Atlas of pathophysiology, 2 Edition

Part I - Central concepts

Fluids and Electrolytes

The body is mostly liquid—various electrolytes dissolved in water. Electrolytes are ions (electrically charged versions) of essential elements—predominantly sodium (Na+), chloride (Cl-), oxygen (O2), hydrogen (H+), bicarbonate (HCO3-), calcium (Ca2+), potassium (K+), sulfate (SO42-), and phosphate (PO43-). Only ionic forms of elements can dissolve or combine with other elements. Electrolyte balance must remain in a narrow range for the body to function. The kidneys maintain chemical balance throughout the body by producing and eliminating urine. They regulate the volume, electrolyte concentration, and acid-base balance of body fluids; detoxify and eliminate wastes; and regulate blood pressure by regulating fluid volume. The skin and lungs also play a vital role in fluid and electrolyte balance. Sweating results in loss of sodium and water, and every breath contains water vapor.

Fluid balance

The kidneys maintain fluid balance in the body by regulating the amount and components of fluid inside and around the cells.

Intracellular fluid

The fluid inside each cell is called intracellular fluid. Each cell has its own mixture of components in the intracellular fluid, but the amounts of these substances are similar in every cell. Intracellular fluid contains large amounts of potassium, magnesium, and phosphate ions.

Extracellular fluid

The fluid in the spaces outside the cells, called extracellular fluid, is constantly moving. Normally, extracellular fluid includes blood plasma and interstitial fluid. In some pathologic states, it accumulates in a so-called third space, the space around organs in the chest or abdomen.

Extracellular fluid is rapidly transported through the body by circulating blood and between blood and tissue fluids by fluid and electrolyte exchange across the capillary walls. It contains large amounts of sodium, chloride, and bicarbonate ions, plus such cell nutrients as oxygen, glucose, fatty acids, and amino acids. It also contains carbon dioxide (CO2), transported from the cells to the lungs for excretion, and other cellular products, transported from the cells to the kidneys for excretion.

Alterations in tonicity

ALTERATIONS

PATHOPHYSIOLOGY

CAUSES

Isotonic

·   Intracellular fluids and extracellular fluids have equal osmotic pressure, but there's a dramatic change in total body fluid volume.

·   No cellular swelling or shrinkage exists because osmosis doesn't occur.

·   Blood loss from penetrating trauma

·   Expansion of fluid volume if a patient receives too much normal saline

Hypertonic

·   Extracellular fluid is more concentrated than intracellular fluid.

·   Water flows out of the cell through the semipermeable cell membrane, causing cell shrinkage.

·   Administration of hypertonic (> 0.9%) saline

·   Hypernatremia from severe dehydration

·   Sodium retention from renal disease

Hypotonic

·   Decreased osmotic pressure forces some extracellular fluid into the cells, causing them to swell.

·   In extreme hypotonicity, cells may swell until they burst and die.

·   Overhydration

The kidneys maintain the volume and composition of extracellular fluid and, to a lesser extent, intracellular fluid by continually exchanging water and ionic solutes, such as hydrogen, sodium, potassium, chloride, bicarbonate, sulfate, and phosphate ions, across the cell membranes of the renal tubules.

Fluid exchange

Four forces act to equalize concentrations of fluids, electrolytes, and proteins on both sides of the capillary wall by moving fluid between the vessels and the interstitial fluid. Forces that move fluid out of blood vessels are:

·   hydrostatic pressure of blood

·   osmotic pressure of tissue fluid.

Forces that move fluid into blood vessels are:

·   oncotic pressure of plasma proteins

·   hydrostatic pressure of interstitial fluid.

Hydrostatic pressure is higher at the arteriolar end of the capillary bed than at the venular end. Oncotic pressure of plasma increases slightly at the venular end as fluid is drawn into the blood vessel. When the endothelial barrier (capillary wall) is normal and intact, fluid escapes at the arteriolar end of the capillary bed and is returned at the venular end. The small amount of fluid lost from the capillaries into the interstitial tissue spaces is drained off through the lymphatic system and returned to the bloodstream.

Acid-base balance

Regulation of the extracellular fluid environment involves the ratio of acid to base, measured clinically as pH. In physiology, all positively charged ions are acids and all negatively charged ions are bases. To regulate acid-base balance, the kidneys secrete hydrogen ions (acid), reabsorb sodium (acid) and bicarbonate

P.29


ions (base), acidify phosphate salts, and produce ammonium ions (acid). This keeps the blood at its normal pH of 7.35 to 7.45. Important pH boundaries include:

·   < 6.8 incompatible with life

·   < 7.2 cell function seriously impaired

·   < 7.35 acidosis

·   7.35 to 7.45 normal

·   > 7.45 alkalosis

·   > 7.55 cell function seriously impaired

·   > 7.8 incompatible with life.

Normal electrolyte values

Sodium

135 to 145 mEq/L

Potassium

3.5 to 5 mEq/L

Chloride

96 to 106 mEq/L

Calcium

8.5 to 10.5 mg/dl

Magnesium

1.8 to 2.5 mEq/L

Phosphate

2.5 to 4.5 mg/dl

Pathophysiologic concepts

The regulation of intracellular and extracellular electrolyte concentrations depends on these factors:

·   balance between intake of substances containing electrolytes and output of electrolytes in urine, feces, and sweat

·   transport of fluid and electrolytes between extracellular and intracellular fluid.

Fluid imbalance occurs when regulatory mechanisms can't compensate for abnormal intake and output at any level from the cell to the organism. Fluid and electrolyte imbalances include edema, isotonic alterations, hypertonic alterations, hypotonic alterations, and electrolyte imbalances. Disorders of fluid volume or osmolarity result. Many conditions also affect capillary exchange, resulting in fluid shifts.

Edema

Despite almost constant interchange through the endothelial barrier, the body maintains a steady state of extracellular water balance between the plasma and interstitial fluid. Increased fluid volume in the interstitial spaces is called edema. It's classified as localized or systemic. Obstruction of the veins or lymphatic system or increased vascular permeability usually causes localized edema in the affected area, such as the swelling around an injury. Systemic, or generalized, edema may be due to heart failure or renal disease. Massive systemic edema is called anasarca.

Edema results from abnormal expansion of the interstitial fluid or the accumulation of fluid in a third space, such as the peritoneum (ascites), pleural cavity (hydrothorax), or pericardial sac (pericardial effusion).

Tonicity

Many fluid and electrolyte disorders are classified according to how they affect osmotic pressure, or tonicity. (See Alterations in tonicity.) Tonicity describes the relative concentrations of electrolytes (osmotic pressure)

P.30


on both sides of a semipermeable membrane (the cell wall or the capillary wall). The word normal in this context refers to the usual electrolyte concentration of physiologic fluids. Normal saline solution has a sodium chloride concentration of 0.9%.

Major electrolytes

ELECTROLYTE

CHARACTERISTICS

Sodium

·   Major extracellular fluid cation

·   Maintains tonicity of extracellular fluid

·   Regulates acid-base balance by renal reabsorption of sodium ion (base) and excretion of hydrogen ion (acid)

·   Facilitates nerve conduction and neuromuscular function

·   Facilitates glandular secretion

·   Maintains water balance

Potassium

·   Major intracellular fluid cation

·   Maintains cell electrical neutrality

·   Facilitates cardiac muscle contraction and electrical conductivity

·   Facilitates neuromuscular transmission of nerve impulses

·   Maintains acid-base balance

Chloride

·   Mainly an extracellular fluid anion

·   Accounts for two-thirds of all serum anions

·   Secreted by the stomach mucosa as hydrochloric acid, providing an acid medium for digestion and enzyme activation

·   Helps maintain acid-base and water balances

·   Influences tonicity of extracellular fluid

·   Facilitates exchange of oxygen and carbon dioxide in red blood cells

·   Helps activate salivary amylase, which triggers the digestive process

Calcium

·   Indispensable to cell permeability, bone and teeth formation, blood coagulation, nerve impulse transmission, and normal muscle contraction

·   Plays a vital role in cardiac action potential and is essential for cardiac pacemaker automaticity

Magnesium

·   Present in small quantities, but physiologically as significant as the other major electrolytes

·   Enhances neuromuscular communication

·   Stimulates parathyroid hormone secretion, which regulates intracellular calcium

·   Activates many enzymes in carbohydrate and protein metabolism

·   Facilitates cell metabolism

·   Facilitates sodium, potassium, and calcium transport across cell membranes

·   Facilitates protein transport

Phosphate

·   Involved in cellular metabolism as well as neuromuscular regulation and hematologic function

·   Phosphate reabsorption in the renal tubules inversely related to calcium levels (an increase in urinary phosphorous triggers calcium reabsorption and vice versa)

Disorders of Fluid Balance: Hypovolemia

CAUSES

PATHOPHYSIOLOGY

SIGNS AND SYMPTOMS

DIAGNOSTIC TEST RESULTS

TREATMENT

Hypovolemia is an isotonic disorder. Fluid volume deficit decreases capillary hydrostatic pressure and fluid transport. Cells are deprived of normal nutrients that serve as substrates for energy production, metabolism, and other cellular functions. Hypovolemia results from these causes:Fluid loss

·   Hemorrhage

·   Excessive perspiration

·   Renal failure with polyuria

·   Abdominal surgery

·   Vomiting or diarrhea

·   Nasogastric drainage

·   Diabetes mellitus with polyuria or diabetes insipidus

·   Fistulas

·   Excessive use of laxatives; diuretic therapy

·   Fever

Reduced fluid intake

·   Dysphagia

·   Coma

·   Environmental conditions preventing fluid intake

·   Psychiatric illness

Fluid shift from extracellular fluid

·   Burns (during the initial phase)

·   Acute intestinal obstruction

·   Acute peritonitis

·   Pancreatitis

·   Crushing injury

·   Pleural effusion

·   Hip fracture

Decreased renal blood flow triggers the renin-angiotensin system to increase sodium and water reabsorption. The cardiovascular system compensates by increasing heart rate, cardiac contractility, venous constriction, and systemic vascular resistance, thus increasing cardiac output and mean arterial pressure (MAP). Hypovolemia also triggers the thirst response, releasing more antidiuretic hormone and producing more aldosterone.
When compensation fails, hypovolemic shock occurs in this sequence:

·   decreased intravascular fluid volume

·   diminished venous return, which reduces preload and decreases stroke volume

·   reduced cardiac output

·   decreased MAP

·   impaired tissue perfusion

·   decreased oxygen and nutrient delivery to cells

·   multiple organ dysfunction syndrome.

·  Orthostatic hypotension

·  Tachycardia

·   Thirst

·  Flattened jugular veins

·   Sunken eyeballs

·   Dry mucous membranes

·  Diminished skin turgor

·   Rapid weight loss

·  Decreased urine output

·  Prolonged capillary refill time

·   Increased blood urea nitrogen

·   Elevated serum creatinine level

·   Increased serum protein, hemoglobin, and hematocrit (unless caused by hemorrhage, when loss of blood elements causes subnormal values)

·   Rising blood glucose

·   Elevated serum osmolality (except in hyponatremia, where serum osmolality is low)

·   Serum electrolyte and arterial blood gas analysis may reflect associated clinical problems resulting from the underlying cause of hypovolemia or the treatment regimen

·   Urine specific gravity > 1.030

·   Increased urine osmolality

·   Urine sodium level < 50 mEq/L

·   Oral fluids

·   Parenteral fluids

·   Fluid resuscitation by rapid I.V. administration

·   Blood or blood products (with hemorrhage)

·   Antidiarrheals as needed

·   Antiemetics as needed

·   I.V. dopamine (lntropin) or norepinephrine (Levophed) to increase cardiac contractility and renal perfusion (if patient remains symptomatic after fluid replacement)

·   Autotransfusion (for some patients with hypovolemia caused by trauma)

·   Isotonic solutions have the same electrolyte concentration and therefore the same osmotic pressure as extracellular fluid.

·   Hypertonic solutions have a greater than normal concentration of some essential electrolyte, usually sodium.

·   Hypotonic solutions have a lower than normal concentration of some essential electrolyte, also usually sodium.

Electrolyte balance

The major electrolytes are the cations sodium, potassium, calcium, and magnesium and the anions chloride, phosphate, and bicarbonate. The body continuously attempts to maintain intracellular and extracellular equilibrium of electrolytes. Too much or too little of any electrolyte will affect most body systems.

P.31


(See Major electrolytes, page 29, and Normal electrolyte values, page 29.)

Disorders of Fluid Balance: Hypervolemia

CAUSES

PATHOPHYSIOLOGY

SIGNS AND SYMPTOMS

DIAGNOSTIC TEST RESULTS

TREATMENT

Hypervolemia is an abnormal increase in the volume of circulating fluid (plasma) in the body. It results from these causes:
Increased risk for sdium and water retention

·   Heart failure

·   Hepatic cirrhosis

·   Nephrotic syndrome

·   Corticosteroid therapy

·   Low dietary protein intake

·   Renal failure

Excessive sodium and water intake

·   Parenteral fluid replacement with normal saline or lactated Ringer's solution

·   Blood or plasma replacement

·   Excessive dietary intake of water, sodium chloride, or other salts

Fluid shift to extracellular fluid

·   Remobilization of fluid after burn treatment

·   Intake of hypertonic fluids

·   Intake of colloid oncotic fluids

Increased extracellular fluid volume causes this sequence of events:

·   circulatory overload

·   increased cardiac contractility and mean arterial pressure (MAP)

·   increased capillary hydrostatic pressure

·   shift of fluid to the interstitial space

·   edema.

Elevated MAP inhibits secretion of antidiuretic hormone and aldosterone and consequent increased urinary elimination of water and sodium. These compensatory mechanisms usually restore normal intravascular volume. If hypervolemia is severe or prolonged or the patient has a history of cardiovascular dysfunction, compensatory mechanisms may fail, and heart failure and pulmonary edema may ensue.

·   Rapid breathing

·  Dyspnea

·  Crackles

·   Rapid, bounding pulse

·  Hypertension

·   Jugular vein distention

·   Moist skin

·   Acute weight gain

·   Edema

·  S3 gallop

·   Decreased serum potassium and blood urea nitrogen

·   Decreased hematocrit due to hemodilution

·   Normal or low serum sodium

·   Low urine sodium excretion

·   Increased hemodynamic values

·   Treatment of underlying condition

·   Oxygen administration

·   Use of thromboembolic disease support hose to help mobilize edematous fluid

·   Bed rest

·   Restricted sodium and water intake

·   Preload reduction agents and afterload reduction agents

·   Hemodialysis or peritoneal dialysis

·   Continuous arteriovenous hemofiltration

·   Continuous venovenous hemofiltration

Electrolyte imbalances can affect all body systems. Too much or too little potassium or too little calcium or magnesium can increase the excitability of the cardiac muscle, causing arrhythmias. Multiple neurologic symptoms may result from electrolyte imbalance, ranging from disorientation or confusion to a completely depressed central nervous system. Too much or too little sodium or too much potassium can cause oliguria. Blood pressure may be increased or decreased. The GI tract is particularly susceptible to electrolyte imbalance:

·   too much potassium—leads to abdominal cramps, nausea, and diarrhea

·   too little potassium—leads to paralytic ileus

·   too much magnesium—leads to nausea, vomiting, and diarrhea

·   too much calcium—leads to nausea, vomiting, and constipation.

Acid-base imbalance

Acid-base balance is essential to life. Concepts related to imbalance include:

·   acidemia—arterial pH less than 7.35, which reflects a relative excess of acid in the blood. The hydrogen ion content in extracellular fluid increases, and the hydrogen ions move to the intracellular fluid. To keep the intracellular fluid electrically neutral, an equal amount of potassium leaves the cell, creating a relative hyperkalemia.

·   alkalemia—arterial blood pH greater than 7.45, which reflects a relative excess of base in the blood. In alkalemia, an excess of hydrogen ions in the intracellular fluid forces them into the extracellular fluid. To keep the intracellular fluid electrically neutral, potassium moves from the extracellular to the intracellular fluid, creating a relative hypokalemia.

·   acidosis—a systemic increase in hydrogen ion concentration. If the lungs fail to eliminate CO2 or if volatile (carbonic) or nonvolatile (lactic) acid products of metabolism accumulate, hydrogen ion concentration rises. Acidosis can also occur if

P.32

P.33


persistent diarrhea causes loss of basic bicarbonate anions or the kidneys fail to reabsorb bicarbonate or secrete hydrogen ions.

·   alkalosis—a bodywide decrease in hydrogen ion concentration. An excessive loss of CO2 during hyperventilation, loss of nonvolatile acids during vomiting, or excessive ingestion of base may decrease hydrogen ion concentration.

·   compensation—the lungs and kidneys, along with a number of chemical buffer systems in the intracellular and extracellular compartments, work together to maintain plasma pH in the range of 7.35 to 7.45.

Disorders of Electrolyte Balance

ELECTROLYTE IMBALANCE

SIGNS AND SYMPTOMS

DIAGNOSTIC TEST RESULTS

Hyponatremia

·   Muscle twitching and weakness

·   Lethargy, confusion, seizures, and coma

·   Hypotension and tachycardia

·   Nausea, vomiting, and abdominal cramps

·   Oliguria or anuria

·   Serum sodium <135 mEq/L

·   Decreased urine specific gravity

·   Decreased serum osmolality

·   Urine sodium >100 mEq/24 hours

·   Increased red blood cell count

Hypernatremia

·   Agitation, restlessness, fever, and decreased level of consciousness

·   Muscle irritability and convulsions

·   Hypertension, tachycardia, pitting edema, and excessive weight gain

·   Thirst, increased viscosity of saliva, and rough tongue

·   Dyspnea, respiratory arrest, and death

·   Serum sodium >145 mEq/L

·   Urine sodium <40 mEq/24 hours

·   High serum osmolality

Hypokalemia

·   Dizziness, hypotension, arrhythmias, electrocardiogram (ECG) changes, and cardiac and respiratory arrest

·   Nausea, vomiting, anorexia, diarrhea, decreased peristalsis, abdominal distention, and paralytic ileus

·   Muscle weakness, fatigue, and leg cramps

·   Serum potassium <3.5 mEq/L

·   Coexisting low serum calcium and magnesium levels not responsive to treatment for hypokalemia usually suggest hypomagnesemia

·   Metabolic alkalosis

·   ECG changes, including flattened T waves, elevated U waves, and depressed ST segment

Hyperkalemia

·   Tachycardia changing to bradycardia, ECG changes, and cardiac arrest

·   Nausea, diarrhea, and abdominal cramps

·   Muscle weakness and flaccid paralysis

·   Serum potassium >5 mEq/L

·   Metabolic acidosis

·   ECG changes, including tented and elevated T waves, widened QRS complex, prolonged PR interval, flattened or absent P waves, and depressed ST segment

Hypochloremia

·   Muscle hyperexcitability and tetany

·   Shallow, depressed breathing

·   Usually associated with hyponatremia and its characteristic symptoms, such as muscle weakness and twitching

·   Serum chloride < 96 mEq/L

·   Serum pH > 7.45, serum CO >32 mEq/L (supportive values)

Hyperchloremia

·   Deep, rapid breathing

·   Weakness

·   Lethargy, possibly leading to coma

·   Serum chloride > 108 mEq/L

·   Serum pH < 7.35, serum CO < 22 mEq/L (supportive values)

Hypocalcemia

·   Anxiety, irritability, twitching around the mouth, laryngospasm, seizures, positive Chvostek's and Trousseau's signs

·   Hypotension and arrhythmias due to decreased calcium influx

·   Serum calcium < 8.5 mg/dl

·   Low platelet count

·   ECG changes: lengthened QT interval, prolonged ST segment, and arrhythmias

Hypercalcemia

·   Drowsiness, lethargy, headaches, irritability, confusion, depression, apathy, tingling and numbness of fingers, muscle cramps, and convulsions

·   Weakness and muscle flaccidity

·   Bone pain and pathological fractures

·   Heart block

·   Anorexia, nausea, vomiting, constipation, dehydration, and abdominal cramps

·   Flank pain

·   Serum calcium >10.5 mg/dl

·   ECG changes: signs of heart block and shortened QT interval

·   Decreased parathyroid hormone level

·   Calcium stones in urine

Hypomagnesemia

·   Nearly always coexists with hypokalemia and hypocalcemia

·   Hyperirritability, tetany, leg and foot cramps, positive Chvostek's and Trousseau's signs, confusion, delusions, and seizures

·   Arrhythmias, vasodilation, and hypotension

·   Serum magnesium <1.8 mEq/L

·   Coexisting low serum potassium and calcium levels

Hypermagnesemia

·   Central nervous system depression, lethargy, and drowsiness

·   Diminished reflexes; muscle weakness to flaccid paralysis

·   Respiratory depression

·   Heart block, bradycardia, widened QRS, and prolonged QT interval

·   Hypotension

·   Serum magnesium > 2.5 mEq/L

·   Coexisting elevated potassium and calcium levels

Hypophosphatemia

·   Muscle weakness, tremor, and paresthesia

·   Tissue hypoxia

·   Bone pain, decreased reflexes, and seizures

·   Weak pulse

·   Hyperventilation

·   Dysphagia and anorexia

·   Serum phosphate < 2.5 mg/dl

·   Urine phosphate >1.3 g/2 hours

Hyperphosphatemia

·   Usually asymptomatic unless leading to hypocalcemia, then evidenced by tetany and seizures

·   Hyperreflexia, flaccid paralysis, and muscular weakness

·   Serum phosphate > 4.5 mg/dl

·   Serum calcium < 8.5 mg/dl

·   Urine phosphorus < 0.9 g/24 hours

Buffer systems

A buffer system consists of a weak acid (one that doesn't readily release free hydrogen ions) and a corresponding base such as sodium bicarbonate. These buffers resist or minimize a change in pH when an acid or base is added to the buffered solution. Buffers work in seconds.

The four major buffers or buffer systems are:

·   carbonic acid–bicarbonate system

·   hemoglobin-oxyhemoglobin system

·   other protein buffers

·   phosphate system.

When primary disease processes alter either the acid or base component of the ratio, the lungs or kidneys (whichever isn't affected by the disease process) act to restore the ratio and normalize pH. Because the body's mechanisms that regulate pH occur in stepwise fashion over time, the body tolerates gradual changes in pH better than abrupt ones.

Renal mechanisms

If a respiratory disorder causes acidosis or alkalosis, the kidneys respond by altering the processing of hydrogen and bicarbonate ions to return the pH to normal. Renal compensation begins hours to days after a respiratory alteration in pH. Despite this delay, renal compensation is powerful.

·   Acidemia—Kidneys excrete excess hydrogen ions, which may combine with phosphate or ammonia to form titratable acids in the urine. The net effect is to raise the concentration of bicarbonate ions in the extracellular fluid and restore acid-base balance.

·   Alkalemia—Kidneys excrete excess bicarbonate ions, usually with sodium ions. The net effect is to reduce the concentration of bicarbonate ions in the extracellular fluid and restore acid-base balance.

Pulmonary mechanisms

If acidosis or alkalosis results from a metabolic or renal disorder, the respiratory system regulates the respiratory rate to return pH to normal. The partial pressure of carbon dioxide in arterial blood (PaCO2) reflects CO2 levels proportionate to blood pH. As the concentration of the gas increases, so does its partial pressure. Within minutes after the slightest change in PaCO2, central chemoreceptors in the medulla that regulate the rate and depth of ventilation detect the change and respond as follows:

·   acidemia—increased respiratory rate and depth to eliminate CO2

·   alkalemia—decreased respiratory rate and depth to retain CO2.

Disorders

Fluid and electrolyte balance is essential for health. Many factors, such as illness, injury, surgery, and treatments, can disrupt fluid and electrolyte balances. (See Disorders of fluid balance: Hypovolemia, page 30; Disorders of fluid balance: Hypervolemia, page 31; and Disorders of electrolyte balance.)

Acid-base disturbances can cause respiratory acidosis or alkalosis or metabolic acidosis or alkalosis. (See Disorders of acid-base balance, pages 34 and 35.)

P.34

P.35

P.36

Disorders of Acid-Base Balance

DISORDER AND CAUSES

PATHOPHYSIOLOGY

SIGNS AND SYMPTOMS

DIAGNOSTIC TEST RESULTS

TREATMENT

Respiratory acidosis

·   Airway obstruction or parenchymal lung disease

·   Mechanical ventilation

·   Chronic metabolic alkalosis as respiratory compensatory mechanisms try to normalize pH

·   Chronic bronchitis

·   Extensive pneumonia

·   Large pneumothorax

·   Pulmonary edema

·   Asthma

·   Chronic obstructive pulmonary disease (COPD)

·   Drugs

·   Cardiac arrest

·   Central nervous system (CNS) trauma

·   Neuromuscular diseases

·   Sleep apnea

When pulmonary ventilation decreases, partial pressure of carbon dioxide in arterial blood (PaCO2) increases and carbon dioxide (CO2) level rises. Retained CO2combines with water (H2O) to form carbonic acid (H2CO3), which dissociates to release free hydrogen (H+) and bicarbonate (HC03) ions. Increased Paco2 and free H+ ions stimulate the medulla to increase respiratory drive and expel CO2.
As pH falls, 2,3-diphosphoglycerate (2,3-DPG) accumulates in red blood cells, where it alters hemoglobin (Hb) to release oxygen. The Hb picks up H+ ions and CO2 and removes them from the serum. As respiratory mechanisms fail, rising PaCO2stimulates kidneys to retain HCO3 and sodium (Na+) ions and excrete H+ ions.
As the H+ ion concentration overwhelms compensatory mechanisms, H+ ions move into cells and potassium (K+) ions move out. Without enough oxygen, anaerobic metabolism produces lactic acid.

·   Restlessness

·   Confusion

·   Apprehension

·   Somnolence

·   Asterixis

·   Headaches

·   Dyspnea and tachypnea

·   Papilledema

·   Depressed reflexes

·   Hypoxemia

·   Tachycardia

·   Hypertension/hypotension

·   Atrial and ventricular arrhythmias

·   Coma

Arterial blood gas (ABG) analysis: PaCO2 > 45 mm Hg; pH <7.35 to 7.45; and normal HCO3 in the acute stage and elevated HCO3 in the chronic stage

For pulmonary causes

·   Removal of foreign body obstructing the airway

·   Mechanical ventilation

·   Bronchodilators

·   Antibiotics for pneumonia

·   Chest tubes for pneumothorax

·   Thrombolytics or anticoagulants for pulmonary emboli

·   Bronchoscopy to remove excess secretions

For COPD

·   Bronchodilators

·   Oxygen at low flow rates

·   Corticosteroids

For other causes

·   Drug therapy

·   Dialysis or activated charcoal to remove toxins

·   Correction of metabolic alkalosis

·   I.V. sodium bicarbonate

Respiratory alkalosis

·   Acute hypoxemia, pneumonia, interstitial lung disease, pulmonary vascular disease, or acute asthma

·   Anxiety

·   Hypermetabolic states, such as fever and sepsis

·   Excessive mechanical ventilation

·   Salicylate toxicity

·   Metabolic acidosis

·   Hepatic failure

·   Pregnancy

As pulmonary ventilation increases, excessive CO2 is exhaled. Resulting hypocapnia leads to reduction of H2CO3 excretion of H+ and HCO3 ions, and rising serum pH.
Against rising pH, the hydrogen-potassium buffer system pulls H+ ions out of cells and into blood in exchange for K+ ions. H+ ions entering blood combine with HC03ions to form H2CO3, and pH falls.
Hypocapnia causes an increase in heart rate, cerebral vasoconstriction, and decreased cerebral blood flow. After 6 hours, kidneys secrete more HCO3 and less H+.
Continued low Paco2 and vasoconstriction increases cerebral and peripheral hypoxia. Severe alkalosis inhibits calcium (Ca+) ionization, increasing nerve and muscle excitability.

·   Deep, rapid breathing

·   Light-headedness or dizziness

·   Agitation

·   Circumoral and peripheral paresthesias

·   Carpopedal spasms, twitching, and muscle weakness

ABG analysis showing PaCO2 < 35 mm Hg; elevated pH in proportion to decrease in Paco2in the acute stage but decreasing toward normal in the chronic stage; normal HCO3 in the acute stage but less than normal in the chronic stage

·   Removal of ingested toxins, such as salicylates, by inducing emesis or using gastic lavage

·   Treatment of fever or sepsis

·   Oxygen for acute hypoxemia

·   Treatment of CNS disease

·   Having patient breathe into a paper bag

·   Adjustments to mechanical ventilation to decrease minute ventilation

Metabolic acidosis

·   Excessive acid accumulation

·   Deficient HCO3scores

·   Decreased acid excretion by the kidneys

·   Diabetic ketoacidosis

·   Chronic alcoholism

·   Malnutrition or a low-carbohydrate, high-fat diet

·   Anaerobic carbohydrate metabolism

·   Underexcretion of metabolized acids or inability to conserve base

·   Diarrhea, intestinal malabsorption, or loss of sodium bicarbonate from the intestines

·   Salicylate intoxication, exogenous poisoning or, less frequently, Addison's disease

·   Inhibited secretion of acid

As H+ ions begin accumulating in the body, chemical buffers (plasma HCO3 and proteins) in cells and extracellular fluid bind them. Excess H+ ions decrease blood pH and stimulate chemoreceptors in the medulla to increase respiration. Consequent fall of partial pressure of Paco2 frees H+ ions to bind with HCO3 ions. Respiratory compensation occurs but isn't sufficient to correct acidosis.
Healthy kidneys compensate, excreting excess H+ ions, buffered by phosphate or ammonia. For each H+ ion excreted, renal tubules reabsorb and return to blood one Na+ ion and one HCO3 ion.
Excess H+ ions in extracellular fluid passively diffuse into cells. To maintain balance of charge across cell membrane, cells release K+ ions. Excess H+ ions change the normal balance of K+, Na+, and Ca+ ions, impairing neural excitability.

·   Headache and lethargy progressing to drowsiness, central nervous system (CNS) depression, Kussmaul's respirations, hypotension, stupor, and coma and death

·   Associated GI distress leading to anorexia, nausea, vomiting, diarrhea, and possibly dehydration

·   Warm, flushed skin

·   Fruity-smelling breath

·   Arterial pH <7.35; PaCO2 normal or < 35 mm Hg as respiratory compensatory mechanisms take hold; HCO3 may be < 22 mEq/L

·   Urine pH < 4.5 in the absence of renal disease

·   Elevated plasma lactic acid in lactic acidosis

·   Anion gap >14 mEq/L in high anion gap metabolic acidosis, lactic acidosis, ketoacidosis, aspirin overdose, alcohol poisoning, renal failure, or other disorder characterized by accumulation of organic acids, sulfates, or phosphates

·   Anion gap 12 mEq/L or less in normal anion gap metabolic acidosis from HCO3 loss, Gl or renal loss, increased acid load, rapid I.V. saline administration, or other disorders characterized by HCO3 loss

·   Sodium bicarbonate I.V. for severe high anion gap

·   I.V. lactated Ringer's solution

·   Evaluation and correction of electrolyte imbalances

·   Correction of underlying cause

·   Mechanical ventilation to maintain respiratory compensation, if needed

·   Antibiotic therapy to treat infection

·   Dialysis for patients with renal failure or certain drug toxicities

·   Antidiarrheal agents for diarrhea-induced HCO3 loss

·   Position patient to prevent aspiration

·   Seizure precautions

Metabolic alkalosis

·   Chronic vomiting

·   Nasogastric tube drainage or lavage without adequate electrolyte replacement

·   Fistulas

·   Use of steroids and certain diuretics (furosemide [Lasix], thiazides, and ethacrynic acid [Edecrin])

·   Massive blood transfusions

·   Cushing's disease, primary hyperaldosteronism, and Bartter's syndrome

·   Excessive intake of bicarbonate of soda, other antacids, or absorbable alkali

·   Excessive amounts of I.V. fluids; high serum concentrations of bicarbonate or lactate

·   Respiratory insufficiency

·   Low serum chloride

·   Low serum potassium