Fluid and Electrolytes

F . Mamdouhi M . DMashhad University of Medical

Sciences

در: محلول ماده یا ذره غلظت اسمواللیته

مایع یک

: پالسما طبیعی 290-275اسمواللیته

: یا هیپوناترمی آب هموستاز اختالالت

هیپرناترمی

یا : ادم سدیم هموستاز اختالالت

هیپوولمی

The major ECF particles are Na+ and its

accompanying anions Cl– and HCO3–.

The predominant ICF osmoles are K+ and

organic phosphate esters (ATP, creatine

phosphate, and phospholipids).

 The normal plasma osmolality (Posm ) is 280 to 295 mosmol/kg.

It usually is held within narrow limits as variations of only 1 to 2 percent initiate mechanisms to return the Posm to normal.

These alterations in osmolality are sensed by receptor cells in the hypothalamus which affect water intake (via thirst) and water excretion (via ADH, which increases water reabsorption in the collecting tubules).

REGULATION OF PLASMA OSMOLALITY

The osmolality of human body fluid is

between 280 and 295 mosmol/kg and

regulated by :

–Vasopressin secretion

–water ingestion, and

– renal water transport.

Hypoosmolality and hyperosmolality can produce

serious neurologic symptoms and death, primarily due

to water movement into and out of the brain,

respectively.

To prevent this, the plasma osmolality (Posm ), which is

primarily determined by the plasma Na+ concentration,

is normally maintained within narrow limits by

appropriate variations in water intake and water

excretion.

This regulatory system is governed by osmoreceptors in

the hypothalamus that influence both thirst and the

secretion of antidiuretic hormone (ADH).

Osmolality

Vasopressin (AVP) is synthesized in the

hypothalamus.

the distal axons of those neurons project

to the posterior pituitary or

neurohypophysis, from which AVP is

released into the circulation.

AVP has a half-life in the circulation of

only 10–20 min.

AVP secretion is stimulated as systemic

osmolality increases above a threshold

level of 285 mosmol/kg,

Thirst sensation and thus water ingestion

also are activated at 285 mosmol/kg.

Changes in blood volume and blood

pressure are also direct stimuli for AVP

release and thirst.

osmoregulation is almost entirely mediated

by changes in

WATER BALANCE

Water intake 

Obligatory water output 

WATER BALANCE

هیپوولمی

:علل

دادن دست ازطریق از GIاب

کلیوی طریق از اب دادن دست از

پوست طریق از اب دادن دست از

سوم فضای به سکستراسیون

ازطریق دادن دست GI:از

استفراغ

NG tube

اسهال

فیستول

Only small amounts of water are normally lost in

the stool, averaging 100 to 200 mL/day.

However, gastrointestinal losses are increased to

a variable degree in patients with vomiting or

diarrhea.

The effect of these losses on the plasma Na+

concentration depends on the sum of the Na+

and K+ concentrations in the fluid that is lost.

Gastrointestinal losses

طریق از دادن دست از:کلیوی

آب کلیوی اتالف) ( نفروژنیک یا مرکزی بیمزه دیابت

سدیم و آب کلیوی اتالف دیورتیک اسموتیک دیورز هیپوآلدوسترونیسم سدیم دهنده دست از نفروپاتی

The obligatory renal water loss is directly related

to solute excretion.

If a subject has to excrete 800 mosmol of solute

per day (mostly Na+ and K+ salts and urea) to

remain in the steady state, and the maximum

Uosm is 1200 mosmol/kg, then the excretion of the

800 mosmol will require a minimum urine volume

of 670 mL/day.

obligatory renal water

طریق از دادن دست از:پوست

نامحسوس اتالف

تعریق

سوختگی

The evaporative losses play an important role in

thermoregulation; the heat required for evaporation,

0.58 kcal/1.0 mL of water, normally accounts for 20

to 25 percent of the heat lost from the body, with the

remainder occurring by radiation and convection.

The net effect is the elimination of the heat produced

by body metabolism, thereby preventing the

development of hyperthermia.

Insensible losses

Sweat is a hypotonic fluid (Na+ concentration equals 30 to 65 meq/L)

It also contributes to thermoregulation, as the secretion and subsequent evaporation of sweat result in the loss of heat from the body.

In the basal state, sweat production is low, but it can increase markedly in the presence of high external temperatures or when endogenous heat production is enhanced, as with exercise, fever, or hyperthyroidism.

As an example, a subject exercising in a hot, dry climate can lose as much as 1500 mL/h as sweat

Sensible loss

سوم اسکستر فضای به :سیون

هیپوآلبومینمی سیروز نفروتیک سندرم

مویرگی نشت حاد پانکراتیت ایسکمیک روده رابدومیولیز

هیپوولمی :عالیم

- - - - تشنگی کرامپ ضعف پذیری خستگی

گیجی

- : اولیگوری انتهایی اعضای ایسکمی

- - خواب- قلبی آنژین شکم درد سیانوز

آلودگی

- غشاهای خشکی پوستی تورگور کاهش

مخاطی

- هیپوتانسیون ژوگولر ورید فشار کاهش

وضعیتی- تاکیکاردی وضعیتی

سدیم تعادل

خارج 85-90% بخش در سدیم. دارد قرار سلولی

منعکس سدیم غلظت تغییراتاب هموستاز خوردن هم بر کننده

است.

به سدیم تام مقدار تغییراتحجم افزایش یا کاهش صورت

ECF . یابد می تظاهر

سدیم : مول 150دریافت میلی

به : بستگی سدیم توبولی GFRدفع بازجذب و

دارد.

سدیم : پروگزیمال – 3/2بازجذب لوله -25در

30 - هنله% - 5در در% بقیه دیستال توبول

کننده جمع مجاری

هیپوناترمی

از: کمتر سدیم 135تعریف

علل:

کاذب- 1 هیپوناترمی

هیپواسموالر- 2 هیپوناترمی

Hyponatremia

In almost all cases, hyponatremia results from the

intake and subsequent retention of water.

A water load will be rapidly excreted as the dilutional

fall in plasma osmolality suppresses the release of

antidiuretic hormone (ADH), thereby allowing the

excretion of a dilute urine.

The maximum rate of water excretion on a regular

diet is over 10 liters per day.

: کاذب هیپوناترمی 1: نرمال- اسمواللیته

هیپرلپیدمی هیپرپروتئینمی پروستاتکتومی

2: باال- اسمواللیته هیپرگلیسمی مانیتول

Pseudohyponatremia Is associated with a normal plasma osmolality, refers to those disorders in which marked elevations of substances, such as lipids and proteins, result in a reduction in the fraction of plasma that is water.

In normal subjects, the plasma water is approximately 93 percent of the plasma volume.

A normal plasma sodium concentration of 142 meq/L (measured per liter of plasma) actually represents a concentration in the physiologically important plasma water of 154 meq/L (142 ÷ 0.93 = 154).

Ion-selective electrodes have been used to

directly measure the plasma water sodium

concentration in this setting but have variable

accuracy.

HYPONATREMIA WITH A HIGH PLASMA OSMOLALITY

Hyponatremia with a high plasma osmolality is most often due to hyperglycemia.

A less common cause is the administration and retention of hypertonic mannitol.

The rise in plasma osmolality induced by glucose or mannitol pulls water out of the cells, thereby lowering the plasma sodium concentration by dilution.

Physiologic calculations suggest that the plasma sodium concentration should fall by 1 meq/L for every 62 rmg/dL rise in the plasma concentration of glucose or mannitol (which have the same molecular weight).

The 1:62 ratio applied when the plasma glucose concentration was less than 400 mg/dL.

At higher glucose concentrations, the ratio of 1:42 provided a better estimate of this association than the usual 1:62 ratio

Normal Plasma Osmolality Isosmotic hyponatremia can be produced by the addition of an isosmotic (or near isosmotic) but non-sodium-containing fluid to the extracellular space.

This problem primarily occurs with the use of nonconductive glycine or sorbitol flushing solutions during transurethral resection of the prostate or bladder or irrigation during laparoscopic surgery, since variable quantities of this solution are absorbed.

DISORDERS IN WHICH ADH LEVELS ARE ELEVATED

The two most common causes of

hyponatremia are:

– effective circulating volume depletion and

– the syndrome of inappropriate ADH

secretion, disorders in which ADH secretion

is not suppressed.

Effective Circulating Volume Depletion

Significantly decreased tissue perfusion is a

potent stimulus to ADH release.

This response is mediated by baroreceptors in the

carotid sinus and can overcome the inhibitory

effect of hyponatremia on ADH secretion.

Heart Failure and Cirrhosis

Even though the plasma volume may be markedly

increased in these disorders, the pressure sensed at the

carotid sinus baroreceptors is reduced due to the fall in

cardiac output in heart failure and to peripheral

vasodilatation in cirrhosis.

The rise in ADH levels tend to vary with the severity of

the disease, making the development of hyponatremia an

important prognostic sign.

Syndrome of Inappropriate ADH Secretion

Persistent ADH release and water retention can

also be seen in a variety of disorders that are

not associated with hypovolemia.

These patients have a stable plasma sodium

concentration between 125 and 135 meq/L.

Hormonal Changes

Hyponatremia can occur in patients with adrenal

insufficiency (in which it is lack of cortisol that is

responsible for the hyponatremia) and with

hypothyroidism.

The release of HCG during pregnancy may be

responsible for the mild resetting of the osmostat

downward, leading to a fall in the plasma sodium

concentration of about 5 meq/L.

DISORDERS IN WHICH ADH LEVELS MAY

BE APPROPRIATELY SUPPRESSED

There are two disorders in which

hyponatremia can occur despite suppression of

ADH release:

– advanced renal failure

– primary polydipsia

Advanced Renal Failure

The relative ability to excrete free water (free water

excretion divided by the glomerular filtration rate)

is maintained in patients with mild to moderate

renal failure.

Thus, normonatremia is usually maintained in the

absence of oliguria or advanced renal failure.

Advanced Renal Failure

In the latter setting, the minimum urine

osmolality rises to as high as 200 to 250

mosmol/kg despite the appropriate suppression of

ADH.

The osmotic diuresis induced by increased solute

excretion per functioning nephron is thought to

be responsible for the inability to dilute the urine.

Primary Polydipsia

Is a disorder in which there is a primary stimulation of thirst.

It is most often seen in anxious and in patients with psychiatric illnesses, particularly those taking antipsychotic drugs in whom the common side effect of a dry mouth leads to increased water intake.

Polydipsia can also occur with hypothalamic lesions (as with infiltrative diseases such as sarcoidosis) which directly affect the thirst centers

Primary PolydipsiaThe plasma sodium concentration is usually normal or only slightly reduced in primary polydipsia, since the excess water is readily excreted.

These patients may feel asymptomatic or may present with complaints of polydipsia and polyuria.

In rare cases water intake exceeds 10 to 15 L/day and fatal hyponatremia may ensue.

Symptomatic hyponatremia can also be induced with an acute 3 to 4 liter water load (as may rarely be seen in anxious patients preparing for a radiologic examination or for urinary drug testing)

Symptomatic and potentially fatal hyponatremia has also been described after ingestion of the designer amphetamine ecstasy (methylenedioxymethamphetamine or MDMA)

Both a marked increase in water intake and inappropriate secretion of ADH may contribute.

Low ِDietary Solute Intake Beer drinkers or other malnourished patients may have a marked reduction in water excretory capacity.

Normal subjects excrete 600 to 900 mosmol/kg of solute per day (primarily Na, K salts and urea); thus, if the minimum urine osmolality is 60 mosmol/kg, the maximum urine output will be 10 to 15 L/day .

Beer contains little or no Na, K , or protein, and the carbohydrate load will suppress endogenous protein breakdown and therefore urea excretion.

Diagnosis of Hyponatremia

Hyponatremia in virtually all patients reflects

water retention due to an inability to excrete

ingested water.

In most cases, this defect represents the persistent

secretion of ADH, although free water excretion

can also be limited in advanced renal failure

independent of ADH.

In the absence of renal failure, the differential

diagnosis begins with the history and physical

examination, looking for one of the causes of

excess ADH secretion:

effective circulating volume depletion (including

gastrointestinal or renal losses, congestive

heart failure, and cirrhosis);

the syndrome of inappropriate ADH secretion

(SIADH);

adrenal insufficiency or hypothyroidism.

DIAGNOSIS

Three laboratory findings also may provide

important information in the differential

diagnosis of hyponatremia:

the plasma osmolality;

the urine osmolality;

the urine sodium concentration.

Plasma Osmolality

The plasma osmolality is reduced in most

hyponatremic patients, because it is primarily

determined by the plasma sodium

concentration and accompanying anions.

In some cases the plasma osmolality is either

normal or elevated.

Since there is no hypoosmolality and

therefore no risk of cerebral edema due to

water movement into the brain, therapy

directed at the hyponatremia is not indicated

in any of these disorders with the exception

of glycine administration.

In this setting, the plasma osmolality may fall

with time as the glycine is metabolized.

Urine Osmolality The normal response to hyponatremia (which is

maintained in primary polydipsia) is to completely

suppress ADH secretion, resulting in the excretion

of a maximally dilute urine with an osmolality below

100 mosmol/kg and a specific gravity < or =1003.

Values above this level indicate an inability to

normally excrete free water that is generally due to

continued secretion of ADH.

پالسما اسمواللیته

باال طبیعی پایینهیپرگلیسمی هیپرپروتئینمی حجیم بسیار ادرار

مانیتول هیپرلپیدمی رقیق بسیار و

مثانه> 100 تحریک

نه بلهحجم اولیه ECFپرنوشی

افزایش طبیعی کاهش

قلبی SIADHادرار Naغلظت نارساییکبدی سیروز هیپوتیرویئدیکلیوی سندرم آدرنال نارسایی

20 < 10<

کلیوی خارج دفع اتالف Naنفروپاتی Na دیورتیک طوالنی مصرف

کشیده طول استفراغ هیپوآلدوسترونیسمدیورتیک

استفراغ

:SIADHعلل عصبی بیماریهای روانی ریوی بدخیم تومورهای بزرگ جراحی داروها

hyponatremia due to the SIADH is characterized by the

following set of findings:

– • A fall in the plasma osmolality

– • An inappropriately elevated urine osmolality

(above 100 mosmol/kg and usually above 300

mosmol/kg)

– • A urine sodium concentration usually above 40

meq/L.

– • A relatively normal plasma creatinine concentration

– • Normal adrenal and thyroid function.

:SIADHعالئم + هیپواسمواللیتی هیپوناترمی Uosm<100 UNa<40 نرموولمی - نرمال – تیرویید آدرنال کلیه فانکشن – – نرمال پتاسیم باز اسید هیپواوریسمی

Plasma Uric Acid and Urea Concentrations

The initial water retention and volume expansion in the SIADH leads to another frequent finding that is the opposite of that typically seen with volume depletion: hypouricemia (plasma uric acid concentration less than 4 mg/dL ) due to increased uric acid excretion in the urine.

It is presumed that the early volume expansion diminishes proximal sodium reabsorption, leading to a secondary decline in the net reabsorption of uric acid.

Cerebral Salt Wasting

All of the changes in electrolyte balance observed in the SIADH have also been described in the putative syndrome of cerebral salt-wasting.

This disorder is characterized by a high urine sodium concentration that is due to defective tubular reabsorption (mediated by the release of a natriuretic hormone, perhaps brain natriuretic peptide) and an elevation in ADH and the subsequent development of hyponatremia due to the associated volume depletion.

Symptoms of Hyponatremia

The symptoms that may be seen with

hyponatremia or hypernatremia are

primarily neurologic and are related both

to the severity and in particular to the

rapidity of onset of the change in the

plasma sodium concentration.

Symptoms of Hyponatremia

The symptoms directly attributable to hyponatremia primarily occur with acute and marked reductions in the plasma sodium concentration and reflect neurologic dysfunction induced by cerebral edema .

In this setting, the associated fall in plasma osmolality creates an osmolal gradient that favors water movement into the cells, leading in particular to brain edema.

The presence of cerebral overhydration generally correlates closely with the severity of the symptoms.

Nausea and malaise are the earliest findings, and may be seen when the plasma sodium concentration falls below 125 to 130 meq/L.

This may be followed by headache, lethargy, and obtundation and eventually seizures, coma and respiratory arrest if the plasma sodium concentration falls below 115 to 120 meq/L.

Hyponatremic encephalopathy may be

reversible, although permanent neurologic

damage or death can occur, particularly in

premenopausal women.

Overly rapid correction also may be

deleterious, especially in patients with

chronic asymptomatic hyponatremia.

بالینی : خصوصیات

عصبی : عالیم

عالمت بی

: از کمتر سدیم بیحالی و 125تهوع

: – – سدیم گیجی آلودگی خواب سردرد

115-120

: از – – کمتر سدیم کما تشنج ستوپور 115ا

عالمت- + 1 بدون هیپوناترمیکاهشحجم :

سالین نرمال

ادم- + :2 هیپوناترمی آب و سدیم محدودیت هیپوکالمی تصحیح + سدیم کردن جایگزین لوپ دیورتیک

و- – 3 کلیه نارسایی اولیه پرنوشیSIADH:

آب محدودیت

سدیم کمبود محاسبه

ODS:– – دیسفازی دیزآرتری شل فلج مزمن هیپوناترمی در بیشتر باال مورتالیته ساز خطر عوامل :ODSسایر

آنوکسی•هیپوکالمی •سوتغذیه •

Na deficit (mmol) = 0.6 x wt(kg) x (desired [Na] - actual [Na])

60 kg women, serum Na 107, seizure recalcitrant to benzodiazepines.

Na defecit = 0.6 x (60) x (120 – 107) = 468 mEq

Want to correct at rate 1.5 mEq/L/h: 13/1.5 = 8.7h

468 mEq / 8.7h = 54 mEq/h

3% NaCl has 513 mEq/L of Na

54 mEq/h = x

513 mEq 1L

x = rate of 3% NaCl = 105 cc/h over 8.7h to correct serum Na to 120 mEq/h

Note: Calculations are always at best estimates, and anyone getting

hyponatremia corrected by IV saline (0.9% or 3%) needs frequent

serum electrolyte monitoring (q1h if on 3% NS).

هیپرناترمی

سدیم : < 145تعریف

هیپراسموالریتی = هیپرناترمی

: هیپرناترمی به مناسب پاسخ

اب دریافت افزایش

ادرار حجم کمترین دفع

Causes of Hypernatremia Hypernatremia is a relatively common problem that can be produced either by the administration of hypertonic sodium solutions or, in almost all cases, by the loss of free water.

It should be emphasized that persistent

hypernatremia does not occur in normal subjects,

because the ensuing rise in plasma tonicity

stimulates both the release of ADH and, more

importantly, thirst.

The net effect is that hypernatremia primarily occurs

in those patients who cannot express thirst normally:

infants and adults with impaired mental status.

The latter most often occurs in the elderly , who also

appear to have diminished osmotic stimulation of

thirst.

Hospitalized persons, whether old or young, can

become hypernatremic iatrogenically as a result of

inadequate fluid prescription or impaired thirst.

Hypernatremia due to water loss is called

dehydration.

This is different from hypovolemia in

which both salt and water are lost.

UNREPLACED WATER LOSS

The loss of solute-free water will, if unreplaced, lead to an elevation in the plasma sodium concentration.

It is important to recognize that the plasma sodium concentration and plasma tonicity are determined by the ratio between total body solutes and the total body water.

Thus, it is the sum of the sodium and potassium concentrations that determines the effect that loss of a given amount of fluid will have.

Patients with secretory diarrheas (cholera, vipoma) have a sodium plus potassium concentration in the diarrheal fluid that is similar to that in the plasma.

Loss of this fluid will lead to volume and potassium depletion, but will not directly affect the plasma sodium concentration.

In contrast, many viral and bacterial enteritides and the osmotic diarrhea induced by lactulose (to treat hepatic encephalopathy) or charcoal-sorbitol (to treat a drug overdose).

Similar considerations apply to urinary

losses during an osmotic diuresis induced by

glucose, mannitol, or urea.

With these considerations in mind, the

sources of free water loss that can lead to

hypernatremia if intake is not increased

include:

Insensible and Sweat Losses

Insensible water loss from the skin and

respiratory tract by evaporation and sweat

are dilute fluids, the loss of which is

increased by fever, exercise, and

exposure to high temperatures.

Gastrointestinal losses

As mentioned above, some

gastrointestinal losses, particularly

osmotic diarrheas, will promote the

development of hypernatremia because

the sodium plus potassium concentration

is less than that in the plasma.

Central or Nephrogenic DiabetesInsipidus Decreased release of ADH or renal resistance to

its effect cause the excretion of a relatively dilute

urine.

Most of these patients have a normal thirst

mechanism . As a result, they typically present

with polyuria and polydipsia.

However, marked and symptomatic

hypernatremia can occur if a central lesion

impairs both ADH release and thirst.

Osmotic Diuresis An osmotic diuresis due to glucose, mannitol, or urea causes an increase in urine output in which the sodium plus potassium concentration is well below that in the plasma because of the presence of the nonreabsorbed organic solute.

Patients with diabetic ketoacidosis or nonketotic hyperglycemia typically present with marked hypertonicity, although the plasma Na concentration may not be elevated due to hyperglycemia-induced water movement out of the cells.

Hypothalamic Lesions Affecting Thirst or Osmoreceptor Function

Hypernatremia can also occur in the absence of

increased water losses if there is primary

hypothalamic disease impairing thirst (hypodipsia).

Two different mechanisms have been described,

which in adults, are most often due to tumors,

granulomatous diseases (eg, sarcoidosis), or

vascular disease.

SODIUM OVERLOAD

Acute and often marked hypernatremia (in which the plasma sodium concentration can exceed 175 to 200 meq/L) can also be induced by the administration of hypertonic sodium-containing solutions.

Examples include accidental or nonaccidental salt poisoning in infants and young children, the infusion of hypertonic sodium bicarbonate to treat metabolic acidosis, hypertonic saline irrigation of hydatid cysts.

The hypernatremia in this setting will correct

spontaneously if renal function is normal, since

the excess sodium will be rapidly excreted in the

urine.

Too rapid correction should be avoided if the

patient is asymptomatic; these patients, however,

are less likely to develop cerebral edema during

correction, since the hypernatremia is generally

very acute with little time for cerebral adaptation.

: هیپرناترمی علل سدیم اولیه دریافت: اب دفع

: کلیوی خارج• - – : سوختگی تب تعریق پوستمکانیکی : • تهویه تنفس

: کلیوی اسموتیک • دیورزدارویی • دیورز• DI

Even with optimal therapy, the mortality rate is

extremely high in adults with a plasma sodium

concentration that has acutely risen to above

180 meq/L.

For reasons that are not well understood,

severe hypernatremia is often better tolerated

in young children.

Diagnosis of Hypernatremia Hypernatremia represents a relative deficit of

water in relation to solute.

Although it can be induced by the administration

of Na in excess of water (as with hypertonic

sodium bicarbonate during a cardiac arrest), a

high plasma Na concentration most often results

from free water loss.

DIAGNOSIS The cause of the hypernatremia is usually evident from the history.

If, however, the etiology is unclear, the correct diagnosis can usually be established by evaluation of the integrity of ADH-renal axis via measurement of the urine osmolality.

A rise in the plasma sodium concentration is a potent stimulus to ADH release as well as to thirst; furthermore, a plasma osmolality above 295 mosmol/kg (which represents a plasma sodium concentration above 145 to 147 meq/L) generally leads to sufficient ADH secretion to maximally stimulate urinary concentration.

Thus, if both hypothalamic and renal function are

intact, the urine osmolality in the presence of

hypernatremia will be above 700 to 800 mosmol/kg.

In this setting:

– unreplaced insensible or

– gastrointestinal losses,

– sodium overload, or

– rarely a primary defect in thirst

is likely to be responsible for the

hypernatremia.

Measurement of the urine sodium

concentration may help to distinguish

between these disorders.

it should be less than 25 meq/L when water

loss and volume depletion are the primary

problems, but is typically well above 100

meq/L following the ingestion or infusion or a

hypertonic sodium solution.

The urine osmolality is lower than that of the plasma, then either central (ADH-deficient) or nephrogenic (ADH-resistant) diabetes insipidus is present.

These conditions can be distinguished simply by administering exogenous ADH.

The urine osmolality will rise, usually by 50 percent or more, in central DI but will have little or no effect in nephrogenic DI.

The history is also often helpful in this setting, since severe nephrogenic DI in adults is uncommon in the absence of chronic lithium use or hypercalcemia.

ECFحجم

افزایش نیافته افزایشیافته

تجویز – غلیظ حجم کم ادرارNACL یاNAHCO3

نه بله < ادرار اسموالریته کلیوی خارج 750دفع

نه بلهبه پاسخ اسموتیک DDAVPدیورز

افزایش اسموالریته تغییر عدماسموالریته

NDI CDI

درمان: اب تجویز دسموپرسین نمک کم غذای تیازید کم دوز کلرپروپامید کلوفیبرات کاربامازپین NSAIDs

Treatment of DIAVP, Aqueous vasopressin (Pitressin)

Only parenteral form, 5-10 U SC q2-4hLasts 2-6hCan cause HTN, coronary vasospasm

Chlorpropamide (OHA which stimulates AVP secretion)

100-500 mg po OD-bidOnly useful for partial DI, can cause hypoglycemia

HTCZ (induces volume contraction which diminishes free water excretion)

50-100 mg OD-bidMainstay of Rx for chronic NDI

Amiloride (blunts Lithium uptake in distal tubules & collecting ducts)5-20 mg po OD-bidDrug of choice for Lithium induced DI

Indomethacin 100-150 mg po bid-tid (PGs antagonize AVP action)

Clofibrate 500 mg po qid (augments AVP release in partial CDI)

Clinical Manifestations of Hypernatremia

The rise in the plasma sodium concentration and

osmolality causes acute water movement out of

the brain; this decrease in brain volume can

cause rupture of the cerebral veins, leading to

focal intracerebral and subarachnoid

hemorrhages and possible irreversible

neurologic damage.

The clinical manifestations of this disorder

begin with lethargy, weakness, and

irritability, and can progress to twitching,

seizures, and coma.

Values above 180 meq/L are associated

with a high mortality rate, particularly in

adults.

Correction of chronic hypernatremia must occur

slowly to prevent rapid fluid movement into the

brain and cerebral edema, changes that can lead

to seizures and coma.

Although the brain cells can rapidly lose potassium

and sodium in response to this cell swelling, the

loss of accumulated osmolytes occurs more slowly,

a phenomenon that acts to hold water within the

cells.

The delayed clearance of osmolytes from

the cell can predispose to cerebral edema if

the plasma sodium concentration is lowered

too rapidly.

As a result, the rate of correction in

asymptomatic patients should not exceed 12

meq/L per day, which represents an average

of 0.5 meq/L per hour.

free-water deficit=

0.4(0.5) x w x{ (Na p – 140) ÷ 140}

50-kg woman with a plasma Na+ concentration

of 160 mmol/L has an estimated free-water

deficit of 2.9 L {[(160 – 140) ÷ 140] x (0.4 x 50)}

160-140= 20

20 x 0.5 = 40 h

2900 ÷ 40= 73

پتاسیم

پتاسیم :تعادلپالسمایی : 5تا 3/5غلظت

سلولی : داخل 150غلظتNa-K-ATPaseپمپ

: پتاسیم روز 120تا40دریافت در مول میلی: پتاسیم ای روده %60-50تا10دفع

: پتاسیم کلیوی دفعمی 90% بازجذب هنله و پروگزیمال لوله توسط

شود.و دیستال لوله در ترشح در CCDتنظیم

principal cell : و الدسترون کنترل تحت استدیستال جریان میزان و پتاسیم

سدیم : افزایشجذب الدسترون اثراتپمپ Na –K-ATPaseتحریک

لومینال پتاسیم افزایشکانالهای

هیپوکالمی

Causes of Hypokalemia

Hypokalemia is a common clinical problem.

Potassium enters the body largely stored in the

cells, and then excreted in the urine.

Decreased intake, increased translocation into

the cells, or, most often, increased losses in the

urine (or gastrointestinal tract or sweat) all can

lead to potassium depletion.

کاهشدریافت :-داری روزهخوری خاک

DECREASED POTASSIUM INTAKE

The normal range of potassium intake is 40 to

120 meq per day, most of which is then excreted

in the urine.

The kidney is able to lower potassium excretion

to a minimum of 5 to 25 meq per day in the

presence of potassium depletion.

INCREASED ENTRY INTO CELLS

The normal distribution of potassium between the cells (which contains approximately 98 percent of exchangeable potassium) and the extra cellular fluid is maintained by the Na-K-ATPase pump in the cell membrane.

In some cases, however, there is increased potassium entry into cells, resulting in transient hypokalemia.

 

Elevation in Extracellular pHEither metabolic or respiratory alkalosis can promote potassium entry into cells.

Hydrogen ions leave the cells to minimize the change in extracellular pH; the necessity to maintain electro neutrality then requires the entry of some K (and Na) into the cells.

This direct effect is relatively small, as the plasma potassium concentration falls less then 0.4 meq/L for every 0.1-unit rise in pH .  

 

Increased Availability of Insulin

Insulin promotes the entry of K into skeletal

muscle and hepatic cells, apparently by

increasing the activity of the Na-K-ATPase

pump.

 

The plasma potassium concentration can also

be reduced by a carbohydrate load.  

 

Elevated Adrenergic Activity

Catecholamines, acting via the B-adrenergic receptors , can promote potassium entry into the cells, primarily by increasing Na-K-ATPase activity.

As a result, transient hypokalemia can be caused in any setting in which there is stress-induced release of epinephrine, as with acute illness, coronary ischemia, or theophylline intoxication.  

lower Gastrointestinal Losses

Hypokalemia is most common when the

losses occur over a prolonged period as

with a villous adenoma or a vasoactive

intestinal peptide secreting tumor

(VIPoma).

INCREASED URINARY LOSSESUrinary potassium excretion is mostly derived from potassium secretion in the distal nephron, particularly by the principal cells in the cortical collecting tubule.

This process is primarily influenced by two factors: aldosterone and the distal delivery of sodium and water.  

Thus, urinary potassium wasting generally requires increases in either aldosterone or distal flow, while the other parameter is at least normal or increased.

Diuretics

Any diuretic that acts proximal to the potassium secretory site – acetazolamide, loop diuretics, and thiazide-type diuretics – will both increase distal delivery and, via the induction of volume depletion, activate the renin-angiotensin-aldosterone system.

As a result, urinary potassium excretion will increase, leading to hypokalemia if these losses are greater than intake.

Primary Mineralocorticoid Excess

Urinary potassium wasting is also

characteristic of any condition associated with

primary hypersecretion of a mineralocorticoid,

as with an aldosterone-producing adrenal

adenoma.

These patients are almost always hypertensive.

Loss of Gastric Secretions

This problem is usually suggested from the

history.

If, however, the history is not helpful, the

differential diagnosis of a normotensive

patient with hypokalemia, urinary potassium

wasting, and metabolic alkalosis includes:

surreptitious vomiting or diuretic use and

Bartter's. syndrome.  

Hypokalemic Periodic Paralysis

Is a rare disorder of uncertain cause characterized

by potentially fatal episodes of muscle weakness

or paralysis which can affect the respiratory

muscles .

Acute attacks, in which the sudden movement of

potassium into the cells can lower the plasma

potassium concentration to as low as 1.5 to 2.5

meq/L.

 

Hypokalemic Periodic Paralysis

The recurrent attacks with normal plasma

potassium levels between attacks distinguish

periodic paralysis.

Hypokalemic periodic paralysis are often

precipitated by rest after exercise, stress, or a

carbohydrate meal, events that are often

associated with increased release of epinephrine

or insulin.

Hypokalemic Periodic Paralysis

The hypokalemia is often accompanied by

hypophosphatemia and hypomagnesemia.

May be familial with autosomal dominant

inheritance (in which the penetrance may be

only partial) or may be acquired in patients

with thyrotoxicosis.

The oral administration of 60 to 120 meq of potassium chloride usually aborts acute attacks of hypokalemic periodic paralysis within 15 to 20 minutes.

Another 60 meq can be given if no improvement is noted.

However, the presence of hypokalemia must

be confirmed prior to therapy, since potassium

can worsen episodes due to the normokalemic

or hyperkalemic forms of periodic paralysis.

Prevention of hypokalemic episodes consists of the restoration of euthyroidism in thyrotoxic patients and the administration of a B blocker in either familial or thyrotoxic periodic paralysis.

B blockers can minimize the number and severity of attacks.

A nonselective B blocker (such as propranolol)

should be given; B1-selective agents are less

likely to inhibit the B2 receptor-mediated

hypokalemic effect of epinephrine.

Other modalities that may be effective for

prevention include:

K+ supplementation,

K+-sparing diuretics,

a low-carbohydrate diet,

and the carbonic anhydrase inhibitor.

(Acetazolamide)

Marked Increase in Blood Cell Production

An acute increase in hematopoietic cell production

is associated with potassium uptake by the new

cells and possible hypokalemia.

This most often occurs after the administration of

vitamin B12 or folic acid to treat a megaloblastic

anemia or of granulocyte-macrophage colony-

stimulating factor (GM-CSF) to treat neutropenia .

Metabolically active cells can also take up

potassium after blood has been drawn. This has

been described in patients with acute myeloid

leukemia.

In this setting, the measured plasma potassium concentration may be below 1 meq/L (without symptoms) if the blood is allowed to stand at room temperature.

This can be prevented by rapid separation of the plasma from the cells or storage of the blood at 4°C

Hypothermia

Accidental or induced hypothermia can

drive potassium into the cells and lower

the plasma potassium concentration to

below 3.0 to 3.5 meq/L.

 

Hypomagnesemia

Hypomagnesemia is present in up to 40 percent of patients with hypokalemia.

In many cases, as with diuretic therapy, vomiting, or diarrhea, there are concurrent potassium and magnesium losses.

In addition, hypomagnesemia of any cause can lead to increased urinary potassium losses via an uncertain mechanism.  

HypomagnesemiaDocumenting the presence of hypomagnesemia is particularly important because the hypokalemia often cannot be corrected until the magnesium deficit is repaired.

The concurrent presence of hypocalcemia (due both to decreased release of parathyroid hormone and resistance to its calcemic effect) is often a clue to underlying magnesium depletion.

Polyuria Normal subjects can, in the presence of the potassium depletion, lower the urine potassium concentration to a minimum of 5 to 10 meq/L.

If, however, the urine output is over 5 to 10 L/day, then obligatory potassium losses can exceed 50 to 100 meq per day.

This problem is most likely to occur in primary (often psychogenic) polydipsia.

-: بالینی خصوصیاتتحتانی- – – - 1 اندام عضالت ضعف ای ماهیچه درد پذیری خستگی

تنفسی عضالت ضعفکامل- 2 فلجرابدومیولیز-3ایلئوس- 4:EKGتغییرات- 5

موج شدن معکوس یا شدن Tصاف موجU قطعه STافت شدن QUطوالنی فاصله شدن PRطوالنی شدن QRSپهن

بطنی- 6 اریتمی خطر افزایشدیگوکسین- 7 با مسمومیت افزایشمتابولیک- 8 الکالوز9-DI

10-GTTمختل

Diagnosis of Hypokalemia

Hypokalemia is a common clinical problem, the

cause of which can usually be determined from

the history (as with diuretic use, vomiting, or

diarrhea).

Measurement of the blood pressure and urinary

potassium excretion and assessment of acid-base

balance are often helpful.

URINARY RESPONSEA normal subject can, in the presence of potassium depletion, lower urinary potassium excretion below 25 to 30 meq per day.

Random measurement of the urine potassium concentration can also be used, but may be less accurate than a 24-hour collection.

It is likely that extrarenal losses are present if the urine potassium concentration is less than 15 meq/L (unless the patient is markedly polyuric). Higher values, however, do not necessarily indicated potassium wasting if the urine volume is reduced.

DIAGNOSIS  

Metabolic acidosis with a low rate of potassium excretion is, in an asymptomatic patient, suggestive of lower gastrointestinal losses due to laxative abuse or a villous adenoma

Metabolic acidosis with potassium wasting is most often due to diabetic ketoacidosis or to type 1 (distal) or type 2 (proximal) renal tubular acidosis.

Metabolic alkalosis with a low rate of

potassium excretion is due to surreptitious

vomiting (often in bulimia in an attempt to

lose weight) or diuretic use (in which the

urinary collection is obtained after the diuretic

effect has worn off).

Metabolic alkalosis with potassium wasting and

a normal blood pressure is most often due to

surreptitious vomiting or diuretic use or to

Bartter's syndrome.

In this setting, measurement of the urine

chloride concentration is often helpful, being

low in vomiting.

Metabolic alkalosis with potassium wasting and

hypertension is suggestive of :

– surreptitious diuretic therapy in a patient with

underlying hypertension,

– renovascular disease,

– or one of the causes of primary

mineralocorticoid excess.

:درمان

پتاسیم کمبود اصالح

پتاسیم کلرید

پتاسیم سیترات

هیپرکالمی

> پتاسیم: 5تعریفپسودوهیپرکالمی

: علل کلیه- 1 نارساییدیستال- 2 جریان کاهشپتاسیم- 3 ترشح کاهش

- سدیم بازجذب در اختالل الف – : کمبود ادرنال نارسایی اولیه هیپوالدوسترونیسم

ادرنال انزیمهای - داروها : هیپورنینمی ثانویه هیپوالدرونیسم – : کاذب هیپوالدرونیسم الدرونیسم به مقاومت

داروها – اینتراستیشیال توبولو بیماریکلر- 4 یون بازجذب افزایش

گوردون سندرم سیکلوسپورین

Causes of Hyperkalemia

The plasma potassium concentration is

determined by the relationship between

potassium intake, the distribution of potassium

between the cells and the extracellular fluid, and

urinary potassium excretion.

In normal subjects, dietary potassium is largely

excreted in the urine.

The degree of potassium secretion is primarily

stimulated by three factors:

– an increase in the plasma potassium

concentration;

– a rise in the plasma aldosterone concentration;

– enhanced delivery of sodium and water to the

distal secretory site.

Ingestion of a K load leads initially to the

uptake of most of the excess K by the cells, a

process that is facilitated by insulin and the B2-

adrenergic receptors, both of which increase the

activity of the Na-K-ATPase pump in the cell

membrane.

This is then followed by the excretion of the

excess K in the urine within six to eight hours .

POTASSIUM ADAPTATION

Hyperkalemia is a rare occurrence in normal

subjects, because the cellular and urinary

adaptations prevent significant potassium

accumulation in the extracellular fluid.

This phenomenon, called potassium adaptation, is mostly due to more rapid potassium excretion in the urine.

INCREASED POTASSIUM RELEASE FROM CELLS

Pseudohyperkalemia

Refers to those conditions in which the

elevation in the measured plasma potassium

concentration is due to potassium movement

out of the cells during of after the blood

specimen has been drawn.

 

PseudohyperkalemiaThe major cause of this problem is mechanical

trauma during venipuncture, resulting in the

release of potassium from red cells .

It can also occur in hereditary spherocytosis and in

familial pseudohyperkalemia in which there is

increased temperature-dependent leakage of

potassium out of red blood cells after the specimen

is collected.

Pseudohyperkalemia

Potassium also moves out of white cells and platelets after clotting has occurred. Thus, the serum potassium concentration normally exceeds the true value in the plasma by 0.1 to as much as 0.5 meq/L.

Although this difference in normals is not clinically important, the measured serum potassium concentration may be as high as 9 meq/L in patients with marked leukocytosis or thrombocytosis.

Metabolic Acidosis

The buffering of excess hydrogen ions in the

cells can lead to potassium movement into the

extracellular fluid; this transcellular shift is

obligated in part by the need to maintain

electroneutrality.

Insulin deficiency, Hyperglycemia, and Hyperosmolality

The combination of insulin deficiency and the hyperosmolality induced by hyperglycemia frequently leads to hyperkalemia in uncontrolled diabetes mellitus, even though the patient may be markedly potassium depleted due primarily to potassium losses in the urine.

 An elevation in plasma osmolality results in osmotic water movement from the cells into the extracellular fluid. This is accompanied by potassium movement out of the cells.

Increased Tissue Catabolism

Any cause of increase tissue breakdown result

in the release of potassium into the extracellular

fluid.

Clinical examples include trauma, the

administration of cytotoxic or radiation therapy

to patients with lymphoma or leukemia.  

Beta-adrenergic Blockade

Nonselective B-adrenergic blockers interfere with

the B2-adrenergic facilitation of K uptake by the

cells.

This effect is associated with only a minor

elevation in the plasma potassium concentration

in normal subjects (less than 0.5 meq/L), since the

excess potassium can be easily excreted in the

urine.

Exercise

K is normally released from muscle cells during exercise. This response may be mediated by two factors:A delay between potassium exit during

depolarization and subsequent reuptake by the Na-K-ATPase pump.

With severe exercise, an increased number of open K channels in the cell membrane. These channels are inhibited by ATP, an effect that is removed by the exercise-induced decline in ATP levels which.

The release of potassium during exercise may

have a physiologically important role.

The local increase in the plasma potassium

concentration has a vasodilator effect, thereby

increasing blood flow and energy delivery to the

exercising muscle.

The degree of elevation in the systemic plasma potassium concentration is less pronounced and is related to the degree of exercise:

0.3 to 0.4 meq/L with slow walking;

0.7 to 1.2 meq/L with moderate exertion (including prolonged aerobic exercise with marathon running);

and as much as 2 meq/L following exercise to exhaustion.

The rise in the plasma K concentration is reversed

after several minutes of rest, and is typically

associated with a mild rebound hypokalemia

(averaging 0.4 to 0.5 meq/L below the baseline

level) that may be arrhythmogenic in susceptible

subjects.

The degree of K release is attenuated by prior physical conditioning , but may be exacerbated by the administration of nonselective B-blockers and, for uncertain reasons, in patients with CHF. 

 

REDUCED URINARY POTASSIUM EXCRETION

Impaired urinary potassium excretion

generally requires an abnormality in one or

both of the two major factors required for

adequate renal potassium handling:

aldosterone and

distal sodium and water delivery.

 

Hypoaldosteronism Any cause of decreased aldosterone release or effect, such as that induced by hyporeninemic hypoaldosteronism or certain drugs, can diminish the efficiency of K secretion.

Rise in the plasma K concentration directly stimulates K secretion, partially overcoming the relative absence of aldosterone.

The net effect is that the rise in the plasma K concentration is generally small in patients with normal renal function. 

Renal Failure The ability to maintain K excretion at near normal levels is generally maintained in patients with renal disease as long as both aldosterone secretion and distal flow are maintained.

Hyperkalemia generally develops in the patient who is oliguric or who has an additional problem such as a high K diet, increased tissue breakdown, hypoaldosteronism, or fasting in dialysis patients (which may both lower insulin levels and cause resistance to B-adrenergic ).

Effective Circulating Volume Depletion

Decreased distal flow due to marked effective

volume depletion (as in heart failure, cirrhosis,

or a salt-wasting nephropathy) can also lead to

hyperkalemia.  

Transtubular Potassium Concentration Gradient

The differential diagnosis of persistent hyperkalemia consists of those disorders in which urinary potassium excretion is impaired.

The three most common causes of this problem are advanced renal failure, marked effective volume depletion (as with severe heart failure), and one of the causes of hypoaldosteronism.

TTKG is dependent upon two assumptions:

1: that the urine osmolality at the end of the cortical collecting tubule is similar to that of the plasma, since equilibration with the isosmotic interstitium will occur in the presence of antidiuretic hormone;

2: little or no potassium secretion or reabsorption takes place in the medullary collecting tubule.

Thus, the TTKG between the tubular fluid

at the end of the cortical collecting tubule

and the plasma can be estimated from:

TTKG = [Urine K ÷ (Urine osmolality

/ Plasma osmolality)] ÷ Plasma K

The TTKG in normal subjects on a regular

diet is 8 to 9, and rises to above 11 with a

potassium load, indicating increased

potassium secretion .

Thus, a value below 7 and particularly

below 5 in a hyperkalemic patient is highly

suggestive of hypoaldosteronism .

for example, the urine potassium

concentration is 30 meq/L, the plasma

potassium concentration is 6.5 meq/L, and

the urine and plasma osmolality are 560

mosmol/kg and 280 mosmol/kg,

respectively, then:

TTKG = [30 ÷ (560/280)] ÷ 6.5

= 2.3

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EKGتغییرات T Tall فاصله مدت PRافزایش QRSو – رفتن بین از بطنی دهلیزی هدایت تاخیر

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