Nephrology Lecture 1

7/24/2019 Nephrology Lecture 1

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Fluid and Electrolytes

Chrisitne S. Caringal. MD, DPPS, DPSN, DPNSP


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FUNCTIONS OF KIDNEY


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Regulation of Water and Electrolyte

Balance

The balance concept states that our bodies are in balancefor any substance when the inputs and outputs of that

substance are matched.

Maintains balance of water by regulating the amount ofurine

Excrete minerals in variable rate to match input


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Excretion of Metabolic Waste

End products of metabolic processes serve no functionand are harmful at high concentration.

Includes: 1) Urea (from protein)

2) Uric acid (from nucleic acid)

3) Creatinine (from muscle creatine)

4) End products of hemoglobin breakdown

5) Metabolite of various hormones


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Regulation of Arterial Blood Pressure

Blood pressure depends on blood volume, and thekidneys maintenance of sodium and water balance

achieves regulation of blood volume.

Kidneys also generates vasoactive substances thatregulate smooth muscle in the peripheral vasculature


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Regulation of Red Blood Cell Production

Erythropoietin stimulates the

bone marrow to increase its production of erythrocytes.


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Regulation of Vitamin D Production

The active form of vitamin D (1,25-dihydroxyvitamin D3) is

actually made in the kidneys, and its rate of synthesis is

regulated by hormones that control calcium andphosphate balance.


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SODIUM

mET BOLISM


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Sodium

Dominant cation of the ECF

Principal determinant of extracellular osmolality

Necessary for the maintenance of intravascular volume.


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Distribution of Sodium in the Body


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Increased

ExtracellularSodiumConc

DecreasedIntracellularSodium Con

Energy for

themovement ofsubstances

into the cell


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SodiumIntake

SodiumExcretion


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Sodium and Water Balance

Increased Sodium Concentration

Increased Plasma Osmolality

Increased thirst

Increased ADH secretion

Renal water conservation and normalsodium concentration


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yponatremia


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TotalSerumSodium

TotalBody

Water

Serum SodiumConcentration


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Pseudohyponatremia

laboratory artifact that is present when the

plasma contains very high concentrations of

protein or lipid

does not occur if a direct ion-selective electrode

determines the sodium concentration


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Pseudohyponatremia

Normal serumosmolality

True Hyponatremia

Low serumosmolality


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Causes of Hyponatremia

Hyperosmolality

Hypovolemic Hyponatremia

Euvolemic Hyponatremia

Hypervolemic Hyponatremia


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Hyperosmolality

water moves down its osmotic gradient from theintracellular space into the extracellular space,

diluting the sodium concentration

do not have symptoms of hyponatremia

When the etiology of the hyperosmolality

resolves, water moves back into the cells and the

sodium concentration increases to its "true"value.


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Hyperosmolality

Hyperglycemia Osmotic diuresis

Mannitol Postobstructive diuresis

Gastrointestinal (emesis, diarrhea) Polyuric phase of ATN

Skin (sweating or burns) Juvenile nephronophthisis

Third space losses Autosomal recessive polycystic kidneydisease

Absent aldosterone (e.g., 21-hydroxylase

deficiency

Tubulointerstitial nephritis

Pseudohypoaldosteronism type I Obstructive uropathy

Urinary tract obstruction and/or urinarytract infection

Cerebral salt wasting

Thiazide or loop diuretics Proximal (Type II) RTA


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combination of sodium loss and water retention tocompensate for the volume depletion

The volume depletion stimulates ADH synthesis, resulting

in renal water retention in the collecting duct.

The volume depletion decreases the GFR and enhances

water reabsorption in the proximal tubule, which reduces

water delivery to the collecting duct.


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develops if the patient receives hypotonic fluid

In diseases with volume depletion due to extrarenal

sodium loss, the urine sodium should be low (


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Extrarenal losses Child abuse

Renal losses Psychogenic

polydipsiaIatrogenic (i.e.,

excess hypotonic

intravenous fluids)

Diluted formula

Swimming lessons Beer potomania

Tap water enema


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an excess of total body water and sodium but theincrease in water is greater than the increase in sodium

sodium concentration decreases because water intake

exceeds sodium intake, and ADH prevents the normal

loss of excess water.

low urine sodium concentration (


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Exception: patient with renal failure and hyponatremia

expanded intravascular volume and hyponatremia ----

suppress ADH production

Water cannot be excreted because very little urine is

being made.


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third spacing offluid or poor

cardiac function

decrease in theeffective blood

volume

regulatory systemsof the body sense

this decrease

ADH causes renalwater retention

Kidney:aldosterone andother intrarenal

mechanisms,retains sodium


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Congestive heart failure

Cirrhosis

Nephrotic syndrome

Renal failure

Capillary leak due to sepsisHypoalbuminemia due to gastrointestinal

disease


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an excess of total body water and a slight decrease in

total body sodium

increase in weight --- technically overloaded

Clinically, they appear normal or have subtle signs of fluid

overload.


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Syndrome of inappropriate

antidiuretic hormone

Desmopressin acetate

Glucocorticoid deficiency

HypothyroidismWater intoxication


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Brain swelling

Because the intracellular space then has a higher

osmolality, water inevitably moves from the extracellular

space to the intracellular space to maintain osmotic

equilibrium.

The increase in intracellular water causes cells to swell.

Acute, severe hyponatremia can cause brainstem

herniation and apnea; respiratory support is often

necessary brain swelling can be significantly obviated if the

hyponatremia develops gradually.


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Treatment

Treat the etiology

monitoring and avoidance of an overly quick

normalization of the serum sodium concentration

Patient with severe symptoms, no matter the etiology,

should be given a bolus of hypertonic saline to produce a

small, rapid increase in the serum sodium.


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Treatment (Euvolemic Hyponatremia)

Intravenous hypertonic saline rapidly increases the serum

sodium, and the effect on serum osmolality leads to a

decrease in brain edema.

Each milliliter of 3% sodium chloride increases the serumsodium by approximately 1 mEq/L

T t t (H l i


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Treatment (Hypovolemic

Hyponatremia)

hypovolemic hyponatremia -- deficiency in sodium and

may have a deficiency in water.

The cornerstone of therapy is to replace the sodium

deficit and any water deficit that is present.

The first step in any dehydrated patient is to restore the

intravascular volume with isotonic saline.

T t t (H l i


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Treatment (Hypervolemic

Hyponatremia)

Administration of sodium leads to worsening volume

overload and edema

cornerstone of therapy: water and sodium restriction

(because these patients are overloaded)

Diuretics may be helpful by causing excretion of both

sodium and water.


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Central Pontine Myelinosis

produces neurologic symptoms, including confusion,

agitation, flaccid or spastic quadriparesis, and death

usually characteristic pathologic and radiologic changes in

the brain, especially in the pons

more common in patients who are treated for chronic

hyponatremia


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Central Pontine Myelinosis

Pathophysiogy: reduced intracellular osmolality that is an

adaptive mechanism for chronic hyponatremia makes

brain cells susceptible to dehydration during rapid

correction of the hyponatremia

avoid correcting the serum sodium by more than 12

mEq/L each day


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ypernatremia


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Hypernatremia

SodiumExcess

Waterdeficit

Water and

Sodiumdeficit


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Sodium Excess

Improperly mixed formula Premature infants

Excess sodium bicarbonate Radiant warmers

Ingestion of seawater or sodium

chloride

Phototherapy

Intentional salt poisoning (child abuse

or Mnchhausen syndrome by proxy)

Ineffective breast-feeding

Intravenous hypertonic saline Child neglect or abuse

Hyperaldosteronism Adipsia (lack of thirst)


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Water Deficit

Nephrogenic diabetes Burns

Central diabetes insipidus Excessive sweating

Increased insensible losses Osmotic diuretics (e.g.,

mannitol)

Inadequate intake Diabetes mellitus

Diarrhea Chronic kidney disease (e.g.,

dysplasia and obstructive

uropathy)Emesis/Nasogastric suction Polyuric phase of acute tubular

necrosis

Osmotic cathartics (e.g.,

lactulose)

Postobstructive diuresis


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Water and Sodium Deficit

Gastrointestinal losses

Cutaneous lossesRenal losses

Clinical Manifestations of


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Clinical Manifestations of

Hypernatremia

Dehydration--- doughy skin

Central nervous system symptoms

--- severity proportional to the degree of

hypernatremia

Increased thirst

Hyperglycemia

Hypoglycemia

Brain Hemorrhage most devastating


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Brain Hemorrhagemost devastating

complication of hypernatremia

IncreasedExtracellularOsmolality

Water moves outof brain cells

Decrease brainvolume

Brain moves awayfrom the skull and

meninges

Tearing ofintracerebal veins

and bridgingnlood vessels

Seizures and

coma


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Other sequelae

Central pontine demyelination

Extrapontine myelinosis

Thrombotic complicatio


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Treatment

Goal: to decrease the serum sodium by less than 12

mEq/L every 24 hr, a rate of 0.5 mEq/L/hr.

The most important component of correcting moderate

or severe hypernatremia is frequent monitoring of theserum sodium so that fluid therapy can be adjusted to

provide adequate correction, neither too slow nor too

fast.

Treatment of Hypernatremic


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Treatment of Hypernatremic

Dehydration

first priority is restoration of intravascular volume with

isotonic fluid

Normal saline > lactated Ringer solution

-- the lower sodium concentration of the lactatedRinger solution can cause the serum sodium to decrease

too rapiidly

Water deficit

= Body weight x 0.6 (1-145/Actual serum Na)

Treat underlying cause

Determinants of the rate of decrease


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Determinants of the rate of decrease

in sodium concentration

Serum concentration of the fluid

Rate of fluid administration

Continuous water losses


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Rapid Correction of Hypernatremia

Rapid decrease in sodium

Movement of water from seruminto brain cells to equalizeosmolality

BRAIN SWELLING


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Treatment of Brain edema

administration of hypotonic fluid should be

stopped

infusion of 3% saline


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POTASSIUM

METABOLISM


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Potassium Distribution

Intracellular

approximately 150mEq/L, is muchhigher than the

plasma concentration

Muscle: majority

(directlyproportional)

Extracellular

Bone: majority

Plasma: 1%

Factors increasing intracellular


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Factors increasing intracellular

potassium

Na-K ATPase

Insulin

Metabolic alkalosis

-adrenergic agnist

Factors decreasing intracellular


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Factors decreasing intracellular

potassium

-adrenergic agonist

Exercise

Mannitol infusion (Increase plasma osmolality)


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Functions of Potassium

electrical responsiveness of nerve and muscle

cells, and for the contractility of cardiac, skeletal,

and smooth muscle (Action Potential)

maintaining cell volume because of its important

contribution to intracellular osmolality


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Hyperkalemia

Most alarming electrolyte

abnormalities due topotential lethal arrythmias


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Fictitious Hyperkalemia

very common in children because of the difficulties in

obtaining blood specimens.

due to hemolysis during phlebotomy

can be the result of prolonged tourniquet application or

fist clinching, which cause local potassium release from

muscle.


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Causes of Hyperkalemia

Spurious Laboratory Value

Increased Intake

Transcelullar Shift

Decreased Excretion


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Spurious Laboratory Value

Hemolysis

Tissue ischemia during blooddrawing

ThrombocytosisLeukocytosis


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Increased Intake

Intravenous or Oral

Blood Transfusion


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Transcellular Shifts

Analyze plasma instead of serum

It is important to analyze the sample promptly to avoid

potassium release from cells.

This occurs if the sample is stored in the cold, whereas

room temperature storage can lead to cellular uptake of

potassium and spurious hypokalemia


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Acidemia Fluoride intoxication

Rhabdomyolysis Beta-adrenergic blockers

Tumor lysis syndrome Exercise

Tissue necrosis Hyperosmolality

Hemolysis/hematomas/GI

bleeding

Insulin deficiency

Succinylcholine Malignant hyperthermiaDigitalis intoxication Hyperkalemic periodic

paralysis


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Acquired Addison disease Urinary tract obstruction

21-hydroxylase deficiency Sickle cell disease

3-hydroxysteroid

dehydrogenase deficiency

Kidney transplant

Lipoid congenital adrenal

hyperplasia

Lupus nephritis

Adrenal hypoplasia congenita

Aldosterone synthasedeficiency

Adrenoleukodystrophy


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Angiotensin-converting enzyme

inhibitors

Angiotensin II blockersPotassium-sparing diuretics

CyclosporinNonsteroidal anti-inflammatories

Trimethoprim


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Decreased Excretion

Renal failure

Primary adrenal diseaseHyporeninemic hypoaldosteronism

Renal tubular diseaseMedications


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Clinical Manifestations

Usually preceeded by cardiac toxicity

paresthesias

weakness

tingling


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Cardiac Toxicity

Peak T waves

Increased PR interval

Flattening of P wave

Widening of QRS complex

Ventricular fibrillation

Transtubular Potassium Gradient


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(TTKG)

Useful method to evaluate renal response to

hyperkalemia

K(urine)/K(plasma)x (plasma osmolality/urine osmolality)

ranging from 5-15

TTKG >10 ---normal renal excretion of potassium

TTKG < 8 ---defect in renal potassium excretion, which is

(lack of aldosterone or an inability to respond to

aldosterone)


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Treatment

stop all sources of additional potassium (oral and

intravenous)

Washed red blood cells can be used for patients who

require blood transfusions

Two basic goals:

(1) to stabilize the heart to prevent life-threatening

arrhythmias

(2) to remove potassium from the body


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Treatment (preventing arrhythmias)

Calcium -- stabilizes the cell membrane of heart cells,

preventing arrhythmias. It is given over a few minutes

intravenously and its action is almost immediate.

Bicarbonate -- causes potassium to move intracellularly,lowering the plasma potassium.

Insulin

Nebulized albuterol (2 agonist)


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Treatment (Potassium removal)

Loop diureticfor non-anuric patients only

Sodium polystyrene sulfonate (Kayexalate) -- an exchangeresin that is given either rectally or orally. Sodium in the

resin is exchanged for body potassium and the potassium-

containing resin is then excreted from the body.


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Treatment (potassium removal)

Dialysis

-- severe renal failure

-- high rate of endogenous potassium release as is

sometimes present with tumor lysis syndrome or

rhabdomyolysis-- Hemodialysis rapidly lowers plasma potassium

levels.

-- Peritoneal dialysis is not nearly as quick or reliable,

even though it is usually adequate as long as the acuteproblem can be managed with medications and the

endogenous release of potassium is not extremely high.


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HYPOKALEMIA


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Spurious Hypokalemia

in patients with leukemia and very elevated white blood

cell counts if plasma for analysis is left at room

temperature, permitting the white cells to take uppotassium from the plasma.


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Causes


Decrease Intake

Renal Losses

Non-renal Losses


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Transcellualr shifts

Alkalemia

Insulin

-adrenergic agonists

Drugs/toxins (theophylline, barium,

toluene)Hypokalemic periodic paralysis


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Decreased Intake

Anorexia nervosa

Bulimia

Laxative or diuretic abuse


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Extrarenal Losses

Diarrhea Tubular toxins: amphotericin,cisplatin, aminoglycosides

Laxative abuse Interstitial nephritis

Sweating Diuretic phase of acute tubular

necrosisDistal renal tubular acidosis

(RTA)Postobstructive diuresis

Proximal RTA Hypomagnesemia

Ureterosigmoidostomy High urine anions (e.g.,penicillin or penicillin derivatives)

Diabetic ketoacidosis


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Extrarenal Losses

Emesis nasogastric suction Adrenal adenoma or hyperplasia

Chloride losing diarrhea Glucocorticoid-remedial

aldosteronism

Cystic fibrosis Renovascular disease

Low chloride formula Renin-secreting tumorPosthypercapnia 17-hydroxylase deficiency

Previous loop or thiazide diuretic use 11-hydroxylase deficiency

Gitelman syndrome Cushing syndrome

Bartter syndrome (MIM 602023) 11-hydroxysteroid dehydrogenasedeficiency

Loop and thiazide diuretics Licorice ingestion

Liddle syndrome


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Extrarenal Losses

Low urine chloride

High urine chloride and normal

blood pressure

High urine chloride and highblood pressure


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Cardiac complications

Flattened T wave

Depressed ST segment

Appearance of U wave

li i l if i


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skeletal muscle include muscle weakness and cramps

Paralysis is a possible complication, at levels less than 2.5

mEq/L. This usually starts with the legs, followed by the

arms. Respiratory paralysis may require mechanicalventilation

Rhabdomyolysis increased with exercise

Slows gastrointestinal motility

Cli i l if i


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impairs bladder function -- urinary retention

polyuria and polydipsia by two mechanisms: primary

polydipsia and impaired urinary concentrating ability,

stimulates renal ammonia production, which is clinically

significant if hepatic failure is present because the liver

cannot metabolize the ammonia

--- worsen hepatic encephalopathy

Distuinguishing Renal from nonrenal

l


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losses

24-hour urine collection

spot potassium/creatine ratio

fractional excretion of potassium,

calculation of the TTKG

-- most widely used approach in children

-- >4: excessive urinary loss of potassium

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Treatment

Oral supplementation is safer than IV but less rapid.

The dose of intravenous potassium is 0.5-1 mEq/kg,

usually given over 1 hr.

Potassium chloride is the usual choice for

supplementation, although the presence of concurrent

electrolyte abnormalities may dictate other options.

Patients with acidosis and hypokalemia can receive

potassium acetate or potassium citrate.

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Treatment

For patients with excessive urinary losses, potassium-

sparing diuretics are effective, but they need to be usedcautiously in patients with renal insufficiency.

If hypokalemia, metabolic alkalosis, and volume depletionsare present (e.g., with gastric losses), then restoration of

intravascular volume with adequate chloride will decrease

urinary potassium losses.

Disease-specific therapy is effective in many of the genetic

tubular disorders.

Nephrology Lecture 1

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