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Definition:
- The functional unit of the kidney

Function:
- To form the ultrafiltrate
- To selectively reabsorb tubule fluids or secrete solute into this

Structure:

A nephron consists of a glomerulus and a tubule.

The glomerulus is a cluster of blood vessels from which the plasma filtrate originates.

The tubule is an epithelial structure consisting of many subdivisions, designed to convert the filtrate into urine.

These two entities meet at the blind end of the tubule epithelium, which is called Bowman’s capsule or the glomerular capsule.

This capsule surrounds the glomerulus and contains Bowman’s space, which is contiguous with the lumen of the tubule.

It is here that filtrate passes from the vascular system into the tubule system.

What are the 2 types of nephrons?
- Superficial: short loops extending between inner and outer medulla
-Juxtamedullary: play a special role in the production of concentrated urine, have long loops that extend as far as the tip of the medulla.

What is the function of the renal tubules?
- The main function of renal tubules is to recover most of the fluid and solutes filtered at the glomerulus

- Proximal tubule: reabsorbs water & solutes:  NaCl, NaHCO3, filtered nutrients, divalent ions

What is the function of the Loop of Henle?
- Forms a concentrated or diluted urine
- Does this by pumping NaCl into the interstitium of the medulla

What is the function of the distal tubule & collecting duct system?
- perform the fine control of NaCl and water excretion

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Effect of changes in resistance on GFR (Vander)

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Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids.

Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function.

= a high glomerular filtration rate is essential for maintaining stable and optimal extracellular levels of solutes and water

Structure/components of glomerulus:
- Basement membrane
- have mechanisms that keep molecules by charge
- repels charged particles by having a charge of its own, so we can keep things like proteins
- if this becomes to thick we will not have proper diffusion
- if there is damage to the integrity of the membrane we lose molecules we want to keep (proteins, maybe even blood)

- Podocytes -> have foot processes (protrusions)
- these protrusions are part of the filtering system
- must then have them be healthy and in shape
- we need to filter what we don't want, but keep the  rest i.e. cellular components (this is why erythrocytes in urine is a sign of malfunction)

- Slit diaphragm:

-

Pay attention to these small but important structures!

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Measurements:
- in NL they use mmol
- mmol vs mEq: mmol refers directly to amount of mol (per Liter), while mEq depends on charge of ions; at charge of 1, 1 mmol = 1 mEq
-> sodium and potassium have basically the same mmol and mEq

→ sodium:

→ potassium:

→ chloride:

→ bicarbonate:

→ calcium:

→ magnesium:

→ phosphate:

→ (BUN, urine osmolality, urine sodium concentration):

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How do the respiratory system and the kidneys work together to maintain homeostatic H+ balance?
- Two biggest buffer systems in the body are in lungs and kidneys
- Respiratory based on CO2, metabolic based on bicarbonate
- compensate for one another (acidosis in one is decreased by the other)
- Keep the blood pH in a narrow range -> deviations above are alkalaemia, below: acidaemia

Balancing:
*During hypoventilation = additional net gain of H+ = kidneys increase H+ elimination to restore balance

*During hyperventilation/vomiting = Net loss of H+ = kidneys replenish H+ to restore balance

*Increased arterial H+ concentration = stimulates ventilation = lowers arterial PCO2 that = reduces H+ concentration

*Decreased plasma H+ concentration = inhibits ventilation =  increasing arterial PCO2 = increases the H+ concentration

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Diagnosis:

What is the anion gap?

The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum.

→ How do we calculate it
The anion gap = (Na+ + K+) - (Cl- + HCO3-)

→ The anion gap can be normal, high, or low. A high anion gap indicated metabolic acidosis, the increased acidity of the blood due to metabolic processes.

→ A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma.

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Acid-base nomogram. Shown are the 90% confidence limits (range of values) of the normal respiratory and metabolic compensations for primary acid-base disorders.

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General definitions:

What are the two distinct categories?

→ Respiratory acidosis or alkalosis:

→ Metabolic acidosis or alkalosis:

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What is respiratory acidosis?

-> Disorder that affects respiration
-> can cause changes in pH and pCO2

What are the causes of respiratory acidosis? (use table in article)
-> Often caused by various lung diseases
-> Anything that can cause hypoventilation

What are the Clinical Findings (signs & symptoms) of respiratory acidosis?
→ The characteristic features of hypercapnia and the resultant respiratory acidosis range from fatigue, irritability, headache, confusion, stupor, and obtundation to coma and are dependent on the severity and chronicity of the hypercapnia.

→ A Pco2 of 70 may result in coma when secondary to an acute respiratory acidosis, while a person with chronic respiratory acidosis may tolerate Pco2 levels higher than this without a decrease in mental status.

What is the Physiology of respiratory acidosis (acute & chronic)?

1. Acute Respiratory Acidosis

→ The increased protons resulting from an acute respiratory acidosis are buffered by intracellular proteins.

→ This results in a rise in [HCO3−] of 1 mEq/L for every 10 mm Hg increase in Pco2 up to a maximum [HCO3−] of 30 mEq/L and a decrease in pH of 0.08.

→ This compensation is complete within minutes and further compensation is limited until renal excretion of acid occurs, which may take several days.

2. Chronic Respiratory Acidosis

→ Chronic respiratory acidosis commonly results from chronic obstructive pulmonary disease (COPD) and extreme obesity.

→ Renal compensation reaches a steady state after 3–4 days and involves the excretion of chloride in addition to acid, with retention of bicarbonate.

→ An increase in the Pco2 of 10 mm Hg is expected to result in an increase in [HCO3−] of 3.5 mEq/L (to a maximum of 45 mEq/L) and a decrease in pH of 0.03.

What is the treatment for respiratory acidosis?
-> primary: identify and treat underlying pathology
-> support of ventilation

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Anion gap in metabolic acidosis (Current)

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What is metabolic acidosis?

Defined as a decrease in [HCO3−] to below 22 with a decrease in pH below 7.36.

What are the causes of metabolic acidosis?
-> overproduction of organic acids
-> loss of bicarbonate through intestinal or renal wasting
-> inability to excrete acids from normal metabolism
-> toxin ingestion

What are the clinical findings of metabolic acidosis?
-> Cardiovascular dysfunctions
-> Neurologic dysfunctions
-> Respiratory dysfunctions
-> largely dependent on underlying cause

What is the physiology of metabolic acidosis?

What is the treatment for metabolic acidosis?

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Diagnosis of metabolic alkalosis (Current)

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What is metabolic alkalosis?

primary elevation of serum [HCO3−] above 28 mEq/L with an elevation in pH above 7.44

What are the causes of metabolic alkalosis?
-> excess loss of acid
-> (very rarely) gaining base
-> gastric losses via vomiting, diuretic use

What are the clinical findings of metabolic acidosis?

Metabolic alkalosis produces hypokalemia, hypocalcemia, and hypomagnesemia.

With severe alkalosis, signs of hypocalcemia may predominate.

Decreased cerebral blood flow may result in altered mental status, ultimately progressing to coma and seizures.

What is the physiology of metabolic alkalosis?

Respiratory compensation for a metabolic alkalosis consists of hypoventilation.

For every increase of 1 mEq/L in the [HCO3−], Pco2 will rise by 0.7 mm Hg and pH increase by 0.015.

The hypoxemic respiratory drive typically prevents hypercapnea above 55 mm Hg from hypoventilation.

What is the treatment for metabolic alkalosis?
-> primarily guided by concentration of chlorine in the urine

Patients with a urine [Cl−] below 10 mEq/L are characterized as chloride responsive and should be treated with volume expansion using normal saline.

-> Potassium replacement (up to 100–500 mEq) may be needed to correct the alkalosis in certain settings.

-> Acetazolamide may be used in posthypercapnic metabolic alkalosis if volume status is normal.

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How do we diagnose electrolyte disorders?

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How do we diagnose electrolyte disorders?

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Assessment for electrolyte and fluid disorders

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Assessment for electrolyte and fluid disorders

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What does the optimal evaluation and treatment of these disorders require?
- Interpretation of serum and urine chemistry in combination with looking at history and physical examination

How is body water and fluid distributed within the body?
- depends on the proportions of muscle and fat in body, age, height, etc
- total body water ~ 60% in men, 50% in women
-> decreases with age
-> 2/3rds in intracellular, 1/3rd in extracellular (28% is interstitial, 7% is plasma fluid)

How do we evaluate changes in total body water content?

→ Changes in total body water content are best evaluated by documenting changes in body weight.

→ Extracellular volume (ECV) may be assessed by physical examination (eg, blood pressure, pulse, jugular venous distention, edema).

→ Quantitative assessments of ECV and intravascular volume may be invasive (ie, central venous pressure or pulmonary wedge pressure) or noninvasive (ie, inferior vena cava diameter and right atrial pressure by echocardiography).

→ Intracellular volume (ICV) is assessed using the serum sodium concentration.

What is the importance of determining the urine concentration of an electrolyte?
→ The urine concentration of an electrolyte is helpful to determine whether the kidney is excreting or retaining the electrolyte in response to high or low serum levels.

Serum Osmolality:

→ units: osmolality = mmol/kg, osmolarity = mmol/L

→ What is plasma osmolality: number of solute particles per Litre of solvent

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What are the four types of electrolyte disorders?
Hyponatremia is commonly defined as a serum sodium concentration <135 mEq/L (135 mmol/L)

Hypernatremia is commonly defined as a serum sodium >145 mEq/L (145 mmol/L)

Hypokalemia is typically defined as a serum potassium concentration of <3.5 mEq/L

Hyperkalemia is typically defined as a serum potassium concentration >5.0 mEq/L

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What is hypernatremia?

Older adults have a decreased ability to concentrate urine and a reduced sensation of thirst, which, if combined with limited access to fluids, may predispose older adults to water depletion and hypernatremia.

Hypernatremia is commonly defined as a serum sodium >145 mEq/L (145 mmol/L).

What are the causes of hypernatremia?

1. Insufficient intake

Many older adults have impaired thirst or hypodipsia

Cognitive impairment and delirium especially in the hospital setting present barriers to adequate hydration.

2. Loss of Water

The loss of water is seen with increased insensible losses (eg, from fever) and in diabetes insipidus (DI).

→ DI is a syndrome characterized by hypotonic polyuria from either inadequate ADH secretion (central DI) or inadequate renal response to ADH (nephrogenic DI).

→ Nephrogenic DI can be induced by medications such as lithium and cisplatin.

→ Patients with DI usually compensate by increasing their fluid intake; thus, when they have adequate access to water, most patients maintain normal sodium concentrations
→ Hypernatremia develops when they have limited access to water or have an inadequate intake.

3. Water Deficiency in Excess of Salt Deficiency

Water deficiency in excess of a salt deficiency can be caused by gastrointestinal losses, such as vomiting and diarrhea; or renal losses, such as osmotic diuresis secondary to hyperglycemia, solute load with parenteral nutrition, or tube feeding.

Diuretics can lead to excess renal loss as well.

Skin losses can occur from burns and severe dermatitis.

4. Salt Excess

Salt excess is usually iatrogenic, for example, from the administration of excess saline or sodium bicarbonate.

What are the clinical findings of hypernatremia?

Symptoms of hypernatremia include confusion, restlessness, hyperreflexia, progressive obtundation, coma, and, in severe cases, death.

What is the treatment for hypernatremia?
= The main goal of treatment is to administer dilute fluids to replace the water deficit and to limit further water loss.

→ Replacement should be with hypotonic fluids (0.5% normal saline or 5% dextrose water), with oral route preferable to IV if feasible.
-> be careful with this replacement; can lead to oedema

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Who is most susceptible?
-> older adults due to underlying structural and functional changes in the kidneys

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What is Hypokalemia?
Hypokalemia is typically defined as a serum potassium concentration of <3.5 mEq/L.

What are the causes of Hypokalemia?

Hypokalemia is usually a result of depletion of serum potassium from extrarenal losses, intrarenal losses, or iatrogenic causes.

1. Extrarenal Losses

-> Extrarenal losses of potassium occur in the GI tract.

→ Chronic diarrhea can cause a loss of serum potassium due to an increase in stool volume.

→ Among older adults, diarrhea is associated with many commonly prescribed medications, including antibiotics

2. Intrarenal Losses

Intrarenal losses of potassium occur as a result of conditions that directly affect the kidney.

3. Iatrogenic Causes

The most common cause of hypokalemia among older adults is medications.

→ Thiazide and loop diuretics are commonly prescribed to older adults for the management of blood pressure, congestive heart failure, and edema.

What are the clinical findings of hypokalemia?

Although mild hypokalemia is generally asymptomatic, more severe hypokalemia (<3 mEq/L) can result in neuromuscular weakness, including paralysis and respiratory muscle dysfunction, rhabdomyolysis, GI disruption including constipation and ileus, and cardiac dysregulation evidenced by electrocardiogram (ECG) changes (eg, increase in amplitude of U wave, prolongation of QT interval) and cardiac arrhythmias (eg, premature atrial and ventricular beats).

What is the treatment for hypokalemia?

Treatment of hypokalemia involves the replacement of potassium.

-> careful of excessive administration of potassium as this may lead to hyperkalemia

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Diagnostic approach to hyperkalemia (Harrison's)

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What is Hyperkalemia?
Hyperkalemia is typically defined as a serum potassium concentration >5 mEq/L.

What are the causes of Hyperkalemia?

- Decreased intravascular volume i.e. due to dehydration secondary to hypodipsia
- Increased potassium consumption
- Medication-induced
- Kidney disease; potassium excretion is proportional to glomerular filtration rate (GFR).

What are the clinical findings of hyperkalemia?

The clinical consequences of hyperkalemia generally occur at severe elevations of serum potassium (>6.5 mEq/L) in chronic hyperkalemia or a lower level in acute potassium rise.

The clinical manifestations involve neuromuscular signs including weakness, ascending paralysis, respiratory failure, and muscle cramping in addition to cardiac abnormalities including chest pain and progressive ECG changes (peaked T waves → flattened P waves → prolonged PR interval → idioventricular rhythm → widened QRS with deep S waves → ventricular fibrillation → cardiac arrest).

What is the treatment for hyperkalemia? (Acute & Chronic)
Acute:
- Calcium infusion
- Insulin with glucose
- B2-adrenergic agonists
- Sodium bicarbonate

Potassium removal:
- Loop or thiazide diuretics
- Cation exchange resins
- Dialysis

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Water concentration:

→ Four factors that modulate renal blood flow and glomerular filtration:

1. The renin angiotensin-aldosterone axis (RAAS)

1. regulates BP and fluid balance

2. Renin -> Angiotensinogen -> Angiotensin I -> Angiotensin II (by way of ACE) -> Vasoconstriction & Aldosterone secretion

3. The renal juxtaglomerular apparatus (JGA) is a vital part of the kidneys involved in RAAS due to its release of renin

2. The sympathetic nervous system

1. Sympathetic tone to the kidney may increase either as part of a general response

2. sympathetic nerve terminals release norepinephrine into the interstitial space.

3. AVP

1.  principal effect of this small polypeptide is to increase water absorption in the collecting duct

2. AVP also increases vascular resistance.

4. Atrial natriuretic peptide (ANP).

1. Able to inhibit secretion of renin

2. Regulates blood pressure

3. Acts as a vasodilator

Inorganic ion balance (electrolytes):

The kidneys regulate the salt balance in the blood by controlling the excretion and the reabsorption of various ions.

Acid-base balance:

The kidneys have the predominant role in regulation the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance

→ This function of the kidneys has two components:

1. reabsorption of virtually all of the filtered HCO3−

2. production of new bicarbonate to replace that consumed by normal or pathologic acids.

Normal arterial pH is between 7.36 and 7.44; intracellular is ~7.2

--> Where does this regulation happen?

Removal of metabolic waste products:
Kidneys excrete toxins and waste products into the urine as fast as they are produced
- keeps products from accumulating
- waste products include urea, uric acid, creatinine

Removal of foreign chemicals:

Gluconeogenesis:
→ During prolonged fasting, the kidneys synthesize glucose from amino acids and other precursors and release it into the blood

→ gluconeogenesis occurs in the cells of the proximal tubule

Hormone production:
the kidneys act as endocrine glands, releasing at least two hormones: erythropoietin, and 1,25-dihydroxyvitamin D

→ The kidneys also secrete an enzyme, renin, that is important in the control of blood pressure and sodium balance

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The serum sodium concentration is the primary determinant of serum tonicity (also known as "effective serum osmolality") (see "Diagnostic evaluation of adults with hyponatremia"). The fall in serum tonicity in patients with hypotonic hyponatremia promotes water movement into the brain and, if the hyponatremia is acute and severe, can lead to cerebral edema and neurologic symptoms. In response to hyponatremia, the brain makes adaptations that lower the cerebral volume toward normal and reduce the likelihood of these complications. The mechanisms responsible for this cerebral adaptation are discussed elsewhere:

●(See 'Brain adaptation to hyponatremia' below.)

●(See "Manifestations of hyponatremia and hypernatremia in adults", section on 'Osmolytes and cerebral adaptation to hyponatremia'.)

However, brain adaptations that reduce the risk of cerebral edema make the brain vulnerable to injury if chronic hyponatremia is too rapidly corrected. The neurologic manifestations associated with overly rapid correction have been called the osmotic demyelination syndrome (ODS; formerly called central pontine myelinolysis or CPM). As will be described below, almost all patients who develop ODS present with a serum sodium concentration of 120 mEq/L or less.

Issues related to ODS and the approach to the patient with unintentional overly rapid correction of hyponatremia will be reviewed here. A general overview of the treatment of hyponatremia is presented separately. (See "Overview of the treatment of hyponatremia in adults".)

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of UpToDate content is governed by the UpToDate Terms of Use. ©2021 UpToDate, Inc. All rights reserved.

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Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia - UpToDate

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The serum sodium concentration is the primary determinant of serum tonicity (also known as "effective serum osmolality") (see "Diagnostic evaluation of adults with hyponatremia").

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What is hyponatremia?
Hyponatremia is commonly defined as a serum sodium concentration <135 mEq/L (135 mmol/L)

Who is most at risk?

Older adults are more vulnerable to developing sodium disorders as a result of age-related changes in water and sodium metabolism

Older adults may have

→ an impaired ability to excrete water and to dilute urine due to reductions in the number of functioning nephrons and decreased renal blood flow with age, predisposing them to water overload and possible hyponatremia.

Geriatric patients also tend to take multiple medications that are associated with sodium disorders, such as diuretics and psychotropic medications

What are the 3 different types of hyponatremia (& their aetiologies)?

1. Hypervolemic Hyponatremia

In older adults with impaired cardiac, renal, or hepatic function, a common etiology of hyponatremia is excessive water retention.

This type of hyponatremia is commonly described as dilutional or hypervolemic hyponatremia.

→ These patients typically exhibit edematous states, resulting from conditions such as congestive heart failure, cirrhosis, or nephrotic syndrome.

→ These conditions decrease effective circulating blood volume, leading to increased antidiuretic hormone (ADH) secretion, which results in water retention.

→ Dilutional hyponatremia can also be iatrogenic, as a result of administration of excess hypotonic intravenous (IV) fluids, especially in hospitalized patients.

2. Hypovolemic Hyponatremia

= a state in which the total body water and sodium content are decreased and the relative decrease in total body sodium is greater than the decrease in total body water

Salt depletion with or without loss of extracellular fluid can cause depletional or hypovolemic hyponatremia.

→ Hypovolemic hyponatremia can be caused by renal losses (eg, diuretic use) or from extrarenal losses, such as vomiting, diarrhea, laxative abuse, ostomies, or the presence of large burns.

→ A particular etiology to consider in geriatric patients is restricted sodium intake, especially in the setting of tube feedings.

3. Euvolemic Hyponatremia

= Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. This occurs in patients who take in excess hypotonic fluids.

The syndrome of inappropriate secretion of ADH (SIADH) is a disorder in which water excretion is partially impaired due to the inability to suppress the secretion of ADH.

→ Patients with SIADH will generally appear euvolemic.

→ Many diseases that are common in older adults are associated with SIADH such as central nervous system disorders and malignancies

→ Medications are also an important cause of SIADH

→ Other causes of euvolemic hyponatremia include hypothyroidism and adrenal insufficiency.

→ An elevated serum potassium level in conjunction with hyponatremia and hypotension should increase suspicion for adrenal insufficiency.

What are the symptoms & signs of hyponatremia?
→ Symptoms associated with hyponatremia include anorexia, nausea, vomiting, headache, weakness, loss of coordination, muscle cramps, agitation, tremors, disorientation, psychosis, delirium, seizures, and coma
→ Hypovolemic patients may have dry mucous membranes and tachycardia in addition to relative or true orthostatic hypotension.

→ Hypervolemic patients may have increased jugular venous pressures, bibasilar pulmonary rales, ascites, and peripheral edema.

How do we diagnose hyponatremia (lab tests)?
- serum osmolality
- urine osmolality
- urine sodium
→ Hyponatremia secondary to pseudohyponatremia or hyperglycemia will have a normal serum osmolality, whereas all other etiologies will demonstrate a low serum osmolality

→ Urine sodium is useful in differentiating between SIADH and a low effective circulating volume.

→ A urine sodium of <25 mEq/L suggests hypovolemia, and a value of >40 mEq/L suggests SIADH.

How is hyponatremia treated (acute & chronic)?
→ Based on the presence, severity, and acuity of symptoms
→ The goal of hyponatremia treatment even in the absence of symptoms is to reduce associated mortality and morbidity (eg, gait disturbances, falls, and cognitive impairment).

Acute: hypertonic IV saline to rapidly raise serum sodium
-> however if the patient is already able to compensate for this, and we treat too rapidly, we can get complications

Chronic: focus on underlying aetiology,  3% hypertonic saline infusion is treatment of choice in severe cases

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Continuing Education Activity

The human body maintains sodium and water homeostasis by concentrating the urine secondary to the action of antidiuretic hormone (ADH) and increased fluid intake by powerful thirst response. These mechanisms to protect against developing hypernatremia are impaired in certain vulnerable populations and conditions with vasopressin deficiency or unresponsiveness at the renal tubular level. Hypernatremia is defined as a serum sodium concentration of greater than 145 meq/l This activity reviews the causes, presentation and highlights the role of the interprofessional team in its management

Objectives:

Review the causes of hypernatremia.

Describe the evaluation of a patient with hypernatremia.

Summarize the treatment of hypernatremia.

Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by hypernatremia.

Access free multiple choice questions on this topic.
Introduction

Sodium is a dominant cation in extracellular fluid and necessary for the maintenance of intravascular volume. The human body maintains sodium and water homeostasis by concentrating the urine secondary to the action of antidiuretic hormone (ADH) and increased fluid intake by a powerful thirst response. These mechanisms to protect against developing hypernatremia are impaired in certain vulnerable populations, vasopressin deficiency, or unresponsiveness at the renal tubular level. Hypernatremia is defined as a serum sodium concentration of greater than 145 meq/L.[1][2][3][4]

Etiology

The basic mechanisms of hypernatremia are water deficit and excess solute. Total body water loss relative to solute loss is the most common reason for developing hypernatremia. Hypernatremia is usually associated with hypovolemia, which can occur in conditions that cause combined water and solute loss, where water loss is greater than sodium loss, or free water loss. Combined loss can be seen in extra-renal conditions such as gastroenteritis, vomiting, prolonged nasogastric drainage, burns, and excessive sweating. Excessive sweating can occur due to exercise, fever, or high heat exposure. Renal losses can be seen in intrinsic renal disease, post-obstructive diuresis, and with the use of osmotic or loop diuretics. Hyperglycemia and mannitol are common causes of osmotic diuresis. Free water loss is seen with central or nephrogenic diabetes insipidus (DI) and also in conditions with increased insensible loss. Central DI can occur due to inadequate production of ADH. Common causes of central DI are idiopathic, head trauma, cranial neoplasm, and pituitary infiltrative diseases, such as sarcoidosis and histiocytosis. Nephrogenic DI occurs due to tubular unresponsiveness to the action of ADH and can be inherited in an X-linked pattern or secondary to certain medications including lithium, foscarnet, and demeclocycline. Rarely, hypernatremia with inadequate fluid intake can be seen in breastfed babies, child or elder abuse, and patients with an impaired thirst response. Excess sodium usually is iatrogenic and seen in the hospital setting but can be associated with improper formula mixing, excess sodium bicarbonate ingestion, salt tablet poisoning, hyperaldosteronism, and seawater drowning.[5][6][7][8]

Epidemiology

Hypernatremia is primarily seen in infants and the elderly population. Infants receiving inadequate water replacement in the setting of gastroenteritis or ineffective breastfeeding are common scenarios. Premature infants are at higher risk due to their relatively small mass to surface area and their dependency on the caretaker to administer fluids. Patients with neurologic impairment also are at risk due to impaired thirst mechanism and lack of water availability. Hypernatremia can occur in the hospital setting due to hypertonic fluid infusions, especially when combined with the patient's inability for adequate water intake.[9]

Pathophysiology

Sodium is important to maintain extracellular fluid (ECF) volume. Changes in the ECF volume provide feedback to maintain total sodium content by increasing or decreasing sodium excretion in the urine. Sodium excretion also involves regulatory mechanisms such as the renin-angiotensin-aldosterone systems. When serum sodium increases, the plasma osmolality increases which triggers the thirst response and ADH secretion, leading to renal water conservation and concentrated urine.[10]

History and Physical

Most patients present with symptoms suggestive of fluid loss and clinical signs of dehydration. Symptoms and signs of hypernatremia are secondary from central nervous system dysfunction and are seen when serum sodium rises rapidly or is greater than 160 meq/L. Infants and Children present with irritability and agitation, which can progress to lethargy, somnolence, and coma. Other symptoms include increased thirst response in alert patients and high-pitched cry in infants. Patients with diabetes insipidus present with polyuria and polydipsia. The skin can feel doughy or velvety due to intracellular water loss. Orthostatic hypotension and tachycardia are usually present in hypovolemic hypernatremia. The patient may have increased tone with brisk reflexes and myoclonus. It is important to remember that the degree of dehydration can be underestimated in children with hypernatremia due to a shift of water from the intracellular space to the extravascular space. Polyuria is one of the common symptoms of diabetes insipidus. [11][12]

Evaluation

The etiology of hypernatremia usually is evident based on history and physical examination. Plasma volume, plasma osmolality, urine volume, concentrating ability, and osmolality can help to further differentiate between renal and extrarenal causes. In DI, the urine is inappropriately diluted with normal urine volume and urine osmolality less than the serum osmolality. When DI is suspected, a water deprivation test may be performed with the administration of desmopressin. In central DI, desmopressin administration demonstrates an increase in urine osmolality, while in the nephrogenic variety, there is no response to desmopressin. In extrarenal causes, the body tries to conserve fluids with appropriately low urine volume, high specific gravity, and urine osmolality greater than serum osmolality.[13]

Treatment / Management

Proper management of hypernatremia involves identifying the underlying condition and correcting the hypertonicity. The goal of therapy is to correct both the serum sodium and the intravascular volume. Fluids should be administered orally or via a feeding tube whenever possible. In patients with severe dehydration or shock, the initial step is fluid resuscitation with isotonic fluids before free water correction. Hypernatremia is corrected by calculating the free water deficit using one of the following formulas.[14][15]

Total Body Water[0.6 in men and 0.5 in women x body weight(kg)] x [(plasma sodium/140) -1]

4ml x bodyweight x (desired change in serum sodium meq/L)

It is important to remember that rapid correction of hypernatremia can lead to cerebral edema because water moves from the serum into the brain cells. The goal is to decrease serum sodium by not more than 12 meq in 24 hours. Close serial monitoring of serum sodium every 2 to 4 hours is essential during the acute phase of correction. Seizures occurring during correction of hypernatremia is a sign of cerebral edema due to rapid shifts in osmolality, and the administration of hypotonic fluids should be halted. The estimated free water deficit should be corrected over 48 to 72 hours with a decrease in serum sodium not exceeding 0.5 meq per hour. Patients should be carefully monitored for the rate of correction, urine output, and ongoing losses. In cases of sodium intoxication, the free water requirement may be too large and cause volume overload, requiring the use of loop diuretics and, at times, peritoneal dialysis to remove excess sodium. Older children and adults with central DI may need desmopressin, which is available in intranasal and oral forms. Water intoxication and hyponatremia are adverse effects seen with the use of desmopressin.

Differential Diagnosis

Complications

The most serious complication of hypernatremia is subarachnoid or subdural hemorrhage due to the rupture of bridging veins and dural sinus thrombosis. It can lead to permanent brain damage or death. Rapid correction of chronic hypernatremia causes cerebral edema, seizure, and permanent brain damage.[16]

Hypernatremia occurs due to net water loss or excess sodium intake.

It is more common in infants or elderly population with neurological or physical impairment.

It is crucial to identify acute versus chronic onset hypernatremia before correcting the free water deficit.

It is important to remember that hypernatremia should be corrected over 48 hours. Rapid correction can lead to cerebral edema and seizures.

Pearls and Other Issues

Enhancing Healthcare Team Outcomes

Hypernatremia is best managed by an interprofessional team that includes an internist, endocrinologist, emergency department physician, nurse practitioner, and the primary care provider. The key is to identify the cause and correct the hypertonicity. The goal of therapy is to correct both the serum sodium and the intravascular volume. In patients with severe dehydration or shock, the initial step is fluid resuscitation with isotonic fluids before free water correction.

Health care providers should be cognizant of the fact that rapid correction of hypernatremia can lead to cerebral edema because water moves from the serum into the brain cells. The goal is to decrease the serum sodium by not more than 10 to 12 meq/L in 24 hours. The acute phase of sodium correction requires monitoring of serum sodium levels every 2 to 4 hours. Frequent communication between the attending physician, the nursing staff, and the pharmacist is crucial to avoid the rapid correction of sodium level. Rapid correction of sodium level can lead to a seizure, cerebral edema, or permanent neurological deficit. Special attention should be given to high-risk nursing home patients with neurological or physical impairments who are prone to develop recurrent hypernatremia. Discharge care coordination among discharging physician, primary care physician, and nursing home staff can prevent readmission due to hypernatremia. Serum sodium and drug levels should be periodically monitored in patients who are taking medications known to cause nephrogenic diabetes insipidus.[17][18] [Level 5]

References

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Sodium is a dominant cation in extracellular fluid and necessary for the maintenance of intravascular volume. The human body maintains sodium and water homeostasis by concentrating the urine secondary to the action of antidiuretic hormone (ADH) and increased fluid intake by a powerful thirst response.

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Causes of respiratory alkalosis (Current)

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What is respiratory alkalosis?

= occurs when the respiratory system eliminates carbon dioxide faster than it is produced

→ The imbalance of arterial H+ concentrations in such cases is completely explainable in terms of mass action

= Respiratory alkalosis is defined as a Pco2 below 35 mm Hg with an increase in serum pH above 7.44.

What are the causes of respiratory alkalosis?
-> hyperventilation secondary to other causes
-> ergo anything that causes hyperventilation

What are the Clinical Findings (signs & symptoms) of respiratory alkalosis?

The clinical findings of respiratory alkalosis vary depending on the severity and chronicity of the process.

Acutely, symptoms attributable to hypocalcemia (such as circumoral and digital paresthesia and carpopedal spasm) may occur from the rapid shift in pH.

More severe hypocapnia may result in cerebral vasoconstriction with light-headedness, dizziness, confusion, and altered consciousness.

Chronically, respiratory alkalosis may result in hypophosphatemia and a lowered seizure threshold.

What is the physiology of respiratory alkalosis? (acute & chronic)

1. Acute Respiratory Alkalosis

→ Compensation for acute hypocapnia begins within minutes and involves the movement of protons from the intracellular to the extracellular space.

→ For every decrease in Pco2 of 10 mm Hg, [HCO3−] should decrease by 2.5 mEq/L and pH should increase by 0.08.

2. Chronic Respiratory Alkalosis

→ Renal compensation for chronic respiratory alkalosis results in decreased proton excretion and the retention of chloride for bicarbonate.

→ Chronically, a decrease in Pco2 of 10 mm Hg will result in a decrease in [HCO3−] of 5 mEq/L. With prolonged hypocapnia (2 weeks or more), pH may be normal.

What is the treatment for respiratory alkalosis?
-> treating underlying pathology

For lecturer: How long do we have to wait and see how the system is compensating?

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Euvolemic vs Hypervolemic hyponatremia

Mixed acid-base disorders