SEMINAR ON Acid-base balance & imbalance

ACIDBASE BALANCE & IMBALANCE INTRODUCTION Nearly all biochemical reactions in the body are dependent on maintenance of a physiological hydrogen ion concentration. The latter is closely regulated because changes in hydrogen ion concentration produce widespread organ dysfunction. This regulationoften referred to as acidbase balanceis of prime importance to anesthesiologists. Changes in ventilation and perfusion and the infusion of electrolyte-containing solutions are common during anesthesia and can rapidly alter acidbase balance. A thorough understanding of acidbase disturbances, their physiological effects, and treatment is thus essential for proper anesthetic management. KEY TERMS Acid a) Any ionic or molecular substance that can act as a proton donor; (b) A sour-tasting sub-stance, like vinegar; (c) A chemical compound that can react with a base to form a salt. Acidosis dangerous condition where the blood and body tissues are less alkaline (or more acidic) than normal. Alkalosis excessive alkalinity of the blood and body tissue. Alkalemia abnormal blood alkalinity.
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Base a) Any ionic or molecular substance that can act as a proton acceptor; (b) A bitter-tasting substance which has a soapy feel; (c) A chemical compound that can react with an acid to form a salt. A base can also be called an alkali. Bicarbonate salt of carbonic acid produced by neutralizing a hydrogen ion. Diabetic ketoacidosis condition characterized by excessive thirst and urination. Other symptoms may include appetite loss, nausea, vomiting, and rapid deep breathing. Diuretic agent or drug that eliminates excessive water in the body by increasing the flow of urine. Electrolyte substance such as an acid, bases, or salt. An electrolyte's water solution will conduct an electric current and ionizes. Acids, bases, and salts are electrolytes. Homeostasis organism's regulation of body processes to maintain internal equilibrium in temperature and fluid content. Hypochloremic alkalosis large loss of chloride. Hypokalemic alkalosis low plasma potassium. pH the negative logarithm of H+ (hydrogen) concentration.

DEFINITION: Acid-base balance can be defined as homeostasis of the body fluids at a normal arterial blood pH ranging between 7.37 and 7.43. Acidbase imbalance is an abnormality of the human body's normal balance of acids and bases that causes the plasma pH to deviate out of the normal range (7.35 to 7.45). In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.18 to 7.38). It can exist in varying levels of severity, some lifethreatening. Blood gas, acid-base, & gas exchange terms Arterial oxygen tension, or partial pressure Alveolar oxygen tension, or partial pressure Arterial carbon dioxide tension, or partial pressure Alveolar carbon dioxide tension, or partial pressure Oxygen tension of mixed venous blood

PaO2

PAO2

PaCO2

PACO2

PvO2

P(Aa)O2

Alveolar-arterial oxygen tension difference. The term formerly used (A-a DO2) is discouraged. Alveolar-arterial tension ratio;

P(a/A)O2 PaO2:PAO2 The term oxygen exchange index describes this ratio. Arteriovenous oxygen content difference Oxygen saturation of the hemoglobin of arterial blood Oxygen saturation as measured by pulse oximetry Oxygen content of arterial blood Symbol relating the hydrogen ion concentration or activity of a solution to that of a standard solution;
pH

C(a-v)O2

SaO2

SpO2

CaO2

approximately equal to the negative logarithm of the hydrogen ion concentration. pH is an indicator of the relative acidity or alkalinity of a solution

 The strong ion difference, PCO2, and total weak acid concentration (ATOT) best explain acidbase balance in physiological systems. The bicarbonate buffer is effective against metabolic but not respiratory acidbase disturbances. In contrast to the bicarbonate buffer, hemoglobin is capable of buffering both carbonic (CO2) and noncarbonic (nonvolatile) acids. As a general rule, PaCO2 can be expected to increase 0.251 mm Hg for each 1 mEq/L increase in [HCO3]. The renal response to acidemia is 3-fold: (1) increased reabsorption of the filtered HCO3, (2) increased excretion of titratable acids, and (3) increased production of ammonia. During chronic respiratory acidosis, plasma [HCO3] increases

approximately 4 mEq/L for each 10 mm Hg increase in PaCO2 above 40 mm Hg. Diarrhea is the most common cause of hyperchloremic metabolic acidosis. The distinction between acute and chronic respiratory alkalosis is not always made, because the compensatory response to chronic respiratory alkalosis is quite variable: plasma [HCO3] decreases 25 mEq/L for each 10 mm Hg decrease in PaCO2 below 40 mm Hg. Vomiting or continuous loss of gastric fluid by gastric drainage (nasogastric suctioning) can result in marked metabolic alkalosis, extracellular volume depletion, and hypokalemia. The combination of alkalemia and hypokalemia can precipitate severe atrial and ventricular arrhythmias. Changes in temperature affect measurements of PCO2 and PO2 directly and measurements of pH indirectly. Both PCO2 and PO2 therefore decrease
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during hypothermia, but pH increases because temperature does not appreciably alter [HCO3]: PaCO2 decreases, but [HCO3] is unchanged.
NORMAL MECHANISMS

A normal range for arterial pH is 7.35 to 7.45. Acidosis is a pH less than 7.35; alkalosis is a pH greater than 7.45. Because pH is measured in terms of hydrogen (H+) ion concentration, an increase in H+ ion concentration decreases pH and vice versa. Changes in H+ ion concentration can be stabilized through several buffering systems: bicarbonate-carbonic acid, proteins, hemoglobin, and phosphates. Acidosis, therefore, can be described as a physiologic condition caused by the body's inability to buffer excess H+ ions. At the other end, alkalosis results from a deficiency in H+ ion concentration. Acidemia and alkalemia refer to the process of acidosis or alkalosis, respectively, occurring in arterial blood. Body acids are formed as end products of cellular metabolism. Under normal physiologic conditions, a person generates 50 to 100 mEq/day of acid from metabolism of carbohydrates, proteins, and fats. In addition, the body loses base in the stool. In order to maintain acid-base homeostasis, acid production must balance the neutralization or excretion. The lungs and kidneys are the main regulators of acid-base homeostasis. The lungs release CO2, an end product of carbonic acid (H2CO3). The renal tubules, with the regulation of bicarbonate (HCO3-), excrete other acids produced from the metabolism of proteins, carbohydrates, and fats. COMPENSATING FOR CHANGES The body has three compensatory mechanisms to handle changes in serum pH:

* Physiologic buffers, consisting of a weak acid (which can easily be broken down) and its base salt or of a weak base and its acid salt. These buffers are the bicarbonate-carbonic acid buffering system, intracellular protein buffers, and phosphate buffers in the bone. * Pulmonary compensation, in which changes in ventilation work to change the partial pressure of arterial carbon dioxide (PaCO2) and drive the pH toward the normal range. A drop in pH, for example, results in increased ventilation to blow off excess CO2. An increase in pH decreases ventilatory effort, which increases PaCO2 and lowers the pH back toward normal. * Renal compensation, which kicks in when the other mechanisms have been ineffective, generally after about 6 hours of sustained acidosis or alkalosis. While respiratory compensation occurs almost immediately, renal mechanisms can take hours to days to make a difference. In acidosis the kidneys excrete H + in urine and retain HCO3-. In alkalosis, the kidneys excrete bicarbonate and retain H+ in the form of organic acids, resulting in near-normalization of pH. Lastly, bone may also serve as a buffer because it contains a large reservoir of bicarbonate and phosphate and can buffer a significant acute acid load. Patients who have low albumin levels and bone density due to malnutrition or chronic disease, and anemic patients, have an ineffective buffering capability COMMON ACID-BASE UPSETS Generally, if your patient has changes in acid-base homeostasis, you'd look for the cause first before intervening to normalize the pH. But because some acid-base disturbances have a limited number of causes, you can systematically eliminate some potential causes.
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Start by looking at the patient's arterial blood gas analysis. Many disorders are mild and don't require treatment, and in some cases, too-hasty treatment can do more harm than the imbalance itself. Also, critically ill patients may have more than one acid-base imbalance simultaneously. The most common acid-base derangements can be divided into four categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Let's look at each and how you'd respond. Normal Electrolyte Values for Adults* VENOUS BLOOD Sodium 135145 mEq/L Potassium 3.55.0 mEq/L Chloride 95108 mEq/L Calcium (total) 4.55.5 mEq/L or 8.510.5 mg/dL (ionized) 56% of total calcium (2.5 mEq/L or 4.05.0 mg/dL) Magnesium 1.52.5 mEq/L or 1.62.5 mg/dL Phosphate (phosphorus) 1.82.6 mEq/L or 2.5 4.5 mg/dL Serum osmolality 280300 Normal Values of ArterialBlood Gases* pH 7.357.45 PaO2 80100 mm Hg PaCO2 3545 mm Hg HCO3 2226 mEq/L Base excess _2 to 2 mEq/L O2 saturation 9598%
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WATER, ELECTROLYTE & ACID-BASE BALANCE

Electrolytes A). Definition Electrolyte: Fluid or electrolyte balance occurs when water and solutes are in the correct portion in each of the body compartments. B). Body fluid compartments

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1.Intracellular space 2. Interstitial spaces 3. Plasma 4. Trans cellula r (movi ng in betwe en cells)

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C. Exchange fluid and solutes among fluid compartments through

Filtration Reabsorption Diffusion Osmosis

D). Electrolyte Balance: electrolyte input = electrolyte output E). Hormonal Controlled 1). aldosterone 2). parathyroid hormone II). Acid-Base Balance A). Sources of H+

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1). Aerobic respiration CO2 + H2O H2CO3 H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)

2). Anaerobic respiration of lactic acid 3). Incomplete oxidation of fatty acids 4). Oxidation of amino acids 5). Break down of phosphoproteins and nucleic acids

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B). First line of defense against shift in pH Acid Base Buffer Systems 1). Bicarbonate buffer system i). HCO3- acts as a weak base acidic H+ + HCO3H2CO3

ii). H2CO3 acts as a weak acidbasic H2CO3 H+ + HCO3-

2). Phosphate Buffer System 3). Protein Buffer System C). Secondary line of defense 1). Renal Excretion of H+ H+ + NH3
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NH4+

(H+) + (ammonia)

(ammonium ion)

2). Respiratory Excretion of CO2 Respiratory center responds to the H+. CO2 + H2O H2CO3 equilibrium CO2 + H2O H2CO3 H+ + HCO3H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)

Thus if pH is low (acidic) breathing can increase CO2 + H2O H2CO3 Thus removing H+ if pH is high (basic) breathing can decrease CO2 + H2O H2CO3 Thus adding H+ So by breathing out CO2 the reaction is driven to the left lowering the H+ concentration (Raising the pH) By holding the breath and not breathing out CO2 it is driven to the right raising the H+ concentration (lowering the pH) H+ + HCO3H+ + HCO3-

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Metabolic acidosis Metabolic acidosis is an increase in the amount of absolute body acid, either from excess production of acids or excessive loss of bicarbonate, sodium, and potassium. Causes of metabolic acidosis include lactic acidosis, diabetic ketoacidosis, and loss of bicarbonate through severe diarrhea or bicarbonate wasting through the kidneys or gastrointestinal (GI) tract. In general, the kidneys attempt to preserve sodium by exchanging it for excreted H+ or potassium. In the presence of an H+ load, H+ ions move from the extracellular fluid into the intracellular fluid. For this process to occur, potassium moves outside the cell into the extracellular fluid to maintain electroneutrality. In severe acidosis, significant overall depletion of total body potassium stores can occur despite serum hyperkalemia. This is why I.V. potassium is given to patients with diabetic ketoacidosis early in treatment, despite the often-elevated serum potassium level. External and internal potassium balances are regulated to maintain an extracellular fluid concentration of 3.5 to 5.5 mEq/L and a total body content of about 50 mEq/kg (40 mEq/kg in females) Metabolic alkalosis Metabolic alkalosis occurs when HCO3- is increased, usually as the result of excessive loss of metabolic acids. Causes of metabolic alkalosis include diuretics, secretory adenoma of the colon, emesis, hyperaldosteronism, Cushing's syndrome, and exogenous steroids. Some causes of metabolic alkalosis respond to treatment with 0.9% sodium chloride solution. If the patient's urine chloride concentration is less than 15 mmol/L, his metabolic alkalosis is saline-responsive; urine chloride levels above
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25 mmol/L indicate nonsaline-responsive metabolic alkalosis. The mechanisms resulting in saline-responsive metabolic alkalosis include GI loss, diuresis, or renal compensation from hypercapnia. Nonsaline responsive metabolic alkalosis results from mineralocorticoid excess or potassium depletion. Fluid administration is the foundation for treatment for saline-responsive metabolic alkalosis. In cases of extreme alkalosis, the patient may be given dilute hydrochloric acid. Saline-resistant alkalosis is treated by addressing the underlying etiology. Respiratory acidosis In respiratory acidosis, the patient's pH is less than 7.35 and his PaCO 2 is above 45 mm Hg (the upper limit of normal). Alveolar hypoventilation is the only mechanism that causes hypercarbia, or a PaCO2 above the upper limit of normal. The amount of alveolar ventilation necessary to maintain normal PaCO 2 varies depending upon CO2 produced. The relationship between PaCO2 and plasma HCO3- determines arterial pH. Generally, acute increases in PaCO2 are accompanied by only minimal changes in serum HCO3-. However, over a period of 1 to 3 days, renal conservation of HCO 3results in an increase in pH. Chronic respiratory acidosis occurs secondary to a chronic reduction in alveolar ventilation-for example, in chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Acute respiratory acidosis is caused by an acute change in alveolar ventilation; respiratory depression from acute opioid ingestion is one cause. Treatment for respiratory acidosis is largely supportive, but if opioid ingestion is suspected, I.V. naloxone may be given as an antidote.
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Respiratory alkalosis Common in critical care, respiratory alkalosis occurs when PaCO2 is reduced, causing an increase in pH. The most common cause of respiratory alkalosis is increased alveolar ventilation, which can happen in hyperventilation, mechanical overventilation, hepatic disease, pregnancy, and septicemia. Determining appropriate compensatory changes in HCO3- is key to determining if the patient also has a concomitant metabolic disorder. In chronic respiratory alkalosis, the compensatory mechanisms result in mild reduction in plasma HCO 3levels to maintain a near normal or normal pH. This causes a mixed acid-base disorder, which will be discussed later. Treatment of respiratory alkalosis is directed at discovering and correcting the underlying etiology. For example, if a patient is hyperventilating from anxiety, have him breathe into a paper bag. In mechanically ventilated patients with mechanical overventilation, reducing the minute ventilation or tidal volume will increase PaCO2 and reduce pH. Monitor the patient closely, because a rapid reduction of PaCO2 in a patient with chronic respiratory alkalosis may cause acute metabolic acidosis. Mixed acid-base imbalances When a patient has two or three acid-base imbalances simultaneously, he's said to have a mixed acid-base imbalance. Examples include: * respiratory alkalosis or acidosis that shrouds a metabolic acidosis or alkalosis * metabolic alkalosis or acidosis that shrouds another metabolic alkalosis acidosis.

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Combined respiratory and metabolic imbalances may occur when the respiratory system compensates inappropriately for metabolic imbalances. Look at the difference between the patient's observed PaCO2 and the calculated changes in PaCO2, or the observed or expected change in HCO3-. If the observed PaCO2 is higher than the calculated PaCO2, the patient has respiratory acidosis with a mixed metabolic disturbance. If the observed PaCO2 is lower than the calculated PaCO2, the patient has respiratory alkalosis mixed with a metabolic imbalance. Generally, the PaCO2 should be similar to the two last digits of the patient's pH. For example, if the patient's pH is 7.25, you'd expect his PaCO2 to be about 25 mm Hg. Mixed metabolic acidosis and alkalosis can be identified by calculating the anion gap. The anion gap is an approximate measure of the additional amount of acid in the body; the HCO3- should decrease by about an amount equaling the increase in the anion gap. If the HCO3- is higher than the calculated increase of the anion gap, a chief metabolic alkalosis is mixed with the metabolic acidosis. Conversely, if the HCO3- is lower than the increase of the anion gap, then a non-anion gap metabolic acidosis is considered to be present and is worsening the anion gap acidosis

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COMPENSATORY MECHANISMS Physiological responses to changes in [H+] are characterized by three phases: (1) immediate chemical buffering, (2) respiratory compensation (whenever possible), and (3) a slower but more effective renal compensatory response that may nearly normalize arterial pH even if the pathological process is still present. Body Buffers Physiologically important buffers in humans include bicarbonate

(H2CO3/HCO3), hemoglobin (HbH/Hb), other intracellular proteins (PrH/Pr), phosphates (H2PO4/HPO42), and ammonia (NH3/NH4+). The effectiveness of these buffers in the various fluid compartments is related to their concentration. Bicarbonate is the most important buffer in the extracellular fluid compartment. Hemoglobin, though restricted inside red blood cells, also functions as an important buffer in blood. Other proteins probably play a major role in buffering
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the intracellular fluid compartment. Phosphate and ammonium ions are important urinary buffers. Buffering of the extracellular compartment can also be accomplished by the exchange of extracellular H+ for Na+ and Ca2+ ions from bone and by the exchange of extracellular H+ for intracellular K+. Acid loads can also demineralize bone and release alkaline compounds (CaCO3 and CaHPO4). Alkaline loads (NaHCO3) increase the deposition of carbonate in bone. Buffering by plasma bicarbonate is almost immediate whereas that due to interstitial bicarbonate requires 1520 min. In contrast, buffering by intracellular proteins and bone is slower (24 h). Up to 5060% of acid loads may ultimately be buffered by bone and intracellular buffers. The Bicarbonate Buffer Although in the strictest sense, the bicarbonate buffer consists of H2CO3 and HCO3, CO2 tension (PCO2) may be substituted for H2CO3, because:

This hydration of CO2 is catalyzed by carbonic anhydrase. If adjustments are made in the dissociation constant for the bicarbonate buffer and if the solubility coefficient for CO2 (0.03 mEq/L) is taken into consideration, the Henderson Hasselbalch equation for bicarbonate can be written as follows:

where pK' = 6.1.

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Note that its pK' is not close to the normal arterial pH of 7.40, which means that bicarbonate would not be expected to be an efficient extracellular buffer (see above). The bicarbonate system is, however, important for two reasons: (1) bicarbonate (HCO3) is present in relatively high concentrations in extracellular fluid, and (2) more importantlyPaCO2 and plasma [HCO3] are closely regulated by the lungs and the kidneys, respectively. The ability of these two organs to alter the [HCO3]/PaCO2 ratio allows them to exert important influences on arterial pH. A simplified and more practical derivation of the HendersonHasselbalch equation for the bicarbonate buffer is as follows:

This equation is very useful clinically because pH can be readily converted to [H+] (Table 302). Note that below 7.40, [H+] increases 1.25 nEq/L for each 0.01 decrease in pH; above 7.40, [H+] decreases 0.8 nEq/L for each 0.01 increase in pH.

Table 302. the Relationship between pH and [H+].

pH

[H+]

nEq/L

6.80

158

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6.90 7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70

126 100 79 63 50 40 32 25 20

Example: If arterial pH = 7.28 and PaCO2 = 24 mm Hg, what should the plasma [HCO3] be?

Therefore,

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 It should be emphasized that the bicarbonate buffer is effective against metabolic but not respiratory acidbase disturbances. If 3 mEq/L of a strong nonvolatile acid such as HCl is added to extracellular fluid, the following reaction takes place:

Note that HCO3 reacts with H+ to produce CO2. Moreover, the CO2 generated is normally eliminated by the lungs such that PaCO2 does not change. Consequently, [H+] = 24 x 40 21 = 45.7 nEq/L and pH = 7.34. Furthermore, the decrease in [HCO3] reflects the amount of nonvolatile acid added. In contrast, an increase in CO2 tension (volatile acid) has a minimal effect on [HCO3]. If, for example, PaCO2 increases from 40 to 80 mm Hg, the dissolved CO2 increases only from 1.2 mEq/L to 2.2 mEq/L. Moreover, the equilibrium constant for the hydration of CO2 is such that an increase of this magnitude minimally drives the reaction to the left:

If the valid assumption is made that [HCO3] does not appreciably change, then

[H+] therefore increases by 40 nEq/L, and since HCO3 is produced in a 1:1 ratio with H+, [HCO3] also increases by 40 nEq/L. Thus, extracellular [HCO3] increases negligibly, from 24 mEq/L to 24.000040 mEq/L. Therefore, the

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bicarbonate buffer is not effective against increases in PaCO2, and changes in [HCO3] do not reflect the severity of a respiratory acidosis. Hemoglobin as a Buffer Hemoglobin is rich in histidine, which is an effective buffer from pH 5.7 to 7.7 (pKa 6.8). Hemoglobin is the most important noncarbonic buffer in extracellular fluid. Simplistically, hemoglobin may be thought of as existing in red blood cells in equilibrium as a weak acid (HHb) and a potassium salt (KHb). In contrast to the bicarbonate buffer, hemoglobin is capable of buffering both carbonic (CO2) and noncarbonic (nonvolatile) acids:

Pulmonary Compensation Changes in alveolar ventilation responsible for pulmonary compensation of PaCO2 are mediated by chemoreceptors within the brain stem (see Chapter 22). These receptors respond to changes in cerebrospinal spinal fluid pH. Minute ventilation increases 14 L/min for every 1 mm Hg increase in PaCO2. In fact, the lungs are responsible for eliminating the approximately 15 mEq of carbon dioxide produced every day as a byproduct of carbohydrate and fat metabolism. Pulmonary compensatory responses are also important in defending against marked changes in pH during metabolic disturbances. Pulmonary Compensation during Metabolic Acidosis Decreases in arterial blood pH stimulate medullary respiratory centers. The resulting increase in alveolar ventilation lowers PaCO2 and tends to restore arterial
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pH toward normal. The pulmonary response to lower PaCO2 occurs rapidly but may not reach a predictably steady state until 12 24 h; pH is never completely restored to normal. PaCO2 normally decreases 11.5 mm Hg below 40 mm Hg for every 1 mEq/L decrease in plasma [HCO3]. Pulmonary Compensation during Metabolic Alkalosis Increases in arterial blood pH depress respiratory centers. The resulting alveolar hypoventilation tends to elevate PaCO2 and restore arterial pH toward normal. The pulmonary response to metabolic alkalosis is generally less predictable than the response to metabolic acidosis. Hypoxemia, as a result of progressive hypoventilation, eventually activates oxygen-sensitive chemoreceptors; the latter stimulates ventilation and limits the compensatory pulmonary response. Consequently, PaCO2 usually does not rise above 55 mm Hg in response to metabolic alkalosis. As a general rule, PaCO2 can be expected to increase 0.251 mm Hg for each 1 mEq/L increase in [HCO3]. Renal Compensation The ability of the kidneys to control the amount of HCO3 reabsorbed from filtered tubular fluid, form new HCO3, and eliminate H+ in the form of titratable acids and ammonium ions (see Chapter 31) allows them to exert a major influence on pH during both metabolic and respiratory acidbase disturbances. In fact, the kidneys are responsible for eliminating the approximately 1 mEq/kg per day of sulfuric acid, phosphoric acid, and incompletely oxidized organic acids that are normally produced by the metabolism of dietary and endogenous proteins, nucleoproteins, and organic phosphates (from phosphoproteins and phospholipids). Metabolism of nucleoproteins also produces uric acid. Incomplete combustion of
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fatty acids and glucose produces keto acids and lactic acid. Endogenous alkali are produced during the metabolism of some anionic amino acids (glutamate and aspartate) and other organic compounds (citrate, acetate, and lactate), but the quantity is insufficient to offset the endogenous acid production.

Renal Compensation during Acidosis The renal response to acidemia is 3-fold: (1) increased reabsorption of the filtered HCO3, (2) increased excretion of titratable acids, and (3) increased production of ammonia. Although these mechanisms are probably activated immediately, their effects are generally not appreciable for 1224 h and may not be maximal for up to 5 days. Increased Reabsorption of HCO3

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Bicarbonate reabsorption is shown in Figure 303. CO2 within renal tubular cells combines with water in the presence of carbonic anhydrase. The carbonic acid (H2CO3) formed rapidly dissociates into H+ and HCO3. Bicarbonate ion then enters the bloodstream while the H+ is secreted into the renal tubule, where it reacts with filtered HCO3 to form H2CO3. Carbonic anhydrase associated with the luminal brush border catalyzes the dissociation of H2CO3 into CO2 and H2O. The CO2 thus formed can diffuse back into the renal tubular cell to replace the CO2 originally consumed. The proximal tubules normally reabsorb 80 90% of the filtered bicarbonate load along with sodium, whereas the distal tubules are responsible for the remaining 1020%. Unlike the proximal H+ pump, the H+ pump in the distal tubule is not necessarily linked to sodium reabsorption, and is capable of generating steep H+ gradients between tubular fluid and tubular cells. Urinary pH can decrease to as low as 4.4 (compared with a pH of 7.40 in plasma).

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Reclamation of filtered HCO3 by the proximal renal tubules.

Increased Excretion of Titratable Acids After all the HCO3 in tubular fluid is reclaimed, the H+ secreted into the tubular lumen can combine with HPO42 to form H2PO4 (Figure 304); the latter is not readily reabsorbed because of its charge and is eliminated in urine. The net result is that H+ is excreted from the body as H2PO4, and the HCO3 that is generated in the process can enter the bloodstream. With a p K of 6.8, the H2PO4 /HPO42 pair is normally an ideal urinary buffer. When urinary pH approaches 4.4,
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however, all the phosphate reaching the distal tubule is in the H2PO4 form; HPO42 ions are no longer available for eliminating H+.

Figure 304.

Formation of a titratable acid in urine.

Increased Formation of Ammonia After complete reabsorption of HCO3 and consumption of the phosphate buffer, the NH3/NH4+ pair becomes the most important urinary buffer (Figure 30 5). Deamination of glutamine within the mitochondria of proximal tubular cells is the principal source of NH3 production in the kidneys. Acidemia markedly increases renal NH3 production. The ammonia formed is then able to passively
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cross the cell's luminal membrane, enter the tubular fluid, and react with H + to form NH4+. Unlike NH3, NH4+ does not readily penetrate the luminal membrane and is therefore trapped within the tubules. Thus, excretion of NH4+ in urine effectively eliminates H+.

Figure 305.

Formation of ammonia in urine.

Renal Compensation during Alkalosis The tremendous amount of HCO3 normally filtered and subsequently reabsorbed allows the kidneys to rapidly excrete large amounts of bicarbonate if necessary (see Chapter 28). As a result, the kidneys are highly effective in protecting against metabolic alkalosis, which therefore generally occurs only in association with concomitant sodium deficiency or mineralocorticoid excess. Sodium depletion decreases extracellular fluid volume and enhances Na +
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reabsorption in the proximal tubule. To maintain neutrality, the Na + ion is brought across with a Cl ion. As Cl ions decrease in number (< 10 mEq/L of urine), HCO3 must be reabsorbed. In addition, increased H+ secretion in exchange for augmented Na+ reabsorption favors continued HCO3 formation with metabolic alkalosis. Similarly, increased mineralocorticoid activity augments aldosteronemediated Na+ reabsorption in exchange for H+ secretion in the distal tubules. The resulting increase in HCO3 formation can initiate or propagate metabolic alkalosis. Metabolic alkalosis is commonly associated with increased mineralocorticoid activity even in the absence of sodium and chloride depletion. Base Excess Base excess is the amount of acid or base that must be added for blood pH to return to 7.40 and PaCO2 to return to 40 mm Hg at full O2 saturation and 37C. Moreover, it adjusts for noncarbonic buffering in the blood. Simplistically, base excess represents the metabolic component of an acidbase disturbance. A positive value indicates metabolic alkalosis, whereas a negative value reveals metabolic acidosis. Base excess is usually derived graphically or electronically from a nomogram originally developed by Siggaard-Andersen and requires measurement of hemoglobin concentration

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Physiological Effects of Alkalosis Alkalosis increases the affinity of hemoglobin for oxygen and shifts the oxygen dissociation curve to the left, making it more difficult for hemoglobin to give up oxygen to tissues. Movement of H+ out of cells in exchange for the movement of extracellular K+ into cells can produce hypokalemia. Alkalosis increases the number of anionic binding sites for Ca2+ on plasma proteins and can therefore decrease ionized plasma [Ca2+], leading to circulatory depression and neuromuscular irritability. Respiratory alkalosis reduces cerebral blood flow, increases systemic vascular resistance, and may precipitate coronary vasospasm. In the lungs, respiratory alkalosis increases bronchial smooth muscle tone (bronchoconstriction) but decreases pulmonary vascular resistance. Respiratory Alkalosis Respiratory alkalosis is defined as a primary decrease in PaCO2. The
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mechanism is usually an inappropriate increase in alveolar ventilation relative to CO2 production. Table 305 lists the most common causes of respiratory alkalosis. Plasma [HCO3] usually decreases 2 mEq/L for each 10 mm Hg acute decrease in PaCO2 below 40 mm Hg. The distinction between acute and chronic respiratory alkalosis is not always made, because the compensatory response to chronic respiratory alkalosis is quite variable: plasma [HCO3] decreases 25 mEq/L for each 10 mm Hg decrease in PaCO2 below 40 mm Hg.

Table 305. Causes of Respiratory Alkalosis.

Central stimulation Pain Anxiety Ischemia Stroke Tumor Infection Fever Drug-induced
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Salicylates Progesterone (pregnancy) Analeptics (doxapram) Peripheral stimulation Hypoxemia High altitude Pulmonary disease Congestive heart failure Noncardiogenic pulmonary edema Asthma Pulmonary embolism Severe anemia Unknown mechanism Sepsis Metabolic encephalopathies Iatrogenic Ventilator-induced

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Treatment of Respiratory Alkalosis Correction of the underlying process is the only treatment for respiratory alkalosis. For severe alkalemia (arterial pH > 7.60), intravenous hydrochloric acid, arginine chloride, or ammonium chloride may be indicated (see below). Metabolic Alkalosis Metabolic alkalosis is defined as a primary increase in plasma [HCO3]. Most cases of metabolic alkalosis can be divided into (1) those associated with NaCl deficiency and extracellular fluid depletion, often described as chloride sensitive, and (2) those associated with enhanced mineralocorticoid activity, commonly referred to as chloride resistant (Table 306). Table 306. Causes of Metabolic Alkalosis.

Chloride-sensitive Gastrointestinal Vomiting Gastric drainage Chloride diarrhea Villous adenoma

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Renal Diuretics Posthypercapnic Low chloride intake Sweat Cystic fibrosis Chloride-resistant Increased mineralocorticoid activity Primary hyperaldosteronism Edematous disorders (secondary hyperaldosteronism) Cushing's syndrome Licorice ingestion Bartter's syndrome Severe hypokalemia Miscellaneous Massive blood transfusion Acetate-containing colloid solutions

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Alkaline administration with renal insufficiency Alkali therapy Combined antacid and cation-exchange resin therapy Hypercalcemia Milk-alkali syndrome Bone metastases Sodium penicillins Glucose feeding after starvation

Chloride-Sensitive Metabolic Alkalosis Depletion of extracellular fluid causes the renal tubules to avidly reabsorb Na+. Because not enough Cl is available to accompany all the Na+ ions reabsorbed, increased H+ secretion must take place to maintain electroneutrality. In effect, HCO3 ions that might otherwise have been excreted are reabsorbed, resulting in metabolic alkalosis. Physiologically, maintenance of extracellular fluid volume is therefore given priority over acidbase balance. Because secretion of K+ ion can also maintain electroneutrality, potassium secretion is also enhanced. Moreover, hypokalemia augments H+ secretion (and HCO3 reabsorption) and will also propagate metabolic alkalosis. Indeed, severe hypokalemia alone can cause alkalosis. Urinary chloride concentrations during a chloride-sensitive metabolic alkalosis are characteristically low (< 10 mEq/L).
38

 Diuretic therapy is the most common cause of chloride-sensitive metabolic alkalosis. Diuretics such as furosemide, ethacrynic acid, and thiazides increase Na+, Cl, and K+ excretion, resulting in NaCl depletion, hypokalemia, and usually mild metabolic alkalosis. Loss of gastric fluid is also a common cause of chloride-sensitive metabolic alkalosis. Gastric secretions contain 25100 mEq/L of H+, 40160 mEq/L of Na+, about 15 mEq/L of K+, and approximately 200 mEq/L of Cl. Vomiting or continuous loss of gastric fluid by gastric drainage (nasogastric suctioning) can result in marked metabolic alkalosis, extracellular volume depletion, and hypokalemia. Rapid normalization of PaCO2 after plasma [HCO3] has risen in chronic respiratory acidosis results in metabolic alkalosis (posthypercapnic alkalosis; see above). Infants being fed formulas containing Na+ without chloride readily develop metabolic alkalosis because of the increased H+ (or K+) secretion that must accompany sodium absorption. Chloride-Resistant Metabolic Alkalosis Increased mineralocorticoid activity commonly results in metabolic alkalosis even when it is not associated with extracellular volume depletion. Inappropriate (unregulated) increases in mineralocorticoid activity cause sodium retention and expansion of extracellular fluid volume. Increased H+ and K+ secretion takes place to balance enhanced mineralocorticoid-mediated sodium reabsorption, resulting in metabolic alkalosis and hypokalemia. Urinary chloride concentrations are typically greater than 20 mEq/L in such cases. Other Causes of Metabolic Alkalosis

39

Metabolic alkalosis is rarely encountered in patients given even large doses of NaHCO3 unless renal excretion of HCO3 is impaired. The administration of large amounts of blood products and some plasma protein-containing colloid solution frequently results in metabolic alkalosis. The citrate, lactate, and acetate contained in these fluids are converted by the liver into HCO3. Patients receiving high doses of sodium penicillin (particularly carbenicillin) can develop metabolic alkalosis. Because penicillins act as nonabsorbable anions in the renal tubules, increased H+ (or K+) secretion must accompany sodium absorption. For reasons that are not clear, hypercalcemia that results from nonparathyroid causes (milkalkali syndrome and bone metastases) is also often associated with metabolic alkalosis. The pathophysiology of alkalosis following refeeding is also unknown. Treatment of Metabolic Alkalosis As with other acidbase disorders, correction of metabolic alkalosis is never complete until the underlying disorder is treated. When ventilation is controlled, any respiratory component contributing to alkalemia should be corrected by decreasing minute ventilation to normalize PaCO2. The treatment of choice for chloride-sensitive metabolic alkalosis is administration of intravenous saline (NaCl) and potassium (KCl). H2-blocker therapy is useful when excessive loss of gastric fluid is a factor. Acetazolamide may also be useful in edematous patients. Alkalosis associated with primary increases in mineralocorticoid activity readily responds to aldosterone antagonists (spironolactone). When arterial blood pH is greater than 7.60, treatment with intravenous hydrochloric acid (0.1 mol/L), ammonium chloride (0.1 mol/L), arginine hydrochloride, or hemodialysis should be considered.

40

Anesthetic Considerations in Patients with Alkalemia Respiratory alkalosis appears to prolong the duration of opioid-induced respiratory depression; this effect may result from increased protein binding of opioids. Cerebral ischemia can occur from marked reduction in cerebral blood flow during respiratory alkalosis, particularly during hypotension. The combination of alkalemia and hypokalemia can precipitate severe atrial and ventricular arrhythmias. Potentiation of nondepolarizing neuromuscular blockade is reported with alkalemia but may be more directly related to concomitant hypokalemia. RISK FACTORS CLINICAL MANIFESTATIONS Increased pulse and Frequently assess respiratory status Respiratory Acidosis respiratory rates Headache, dizziness and lung sounds. INTERVENTIONS

Acute lung conditions that Confusion, decreased Monitor airway and ventilation; insert impair level of artificial airway and prepare for mechanical ventilation as necessary. Administer measures such as inhalation therapy, percussion and postural drainage, bronchodilators, and pulmonary therapy

alveolar gas exchange (e.g., consciousness pneumonia, (LOC)

acute pulmonary edema, Convulsions aspiration of foreign drowning) body, Warm, flushed skin near- Chronic: Weakness

Chronic lung disease (e.g., Headache asthma, cystic fibrosis, Laboratory findings:

or Arterial blood pH less antibiotics as

41

emphysema)

than 7.35

ordered.

Overdose of narcotics or PaCO2 above 45 mm Monitor fluid intake and output, vital sedatives that Hg signs, and arterial blood gases.

depress respiratory rate and HCO3 depth

_ normal or slightly Administer narcotic antagonists as indicated. above 26 mEq/L in Maintain adequate hydration (23 L chronic of fluid per day).

Brain injury that affects the elevated in acute; respiratory center Airway obstruction Mechanical chest injury

Respiratory Alkalosis Hyperventilation due to Extreme anxiety Elevated

Complaints

of Monitor vital signs and ABGs.

shortness of breath, Assist client to breathe more slowly. chest Help client breathe in a paper bag or apply a rebreather mask (to inhale CO2).

body tightness Light-headedness circumoral

temperature

Overventilation with a with mechanical ventilator Hypoxia Salicylate overdose Brain stem injury Fever

paresthesias and numbness and tingling extremities Difficulty concentrating of the

Increased basal metabolic Tremulousness, rate blurred vision Laboratory findings

(in uncompensated

42

respiratory alkalosis): Arterial blood pH

above 7.45 PaCO2 less than 35 mm Hg Metabolic Acidosis Kussmauls Monitor ABG values, intake and (deep, output, and LOC. Administer IV sodium bicarbonate carefully if ordered. Treat underlying problem as ordered.

Conditions that increase respirations nonvolatile rapid

acids in the blood (e.g., respirations) renal impairment, mellitus, starvation) Lethargy, confusion diabetes Headache Weakness Nausea and vomiting

Conditions that decrease Laboratory findings: bicarbonate (e.g., prolonged diarrhea) Excessive infusion Arterial blood pH

below 7.35 of Serum bicarbonate

chloride-containing IV fluids (e.g., NaCl) Excessive acids such as salicylates Cardiac arrest Metabolic Alkalosis ingestion

less than 22 mEq/L PaCO2 less than 38 of mm Hg with

respiratory compensation

Decreased respiratory Monitor intake and output closely. Monitor vital signs, especially

Excessive acid losses due rate and depth

43

to Vomiting Gastric suction Excessive use

Dizziness Circumoral paresthesias, of numbness and tingling extremities of

respirations, and LOC. Administer carefully. the Treat underlying problem. ordered IV fluids

potassium-losing diuretics

Excessive adrenal corticoid Hypertonic muscles, hormones due to Cushings syndrome Hyperaldosteronism Excessive intake from Antacids Parenteral NaHCO3 tetany Laboratory findings: Arterial blood pH

above 7.45 bicarbonate than 26

bicarbonate Serum greater mEq/L

PaCO2 higher than 45 mm Hg with

respiratory compensation Diagnosis of AcidBase Disorders Interpretation of acidbase status from analysis of blood gases requires a systematic approach. A recommended approach follows (Figure 306): 1. Examine arterial pH: Is acidemia or alkalemia present? 2. Examine PaCO2: Is the change in PaCO2 consistent with a respiratory component?

44

3. If the change in PaCO2 does not explain the change in arterial pH, does the change in [HCO3] indicate a metabolic component? 4. Make a tentative diagnosis 5. Compare the change in [HCO3] with the change in PaCO2. Does a compensatory response exist (Table 307)? Because arterial pH is related to the ratio of PaCO2 to [HCO3], both pulmonary and renal compensatory mechanisms are always such that PaCO2 and [HCO3] change in the same direction. A change in opposite directions implies a mixed acid base disorder. 6. If the compensatory response is more or less than expected, by definition a mixed acidbase disorder exists. 7. Calculate the plasma anion gap in the case of metabolic acidosis. 8. Measure urinary chloride concentration in the case of metabolic alkalosis. An alternative approach that is rapid but perhaps less precise is to correlate changes in pH with changes in CO2 or HCO3. For a respiratory disturbance, every 10 mm Hg change in CO2 should change arterial pH by approximately 0.08 U in the opposite direction. During metabolic disturbances, every 6 mEq change in HCO3 also changes arterial pH by 0.1 in the same direction. If the change in pH exceeds or is less than predicated, a mixed acidbase disorder is likely to be present.

45

Table 307. Normal Compensatory Responses in AcidBase Disturbances.

Disturbance Respiratory acidosis Acute

Response Expected Change

[HCO3] 1 mEq/L/10 mm Hg increase in PaCO2

Chronic

[HCO3] 4 mEq/L/10 mm Hg increase in PaCO2

Respiratory alkalosis Acute [HCO3] 2 mEq/L/10 mm Hg decrease in PaCO2

Chronic

[HCO3] 4 mEq/L/10 mm Hg decrease in PaCO2

Metabolic acidosis

PaCO2

1.2

the

decrease

in

[HCO3]

Metabolic alkalosis

PaCO2

0.7

the

increase

in

[HCO3]

46

Measurement of Blood Gas Tensions & pH Values obtained by routine blood gas measurement include oxygen and carbon dioxide tensions (PO2 and PCO2), pH, [HCO3], base excess, hemoglobin, and the percentage oxygen saturation of hemoglobin. As a rule, only PO 2, PCO2, and pH are measured. Hemoglobin and percentage oxygen saturation are measured with a cooximeter. [HCO3] is derived using the HendersonHasselbalch equation and base excess from the Siggaard-Andersen nomogram. Sample Source & Collection Arterial blood samples are most commonly utilized clinically, though capillary or venous blood can be used if the limitations of such samples are recognized. Oxygen tension in venous blood (normally 40 mm Hg) reflects tissue extraction, not pulmonary function. Venous PCO2 is usually 46 mm Hg higher than PaCO2. Consequently, venous blood pH is usually 0.05 U lower than arterial blood pH. Despite these limitations, venous blood is often useful in determining acidbase status. Capillary blood represents a mixture of arterial and venous blood, and the values obtained reflect this fact. Samples are usually collected in heparincoated syringes and should be analyzed as soon as possible. Air bubbles should be eliminated, and the sample should be capped and placed on ice to prevent significant uptake of gas from blood cells or loss of gases to the atmosphere. Although heparin is highly acidic, excessive amounts of heparin in the sample syringe usually lower pH only minimally but decrease PCO2 in direct proportion to percentage dilution, and have a variable effect on PO2. Temperature Correction

47

 Changes in temperature affect measurements of PCO2 and PO2 directly and measurements of pH indirectly. Decreases in temperature lower the partial pressure of a gas in solutioneven though the total gas content does not changebecause gas solubility is inversely proportionate to temperature. Both PCO2 and PO2 therefore decrease during hypothermia, but pH increases because temperature does not appreciably alter [HCO3]: PaCO2 decreases, but [HCO3] is unchanged. Because blood gas tensions and pH are always measured at 37C, controversy exists over whether to correct the measured values to the patient's actual temperature. "Normal" values at temperatures other than 37C are not known. Many clinicians use the measurements at 37C directly, regardless of the patient's actual temperature pH Measurement When a metal is placed in solution with its salt, the tendency of the metal to ionize into the solution leaves the metal with a negative charge. If two different metals (electrodes) and their salts are separated by a porous partition (allowing transfer of charge), the tendency for one metal to go into solution more than the other results in an electromotive force between the two electrodes. For pH measurements, a silver/silver chloride electrode and a mercury/mercurous chloride (calomel) electrode are most commonly used. The silver electrode is in contact with the test solution through pH-sensitive glass. The calomel electrode interfaces with the test solution through a potassium chloride solution and a porous plug. The electromotive force developed between the two electrodes is proportionate to [H+]. Carbon Dioxide Measurement Modification of the pH electrode system allows measurement of PCO 2. In
48

this system (the Severinghaus electrode), the two electrodes are separated by a sodium bicarbonate and potassium chloride solution. The test sample is in contact with the bicarbonate solution through a thin Teflon membrane that allows CO 2 to equilibrate between the two. As a result, the pH of the bicarbonate solution reflects the PCO2 of the test solution. Oxygen Measurement PO2 is most commonly measured polarographically using the Clark electrode. In this system, platinum communicates with a silver/silver chloride electrode through an electrolyte solution (NaCl and KCl). The test sample is separated from the electrolyte solution by a membrane allowing oxygen to diffuse freely. When a negative voltage is applied to the platinum electrode, the electrical current that flows between the two electrodes is directly related to PO2. In the process, molecules of oxygen take up electrons from the cathode and react with water to form hydroxide ions. ACID-BASE IMBALANCE and COMPENSATION Introduction Acid-Base Imbalance: A disruption to the normal acid-base equilibrium in the body. There are four main groups of disorder involving an acid-base imbalance: respiratory acidosis or alkalosis and metabolic acidosis or alkalosis. Obviously the severity of symptoms is determined by the degree of imbalance Definitions When pHa (arterial blood pH) differs from 7.4 +/- 0.02 (or the [H+] differs from 40

49

+/- 2 nEq/L) there occurs acidemia (pHa < 7.38, [H+] > 42 nEq/L) or alkalemia (pHa > 7.42, [H+] < 38 nEq/L). If the pHa change is due primarily to a change in PaCO2, there is respiratory acidosis (PaCO2 > 42 mmHg) or respiratory alkalosis (PaCO2 < 38 mmHg). When the pHa change is due primarily to a change in [HCO3-] from its normal value of 24 mM, there is metabolic acidosis ([HCO3-] < 22 mM) or metabolic alkalosis ([HCO3-] > 26 mM). Note: -emia refers to changes in blood; acidosis and alkalosis refer to pathophysiologic processes that lead to pH changes in blood (A) Metabolic acidosis: pH < 7.38; HCO3- < 22 mM; PaCO2 1 mmHg decrease per 1 mM decrease in HCO3- (acute or chronic) Causes: Metabolic acidosis is the most frequent acid-base imbalance and may be due to: (1) Extrarenal loss of bicarbonate, with hyperchloremia and increased urinary excretion of NH4+ (evident as high urinary cation gap: [Cl-] - [Na+] - [K+] >> 0) (2) Urinary loss of HCO3- (alkaline urine, with high bicarbonate, and little NH4+ and thus no urine cation gap) (3) Accumulation of organic anions (lactacidosis, ketoacidosis) with large plasma anion gap (due to organic anions, [Na+]+[K+]-[Cl-]-[HCO3-]>>15), abundant urinary NH4+ but no urinary cation gap (NH4+ is excreted with organic anions so that there is a large urinary osmolar gap: Uosm - 2([Na+]+[K+]) - [urea] - [glucose]
50

>>0. Only lactacidosis can develop in minutes (as in shock). (4) Decreased kidney production of HCO3- (hyperchloremia, no plasma anion gap, and low urinary excretion of ammonium, (urinary cation gap =0); severe chronic renal failure may result in metabolic acidosis with increased plasma anion gap (due to high plasma [Pi]) and low urinary NH4+ excretion. Compensations: (1) Immediate buffering by reaction with ECF HCO3- represents ~40% of rapid (~2 hrs) buffering of acid. HCl + NaHCO3 => NaCl+ H2CO3 + CO2 + H2O (2) Respiratory compensation. A low pHa stimulates VA, so PaC02 decreases minimizing the decrease in pHa. For each 1 mM decrease in [HCO3-] a 1 mmHg drop in PaC02 is expected. Note: Because of respiratory compensation for metabolic acidosis, PaCO2 is expected to be below its normal range or (PaCO2 < 38 mmHg). If , because of disease, there is no respiratory compensation, then PaCO2 will be normal or elevated, and the respiratory system is contributing to the acidemia (see Respiratory Acidosis below).. (3) Tissue phase. Entry of H+ into cells accounts for ~60% of rapid (~2 h) buffering of poorly permeable acids (HCl or H2SO4). This phase is capable of buffering 100% of the acid by 24 h, and is due to the following ion exchanges and buffering of H+ by cell proteins and HCO3-: (a) Na+ in the ICF for H+ from the ECF; occurs in most tissues including bone; accounts for 65% of the entry of protons into the ICF (and bone).

51

(b) ICF K+ for ECF H+; accounts for 25% of the entry of H+ into the ICF. May result in hyperkalemia (6-7 mEq/L) that affects muscle and nerve cells and induces cardiacarrythmias. (c) ECF Cl- for ICF HC03-; accounts for 10% of the ICF buffering of H+; reduces ICF HC03- and intracellular pH; excess H+. (4) Renal phase. Generation of bicarbonate through urinary excretion of ammonium and titratable acids, restores the depleted cell HCO3- and buffer base reserves over 2-3 days. Manifest only in chronic stage. (B) Metabolic alkalosis: pHa > 7.42; [HCO3-] > 26 mM; PaCO2 0.75 mmHg increase for each 1 mM increase in [HCO3-] (chronic or acute) Causes: (1) Loss of gastric juice (vomiting, suction) (2) Side effect of diuretics and other forms of ECFV contraction. (3) Hyperaldosteronism of volume depletion promotes renal H+ secretion, generation and retention of HCO3-. (4) In hypokalemia, K+ shifts out of cells in exchange for H+, inducing extracellular alkalosis and intracellular acidosis. Compensations: occurs mostly in red cells where Hb buffers

52

(1) Respiratory. As pHa increases, VA is depressed and PaCO2 increases (PaCO2 > 42 mmHg). This normalizes blood pH but is limited by ensuing hypoxia. For each 1 mM rise in HCO3- there is expected a 0.75 mmHg rise in PaCO2; if this does not occur, there is a respiratory tendency to alkalosis.

(2) Cell ionic exchanges. Some 25% of the bicarbonate load is neutralized by H+ derived from intracellular buffers that exchange the H+ for extracellular Na+. In addition, ~2% of extracellular HCO3- enters red cells in exchange for Cl-. (3) Metabolic. Increases in endogenous organic acid production neutralize ~5 % of an acute HCO3- load. High pHa increases production of lactic and citric acids which decrease [HCO3-]. High blood pH stimulates glycolysis and inhibits the citric acid cycle.

(4) Renal excretion of HCO3- rises when its concentration in plasma increases. Lowering of [HCO3-]pl is limited by high renal reabsorption rate stimulated by high PaCO2, by ECF volume contraction, by hyperaldosteronism, by K+ depletion, and by hypochloremia. These tend to perpetuate the high [HCO3-]pl. Beta-intercalated cells in CCD secrete bicarbonate, increasing its urinary excretion. (C) Respiratory alkalosis: pH > 7.44; PaCO2 < 38 mm Hg; [HCO3-] decreases (<24 mM) by 0.5 mM (chronic) or 0.1 mM (acute) per each 1 mmHg drop in PaC02 Cause: Alveolar hyperventilation (altitude, hysteria, aspirin excess) Compensations (1) Cell buffers. In the acute state there is a 0.1 mM decrease in [HCO3-] for each
53

mmHg decrease in PaCO2. This decrease is due to enhanced dissociation of H+ from cell buffers when the [H+]i decreases due to the low PaCO2. Cell H+ exchange for ECF Na+ and K+ and react with the ECF HCO3-, reducing its concentration. Some extracellular HCO3- enters cells in exchange for Cl- and is titrated by H+ dissociating from the cell buffers. In the chronic state, there is a 0.5 mM decrease in [HCO3-] for each one mmHg decrease in PaCO2. This is due to: (2) Renal compensation due to increased HCO3- excretion associated with the low PaCO2, which decreases HCO3- reabsorption. Urinary excretion of NH4+ and titratable acid are transiently reduced, leading to accumulation of metabolic and dietary acids which help reduce ECF [HCO3-] ([HCO3-] < 22 mM). Eventually urinary HCO3- excretion ceases and excretion of NH4+ and titratable acid resumes. (3) Metabolic compensation by increased production of lactic and citric acids that react with and reduce [HCO3-]ecf (D) Respiratory acidosis: pH < 7.38; PaC02 > 42 mm Hg; [HCO3-] increases (>24 mM) by 0.25 mM (chronic) or 0.05 mM (acute) per each 1 mmHg rise in PaC02 Cause: Alveolar hypoventilation Compensations: (1) Fast cell ion exchanges. An acute small rise in [HCO3-]pl is due to exchange of ECF H+ for ICF (or bone) Na+ (37%) or for ICF K+ (13%) and to exchange of ECF Cl- for ICF (red cells) HCO3- (30%). These rapid ionic exchanges are associated with CO2 buffering by intracellular proteins. For each 1 mmHg increment in PaCO2
54

there

is

small

acute

0.06

mM

increment

in

HCO3-.

(2) Metabolic. Reduced production of lactic acid contributes about 5% to the acute increase in [HCO3-]pl.

(3) Renal. Increased HCO3- reabsorption stimulated by high PaCO2 prevents urinary loss of bicarbonate. In the transition to the chronic stage (1-3 days), enhanced renal NH4+, and titratable acid excretion contribute to further increase [HCO3-] in ECF and ICF above normal ([HCO3-] > 26 mM), returning pH towards normal. As the pH stimulus decreases, renal NH4+ and titratable acid excretion subside. Renal reabsorption of bicarbonate remains elevated as long as the PaCO2 is high.

Acid-base disturbances, causes, and compensatory mechanisms SOURCE: Pagana, K.D. and T.J. Pagana. Mosby's Diagnostic and Laboratory Test Reference. 3rd ed. St. Louis: Mosby, 1997. Acid-base disturbance Respiratory acidosis Respiratory depression (drugs, Kidneys increased will retain of Common cause Mode of compensation

central nervous system trauma)

amounts

HCO3/sub> to increase pH Pulmonary disease (pneumonia,

55

chronic disease,

obstructive

pulmonary respiratory

underventilation) Respiratory alkalosis Hyperventilation (emotions, pain, Kidneys respirator overventilation) increased will excrete of

amounts

HCO3/sub> to lower pH Metabolic acidosis Metabolic alkalosis Diabetes, shock, renal failure, Lungs "blow off" CO2 to raise pH overdose, Lungs retain CO2 to nasogastric lower pH intestinal fistula Sodium prolonged drainage Symptoms of Acid-Base Imbalance

bicarbonate vomiting,

Hypercapnia - metabolic alkalosis Dilated brain blood vessels - respiratory acidosis Increased pressure inside skull - respiratory acidosis Headache - metabolic alkalosis Confusion - respiratory alkalosis

Types of Acid-Base Imbalance

Cardiomyopathy -- hypotonia -- lactic acidosis Diabetic Ketoacidosis Respiratory acidosis Respiratory alkalosis Alkalosis

Acid-Base Imbalance: Complications

56

Coma - metabolic acidosis

Causes of Acid-Base Imbalance

Acid-Base Imbalance as a symptom

Acid-Base Imbalance: Undiagnosed Conditions Commonly undiagnosed diseases in related medical categories:

Chronic Digestive Disorders that can remain Undiagnosed:

o o o o o o o o o

Crohn's Disease -- Undiagnosed Ulcerative Colitis -- Undiagnosed Celiac Disease -- Undiagnosed Heartburn -- Undiagnosed GERD -- Undiagnosed Inflammatory Bowel Disease -- Undiagnosed Irritable Bowel Syndrome -- Undiagnosed Carcinoid Syndrome -- Undiagnosed Pancreatitis -- Undiagnosed

Misdiagnosis and Acid-Base Imbalance Unnecessary hysterectomies due to undiagnosed bleeding disorder in women: The bleeding disorder called Von Willebrand's disease is quite common in women, but often fails to be correctly diagnosed. Chronic digestive conditions often misdiagnosed: When diagnosing chronic symptoms of the digestive tract, there are a variety of conditions that may be misdiagnosed. Intestinal bacteria disorder may be hidden cause: One of the
57

lesser known causes of diarrhea is an imbalance of bacterial in the gut, sometimes called intestinal imbalance. Antibiotics often causes diarrhea: The use of antibiotics are very likely to cause some level of diarrhea in patients. The reason is that antibiotics kill off not Food poisoning may actually be an infectious disease: Many people who come down with "stomach symptoms" like diarrhea assume that it's "something I ate" (i.e. food poisoning). Alzheimer's disease over-diagnosed: The well-known disease of Alzheimer's disease is often over-diagnosed. Patients tend to assume that any memory loss or forgetulness symptom might be Alzheimer's, whereas there are many other less Dementia may be a drug interaction: A common scenario in aged care is for a patient to show mental decline to dementia. Whereas this can, of course, occur due to various medical conditions, such as a stroke Mesenteric adenitis misdiagnosed as appendicitis in children: Because appendicitis is one of the more feared conditions for a child with abdominal pain, it can be over-diagnosed (it can, of course, also fail Tremor need not be Parkinson's disease: There is the tendency to believe that any tremor symptom, or shakiness, means Parkinson's disease. Rare diseases misdiagnosed as Parkinson's disease: A rare genetic disorder is often misdiagnosed as Parkinson's disease for men in their 50's. The disease Fragile X disorder can show only mild symptoms Celiac disease often fails to be diagnosed cause of chronic digestive symptoms: One of the most common chronic digestive conditions is celiac disease, Chronic
58

digestive diseases hard to diagnose: There is an inherent difficulty in diagnosing the various types of chronic digestive diseases Acid-Base Imbalance: Research Doctors & Specialists Research related physicians and medical specialists:

Digestive Health Specialists (Gastroenterology):

o o

Gastroenterology (Digestive Specialists) Pediatric Gastroenterology (Child Digestive Health)

Blood Health Specialists (Hematology):

o o o

Hematology (Blood Specialists) Pediatric Hematology / Oncology (Child Cancer/Leukemia) Hematopathology (Blood Diagnostics)

Senior Health Specialists (Geriatrics):

o o

Geriatric Medicine (Senior Health Specialist) Geriatric Psychiatry (Senior Mental Health)

Acid-Base Imbalance: Rare Types Rare types of diseases and disorders in related medical categories:

Chronic Digestive Disorders -- Rare Types:

o o o o o o

Crohn's Disease -- Rare Types Ulcerative Colitis -- Rare Types Celiac Disease -- Rare Types Inflammatory Bowel Disease -- Rare Types Irritable Bowel Syndrome -- Rare Types Carcinoid Syndrome -- Rare Types
59

o o o

Pancreatitis -- Rare Types Gallstones -- Rare Types Lactose Intolerance -- Rare Types

Evidence Based Medicine Research for Acid-Base Imbalance Medical research articles related to Acid-Base Imbalance include:

Guidelines on the use of the Laboratory Acute kidney injury Oliguria (Treatment) Hemorrhagic Fever With Renal Failure Syndrome (Follow-up) Alkalosis, Metabolic (Treatment) Pediatrics, Pyloric Stenosis (Treatment) Critical Care Considerations in Trauma

Arterial blood pH is normally closely regulated to between 7.35 and 7.45. Maintaining the pH within these limits is achieved by bicarbonate, other buffers, the lungs and the kidneys. Primary changes in bicarbonate are metabolic and primary changes in carbon dioxide are respiratory.

In the absence of any significant respiratory disease or hyperventilation it can be assumed that the primary cause is metabolic.

In general the kidneys compensate for respiratory causes and the lungs compensate for metabolic causes. Therefore hyperventilation may be a cause of respiratory alkalosis or a compensatory mechanism for metabolic acidosis. Deep sighing respiration (Kussmaul breathing) is a common feature of acidosis (hyperventilation in an attempt to remove carbon dioxide) but may take some hours to appear.
60

Investigations Analysis of arterial blood gases provides:

pH: determines whether there is an overall acidosis or alkalosis. Venous pH is in practice as reliable as arterial pH.

Carbon dioxide partial pressure (PaCO2): if raised with acidosis then the acidosis is respiratory. If decreased with alkalosis then the alkalosis is respiratory. Otherwise any change is compensatory.

Standard bicarbonate (SBCe): analysis of blood gases provides a bicarbonate level which is calculated from the PaCO2 using the Henderson-Hasselbalch equation.

Bicarbonate (HCO3): increased with metabolic alkalosis and decreased in metabolic acidosis. Otherwise the change is compensatory (ie normal or raised in respiratory acidosis; normal or decreased in respiratory alkalosis).

Assessment of acid-base imbalance

Check pH: if below 7.35 then is an acidosis; if below 7.45 then is an alkalosis

Check PaCO2: if it has moved in the same direction as pH then the primary cause is metabolic, if it has moved in the opposite direction the primary cause is respiratory.

If there is a respiratory cause, then changes in pH and HCO3 should be as follows:

o

If acute acidosis: pH falls by 0.08 and HCO3 rises by 1 mmol/L for each 10 mm Hg PaCO2 is above 40 mm Hg. If chronic acidosis: pH falls by 0.03 and HCO3 rises by 2-4 mmol/L
61

for each 10 mm Hg of PaCO2 above 40 mm Hg.

o

For respiratory alkalosis, the opposite directions are present for all changes.

If there is a metabolic acidosis then calculate the expected PaCO 2 and compare to measured value to see if there is also a respiratory component. Expected PaCO2 = ( 1.5 x [HCO3] + 8 ) +/- 2. A lower than expected PaCO2 indicates a superimposed respiratory alkalosis and a higher than expected PaCO2 indicates a respiratory acidosis.

If metabolic alkalosis: calculate the expected PaCO2 and compare to measured value to see if there is also a respiratory component. Expected PaCO2 = ( 0.9 x [HCO3] + 9 ) +/- 2.

Also work out anion gap (see below).

Anion gap In plasma, the sum of the cations (sodium plus potassium) is normally greater than that of the anions (chloride plus bicarbonate) by approximately 14 mmol/L. This is known as the anion gap. The normal reference range for the anion gap is 8-16 mmol/L when not including potassium in the equation and 10-20 mmol/L when including potassium.

The anion gap exists because there are more unmeasured anions (mostly albumin, but others include lactate and sulfate) than cations (includes calcium and magnesium).

Metabolic acidosis is generally divided into those with high and those with normal anion gap. High chloride (Cl-) associated with metabolic acidosis is usually due to impaired renal handling of acid, eg renal tubular acidosis.
62

Causes of metabolic acidosis

Increased anion gap:

o o o o

Lactic acidosis: shock, infection, hypoxia. Urate (renal failure). Ketones (diabetes mellitus, alcohol). Drugs or toxins: salicylates, metformin, ethylene glycol, methanol, cyanide.

Normal anion gap (due to loss of bicarbonate or ingestion hydrogen ions):

o o o o o

Renal tubular acidosis. Diarrhoea. Addison's disease. Pancreatic fistulae. Drugs or toxins: acetazolamide, ammonium chloride.

Causes of metabolic alkalosis These include:

Vomiting. Hypokalaemia, eg diuretics. Excessive alkali drugs, such as for acid dyspepsia. Burns.

Causes of respiratory acidosis

Acute:
o

Depression of the central respiratory centre by cerebrovascular disease or drugs.

63

Inability to ventilate adequately due to neuromuscular disease, eg myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barr syndrome, muscular dystrophy.

Airway obstruction related to asthma or exacerbation of chronic obstructive pulmonary disease (COPD).

Chronic:
o

Chronic respiratory acidosis may be secondary to many disorders, eg COPD, obesity hypoventilation syndrome (Pickwickian syndrome), neuromuscular disorders and restrictive ventilatory defects such as interstitial fibrosis or thoracic deformities.

Causes of respiratory alkalosis Respiratory alkalosis results from hyperventilation, eg anxiety, stroke, meningitis, altitude, pregnancy (see separate Hyperventilation article). Management Treatment is of the underlying condition. Complications

Cardiovascular effects: acidosis reduces cardiac contractility and both acidosis and alkalosis predispose to arrhythmias.

Nervous

system

effects:

severe

acidosis

often

causes

impaired

consciousness, ranging from mild drowsiness to coma. FACTORS AFFECTING BODY FLUID,ELECTROLYTES, ANDACID BASE BALANCE The ability of the body to adjust fluids, electrolytes, and acid base balance is
64

influenced by age, gender and body size, environmental temperature, and lifestyle. Age Infants and growing children have much greater fluid turn over than adults because their higher metabolic rate increases fluid loss. Infants lose more fluid through the kidneys because immature kidneys are less able to conserve water than adult kidneys. In addition, infants respirations are more rapid and the body surface area is proportionately greater than that of adults, increasing insensible fluid losses. The more rapid turnover of fluid plus the losses produced by disease can create critical fluid imbalances in children much more rapidly than in adults. In elderly people, the normal aging process may affect fluid balance. The thirst response often is blunted. Antidiuretic hormone levels remain normal or may even be elevated, but the nephrons become less able to conserve water in response to ADH. Increased levels of atrial natriuretic factor seen in older adults may also contribute to this impaired ability to conserve water. These normal changes of aging increase the risk of dehydration. When combined with the increased likelihood of heart diseases, impaired renal function, and multiple drug regimens, the older adults risk for fluid and electrolyte imbalance is significant., it is important to consider that the older adult has thinner, more fragile skin and veins, which can make an intravenous insertion more difficult. Gender and Body Size Total body water also is affected by gender and body size. Because fat cells contain little or no water, and lean tissue has a high water content, people with a higher percentage of body fat have less body fluid. Women have proportionately more body fat and less body water than men. Water accounts for approximately 60% of an adult mans weight, but only 52% for an adult woman. In an obese
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individual this may be even less, with water responsible for only 30% to 40% of the persons weight. ENVIRONMENTAL TEMPERATURE People with an illness and those participating in strenuous activity are at risk for fluid and electrolyte imbalances when the environmental temperature is high. Fluid losses through sweating are increased in hot environments as the body attempts to dissipate heat. These losses are even greater in people who have not been acclimatized to the environment. Both salt and water are lost through sweating. When only water is replaced, salt depletion is a risk. The person who is salt depleted may experience fatigue, weakness, headache, and gastrointestinal symptoms such as anorexia and nausea. The risk of adverse effects is even greater if lost water is not replaced. Body temperature rises, and the person is at risk for heat exhaustion heatstroke. Heatstroke may occur in older adults or ill people during prolonged periods of heat; it can also affect athletes and laborers when their heat production exceeds the bodys ability to dissipate heat. Consuming adequate amounts of cool liquids, particularly during strenuous activity, reduces the risk of adverse effects from heat. Balanced electrolyte solutions and carbohydrate-electrolyte solutions such as sports drinks are recommended because they replace both water and electrolytes lost through sweat. LIFESTYLE Other factors such as diet, exercise, and stress affect fluid, electrolyte, and acid base balance. The intake of fluids and electrolytes is affected by the diet. People with anorexia nervosa or bulimia are at risk for severe fluid and electrolyte imbalances because of inadequate intake or
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purging regimens (e.g., induced vomiting, use of diuretics and laxatives). Seriously malnourished people have decreased serum albumin levels, and may develop edema because the osmotic draw of fluid into the vascular compartment is reduced. When calorie intake is not adequate to meet the bodys needs, Fat stores are broken down and fatty acids are released, increasing the risk of acidosis. Regular weight-bearing physical exercise such as walking, running, or bicycling has a beneficial effect on calcium balance. The rate of bone loss that occurs in postmenopausal women and older men is slowed with regular exercise, reducing the risk of osteoporosis. Stress can increase cellular metabolism, blood glucose concentration, and catecholamine levels. In addition, stress can increase production of ADH, which in turn decreases urine production. The overall response of the body to stress is to increase the blood volume. Other lifestyle factors can also affect fluid, electrolyte, and acidbase balance. Heavy alcohol consumption affects electrolyte balance, increasing the risk of low calcium, magnesium, and phosphate levels. The risk of acidosis associated with breakdown of fat tissue also is greater in the person who drinks FOCUSED PHYSICAL ASSESSMENT FOR FLUID, ELECTROLYTE, OR ACIDBASE IMBALANCES

SYSTEM

ASSESSMENT FOCUS

TECHNIQUE

POSSIBLE FINDINGS

ABNORMAL

Skin

Color, temperature, Inspection, moisture Turgor Edema palpation

Flushed, warm, very dry Moist or diaphoretic

Gently pinch up a Cool and pale fold of skin over

Poor turgor: Skin remains tented

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sternum or inner for aspect of thigh for adults, on several seconds instead of

the immediately returning to normal

abdomen or medial position thigh for children

Skin around eyes is puffy, lids

Inspect for visible appear swelling around eyes, in

swollen; rings are tight; shoes

fingers, leave impressions on feet Depression remains (pitting

and in lower extremities Compress the skin over the dorsum of the foot, around the ankles, over the tibia, in the sacral area Mucous membranes Color, moisture Inspection

Mucous membranes dry, dull in appearance; cracked tongue dry

and

Eyes

Firmness

Gently eyeball closed

palpate Eyeball feels soft to palpation with lid

Fontanels (infant)

Firmness, level

Inspect and gently Fontanel bulging, firm palpate anterior fontanel Fontanel sunken, soft

Cardiovascular Heart rate

Auscultation,

Tachycardia,

bradycardia;

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system

Peripheral pulses Blood pressure Capillary refill Venous filling

cardiac monitor Palpation Auscultation

irregular; dysrhythmias of Weak and thready; bounding

Korotkoffs sounds Hypotension BP assessment Postural hypotension Slowed capillary refill

lying and standing Palpation Inspection

Jugular venous distention; flat of jugular

jugular veins and veins, poor venous refill hand veins

Respiratory system

Respiratory rate and Inspection pattern Lung sounds Level consciousness (LOC) Orientation, cognition Motor function Reflexes Abnormal reflexes of Auscultation

Increased or decreased rate and depth of respirations Crackles or moist rales

Neurologic

Level consciousness (LOC)

of Observation, stimulation Questioning

Decreased LOC, lethargy, stupor or coma

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Orientation, cognition Motor function Reflexes Abnormal reflexes

Strength testing

Disoriented, confused; difficulty

Deep-tendon reflex concentrating (DTR) testing Chvosteks Tap nerve over Weakness, sign: strength facial Hyperactive or depressed DTRs decreased

motor

Facial muscle twitching including

about 2 cm anterior eyelids and lips on side of to tragus of ear stimulus

Trousseaus sign: Carpal spasm: contraction of Inflate a blood hand

pressure cuff on and fingers on affected side the upper arm to 20 mm Hg greater than the systolic pressure, leave in place for 2 to5 MIN

CONCLUSION Acid-base balance can be defined as homeostasis of the body fluids at a normal arterial blood pH ranging between 7.37 and 7.43. so we are discussed acid-base balance and imbalance definition mechanism causes types management of acid base balance and imbalance. BIBLIOGRAPHY: Hoyt J W, Page C, Considerations For ICU Bedside Design, Critical Care
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Medicine, 1993, 11th Edition, Pp: 256. Kundlers GD, Kopinath S, Katakm A, Hospitals Planning And Design And Management,1998, 1st Ed,Tata MC Grow Hill Publishing Company Limited, New Delhi,Pp:1-45, 52-66. Peterson Etal, Hospitals, 1982, Charlotte NC Publishers, New Delhi, P-6465. Shakti Kumar Gupta, Suit Kant Etal,Modern Trends In Planning And Designing Of Hospitals, Principles And Practice, 1st Edition, 2007, Jaypee Medical Publishers, New Delhi,P:1-10. Piergeorge A R, Ceserno FL Etal, Designing the Critical Care Unit: A Multidisciplinary Approach, Critical Care Medicine, 1988, 16th Ed, 796806. Guidelines/Practice American College Parameters of Committee Critical Care of the Medicine

Society of Critical Care Medicine Pp: 1-10.

WEBSITE www.aci.com www.health.com www.imbalance.com

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