Na /K Disorders Dr Mojgan Mortazavi

SODIUM

Hyponatremia

Hyponatremia Hyponatremia defined as a Na+ <135meq/l that usually reflects hypoosmolality. Low plasma osmolality causes water movement into the cells and then cellular overhydration particularly in brain cells

Symptoms of hyponatremia The changes induced by acute hyponatremia (developing over 1-3 days) may result in permanent neurological damage and are primarily duo to cerebral overhydration Nausea and malaise as the plasma Na+ falls acutely below 125 meq/l Headache, lethargy, and obtundation may appear in Na+ between 115-120

Symptoms of hyponatremia….. The more sever changes of seizures and coma are not seen until the plasma Na+ is less than 110-115 meq/l Women particularly premenopausal women ,appear to be at much greater risk of developing sever neurologic symptoms and of irreversible neurologic damage than men that may be related to differences in cerebral metabolism and sex hormones.

Treatment There are two basic principles involved in the treatment of hyponatremia: 1-rasing the plasma Na+ at a safe rate 2-treating the underlying cause

Treatment with Nacl True volume depletion Diuretics Adrenal insufficiency

Treatment with H2O restriction SIADH Edematous state Renal failure Primary polydipsia

The risk factors for developing osmotic demyelination 1-More than a 12 meq/l elevation in Na+ in the first day 2-Over correction of the Na+ to above 140 meq/l within the first 2 days 3-Hypoxic or anoxic episodes prior to therapy

TREATMENT OF SIADH Acute: 1-water restriction 2-hypertonic saline or Nacl tablets 3-loop diuretics Chronic: 2-high salt ,high-protein diet 3-loop diuretic 4-demeclocycline ,lithium

TREATMENT OF SIADH Asypmtomatic or Chronic SIADH Water restriction 0.5-1 liter/day Salt tablets Demeclocycline Inhibits the effects of ADH Onset of action may require up to one week

Treatment Goal: raise Na by <10 meq/L in the 1st 24 hours

Central Pontine Myelinosis Correction of Na too FAST more common w/alcoholism, malnutrition, chronic illness Symptoms: flaccid paralysis, dysarthria, dysphagia Evolve over days – weeks May extend dorsally  Sensory Tracts locked-in syndrome Turn off ADH & prompt diuresis  Sudden & Dramatic Inc serum Na

Hyponatremia Example: Answer: a 60 kg women with a plasma sodium of 110 meq/L Formula: ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1) What is the TBW? How high will 1 liter of normal saline raise the plasma sodium? Answer: TBW is 30 L Serum sodium will increase by approximately 1.4 meq/L for a total SNa of 111.4 meq/L

Hyponatremia Example: Answer: a 90 kg man with a plasma sodium of 110 meq/L Formula: ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1) What is the TBW? How high will 1 liter of 3% saline raise the plasma sodium? Answer: TBW is 54 L Serum sodium will increase by approximately 7.3 meq/L for a total SNa of 117.3 meq/L

Hyponatremia Example: 63 y/o female at 75 Kg with N/V/D for 4 days SNa is 108 mEq/L She has had one seizure in the ambulance Plasma osmolality is 251 mosmol/kg Urine osmolality is 47 mosmol/kg Uric acid is 6mg/dl What type of hyponatremia does this patient have? What additional labs/studies would you want? hollywoodphony.files.wordpress.com

Hyponatremia How will you Tx her? Calculate the total body water 0.5 x weight = 37.5 L What rate of correction do you want? 8 to 10 mEq/L in 6 to 8 hours What fluid will you use? 3% Saline How will you calculate the amount of sodium to give her? ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1) How will her sodium increase after 1 liter of 3% saline? By 10.8 mEq/L to 118.8 mEq/L

Hyponatremia What other medication will she need? Lasix and a foley Her sodium increases to 118.8 mEq/L over the next 8-10 hours. How will you continue to correct her hyponatremia? ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1) ΔSNa = 154mEq/L – 118.8mEq/L ÷ 38.5L = 0.9 mEq/L So 2 liters of normal saline over the next 14 hours

Hypernatremia

HYPERNATREMIA Hypernatremia is defined as a plasma Na+>145 meq/l Hypernatremia represent hyperosmolality that results in water movement out of the cells into the extracellular fluid that causes cellular dehydration in the brain that is primarily responsible for the neurologic symptoms.

Generation of hypernatremia Water loss: hypernatremia due to water loss occurs only in patients who have hypodipsia, in adults with altered mental status, and in infants. Na+ concentration > 150 is virtually never seen in an alert adult with a normal thirst mechanism and access to water.

Fluid volume status assessed by physical eaxam Hypernatremia Fluid volume status assessed by physical eaxam Hypovolemic Loss of H2O>Na+ loss Isovolemic Loss of H2O Hypervolemic Gain H2O and Na+ Check urine Na+ Check urine Na+ Check urine Na+ >20 mEq/L <10 mEq/L >20 mEq/L Renal loss Diuretic Glycosuria Renal failure Extrarenal loss GI-vomiting GI-diarrhea Excess sweating Respiratory loss Renal loss Diabetic insipidis Central Nephrogenic Extrarenal loss Insensible losses Skin Respiration Iatrogenic Hypertonic NaHCO3 NaCl tablets Hypertonic solutions Mineralocorticoid 1 Hyperaldosteronism Cushing disease Adrenal o Hypertonicdialysis Hemodilysis Peritoneal dialysis Treatment Water replacement D5W at 1-2 mEq/L/hr ± vasopressin for Central DI Treatment Saline then hypotonic solution Treatment Diuretics ± dialysis

Symptoms of hypernatremia Lethargy ,weakness, irritability, are the earliest findings which can then progress to twitching ,seizures, coma, and death that are more related to cellular dehydration in the brain. Patients with chronic hypernatremia may be relatively asymptomatic despite a plasma Na+ >170 The severity of the neurologic symptoms is related to the both the degree and more importantly ,the rate of rise in the effective plasma osmolality.

Treatment of hypernatremia Rapid correction of hypernatremia can induce cerebral edema, seizures, permanent neurologic damage, and death therefore the plasma Na+ must be slowly lowered unless the patient has symptomatic hypernatremia.

Treatment of hypernatremia…… Water deficit= 0.4 LBW( plasma Na-140/ 140) The maximum safe rate at which the plasma Na+ should be lowered (in the absence of hypernatremic symptoms) is 0.5 meq/L/h or 12 meq/L/per day

Formula for Managing Hypernatremia CLINICAL USE Estimate the effect of 1 liter of any infusate on serum Na+ Estimate the effect of 1 liter of any infusate containing Na+ and K+ on serum Na+ FORMULA* 1. Change in serum Na+ = 2. Change in serum Na+ = infusate Na+ - serum Na+ total body water + 1 (infusate Na+ + infusate K+) -serum Na+

Characteristics of Infusate Infusate Na+ Extracellular-Fluid Distribution mmol per liter % 5% Dextrose in H20 40 0.2% NaCl in 5% dextrose in H2O 34 55 0.45% NaCl in H2O 77 73 Ringer’s lactate 130 97 0.9% NaCl in H2O 154 100

Summary of Managing Hypernatremia Isotonic saline unsuitable except in ECF volume depletion causing hemodynamic instability Switch to hypotonic solutions as soon as circulatory status stabilized Avoid excessive rapid correction or over correction Select the most hypotonic infusate suitable with appropriate allowances for ongoing fluid losses Most important - reassess infusion prescriptions at regular intervals based on pt’s clinical status and electrolyte values

POTASSIUM

POTASSIUM BALANCE Potassium is the major intracellular cation that is essential for a variety of cellular and neuromuscular functions. The total body K+ stores in a normal adult are 3000-4000 meq(50-55meq/kg) and the normal plasma concentration is 3.5-5 meq/l and inside cells is about 140 meq/l

Regulation of potassium balance The maintenance of K+ balance involves two functions: 1-the normal distribution of K+ between the cells and extra cellular fluid 2-the renal excretion of the K+ added to the extra cellular fluid from dietary intake and endogenous cellular breakdown

Factors influencing the distribution of K+ between the cells and extra cellular fluid Physiologic: 1-Na+k+ ATPase 2-catecholamines 3-insulin 4-plasma potassium concentration 5-exercise Pathologic: 1-chronic disease 2-extra cellular PH 3-hyperosmolality

Renal excretion of k+ The urine is major route by which the K+ derived from diet and endogenous cellular breakdown , is eliminated from the body. The primary event in urinary K+ excretion is the SECRETION of K+ from the tubular cell in to the lumen in the distal nephron.

Renal Handling of K+ Glomerulus: freely filtered PCT, Thick As limb LOH : reabsorbed

Hypokalemia

Hypokalemia Hypokalemia is defined as a K+ <3.5 meq/l, may result from one or more of the following: 1-decreased net intake 2-shift into the cells 3-increased net loss

Hypokalemia Exclude reredistribution Alkalosis Insulin Periodic paralysis Barium poisoning Vitamin B12 therapy Extrarenal K losses Urine electrolytes K+<20 mEq/day Na+>100 mEq/day (If Na+<100 mEq/day repeat Test after increasing dietary Na+>100 mEq/day) Biliary losses Lower GI losses Fistula Skin losses Renal K losses Urine electrolytes K+>20 mEq/day Na+>100 mEq/day High blood pressure Normal blood pressure Plasma renin levels Serum HCO3 -

Plasma renin levels Serum HCO3 - High plasma renin Malignant HTN Renovascular disease Renin secreting tumor Low plasma renin Low HCO3 – RTA High HCO3 - Aldoserone Urine chloride High Hyperlado- Steronism Bilateral hyperplasia Low Mineralocorticoid Ingestion Adrenal hyperpasia (congenital) Cushing syndrome Serum K+ (mEq/L) <10 mEq/day Vomiting <10 mEq/day Bartter Syndrome Diuretics Magnesium deficiency Normal 4 Normal T U Low T wave High U wave 3 Hypokalemia T U Inverted T wave High U wave Low ST segment 3.5

Symptoms of hypokalemia Marked symptoms are unusual unless the plasma K+ concentration is below 2.5-3 meq/l ,but in susceptible patients even mild reductions in the plasma potassium can predispose to potential fatal arrhythmia.

Clinical Features Hypokalemia < 3 mEq/L : Symptomatic Mild hypokalemia : generally asymptomatic Increased risk of mortality for pts with cardiovascular disease – trigger ventricular tachycardia / ventricular fibrillation (decrease K+ : d/t sympathetic stimulation) Digitalis induced arrhythmias – can occur with normal drug levels if hypokalemia is present Diuretic induced hypokalemia & hypomagnesemia must be avoided in pts on drugs that prolong QT interval : as it predisposes to polymorphic VT / Torsade de pointes Hypokalemia < 3 mEq/L : Symptomatic

Cardiac Digitalis Intoxication : ventricular extrasystoles ventricular tachycardia ventricular fibrillation partial-complete AV block bradycardia atrial flutter atrial fibrillation Ventricular arrhythmias : tachycardia / fibrillation

Neuro-muscular Fatigue Myalgia Muscular weakness involving lower limbs Severe Hypokalemia : Paralysis ( extremities ) Weakness of respiratory muscles ( dyspnea ) Rhabdomyolysis (exercise induced)

Gastro-intestinal Constipation Paralytic ileus

Fluid – Electrolyte Polyuria ( nephrogenic diabetes insipidus ) Polydipsia ( nephrogenic diabetes insipidus ) Increased ammonia production ( intracellular acidosis ) precipitate hepatic coma in pts with advanced liver ds Edema Chloride wasting Metabolic alkalosis Hypercalciuria Phosphaturia

Endocrine Glucose intolerance ( decreased insulin secretion ) Growth retardation ( Reduced Growth hormone receptors Reduced IGF-1 )

Hemodynamic Hypertension ( increased renin secretion )

Abnormalities induced by hypokalemia Muscle weakness or paralysis Cardiac arrhythmias Rhabdomyolysis Renal dysfunction 1-impaired concentrating ability 2-increased ammonia production 3-impaired urinary acidification 4-increased bicarbonate reabsorption 5-renal insufficiency Hyperglycemia

Basic Investigations ECG : Initially : flattening of t wave depression of ST Segment development of prominent u waves Severe hypokalemia : increased amplitude of p wave increased QRS duration S.Potassium

Treatment of hypokalemia Monitoring of ECG and muscle strength, is an essential part of the management of patients with sever hypokalemia There is no definite correlation between the PLASMA k+ and BODY K+ stores. A reduction in the plasma K+ from 4 to 3 meq/l requires the loss of 200-400 meq of K+

Renal Vs Extra renal loss Urinary K+: > 20 mEq/L – Renal loss Urinary K + : < 20 mEq/L – Extrarenal loss TTKG : Transtubular Potassium Gradient ( Urine K+ / Plasma K+ ) ( Urine Osm / Plasma Osm ) TTKG : Renal loss : > 4 Extra renal loss : < 4

Extra Renal Loss Urinary K+ < 20 mEq/L Metabolic Acidosis Normal pH GI Loss Diarrhoea Laxative Abuse Normal pH Villous Adenoma Geophagia Metabolic Alkalosis Laxative abuse : rare GI Loss: rare

Renal Loss Urinary loss K+ > 20 mEq/L Metabolic Acidosis RTA DKA Ureterosigmoidostomy Variable pH ATN recovery Post obstructive diuresis Drugs Metabolic Alkalosis Urinary chloride level

Renal loss - Drugs Amphotericin B : tubular damage increased excretion of K+ Aminoglycosides : renal wasting of K+ Thiazides, Furosemide, Acetazolamide : renal loss K+ Cisplatin HYPOMAGNESEMIA : Significant renal K+ wasting

Renal Loss + Metabolic Alkalosis Urinary Chloride < 20 mEq/L Vomiting Diuretics > 20 mEq/L Check BP

Renal loss +Urine Cl > 20 mEq/L Check BP,ECF Low BP Check Bicarb Low - RTA High : Bartter, Gitelman HTN , Increased ECF Check Renin, Aldosterone

Treatment of hypokalemia……. A variety of potassium preparations are available for oral and IV use including the CL-, HCO3-, phosphate ,gluconate. In metabolic alkalosis and hypokalemia KCL preparation is choice In metabolic acidosis and mild degree of hypokalemia KHCO3 is preferred ORAL: KCL can be given orally in salt substitutes as a liquid or in a slow release tablet or capsule

Treatment of hypokalemia……. IV: the standard IV kcl solution contains 2meq/ml each of k+ and cl-. 20-40 meq of k+(10-20 ml) is added to each liter of saline solution. In general ,no more than 60 meq/l should be given through a peripheral vein ,since higher concentration of k+ are very irritating ,resulting in pain and sclerosis of the vein.

Treatment of hypokalemia…….. 1-If k+ is between 3 to 3.5 meq/l treatment is not urgent and these patients can usually be treated with oral kcl at an initial dose of 60-80 meq/day 2-In patients with sever symptoms or marked hypokalemia ,k+ must be give more rapidly. The plasma k+ will acutely rise by as much as 1-1.5meq/l after 40-60 meq oral kcl and by 2.5-3.5 meq/l after 135- 160 meq/l but these maximum effect is transient ,why?

Rate of potassium repletion IV potassium is administered at a maximum rate of 10-20 meq/h although as much as 40-60 meq/h has been given to patients with paralysis or life threatening arrhythmias. This solution containing as much as 200 meq of k+ /L and are best tolerated if given into a large vein such as femoral vein (infusion through a central venous line should probably be avoided, why?

Rapid administration of k+ is potentially dangerous even in severely k+ depleted patients and should be used only in life threatening situation

HYPERKALEMIA

HYPERKALEMIA Hyperkalemia defined as a k+>5meq/l occurs as a result of either k+ release from cells or decreased renal loss. There is an adaptive response in hyperkalemia

Hyperkalemia Spurious Hemolysis Thrombocytosis Leukocytosis Mononucleosis (leaky RBC) Redistribution Acidosis Diabetic ketoacidosis β-Blockade Succinylcholine Periodic paralysis Digoxin toxicity Potassium excess Increased intake/ tissue release Interavenous/oral intake Hemolysis Rhabdomyolysis Tumor lysis Stored blood Renal function Serum K+ (mEq/L) Atrial standstill Intraventricular block GFR >20 mL/min GFR <20 mL/min Acute renal failure Chronic renal failure 9 Hyperkalemia 7 Aldosterone Deficient Addison disease Hereditary Adrenal defects Drugs Heparin NSAID ACE inhibitors Cyclosporine spironolactone Tubular hyperkalemia Without aldosterone Deficient Acquired Obstruction Renal transplants SLE Amyloidosis Sickle cell Drugs K-sparing diuretics High T wave Normal 4 Normal

Symptoms of hyperkalemia 1-Muscle weakness : most often begins in the lower extremities and ascends to the trunk and upper extremities. *The respiratory muscles and those supplied by the cranial nerves are usually spared 2-Abnormal cardiac conduction: the cardiac toxicity is enhanced by hypocalcemia, hyponatremia, acidemia, and a rapid elevation in the plasma k+ concentration

EKG Changes Peaked T Waves

EKG Changes Widening of QRS Complex

EKG Changes Ventricular Tach/Torsades

Treatment of hyperkalemia Emergency Modality Mechanism of action Onset Duration Prescription K+ Removed From Body Calcium Antagonizes cardiac Conduction abnor- malities 0-5 minutes 1 hour Calcium gluconate 10%,5-30 mL IV; Or calcium chloride 5%,5-30 mL IV Bicarbonate Distributes K+ into cells 15-30 minutes 1-2 hours NaHCO3, 44-88 meq (1-2 ampules) IV Insulin 15-60 minutes 4-6 hours Regular insulin, 5-10 units IV,plus glucose 50%,25 g (1 ampule) IV Albuterol 2-4 hours Nebulized albuterol, 10-20 mg in 4 mL normal saline,in Haled over 10 minutes

No emergency Modality Mechanism of action Duration of Treatment Prescription K+ removed From body Loop diuretic Renal K+ excreation 0.5-2 hours Furosemide,40-160 mg IV or orally with Or without NaHCO3, 0.5-3 meq/ kg daily Variable Sodium polystyrene Sulfonate (kayexalate) Lon exchange resin binds K+ 1-3 hours Oral: 15-30 g in 20% Sorbitol (50-100 mL) Rectal: 50 g in 20% sorbitol 0.5-1 meq/q Hemodialysis Extracorporeal K+ removal 48 hours Blood flow ≥ 200- 300 mL/min, Dialysate [K+] ~ 0 200-300 meq Peritoneal dialysis Peritoneal K+ removal Fast exchange , 3-4 L/h