of potassium, calcium, magnesium, phosphate, and organic acid ions. The composition of extracellular fluid is carefully regulated by various mechanisms, but especially by the Kidneys. Source: Guyton and Hall. Textbook of Medical Physiology

SIGNS OF ECF VOLUME CONTRACTION PATIENT’S PROFILE Body malaise Weakness Poor skin turgor Dry mouth and tongue Dry axillae Postural hypotension Postural tachycardia Decreased JVP 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. SIGNS OF ECF VOLUME CONTRACTION

ECF VOLUME CONTRACTION a state of combined salt and water loss exceeding intake Hypovolemia ECF VOLUME CONTRACTION 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.

IMPORTANCE OF SODIUM Essential for regulation of body fluids and blood. Transmits nerve impulses and controls heart activity. Assists in metabolic functions. Helps maintain BP levels.

HYPONATREMIA 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. Patient’s Na: 123 mEq/L Patient’s plasma osmolality: 259.3 mOsm/L

A plasma sodium < 135 usually reflects a hypotonic state A plasma sodium < 135 usually reflects a hypotonic state. However, plasma osmolality may be normal or increased in some cases. HYPERTONIC hyponatremia is usually due to hyperglycemia, or occasionally, IV administration of mannitol (osmotic diuretic). ** Relative insulin deficiency causes myocytes to become impermeable to glucose. Therefore, during DM, glucose is an effective osmole and draws water from muscle cells, resulting in hyponatremia. Plasma Na concentration falls by 1.4 mmol/L for every 100 mg/dL rise in plasma glucose. Mannitol is a diuretic that produces an osmotic diuresis because the renal tubule is impermeable to mannitol. 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.

A plasma sodium < 135 usually reflects a hypotonic state A plasma sodium < 135 usually reflects a hypotonic state. However, plasma osmolality may be normal or increased in some cases. HYPERTONIC hyponatremia is usually due to hyperglycemia, or occasionally, IV administration of mannitol (osmotic diuretic). ** Relative insulin deficiency causes myocytes to become impermeable to glucose. Therefore, during DM, glucose is an effective osmole and draws water from muscle cells, resulting in hyponatremia. Plasma Na concentration falls by 1.4 mmol/L for every 100 mg/dL rise in plasma glucose. Mannitol is a diuretic that produces an osmotic diuresis because the renal tubule is impermeable to mannitol. 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. Source: Braunwald, et. al. Harrison’s Principles of Internal Medicine, 17th edition.

3 TYPES OF HYPONATREMIA DIFFERENTIATED BY VOLUME STATUS Hyponatremia results from a relative excess of water in relation to sodium.1 In dilutional hyponatremia, total body water is increased.2

CLINICAL FEATURES OF HYPONATREMIA The clinical manifestations of hyponatremia are related to osmotic water shift leading to increased ICF volume, specifically cerebral edema.

CLINICAL FEATURES OF HYPONATREMIA SERUM SODIUM LEVELS: 125 mEq/L 120 mEq/L 115 mEq/L Nausea and malaise Headache, lethargy, obtundation Seizure and coma Patient profle: Serum Na+: 123 mEq/L Headache, body malaise, nausea, weak looking, wheelchair-borne

FACTORS WHICH CONTRIBUTED TO THE PATIENT’S HYPONATREMIA Renal sodium loss Medications Telmisartan HCTZ Extra-renal sodium loss Vomiting 3x 50cc/episode

FACTORS WHICH CONTRIBUTED TO THE PATIENT’S HYPONATREMIA HYDROCHLOROTHIAZIDE TELMISARTAN Inhibits reabsorption of sodium and chloride in the distal convoluted tubule, thus promoting water loss. Leads to Na+ and K+ depletion and AVP-mediated water retention. Angiotensin II receptor blocker

Source: http://upload. wikimedia

3. Compute for the plasma osmolality and effective plasma osmolality 3. Compute for the plasma osmolality and effective plasma osmolality. What is the importance of computing for such?

2 [ plasma Na ] + [ Glucose ] + [ BUN ] Plasma osmolality (mOsm/kg) = 2 [ plasma Na ] + [ Glucose ] + [ BUN ] 18 2.8 http://www.merck.com/mmpe/print/sec12/ch156/ch156b.html

2 [ 123 mEq/L] + [ 98 mg/dL ] + [ 22 mg/dL ] Plasma Osmolality Plasma Na 123mEq/L Glucose 98mg/dL BUN 22mg/dL Plasma osmolality (mOsm/kg) = 2 [ 123 mEq/L] + [ 98 mg/dL ] + [ 22 mg/dL ] 18 2.8 Plasma osmolality = 259.3 mOsm/kg

Effective Plasma Osmolality Plasma Na 123mEq/L BUN 22mg/dL Effective Plasma osmolality = PlasmaOsmolality - BUN_ 2.8 = 259.3 mOsm/kg – 22 mg/dL = 251.44 mOsm/kg http://cmbi.bjmu.edu.cn/uptodate/critical%20care/Fluid%20and%20electrolyte%20disorders/.htm

Significance of Plasma Osmolality The osmolality of plasma is closely regulated by anti-diuretic hormone (ADH). In response to even small increases in plasma osmolality, ADH release from the pituitary is increased causing water resorption in the distal tubules and collecting ducts of the kidney and correction of the increased osmolality. The opposite happens in response to a low plasma osmolality with decreased ADH secretion and water loss through the kidneys.

Significance of Plasma Osmolality Plasma osmolality is used in two main circumstances: Investigation of hyponatremia Identification of an osmolar gap

Significance of Plasma Osmolality Serum osmolality is a useful preliminary investigation for identifying the cause of hyponatremia.

Significance of Effective Plasma Osmolality Solutes that are restricted to the ECF or the ICF determine the effective osmolality (or tonicity) of that compartment. In a patient with hyponatremia, normal or elevated effective serum osmolality suggests the presence of either pseudohyponatremia or increased concentrations of other osmoles, such as glucose and mannitol. ECF ICF Na+ K+ Cl- Organic phosphate esters (ATP, creatinie phosphate, phospholipids ) HCO3-

4. What are the significance of urine osmolality and urine sodium?

Significance of Urine Osmolality Urine osmolality may vary between 50 and 1200 mmol/kg in a healthy individual depending on the state of hydration. The urine osmolality is the best measure of urine concentration with high values indicating maximally concentrated urine and low values very dilute urine. The main factor determining urine concentration is the amount of water which is resorbed in the distal tubules and collecting ducts in response to ADH.

Significance of Urine Osmolality The test is useful in the following areas: For determining the differential diagnosis of hyper- or hyponatraemia. For identifying SIADH For differentiating pre-renal from renal kidney failure (high urine osmolality is consistent with pre-renal impairment, in renal damage the urine osmolality is similar to plasma osmolality). For identifying and diagnosing diabetes insipidus (low urine osmolality not responding to water restriction).

Significance of Urine Sodium In patients with hyponatremia and inappropriately concentrated urine, it is particularly important to assess the effective arterial blood volume.

5. Compute for the sodium deficit

Sodium Deficit Plasma Na 123mEq/L Weight 53 kg Sodium deficit = (desired serum Na – actual Na) x TBW = (140 mEq/L – 123 mEq/L) x (0.6 x [53]) = 540.6 mEq/L total needed

6. What are the basic principles in the treatment of hyponatremia?

Hyponatremia Goals of therapy To raise the plasma Na+ concentration by restricting water intake and promoting water loss To correct the underlying disorder

Treatment Mild asymptomatic hyponatremia Generally of little clinical significance and requires no treatment Asymptomatic hyponatremia associated with ECF volume contraction Na+ repletion isotonic saline Restoration of euvolemia removes the hemodynamic stimulus for AVP release The direct effect of the administered NaCl on the plasma Na+ concentration is trivial. However, restoration of euvolemia removes the hemodynamic stimulus for AVP release, allowing the excess free water to be excreted.

Treatment Hyponatremia associated with edematous states Have increased total body water that exceeds the increase in total body Na+ content Restriction of Na+ and water intake, correction of hypokalemia, and promotion of water loss in excess of Na+ The hyponatremia associated with edematous states tends to reflect the severity of the underlying disease and is usually asymptomatic. These patients have increased total body water that exceeds the increase in total body Na+ content. Treatment should include restriction of Na+ and water intake, correction of hypokalemia, and promotion of water loss in excess of Na+. The latter may require the use of loop diuretics with replacement of a proportion of the urinary Na+ loss to ensure net free-water excretion. Dietary water restriction should be less than the urine output. Correction of the K+ deficit may raise the plasma Na+ concentration by favoring a shift of Na+ out of cells as K+ moves in. Water restriction is also a component of the therapeutic approach to hyponatremia associated with primary polydipsia, renal failure, and SIADH. The recent development of nonpeptide vasopressin antagonists has introduced a new selective treatment for euvolemic and hypervolemic hyponatremia.

Treatment Acute or severe hyponatremia (plasma Na+ concentration <110–115 mmol/L) Tends to present with altered mental status and/or seizures Requires more rapid correction Treated with hypertonic saline

Asymptomatic Hyponatremia Acute or severe hyponatremia Rate of Correction depends on the absence or presence of neurologic dysfunction Asymptomatic Hyponatremia Acute or severe hyponatremia Raised by no more than 0.5–1.0 mmol/L per h 1–2 mmol/L per hour for the first 3–4 h or until the seizures subside Less than 10–12 mmol/L over the first 24 h raised by no more than 12 mmol/L during the first 24 h

7. What is the complication of the rapid correction of the hyponatremia?

Osmotic demyelination syndrome (ODS)  Follows too-rapid correction of hyponatremia Neurologic disorder characterized by flaccid paralysis, dysarthria, and dysphagia Diagnosis is usually suspected clinically and can be confirmed by appropriate neuroimaging studies No specific treatment for the disorder Associated with significant morbidity and mortality

Osmotic demyelination syndrome (ODS) Chronic hyponatremia  Most susceptible to ODS, since their brain cell volume has returned to near normal as a result of the osmotic adaptive mechanisms Administration of hypertonic saline to these individuals can cause sudden osmotic shrinkage of brain cells

Osmotic demyelination syndrome (ODS) Risk factors Prior cerebral anoxic injury Hypokalemia Malnutrition, especially secondary to alcoholism

8. What intravenous fluid would you use 8. What intravenous fluid would you use? At what rate should it be given?

Correction of Sodium Deficit A 53kg woman with plasma Na concentration of 123 meq/L Sodium Deficit = 318 meq O.9% NaCl = 154meq/L Volume of 0.9% NaCl needed: At 0.5 meq/L/hr, a correction of 12 meq (135-123) should be done over 24 hours. Rate of infusion: Rate of infusion in drops/min: 22 drops/min

Correction of Sodium Deficit A 53kg woman with plasma Na concentration of 123 meq/L Sodium Deficit = 318 meq 3% NaCl = 513 meq/L Volume of 3% NaCl needed: At 0.5 meq/L/hr, a correction of 12 meq (135-123) should be done over 24 hours. Rate of infusion: Rate of infusion in drops/min: 7 drops/min