Fluid And Electrolyte Disturbances Question and Answers

Fluid And Electrolyte Disturbances

Disorders Of Sodium And Water Balance

Question 1. Write a short note on the normal distribution of water in the body of an average adult male.
Answer:

Sodium And Water Balance Composition of Body Fluids

• Water is the most abundant constituent of the body, accounting for about 50% of body weight in women and 60% of the body weight in men.
• Total body water is distributed in two major compartments:

Read And Learn More: General Medicine Question And Answers

1. Intracellular fluid compartment (IFC) = 2/3rd of body water
2. Extracellular fluid compartment (ECF) = 1/3rd of body water

Sodium And Water Balance ECF consists of:

• Intravascular (plasma water) compartment: 3/4th of ECF or 15% of total body weight.
• Extravascular (interstitial) compartment: 1/4th of ECF or 5% of total body weight.

For example, the distribution of body fluid in a man of 70 kg is as mentioned.

Normal Water Balance

• In a normal person, daily fluid requirement = sum of urine output + net insensible fluid losses.
  • Insensible fluid loss = 500 mL through skin + 400 mL through lung + 100 mL through stool = 1,000 mL
  • Insensible fluid input = 300 mL water through oxidation
  • Net normal daily insensible fluid loss = 1,000 mL 300 mL = 700 mL
• Hence, daily fluid requirement = urine output + 700 mL
• Abnormal fluid loss:
  • 500 mL through moderate sweating
  • 1–1.5 L through severe sweating/high fever
  • 0.5–3 L through exposed wound surface (burns) and body cavity (laparotomy)
  • These parameters help to determine the daily fluid requirement in patients, especially those on
    intravenous fluids.

Sodium And Water Balance Electrolytes

• Electrolytes are ions that are either positively charged (cations) or negatively charged (anions).
• Sodium (Na+) is the main cation, while chloride (Cl–) and bicarbonate (HCO3–) are the major anions in the extracellular (ECF) compartment.
• Potassium (K+) and magnesium (Mg2 +) are the major cations, while phosphate, sulfate, and protein are the major anions in the intracellular (ICF) compartment.
• The normal range of different electrolytes in the blood.

Osmolality, Osmolarity, And Tonicity

• Osmolality: The osmolality of a solution is determined by the amount of solute dissolved in a solvent (i.e., water) measured in weight (kg).
• When osmolality is high, the solution is more concentrated, and when the osmolality is low, the solution is diluted.
• Osmolarity: Osmolarity is the concentration of osmotically active particles, expressed as milliosmoles per liter (mOsm/L).
• Plasma osmolarity = 2 × Na+ (mEq/L) + glucose (mg/dL)/18 + BUN (mg/dL)/2.8 In practice, osmolarity is the same as osmolality (mOsm/kg H2O) because 1 L of water is equivalent to 1 kg of water.
• Tonicity vs osmolality:
• Osmolality refers to all particles in the solution
• Tonicity describes whether the particles are effective or ineffective osmoles.

Volume Regulation And Osmoregulation

Question 2. What are the factors that determine the control of ECF volume? or Write a note on sodium balance.
Answer:

Total body sodium is the main determinant of ECF volume:

Regulation of the sodium balance, i.e., the difference between sodium intake and output, is crucial to maintaining normal ECF and plasma volume, with the kidney matching the urinary output of sodium with that of sodium intake.

A positive Na+ balance would lead to ECF volume expansion, while conversely, a negative Na+ balance would lead to ECF volume contraction.

Sodium intake: Daily sodium consumption varies widely between low-Na+ diets containing 20 mmol/day (approximately 1.2 g salt/day) and high-Na+ diets containing 200 mmol/day (approximately 12 g salt/day).

Sodium excretion: the renal handling of sodium by the nephron.

Na+ is freely filtered across glomerular capillaries and is subsequently reabsorbed throughout the nephron.

1. Proximal convoluted tubule (PCT): Approximately 2/3rd (67%) of Na+ is reabsorbed.
2. The loop of Henle: About 25–30% is reabsorbed via apical Na+ K+ 2Cl transporter.
3. Distal convoluted tubule (DCT): About 5% by thiazide
   sensitive Na+ Cl cotransporter.
4. Collecting ducts: About 3% of Na+ reabsorption takes place in the cortical and medullary collecting ducts.

The excretion of Na+ is less than 1% of the filtered load, with more than 99% of the filtered load being reabsorbed.

Renal excretion of sodium is regulated by four major steps:

1. Renin–angiotensin–aldosterone system:

• The renin–angiotensin–aldosterone system is activated in response to decreased renal perfusion pressure.
• Angiotensin II stimulates Na+ reabsorption in the proximal tubule (Na+–H+ exchange).
• Aldosterone stimulates Na+ reabsorption in the late distal tubule and the collecting duct.

2. Sympathetic nervous system (SNS) activity: Baroreceptors sense a decrease in arterial pressure and stimulate the SNS and cause vasoconstriction of afferent arterioles and increased proximal tubular sodium reabsorption.

3. Atrial natriuretic peptide (ANP):

• ANP, secreted by the atria in response to an increase in ECF volume, causes vasodilation of afferent arterioles, vasoconstriction of efferent arterioles increased GFR, and decreased Na+ reabsorption in the late distal tubule and collecting ducts.
• Other peptides in the ANP family, including urodilatin (secreted by the kidney) and brain natriuretic peptide (BNP) (secreted by cardiac ventricular cells and the brain), have similar effects to increase GFR and decrease renal sodium reabsorption.

4. Starling forces in peritubular capillaries:

• An increase in ECF volume reduces the peritubular capillary oncotic pressure and inhibits proximal tubule Na+ reabsorption.
• A decrease in ECF volume increases the peritubular capillary oncotic pressure and stimulates proximal tubule Na+ reabsorption.

Body fluid osmolarity is maintained at a value of about 285–290 mOsm/L by processes called osmoregulation.

Even minor changes in body fluid osmolarity produce a series of hormonal responses that influence the reabsorption of water by the kidneys, attempting to restore osmolarity back to normal value.

These renal mechanisms for the reabsorption of water are responsible for maintaining constant body fluid osmolarity.

Vasopressin, also known as arginine vasopressin (AVP) or antidiuretic hormone (ADH), by its effect on the renal collecting system, is the major determinant that regulates the excretion of free water.

Increased serum osmolality stimulates osmoreceptors in the anterior hypothalamus, which in turn stimulates thirst and the secretion of ADH from the posterior pituitary gland.

ADH circulates via the blood to the kidneys, where it leads to an increase in the water permeability of the principal cells of the late distal tubule and the collecting duct, resulting in increased water reabsorption.

Because more water is reabsorbed by these segments, the osmolarity of urine increases, and the amount of urine decreases.

This, along with increased water intake, restores serum osmolarity to normal levels.

Conversely, reduced serum osmolarity, via inhibition of the osmoreceptors in the anterior hypothalamus, suppresses thirst as well as the secretion of ADH, which results in the excretion of large amounts of dilute urine, restoring serum osmolarity to normal levels.

Summarizes the factors that determine volume and osmoregulation.

Assessing Volume Status

Question 3. How do you assess volume status?
Answer:

• Hemodynamic assessment methods include:
• Interpretation of history and physical examination findings
• Assessment and interpretation of laboratory results
• Ultrasound and echocardiography
• Use of noninvasive monitoring
• Use of minimally invasive procedures

No single assessment is sufficient in isolation and must be considered in the context of other available assessments and clinical information.

Some of the methods used in clinical practice.

Disturbances Of Body Fluids

The disturbances of body fluids can be grouped according to whether they involve volume contraction or volume expansion and whether they involve an increase or a decrease in body fluid osmolarity.

Volume Depletion (Hypovolemia)

Question 4. What is hypovolemia?
Answer: Hypovolemia, synonymous with ECF volume contraction, refers to a loss of salt and water.

Question 5. Describe the causes, clinical features, laboratory features, and treatment of volume depletion.
Answer:

Causes of Hypovolemia

Volume Depletion Clinical Features

Mild to Moderate Volume Loss

• Thirst
• Postural dizziness, weakness
• Dry mucous membranes and axillae
• Cold, clammy extremities
• Collapsed peripheral veins
• Delayed capillary refill time
• Tachycardia (pulse rate >100 beats/min)
• Postural increase in pulse of 30 beats/min or more

• Postural hypotension (systolic blood pressure decrease >20 mm Hg on standing)
• Low jugular venous pulse
• Decreased urine output

Severe Volume Loss and Hypovolemic Shock

• Altered mental status (or loss of consciousness)
• Peripheral cyanosis
• Reduced skin turgor (in young patients)
• Marked tachycardia, low pulse volume
• Supine hypotension (systolic blood pressure <100 mm Hg)

Volume Depletion Laboratory Features

Hematocrit: Increased due to hemoconcentration. May be reduced if hypovolemia is secondary to hemorrhage.

Blood urea nitrogen (BUN) and creatinine: BUN/creatinine ratio >20:1 is usually seen.

This is due to a differential increase in urea reabsorption in the collecting duct.

Confounding factors include upper gastrointestinal tract hemorrhage and administration of corticosteroids, which increase urea production, as well as malnutrition and liver disease, which diminish urea production.

Serum sodium: Normal, reduced, or elevated depending on the proportion of loss between water and sodium.

Urine osmolality and specific gravity: These are often elevated in hypovolemic states.

However, these may be altered by an underlying renal disease that leads to renal sodium wasting, concomitant intake of diuretics, or solute diuresis.

Urinary sodium: Hypovolemia normally promotes renal sodium reabsorption.

Hence, urine sodium is low, typically less than 25 mmol/L in most cases of hypovolemia and states of low effective arterial volume.

However, urine sodium concentration may be misleading in cases of:

• Metabolic alkalosis (e.g. nasogastric suction or vomiting), as bicarbonaturia obligates excretion of a cation. Hence, the urine sodium concentration might not be low. In this circumstance, the urine chloride concentration should be measured, which will typically be <15 mEq/L.
• Presence of acute tubular necrosis—kidney tubular function is impaired, thus the urine sodium concentration may not be low.
• Use of diuretics

Urine chloride levels (Low): It follows a similar pattern of urine sodium concentration because sodium and chloride are generally reabsorbed together.

Urine chloride is a better measure than urine sodium in cases of volume depletion with metabolic alkalosis, as described above.

Fractional excretion of sodium:

• [U_Na × P_creat/U_creat × P_Na] × 100.
• In an oliguric patient with AKI, FE Na less than 1% is consistent with volume depletion; FE Na greater than 1% is more consistent with acute tubular necrosis.

Volume depletion Treatment

• The goal of treatment is to replace the fluid deficit and ongoing losses with a fluid that resembles the lost fluid.
• The cause of hypovolemia should be treated, where possible.
• Mild-to-moderate volume depletion (often due to gastroenteritis) should be corrected by increasing oral intake of sodium and water with an oral rehydration solution.
• In severe volume depletion, intravenous crystalloids such as normal saline or Ringer’s lactate are usually the preferred initial choice for volume resuscitation.
• Transfusion of blood products is crucial for hemorrhage.

Question 6. What is dehydration? Describe the clinical features of dehydration.
Answer:

• Dehydration refers to a loss of water.
• This should be differentiated from hypovolemia, which implies a loss of salt and water.
• Dehydration may cause manifestations of hypernatremia.
• Describes the signs of dehydration depending on the degree of dehydration.

Dehydration Volume Expansion (Hypervolemia)

• Hypervolemia is an expansion of the ECF compartment, due to an excess of total body sodium and water.
• Hypervolemia is typically due to renal retention of sodium and water.
• This renal retention may be primary or secondary.
• Secondary causes are secondary to reduced effective arterial blood volume depletion (arterial underfilling).
• Major causes of hypervolemia.

Edema

Question 7. Define edema. What is anasarca? (or) What are the common causes of generalized edema? (or) List medications that can cause edema. (or) Discuss the mechanism of edema formation. (or) How will you differentiate between cardiac, renal, and hepatic edema?
Answer:

Edema Definition:

Edema: Edema is an accumulation of fluid in the interstitial space that occurs when local or systemic conditions cause capillary filtration to exceed the limits of lymphatic drainage.

Edema Anasarca: It refers to generalized and massive edema, often accompanied by large effusions into the peritoneal, pleural, and pericardial spaces the medications that cause edema.

Differences between the principal causes of edema are-

Pitting edema may be divided into two categories:

1. Rapid pitting recovery within <40 seconds and is seen with hypoproteinemia.
2. Slow pitting edema (>40 seconds) is usually seen in patients with normal albumin levels.

Treatment of Extracellular Volume Expansion

Question 8. Discuss the principles of management of extracellular volume expansion/generalized edema.
Answer:

Treatment of Extracellular Volume Expansion General Management

• Recognize and treat the underlying cause
• Medications that promote sodium retention (for example, NSAIDs) should be discontinued.
• Achieving negative sodium balance, by dietary sodium restriction and administration of diuretics.
  • Moderate dietary sodium restriction (2 g Na+/day) should be encouraged.
  • Restriction of total fluid intake in patients with hypervolemic hyponatremia.
  • Diuretic therapy: Cornerstone of management of extracellular volume overload (described later).

Additional specific therapy based on the etiology:

• Liver cirrhosis: Large volume paracentesis with albumin infusion, TIPS (Transjugular intrahepatic portosystemic shunt)
• Heart failure: Use of ACE inhibitors and angiotensin receptor blockers (ARBs) to inhibit RAAS, ultrafiltration, and left ventricular assist devices
• Chronic kidney disease: ACE inhibitors and ARBs, renal replacement therapy (dialysis and kidney transplant)
• Nephrotic syndrome: Use of glucocorticoids, ACE inhibitors, and ARBs
• Edema of nutritional origin: Thiamine for beriberi, high protein diet.

Diuretic Therapy

Question 9. Describe various diuretics in use. (or) Add a note on diuretic therapy in edematous patients.
Answer:

• Diuretics are the cornerstone in the management of extracellular volume overload.
• They are also used in the management of hypertension.
• They act by inhibiting sodium reabsorption at various locations along the nephron providing a summary of the various subclasses of diuretics.
• Caution should be exercised during therapy with diuretics as ECF volume expansion may have occurred in order to compensate for arterial underfilling, as in cirrhosis and heart failure.
• In these cases, overly rapid diuresis may lead to a significant reduction in the vascular space, which leads to a decreased venous return to the heart, decreased cardiac filling pressures, decreased stroke volume, decreased cardiac output, and ultimately hypotension.
• Impaired renal perfusion may lead to prerenal AKI.
• This situation is more commonly seen in those patients with ascites but without pedal edema.
• A rapid removal of excess fluid is generally necessary only in life-threatening situations, such as pulmonary edema and hypervolemia-induced hypertension.
• Most patients generally tolerate gradual correction of volume overload.

Lymphedema: Nonpitting Edema

Characteristics: Edema due to impaired ability of the lymphatic vasculature to collect and transport interstitial fluid, which in the latter stages is characterized by nonpitting edema.

which does not resolve on limb elevation and is often associated with trophic skin changes such as fibrosis, induration, acanthosis, and warty overgrowths. Lymphedema may be primary or secondary. It may involve the upper limb or the lower limb.

Classification of primary lymphedema: Based on age at lymphedema onset:

• Lymphedema congenital—at or shortly after birth (<1 year old)
• Lymphedema praecox—from ages 1–35 years
• Lymphedema tarda—>35 years old

Causes of lymphedema:

Lymphedema: Nonpitting Edema Primary causes:

• Milroy disease
• Lymphedema-distichiasis syndrome
• Hypertrichosis–lymphedema–telangiectasia syndrome
• Yellow nail syndrome: Lymphedema, yellow nail beds, pleural effusion, and bronchiectasis

Lymphedema: Nonpitting Edema Secondary causes:

• Infections:
  • Filariasis—most common secondary cause worldwide
  • Recurrent bacterial infections
  • Tuberculosis
  • Malignancy and malignancy-related treatments—most common secondary cause in developed countries
• Associated malignancies:
  • Breast cancer—most common
  • Lower extremity melanoma
  • Gynecologic cancer
  • Genitourinary cancer
  • Head and neck cancer
• Mechanism:
  • Neoplastic disruption of lymphatics
  • Radiotherapy-induced damage to lymphatics
  • Surgical removal of lymph nodes
• Inflammatory disorders:
  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Sarcoidosis
• Circumferential wounds to extremities
• Burns

Clinical features and staging of lymphedema:

• Typically unilateral or asymmetric
• Features of underlying etiology
• The International Society of Lymphology (ISL) provides a staging system for staging lymphedema:
  • Stage 0 or Ia: Usually asymptomatic
  • Stage 1: Edema present; edema reduced by limb elevation
  • Stage 2:
    • Early stage 2: Pitting edema present
    • Late stage 2: Non pitting edema
    • Limb elevation does not reduce edema
  • Stage 3: Elephantiasis presents with fibrotic changes. Non pitting edema.

Kaposi-Stemmers sign The thickened skin folds at the base of the second finger/toe, making it difficult for the examiner to lift the dorsum of the fingers/toes of the affected limb.

• This can be seen at any stage of lymphedema.
• Peau d’orange appearance
• Look for scrotal swelling in patients with suspected filariasis.

Complications of Lymphedema

• Infection: Recurrent cellulitis, lymphangitis
• Lymphangiosarcoma (Stewart-Treves syndrome)

Evaluation

• Blood smear to evaluate for the presence of microfilaria
• Radionuclide lymphoscintigraphy (isotope lymphography) is the preferred test if the diagnosis is unclear.
• Duplex Doppler ultrasound for examining the deep venous system may supplement the evaluation of extremity edema.
• MRI and CT: Both provide objective evidence of structural changes such as cutaneous thickening, and the presence of edema within the epi fascial plain and can also detect characteristic “honeycomb” patterns of subcutaneous tissue.

Treatment

Localized Edema

Various types of localized edema.

• Facial edema: Trichinosis, hypothyroidism, allergies, nephrotic syndrome, and angioedema
• Pretibial myxedema: Graves’ thyrotoxicosis
• Neurogenic edema: Secondary to autonomic dysfunction
• Lipedema: Adiposity of the legs
• Pseudothrombophlebitis: It is a unilateral edema with raised venous pressure caused by a popliteal cyst

Disorders Of Sodium Balance

Hyponatremia

Question 10. Write a short essay/note on the definition, causes, clinical features, approach, and treatment of hyponatremia. (or) List causes of drug-induced hyponatremia.
Answer:

Drugs causing hyponatremia.

• Vasopressin analogs: Desmopressin, oxytocin
• Medications that stimulate the release of vasopressin or potentiate the effects of vasopressin: SSRIs, antidepressants, morphine, and other opioids.
• Medications that impair urinary dilution: Thiazide diuretics
• Medications that cause hyponatremia by unknown mechanisms: Carbamazepine, antipsychotics, NSAIDs, cyclophosphamide, vincristine, nicotine, and chlorpropamide.
• Illicit drugs: Ecstasy (MDMA)—associated with acute, life-threatening hyponatremia.

Hyponatremia Definition: Hyponatremia is defined as a condition in which serum sodium is <135 mEq/L.

It is a disorder of water regulation, i.e., it usually results from increased water retention.

It is the most common disorder of electrolytes in clinical practice, being reported in 10–30% of acutely or chronically hospitalized patients.

Classification of hyponatremia:

• Based on the duration and rate of development of hyponatremia:
  • Acute hyponatremia < 48 hours
  • Chronic hyponatremia ≥ 48 hours—more common
• Based on the serum sodium concentration of hyponatremia:
  • Mild: Serum sodium 130–135 mEq/L
  • Moderate: Serum sodium 125–129 mEq/L
  • Severe: Serum sodium <125 mEq/L
  • Based on serum osmolality and volume status, hyponatremia is subdivided into 3 main types:

Hypotonic Hyponatremia:

• Serum osmolality < 280 mOsm/kg H2O
• Most common type of hyponatremia
• Due to:
  • Inadequate solute intake
  • Excess electrolyte-free water intake
  • Retention of electrolyte-free water due to:
• Presence of AVP
• Kidney disease
• Use of diuretics: Diuretics cause volume depletion and release of AVP; and may also lead to diminished sodium transport in renal diluting sites.
• Consequences of hypotonic hyponatremia: Cell edema, predominantly cerebral edema.
• Subtypes:
  • Hypovolemic hyponatremia
  • Hypervolemic hyponatremia
  • Euvolemic hyponatremia

Hypovolemic hyponatremia:

• Hypovolemic hyponatremia results from the loss of fluids rich in sodium and/or potassium.
• This stimulates thirst and AVP secretion, leading to water retention.

Alternate classification of hypotonic hyponatremia based on the ability to excrete dilute urine.

• Unimpaired urine dilution (ADH levels are not elevated)
  • Primary polydipsia
  • Low dietary solute intake (beer potomania, tea and toast diet)
• Impaired urine dilution but normal suppression of ADH
  • Advanced renal failure
  • Diuretic-induced hyponatremia
• Impaired urine dilution due to unsuppressed ADH secretion
  • Reduced effective arterial blood volume
    • Hypovolemic hyponatremia
    • Heart failure and cirrhosis (hypervolemic hyponatremia)
    • Addison’s disease
  • SIADH
• Disorders with impaired urine dilution due to abnormal V2 receptor (nephrogenic SIADH)
• Abnormally low osmostat which leads to a low threshold for the release of ADH
• Exercise-induced hyponatremia
• Cerebral salt wasting

Hyponatremia Causes:

• GI losses:
  • Diarrhea
  • Vomiting
• Renal losses:
  • Diuretics (predominantly thiazide diuretics)
  • Cerebral salt wasting
  • Adrenal insufficiency
  • Salt-losing nephropathies
• Dermal losses:
  • Burns
  • Sweating
• Third spacing:
  • Pancreatitis
  • Sepsis
  • Bowel obstruction

Hypervolemic hyponatremia:

• Caused by renal sodium and water retention
• Causes:
  • Cirrhosis of liver
  • Heart failure
  • Chronic kidney disease
  • Nephrotic syndrome

Euvolemic hyponatremia:

• Most common hyponatremia in hospitalized patients
• Causes:
  • SIADH
  • Nephrogenic syndrome of inappropriate antidiuresis
    • Due to mutation causing activation of V2 vasopressin receptor (V2R)
• Low solute intake: “tea and toast” diet, beer potomania
• Hypothyroidism
• Glucocorticoid deficiency
• Exercise associated hyponatremia
  • Due to excessive water intake combined with impaired water excretion due to persistent ADH secretion
• Water intoxication

Isotonic Hyponatremia

• Serum osmolality 280–295 mOsm/kg H2O
• Pseudohyponatremia due to hyperlipidemia or hypoproteinemia (e.g. multiple myeloma)

Hypertonic Hyponatremia

• Serum osmolality > 295 mOsm/kg H2O
• Due to the presence of additional osmoles (glucose/mannitol)
• Hyperglycemia
• Note: Sodium correction in hyperglycemia: For every 100 mg/dL increase in blood sugar, sodium concentration will fall by approximately 2 mEq/L
• Hypertonic fluid infusion
• Radiocontrast.

Effect of Hypotonic Hyponatremia on the Brain

Hyponatremia induces generalized cellular swelling due to the entry of water from ECF to ICF.

The symptoms of hyponatremia are primarily neurological and are due to the development of cerebral edema within a rigid skull.

• Swelling and reduced osmolality: Within minutes of hyponatremia, the reduced osmolality causes a shift of fluid from the ECF to the ICF, leading to brain swelling. This usually occurs when the hyponatremia develops rapidly.
• Rapid adaptation: The brain tries to rapidly adapt to this hypotonic environment by the loss of electrolytes such as sodium, potassium, and chloride. These are osmotically active and help partially restore the brain volume.
• Slow adaptation: Further loss of osmotically active organic compounds such as glutamate, myoinositol, and taurine from the brain cells also helps in restoring brain volume.

• The adaptation process takes about 48 hours, which is the basis for the classification of acute and chronic hyponatremia based on the threshold of 48 hours.

Slow versus rapid correction of hypotonicity:

• Before adaptation (<48 hours), decreased extracellular osmolality triggers water to enter brain cells, increasing the risk of cerebral edema.
• After adaptation (>48 hours), a rapid increase in serum sodium concentration can cause brain cells to release water, increasing the risk of osmotic demyelination. Hence sodium should be corrected at a slow rate in chronic hyponatremia.

Hyponatremia Clinical Features

• Hyponatremia is essentially a laboratory diagnosis.
• History and physical examination should determine the volume status of the patient and try to identify the cause of the hyponatremia.
• Symptoms due to hyponatremia depend on the acuity of presentation and the serum sodium levels.

Hyponatremia Investigations

Step 1: Serum sodium:

• Hyponatremia is diagnosed when serum sodium is <135 mEq/L
• Based on severity, hyponatremia is classified as:
  • Mild: Serum sodium 130–135 mEq/L
  • Moderate: Serum sodium 125–129 mEq/L
  • Severe: Serum sodium < 125 mEq/L

Step 2: Serum osmolality:

• Serum osmolality < 275 mOsm/kg H2O indicates hypotonic hyponatremia.
• Serum osmolality between 280 and 295 mOsm/kg H2O indicates isotonic hyponatremia (pseudo hyponatremia).
• Serum osmolality > 295 mOsm/kg H2O indicates hypertonic hyponatremia.

Step 3: Urine osmolality:

• It should be measured in patients with hypotonic hyponatremia to confirm if urine is appropriately dilute.
• If the urine osmolality is less than 100 mOsm/kg H2O
• It indicates that there is no diluting defect.
  • This may be seen in primary polydipsia or due to low solute intake (e.g., beer potomania)
  • Low urine osmolality may also be seen in patients with hypovolemic hyponatremia who have been volume resuscitated if osmolality is measured after administration of isotonic saline.
  • If the urine osmolality is more than 200 mOsm/kg H2O, assess volume status and urine sodium.

Step 4: Urine sodium:

Other investigations:

• Thyroid function test: To rule out hypothyroidism
• Serum cortisol ± ACTH: To exclude adrenal insufficiency
• Serum creatinine: To look for renal insufficiency
• Serum uric acid: May help assess the volume status
• Other tests to diagnose the underlying cause, as guided by history and physical examination:
  • Serum lipids and serum protein electrophoresis in cases of pseudo hyponatremia to look for hypercholesterolemia and multiple myeloma, respectively.
  • Echocardiogram, BNP: For heart failure
  • Ultrasound abdomen: Cirrhosis
  • Urine for proteinuria
  • CT brain/chest/abdomen: To help detect paraneoplastic SIADH.

Approach to the diagnosis of the cause of hyponatremia.

Hyponatremia Management

The management of hypotonic hyponatremia depends on the severity, duration of symptoms, and the underlying cause.

Goals of treatment

• To correct serum sodium levels to avoid complications of severe hyponatremia.
• To avoid overly rapid correction of hyponatremia, which may lead to osmotic demyelination.
• Correct underlying causes

1. Severe symptomatic hyponatremia:

• Goal: Rapid increase of serum sodium by 4–6 mEq/L is recommended irrespective of whether hyponatremia is acute or chronic. This is done by IV infusion of hypertonic saline.
  • Protocol 1: 100 mL bolus of 3% saline is infused over 10 minutes; repeat up to 3 times, as necessary.
  • Protocol 2: 150 mL bolus of 3% saline over 20 minutes.

Check serum sodium concentration after 20 minutes. Consider repeating twice or until a target of 5 mEq/L increase in serum sodium concentration.

Follow-up management:

If symptoms improve:

• Stop infusion of hypertonic saline
• Start treatment based on etiology, if identified

If symptoms do not improve:

• Continue IV infusion of 3% hypertonic saline aiming for an increase in sodium concentration by 1 mmol/L/hr
• Symptoms improve or Serum sodium concentration increases by 10 mEq/L in total or Serum sodium concentration reaches 130 mEq/L

2. Mild or asymptomatic hyponatremia:

Treatment depends on whether hyponatremia is acute or chronic and based on the underlying etiology

Rate of correction:

• Acute hyponatremia:
  • The rate of correction does not need to be restricted in well-documented cases of acute hyponatremia.
• Chronic hyponatremia/duration of hyponatremia unknown:
  • Increase serum sodium with a goal of ≤6–8 mEq/L/day and not more than 18 mEq/L in 48 hours
  • Monitor serum sodium every 2–4 hourly

3. Estimating the effect of 1 L of any IV saline infusion on serum sodium levels:

Change in serum sodium = [(infusion sodium concentration + infusion potassium concentration) serum sodium concentration/Total body water + 1]

The sodium content of various intravenous fluids

• This formula may be used to determine the amount of saline and the rate of fluid infusion required to correct hyponatremia.
• However, this formula is only a rough guide and is limited by the fact that it does not account for ongoing electrolyte or water losses.
• The use of this formula does not serve as a replacement for regular serum sodium monitoring.
• Sodium levels should be monitored every 2–4th hours.

4. Additional treatment based on the underlying etiology (in mild or asymptomatic disease)

Hypovolemic hyponatremia:

• In patients with asymptomatic hypovolemic hyponatremia, isotonic saline can be used to restore the intravascular volume.
• The amount of 0.9% saline to be replaced may be calculated by the above formula and overcorrection of chronic hyponatremia should be avoided.
• Fludrocortisone can be used in cerebral salt-wasting syndrome

Hypervolemic hyponatremia:

• Fluid restriction:
  • The amount of fluid intake should be [urine output 500 mL]
  • The amount of fluid to be restricted can also be determined by calculating the urine: plasma electrolyte ratio (urinary [Na] + [K]/ Plasma [Na]

1. If the ratio is more than 1, then the fluid can be aggressively restricted up to less than 500 mL/day.
2. For approx 1 then the fluid can be restricted up to 500–700 mL
3. For a ratio less than 1, flids can be restricted up to 1 L.

• Loop diuretics
• Vasopressin antagonists may be useful when the above measures fail (see the section on Vaptans below)

Euvolemic hyponatremia:

• Treat the underlying cause where possible
• Fluid restriction
• Loop diuretics
• Oral salt tablets in patients with SIADH
• Oral urea tablets in patients with SIADH
• Demeclocycline in patients with chronic asymptomatic hyponatremia due to SIADH if unresponsive to fluid restriction
• Vasopressin antagonists

5. Correction of inadvertent rapid overcorrection of sodium:

• Discontinue hypertonic saline/other measures of active sodium correction
• Infusion of electrolyte-free water (e.g.,5% Dextrose)
• desmopressin

Question 11. Write a short note on VAPTANS.
Answer:

Vasopress in Receptor Antagonists (VAPTANS)

• Nonselective (mixed V1A/V2):
  • Conivaptan: Intravenous
• Selective:
• V1A selective (V1RA): Relcovaptan
• V1B selective (V3RA): Nelivaptan
• V2 selective (V2RA): Tolvaptan, lixivaptan, mozavaptan, satavaptan. V2
• selective (V2RA) can cause an electrolyte-free aquaresis, reduce urine osmolality and raise serum Na. Their mechanism of action is presented.

• Tolvaptan and conivaptan are FDA-approved drugs.
• Tolvaptan, an oral V2 selective agent, is the most commonly used agent.
• Indication:
  • Use in euvolemic or hypervolemic hyponatremia (heart failure).
• Dose:
  • Initially 15 mg/day
  • Maximum 60 mg/day
• Treatment should be limited to 30 days
• Monitor serum sodium and volume status
• Contraindicated in:
  • Hypovolemic hyponatremia
  • Acute hyponatremia and severe symptomatic hyponatremia (urgent need to raise serum sodium levels)
  • Pregnancy
  • Severe liver dysfunction and cirrhosis

Vaptans are not suitable for hyponatremia due to cerebral salt wasting and psychogenic polydipsia where the ADH level is appropriate.

• Caution: It should NOT be used along with hypertonic saline.
• Adverse effects Thirst 8–16%; dry mouth 4–13%, polyuria
  • Hypernatremia develops in 5%.
  • Rapid correction of serum sodium levels may predispose to osmotic demyelination syndrome.
  • Hyperglycemia
  • GI hemorrhage in cirrhosis

Other Uses of Vaptans

Polycystic kidney disease: Polycystin defects may promote cyst development because they increase intracellular cAMP (a second messenger for AVP acting at the V2R), therefore, V2R antagonists may reduce cyst volume.

Congenital nephrogenic diabetes insipidus: Type 2 V2R mutations cause misfolding and interfere with the trafficking of the receptor from the endoplasmic reticulum to the cell membrane—VRA can bind to misfolded intracellular V2R and improve transport to the cell membrane.

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH/SIAD)

Question 12. Write a short note on the syndrome of inappropriate antidiuretic hormone secretion.
Answer: The syndrome of inappropriate antidiuretic hormone is a disorder of water and sodium balance characterized by hypotonic euvolemic hyponatremia due to impaired free water
excretion, which is caused by nonphysiologic secretion of ADH which persists in the absence of an osmotic or hemodynamic stimulus.

Criteria for the diagnosis of SIADH are enlisted

Bartter’s criteria for diagnosis of syndrome of inappropriate antidiuretic hormone secretion.

• Hyponatremia
• Serum osmolality < 270 mOsm/kg (hypotonic)
• Euvolemia
• Urinary osmolality > 100 mOsm/kg of H2O
• Urinary sodium > 30 mEq/L without restricted dietary intake of salt
• Normal renal, cardiac, hepatic, adrenal, pituitary, and thyroid function
• Exclusion of diuretic use

SIADH is the most common cause of hyponatremia.

Plasma levels of arginine vasopressin (AVP) in various types of SIADH.

Hormone Secretion Five types of SIADH.

• Type 1: Characterized by unregulated secretion of vasopressin—most common pattern.
• Type 2: Elevated basal secretion of vasopressin despite normal regulation by osmolality.
• Type 3: “Reset osmostat”
• Type 4: Nephrogenic SIAD—undetectable vasopressin (AVP) levels (these patients may have a gain of function mutation of the V2-receptor)
• Type 5: “Barostat”—altered baroreceptor signaling despite normovolemia.
• Thus there is a large increase in vasopressin secretion with a minor reduction in blood pressure or volume.

Hormone Secretion Etiology of SIADH

• Various causes of SIADH.
• Malignancies: Bronchogenic carcinoma (small cell carcinoma), carcinoma of duodenum, stomach, pancreas, prostate, bladder, lymphoma, and mesothelioma
• Respiratory: Pneumonia, lung abscess, tuberculosis, aspergillosis, positive pressure ventilation (PPV), pneumothorax, and asthma
• Neurological: Encephalitis, meningitis, brain abscess, head trauma, GB syndrome, subarachnoid hemorrhage, subdural hemorrhage, cerebrovascular accident, cerebral and cerebellar atrophy, multiple sclerosis (MS), hydrocephalus

Hormone Secretion Others:

AIDS

1. Drugs: Chlorpropamide, SSRI, MAOI, tricyclic antidepressants, carbamazepine, oxytocin, vasopressin, desmopressin, cyclophosphamide, and vincristine Acute intermittent porphyria.
2. Idiopathic

Hormone Secretion Clinical Features

• Clinical euvolemia: No edema observed
• Features of hyponatremia, based on the severity of hyponatremia, as described in the earlier section.
• Features suggestive of underlying etiology.
• Differentiating features of SIADH, cerebral salt wasting (CSW), and diabetes insipidus are presented.

Hormone Secretion Treatment

• Treat the underlying cause
• In severe hyponatremia, infusion of hypertonic saline as described above
• Restrict the fluid intake to 500–1,000 mL/day, as described above
• Oral salt tablets can be advocated
• Oral urea
• Combination of loop diuretics and oral salt tablets
• Vasopressin-2 receptor antagonists (aquaretics: tolvaptan, conivaptan)
• Demeclocycline:
  • It inhibits AVP in the collecting duct.
  • Indicated for chronic asymptomatic hyponatremia due to SIADH if unresponsive to fluid restriction
  • Adverse effects: Nephrotoxicity

Hormone Secretion Cerebral Salt Wasting

Hormone Secretion Causes:

• Typically described in subarachnoid hemorrhage.
• Also seen in other CNS disorders such as closed head injury, CNS surgery, CNS tumors, CNS infections, and meningitis.
• Mechanism: Postulated that brain natriuretic peptide increases urine volume and Na+ excretion.

Hormone Secretion Signs/Symptoms:

• Typical onset is within the first 10 days following a neurosurgical procedure or event.
• Polyuria, weight loss, dehydration/hypovolemia, hypotension, and low CVP.

Hormone Secretion Laboratory Values

• Hyponatremia due to excessive renal Na loss
• High urine Na >30 mmol/L
• Urine osmolality inappropriately elevated >100 mOsm/kg
• Low serum uric acid concentration

Hormone Secretion Treatment

• 3% saline to raise the serum sodium levels, as described in the section on hyponatremia
• Volume replacement with 0.9% normal saline
• Salt supplementation
• Fludrocortisone

Hypernatremia

Question 13. Write a short note on hypernatremia.
Answer:

Hypernatremia Definition: It is defined as serum Na+ concentration >145 mmol/L.

Hypernatremia is usually the result of loss of water in excess of sodium.

Hypernatremia is generally mild unless the thirst mechanism is abnormal or access to water is limited, e.g., in infants, physically challenged, impaired mental status, postoperative patients, and intubated patients in ICU.

Drugs causing hypernatremia

• Drugs associated with nephrogenic DI:
  • Lithium
  • Cisplatin
  • Aminoglycosides
  • Amphotericin B
  • Demeclocycline
  • Vitamins A and D

Hypernatremia Drugs associated with central diabetes insipidus:

• Phenytoin
• Ethanol

Hypernatremia Drugs that lead to renal water loss:

• Loop diuretics
• Mannitol

Hypernatremia Other drugs:

• Lactulose and sorbitol—lead to hypotonic GI losses
• Hypertonic saline
• Sodium bicarbonate

Classification of Hypernatremia based on Duration of Symptoms

• Acute hypernatremia <48 hours
• Chronic hypernatremia >48 hours

Clinical Features

• Features of underlying etiology
• Features due to hypernatremia:
  • Marked thirst
  • Increased urine frequency/volume
  • Lethargy
  • Weakness
  • Irritability
  • Seizures
    • Coma
    • Neurological symptoms are more common with acute hypernatremia, but patients with chronic hypernatremia may progress to altered mental status and coma
• Volume status should be determined to classify hypernatremia.

Hypernatremia Investigations

• Serum sodium levels
  • Hypernatremia if serum sodium > 145 mEq/L
• 24-hour urine volume measurement:
• The appropriate response to hypernatremia is a small amount of concentrated urine.
  • Urine volume <800 mL
  • Urine osmolality >800 mOsm/L
  • May be seen in GI or insensible losses, primary hypodipsia
• Urine volume >1,000 mL suggests a defect in renal water conservation.
• Urine osmolality and serum osmolality
  • Possible etiologies based on urine osmolality.

Other testing based on etiology:

• Further testing for DI:
• Water deprivation test
• Desmopressin challenge test
• Serum AVP levels
• Imaging of the brain with MRI/CT in central DI
  • Renal USG and RFTs: For renal disease
  • Gastric sodium or stool sodium: In salt poisoning
  • CPK: For hypernatremia associated with rhabdomyolysis

Management of Hypernatremia

Hypernatremia Management depends upon:

• The onset of hypernatremia: Acute vs chronic
• Volume status

Management of chronic hypernatremia

1. Fluid replacement:

• If hypovolemic, treat with 0.9% saline until vital signs are normal.
• Once the patient is euvolemic, calculate the free water deficit as follows:
• Calculation of free water deficit for chronic hypernatremia
  • Free water deficit = Plasma Na + concentration- 140/140 × Total body water
• Also, correct ongoing water losses
• Choice of fluids for correction of free water deficit includes:
  • Water by NG tube or orally
  • IV 5% dextrose
  • Hypotonic saline: IV quarter or half normal saline

The goal of treatment: To lower sodium by 8–10 mmol/day Rapid correction of hypernatremia is dangerous because the sudden decrease in osmolality can cause a rapid shift of water into the cells resulting in swelling of brain cells.

Typical requirements of fluids depend on the degree of fluid depletion.

2. Treatment based on volume status and etiology:

Hypovolemic hypernatremia:

• Correct hypovolemia with isotonic saline
• Treat the underlying cause of hypovolemia (e.g., diarrhea)
• 5% dextrose or hypotonic saline to correct water deficit

Euvolemic hypernatremia:

• Replace water losses
• For central DI:
  • Desmopressin
• For nephrogenic DI:
  • Stop causative agent
  • Amiloride for lithium-associated nephrogenic DI
  • A low sodium diet, combined with thiazide diuretics may be useful.
• This enhances the proximal reabsorption of salt and water thus decreasing urinary free water loss

Hypervolemic hypernatremia:

• Discontinue salt intake
• Diuretics to lower serum sodium and treat volume expansion
• 5% dextrose to correct water deficit
• Management of acute hypernatremia
• Correction of serum sodium by 1 mEq/L/hr in the first 6–8 hours is recommended.

Indicators of adequate correction: Relief of thirst, urine output of more than 1,500 mL/24 hours, and normal plasma sodium levels

Osmotic Demyelination Syndrome or Central Pontine Myelinolysis

Question 14. Write a short note on osmotic demyelination.
Answer: It was first described by Adams et al. in 1959.

Osmotic Demyelination  Risk factors:

• Alcoholism, chronically ill patients, elderly/malnourished, and cirrhosis predispose to demyelination (due to depletion of intracellular organic solutes).
• Hypokalemia is a strong predictor.
• Demyelination can be diffuse and not involve the pons.
• Extrapontine areas include cerebellar and neocortical white/gray junctional areas, thalamus, subthalamus, amygdala, globus pallidus, putamen, caudate, and lateral geniculate bodies.
• The rate of correction over 24 hours is more important than the rate of correction in any one particular hour.
• More common, if sodium increases by more than 20 mEq/L in 24 hours Very uncommon, if sodium increases by 12 mEq/L or less in 24 hours
• Symptoms generally occur 2–6 days after elevation of sodium and are usually either irreversible or only partially reversible.

Osmotic Demyelination Clinical Features

• Dysarthria, dysphagia, parkinsonism, catatonia, locked-in syndrome, lethargy and coma, seizures, nystagmus, ataxia, emotional lability, akinetic mutism, gait disturbance, myoclonus, behavioral disturbances, paraparesis, or quadriparesis.
• MRI with diffusion-weighted imaging will be helpful in early detection.

Osmotic Demyelination Treatment

• There is no effective therapy.
• Changes are permanent.
• Mortality is very high.
• Case reports of improvement with aggressive plasmapheresis immediately after diagnosis.
• Case reports of treatment with a thyrotropin-releasing hormone.
• Infusion of myoinositol (a major osmolyte lost in the adaptation to hyponatremia) protects against mortality and myelinolysis from rapid correction of hyponatremia.

Osmotic Demyelination Disorders of Potassium Balance

Potassium

Question 15. Write a short note on the normal physiology of potassium in the body.
Answer: 

• Potassium is the major intracellular cation.
• Distribution of potassium:
  • Total body potassium in a person weighing 70 kg is about 4,000 mEq.
  • 99% of the potassium is located inside the cells, predominantly within muscle cells.
    • 28 L of ICF contains ~4,000 mEq = 150 mEq/L
• <1% of the total body potassium is extracellular.
  • 14 L of ECF contains ~70 mEq = 4 mEq/L
• Potassium levels are maintained within a narrow range of 3.5–5.5 mEq/L in the ECF.
• The electrochemical gradient of potassium across the cell membrane is maintained by the Na+/K+ ATPase system in the cell membrane which actively transports potassium into and sodium out of the cell.
• This gradient is required for the proper functioning of excitable tissues such as nerves and muscles.

Overall potassium balance:

• Normal intake: 100 mEq/day
• Normal excretion:
  • Urine: 90 mEq/day
  • Fecal excretion: 10 mEq/day

Internal potassium balance: Sudden changes in plasma K+ are prevented by:

• The shift of K+ into the cell via the Na+/K+ ATPase under the influence of insulin and beta-adrenergic stimulation
• Renal K+ excretion

Potassium Renal excretion:

Excretion through the kidney is the major route of elimination of dietary and other sources of excess K+.

Potassium reabsorption:

• About 65% of filtered potassium is absorbed in the proximal convoluted tubule. It is absorbed passively with sodium and water, through the paracellular pathway.
• 25% of the filtered potassium is reabsorbed at the thick ascending limb by the Na+/K+/2Cl transporter.
• Only 10% of the filtered potassium reaches the distal nephron.
• Potassium secretion (and hence excretion):
  • In the distal nephron and the collecting duct
  • Increased distal fluid and sodium delivery increases K+ secretion
  • Hyperkalemia and metabolic alkalosis also directly increase K+ secretion
  • However, the most important factor that influences potassium secretion is aldosterone.
• A negative feedback mechanism exists between plasma potassium concentration and aldosterone.
• Hyperkalemia leads to increased release of aldosterone (via the Renin-angiotensin-aldosterone mechanism or via direct release of aldosterone from the adrenal cortex), which then leads to increased K+ secretion, H+ secretion, and sodium
  reabsorption by the kidneys.

Hypokalemia

Question 16. Write short note on:

• Normal serum potassium level and causes of hypokalemia.
• Hypokalemia

Answer:

• Normal serum potassium level is maintained within a narrow range of 3.5–5.5 mEq/L.
• An abnormally low level (<3.5 mmol/L) of serum potassium (K+) is called hypokalemia.

Clinical Features of Hypokalemia

• The severity of clinical manifestations depends on the degree and duration of hypokalemia.
• Patients with mild hypokalemia (K+ 3–3.5 mEq/L) are usually asymptomatic.
• Nervous system manifestations:
  • Leg cramps
  • Generalized weakness
  • Fasciculations and tetany
  • Ascending paralysis including respiratory muscle paralysis
• Cardiac manifestations:
  • Arrhythmias
  • ECG changes
• GI manifestations:
  • Paralytic ileus

Renal manifestations:

• • Metabolic acidosis
  • Rhabdomyolysis in severe hypokalemia
  • Hypokalemic nephropathy—renal tubular damage
  • Cyst formation
  • Nephrogenic diabetes insipidus
  • Polyuria
• Features of the underlying cause of hypokalemia

Hypokalemia Investigations

• Initial tests:
  • Measurement of serum electrolytes, including bicarbonate, calcium, and magnesium.
  • Blood glucose testing
  • Urea and creatinine

• ECG:
  • ECG changes

• The electrocardiographic changes of hypokalemia are due to delayed ventricular repolarization and do not correlate well with plasma-potassium concentration.
• Urine potassium
• Urine potassium to creatinine ration

Question 17. Discuss approaches to the management of hypokalemia. Add a note on TTKG.
Answer:

Approach to Diagnosis of a Patient with Hypokalemia

• Exclude pseudo hypokalemia and potassium redistribution from the ECF to the ICF, e.g., with marked leukocytosis (e.g., AML), recent IV insulin, and prolonged storage of samples.
• A thorough history and physical examination to determine the etiology, e.g., diuretic and laxative abuse, vomiting, and severity of symptoms.
• In patients with hypokalemic paralysis, life-threatening ventricular arrhythmias or patients with severe hypokalemia who require emergency surgery, emergency treatment should be initiated.
• In the absence of such life-threatening features:
• Assess intake of potassium. If low, consider oral replacement of potassium
• If potassium intake is normal, measure urinary K+ and creatinine.
  • If 24-hour urinary K+ is less than 15 mEq/day or spot urine K+/creatinine ratio is less than 15 mEq/g, it suggests extrarenal potassium loss, such as GI potassium loss.
  • If 24-hour urinary K+ is more than 15 mEq/day or spot urine K+/creatinine ratio is more than 15 mEq/g, it suggests abnormal renal potassium loss.
• If renal loss is present, the next step is to assess the trans tubular potassium gradient (TTKG).
  • TTKG is a measurement of net K+ secretion by the collecting duct after correcting for changes in urine osmolality.
  • TTKG = Urinary K+ × Plasma osmolality/Serum K+ × Urinary osmolality
  • In hypokalemia, TTKG should be <3
  • TTKG > 4 suggests increased distal K+ secretion.
• The next step would be to assess the blood pressure and volume status.
  • If hypertension is found, then measure plasma renin, aldosterone, and cortisol levels
  • If no hypertension is found, look for acid-base status.

If metabolic acidosis is present, the causes include:

• Renal tubular acidosis
• Diabetic ketoacidosis or
• Acetazolamide use

If metabolic alkalosis is present:

• Measure urine chloride levels.
• If urine chloride is <10 mmol/L, consider chloride secreting diarrhea or vomiting
• If urine chloride is >20 mmol/L, measure urine calcium to creatinine ratio
  • Urine calcium to creatinine ratio <0.15:
  • Gitelman syndrome or thiazide diuretic use
  • Urine calcium to creatinine ratio > 0.20: Bartter’s syndrome or loop diuretic use

metabolic alkalosis Additional testing

• Serum digoxin levels if the patient is receiving treatment with digoxin
• Thyroid function tests, especially in patients with paralysis, to rule out thyrotoxic periodic paralysis
• Serum magnesium levels, such as hypomagnesemia, are often associated with hypokalemia, and such patients are often refractory to K+ replacement alone.
• Another testing as per etiology (For Example, CT of adrenal glands mineralocorticoid/ glucocorticoid/ catecholamine excess is suspected).

metabolic alkalosis Treatment

• Therapeutic goals:
  • To correct the potassium deficit
  • To minimize the ongoing losses
  • To treat the underlying cause to prevent further episodes
  • To prevent overly rapid correction, which can cause acute hyperkalemia, which in turn can cause ventricular fibrillation and sudden death
• It should be noted that a decrement of 1 mmol/L in the plasma-potassium concentration (from 4.0 to 3.0 mmol/L) may represent a total body potassium deficit of 200–400 mmol.

Metabolic Alkalosis Oral Therapy

• Oral or enteral therapy is preferred in nonemergent patients who can take it orally and have normal GI tract function.
• Potassium chloride (15 mL = 20 mEq) is the preferred agent. Especially useful in Cl–responsive metabolic alkalosis.
• Potassium phosphate is useful when coexistent phosphorus deficiency.
• Potassium bicarbonate, acetate, gluconate, or citrate is useful in metabolic acidosis.
• Usual dose: 40–100 mEq/day in 2–4 divided doses

metabolic alkalosis IV Therapy

• Indicated for patients with severe hypokalemia (<2.5 mEq/L), symptomatic hypokalemia, those with a nonfunctioning GI tract, or those who are unable to take it orally.
• The maximum concentration of administered potassium should be no more than:
  • 40 mEq/L via a peripheral vein or
  • 100 mEq/L via central vein
• The rate of infusion should not exceed 10–20 mEq/hr unless paralysis or malignant ventricular arrhythmia is present.
• The maximum rate of infusion should not exceed 40 mEq/hr in these cases.
• Maximum dose per day: 240–400 mEq/day

Choice of fluid during the IV therapy

• KCL should always be administered in saline solutions, rather than dextrose-containing solutions.
• This is because dextrose-containing solutions can stimulate cellular potassium uptake, resulting in worsening of the hypokalemia.

Choice of central line placement for IV therapy

In cases of infusion of potassium chloride through central lines, femoral lines are preferred to internal jugular or subclavian central lines, as the infusion through the latter can lead to rapid changes in the local concentration of potassium and affect.

Monitoring during the IV therapy

• Continuous ECG monitoring should be done, especially if the rate of infusion is more than 10 mEq/hr.
• Serum potassium levels should be monitored 1–4 hours after a dose of 60–80 mEq/L is given, before giving further potassium doses.

metabolic alkalosis Additional therapy

• Replace magnesium, if magnesium deficiency is present.
• High potassium diet
• Treat the underlying cause

Hyperkalemia

Question 18.  Write a short essay/note on:

• Causes and treatment of hyperkalemia.
• ECG changes in hyperkalemia.
• Clinical features, diagnosis, and treatment/management of hyperkalemia.
• Drugs used to treat hyperkalemia.

Answer:

Hyperkalemia Definition: Hyperkalemia is defined as plasma potassium greater than 5.5 mEq/L.

Based on severity, it may be classified as:

• Mild hyperkalemia: Serum potassium: 5.5–5.9 mEq/L
• Moderate hyperkalemia: Serum potassium: 5.9–6.4 mEq/L
• Severe hyperkalemia: Serum potassium: ≥6.5 mEq/L

Causes of Hyperkalemia

Hyperkalemia Clinical Features

• Often asymptomatic until plasma K + concentration is greater than 6.5–7.0 mEq/L, when it may lead to fatal cardiac arrhythmia, hence it is called a silent killer. Hence, suspected hyperkalemia is a potential cause in all patients presenting with cardiac arrest.
• Signs and symptoms of underlying disease: For example:
  • CKD
  • History of drugs causing hyperkalemia

Signs and symptoms due to hyperkalemia:

• Cardiac:
  • Arrhythmias

Hyperkalemia Musculoskeletal:

• Weakness
• Paresthesia
• Ascending paralysis

Hyperkalemia Gastrointestinal:

• Nausea
• Vomiting
• Diarrhea

Hyperkalemia Investigations

1. Initial tests:
   1. Measurement of urea, creatinine, and electrolytes, including bicarbonate
   2. Blood glucose levels
   3. Blood gas analysis to look for metabolic acidosis
   4. ECG: ECG changes are shown in Figures 14.12 and 14.13.
   5. The earliest electrocardiographic changes are increased T-wave, amplitude or peaked T-wave.
   6. Urine electrolytes
2. Additional tests:
   1. CPK levels in suspected rhabdomyolysis
   2. LDH levels in suspected hemolysis
   3. Uric acid and phosphorous levels in suspected tumor lysis syndrome
   4. Plasma cortisol, renin, and aldosterone levels to assess
      mineralocorticoid deficiency
   5. Serum digoxin levels in patients receiving digoxin

Hyperkalemia Approach

• Rule out pseudohyperkalemia, transcellular shifts, and excess intake of potassium
• A thorough history and physical examination to determine the etiology (e.g., renal disease, drugs) and severity of symptoms In asymptomatic patients with serum potassium >6.5 mEq/L or those with hyperkalemia and additional ECG changes/muscle weakness/paralysis or significant tissue injury, emergency treatment should be initiated.
• Urine K+ less than 40 mEq/day suggests reduced renal excretion.
• Urine Na+ less than 25 mEq/day suggests that distal sodium delivery is a limiting factor in potassium excretion. Volume correction with normal saline or treatment with furosemide may be effective in reducing potassium levels.
• Measurement of trans tubular potassium gradient (TTKG) helps to determine whether hyperkalemia is caused by aldosterone deficiency/resistance or whether hyperkalemia is secondary to nonrenal cause.
  1. TTKG = Urinary K+ × Plasma osmolality/Serum K+ × Urinary osmolality
  2. Normally expected in the presence of hyperkalemia: 6–12
  3. If <5: Suggests reduced distal potassium secretion
  4. If >8–10: Suggests reduced tubular flow
• In cases of hypokalemia due to reduced distal potassium secretion, 0.05 g of 9α-fludrocortisone is given:
  • If TTKG < 8, it suggests tubular resistance. Likely causes include:
• Tubulointerstitial diseases
• Urinary tract obstruction
• Pseudohypoaldosteronism type 1 or 2
• Drugs: Amiloride, triamterene, spironolactone, calcineurin inhibitors, and trimethoprim
• If TTKG > 8–10, hypoaldosteronism is likely

• In cases of hypoaldosteronism, renin levels should be measured:
  1. Renin high: Primary adrenal insufficiency, isolated aldosterone deficiency, ACE-I, and ARB
  2. Renin low: Pseudohypoaldosteronism type 2, acute glomerulonephritis, diabetes mellitus, beta-blockers, and NSAIDs.

Hyperkalemia Treatment

• The urgency and aggressiveness of the treatment of hyperkalemia depend on its degree and clinical status.

Hyperkalemia Emergency treatment

• Indications for emergency treatment:
  • Asymptomatic potentially fatal hyperkalemia (serum potassium >6.5 mEq/L)
  • Profound weakness including paralysis
  • Absence of P wave, QRS widening, or ventricular arrhythmia on ECG

Other drugs which can be considered in acute hyperkalemia:

• Sodium bicarbonate:
  • Useful in patients who have metabolic acidosis (pH <7.2)
  • Mechanism: Shifts potassium into the cell
  • Adverse effects:
  • Can worsen intravascular volume overload, especially in patients with oliguric AKI
  • Acute hypernatremia
• IV normal saline:
  • Mechanism: Increases distal sodium delivery, thus helping in renal excretion

Hyperkalemia Diuretics:

• Useful for chronic or mild hyperkalemia
• Used in volume-expanded patients or along with IV normal saline
• Mechanism: Increased renal excretion
• Not very effective in patients with severe renal impairment, who constitute the majority of the population with severe hyperkalemia.
• Hence, it is not used routinely in the emergency management of hyperkalemia.

Hyperkalemia Chronic treatment

• Treat the underlying cause
• Stop the offending drug
• Reduction of dietary potassium intake
• Use of medications such as:
  • Diuretics
  • Sodium bicarbonate in patients with acidosis
  • Potassium-binding resins
• Sodium polystyrene sulfonate, Patiromer, Sodium zirconium cyclosilicate
  • Fludrocortisone has been used in patients with chronic hypotension secondary to adrenal insufficiency in patients with normal renal function.

Acid-base Balance

Question 19. Write a short essay/note on:

• Physiology of acid-base balance.
• Different terminologies are used in the assessment of the acid-base status of a patient.

Answer:

Acid-base Balance Definitions

• Acid: Any compound which forms H+ ions in solution (proton donors), e.g., carbonic acid releases H+ ions.
• Base: Any compound that combines with H+ ions in solution (proton acceptors), e.g., bicarbonate (HCO–) accepts H+ ions.

Acid-base Balance Regulation of Acid-Base Balance

• The maintenance of blood pH is an important homeostatic mechanism of the body.
• The pH of the blood is maintained between 7.35 and 7.45.
• Normal pH and its variation are indicated

Acid-base Balance Normal pH and its variation.

• Normal pH: 7.35–7.45
• Acidosis: Physiological state resulting from abnormally low plasma pH
• Alkalosis: Physiological state resulting from abnormally high plasma pH
• Acidemia: Plasma pH < 7.35
• Alkalemia: Plasma pH > 7.45

Maintenance of Acid-Base Balance/pH

• Many physiological mechanisms maintain the pH of the ECF within narrow limits.

Approach To Acid-Base Disorder

Step 1: Determine if the patient has academia (plasma pH < 7.35) or alkalemia (plasma pH > 7.45)

Step 2: Determine the primary abnormality and the compensatory response, as described in Table 14.26

Step 3: Determine whether the compensation is appropriate, If the compensation is not appropriate, it suggests the presence of a combined acid-base disorder.

• Response of the body to acid-base challenge.

1. Buffering: Two most common chemical buffer groups

1. Bicarbonate
2. Nonbicarbonate (hemoglobin, protein, and phosphate):

• Blood buffer systems act instantaneously
• Regulate pH by binding or releasing H+

2. Respiratory acid-base control mechanisms

3. Renal acid-base control mechanisms

Acid-base Balance For example:

• In a patient with metabolic acidosis, the body tries to compensate by lowering the pCO
• If the pCO 2 is lower than expected: Compensation is excessive.
• The patient has an additional respiratory alkalosis.
• If the pCO 2 is higher than expected: Compensation is inadequate.
• The patient has an additional respiratory acidosis.

Step 4: For patients with metabolic acidosis:

• Determine the anion gap.
• Assess the delta ratio

Classification of Acid-Base Disorders

Anion Gap

Question 20. What is the anion gap? Enumerate conditions associated with increased anion gap.
Answer:

• Anion gap (AG) denotes the concentration of the unmeasured anions in the plasma, namely—phosphates, sulfates, organic acids, and protein anions.
• Anion gap = {[Na+] + [K+]} – {[HCO3–] + [Cl–]}
  • Normal cations in plasma: Na+, K+, Ca2+, Mg2+
  • Normal anions in plasma are Cl–, HCO –, and negative charges present on albumin, phosphate, sulfate, lactate, and other organic acids.
  • The sums of the positive and negative charges are equal.
• A normal anionic gap is 8–12 mEq/L.
• Albumin is the principal unmeasured anion.
• Hence, if there are gross changes in serum albumin levels, the following correction should be applied.
• AG corrected = AG + {(4 – albumin) x 2.5}

Elevated anion gap:

• An elevated anion gap suggests the presence of metabolic acidosis with a circulating anion
• Usually found in some forms of metabolic acidosis.

Normal anion gap:

• Normal anion gap metabolic acidosis can result from renal or nonrenal causes

Urinary anion gap (UAG):

• UAG (in mEq/L or mmol/L) = (UNa+ + UK+)- UCl–
• In cases of normal anion gap metabolic acidosis (NAGMA), urine anion gap is useful to distinguish between renal and extrarenal causes.
• UAG is normally a positive value: +30 to +50 mmol/L.

Anion Gap Positive UAG:

• Renal tubular acidosis (types 1, 2, and 4)
• Renal failure
• Negative UAG: Increased renal excretion of an unmeasured cation such as NH4+
• Diarrhea
• Biliary or pancreatic fistulas
• GI-ureteral connections

Anion Gap “Delta Ratio”/“GAP-GAP”

• The ratio of delta anion gap (difference in the anionic gap from the normal anion gap) to delta bicarbonate (the difference in bicarbonate from the normal bicarbonate levels).
• Delta ratio = Δ AG/Δ HCO3–
• It can be used to identify concurrent metabolic disorders.
• Interpretation of delta ratio:
  • 0.8–1.2 = Anion gap metabolic acidosis alone
  • 0.3–0.7 = Anion gap metabolic acidosis + Nonanion gap metabolic acidosis
  • 1.2 = Anion gap metabolic acidosis + Metabolic alkalosis

Metabolic Acidosis

Question 21. Write short note on:

• Causes of metabolic acidosis.
• Clinical features and management of metabolic acidosis.

Answer:

• Metabolic acidosis is a primary acid-base disorder characterized by a fall in both pH of blood (↓ pH) and bicarbonate level in the plasma (↓ HCO₃–).
• Metabolic acidosis can develop when there is an imbalance between net acid production and net acid excretion

• Metabolic acidosis occurs when an acid other than carbonic acid (due to CO2 retention) accumulates in the body, leading to a fall in the plasma bicarbonate.
• Thus, it is due to the gain of strong acid or loss of base (HCO–).

Metabolic Acidosis Clinical Features 

Symptoms are specific and a result of the underlying pathology.

Metabolic Acidosis Treatment

• Correct the underlying disorder
• Sodium bicarbonate may be administered in severe acidosis.
• Tromethamine (tris-hydroxymethyl aminomethane; THAM) is an alternative to NaHCO3.
• Dialysis may be necessary for renal failure with metabolic acidosis.

Metabolic Alkalosis

Question 22. Write a short note on metabolic alkalosis.
Answer: Metabolic alkalosis is characterized by a rise in both plasma bicarbonate levels and plasma pH. The primary event is the elevation of pH due to raised plasma bicarbonate concentration (HCO₃–) or decreased acid.

Metabolic Alkalosis Types: Metabolic alkalosis may be hypovolemic or normovolemic. The causes of metabolic alkalosis are listed

Metabolic Alkalosis Management

• Correct the underlying cause to stop the loss of acid
• Metabolic alkalosis with hypovolemia: Corrected by intravenous infusions of 0.9% saline with potassium supplements.
• This reverses the secondary hyperaldosteronism and the kidneys excrete the excess alkali in the urine.
• Metabolic alkalosis with normal or increased volume: Treatment of the underlying endocrine cause.
• Acetazolamide may be considered for patients with post-hypercapnic metabolic alkalosis
• Dialysis may be required if severe alkalosis or renal failure is present.

Respiratory Acidosis

Question 23. Write a short note on respiratory acidosis.
Answer:

Respiratory acidosis is a primary acid-base disorder characterized by ↑ PCO2↓ pH.

• Acute (<24 hours)
• Chronic (>24 hours)

Causes of Respiratory Acidosis

Clinical features of respiratory acidosis.

• RS (respiratory system):
  • Stimulation of ventilation (tachypnea)
  • Dyspnea
• CNS (central nervous system):
• • ↑cerebral blood flow • ↑ ICT, papilledema
  • CO2 Narcosis (disorientation, confusion, headache, lethargy)
  • Coma (arterial hypoxemia, ↑ ICT, anesthetic effect of ↑ PCO₂
    >100 mm Hg)
• CVS: Tachycardia, bounding pulse
• Others: Peripheral vasodilatation (warm, flushed, sweaty)

Respiratory Acidosis Treatment

• The underlying causes should be corrected.
• Consider ventilatory support:
  • Noninvasive positive pressure ventilation
  • Intubation and mechanical ventilation
  • Rapid infusion of alkali is justified only in prolonged cardiopulmonary arrest.
  • Avoid overfeeding as changes in metabolism may worsen acidosis by increasing the rate of elimination of carbon dioxide.

Respiratory Alkalosis

Question 24. Write a short note on respiratory alkalosis and its causes.
Answer:

• The most common acid-base abnormality in the critically ill is characterized by ↓PCO₂ → ↑pH.
• Primary process: Hyperventilation:
  • Acute: PaCO₂ ↓, pH-alkalemia
  • Chronic: PaCO₂ ↓, pH normal/near normal

Respiratory Alkalosis Treatment

• Elimination of the underlying disorder
• In acute hyperventilation syndrome, sedation and rebreathing into a bag may terminate the attack.

Genetic Syndromes With Acid-Base And Potassium Abnormalities.