Transcript Acid-Base Balance
Acid-Base Balance
205b
Educational Objectives
• Describe the relationship between the lungs and the kidneys in maintaining acid-base homeostasis (normalcy of the body) • Given values for carbonic acid and bicarbonate, calculate the pH using the Henderson Hasselbalch equation
Educational Objectives
• Define base excess/base deficit • Define buffer system and list the electrolytes commonly associated with buffering in the blood • List the components of non-bicarbonate buffer systems
Normal ABG values
• pH • PaO2 • PaCO2 • HCO3 • BE 7.35-7.45
80-100 mmHg 35-45 mmHg 22-26 mEq/L +/- 2 • When reading a ABG: • 7.36, 40, 25, 80
Acid Base Balance Introduction
• To maintain homeostasis, the body tries to keep the hydrogen ion concentration ([H + ]) at approximately 40 nmoles/L or the pH close to 7.40. Deviation from this [H + ] is minimized by buffering systems, all of which are in equilibrium with one another; the largest is the bicarbonate buffer system. Any change in acidbase status is reflected in the components of the bicarbonate buffer systemthe bicarbonate ion (HCO 3 ) and the arterial partial pressure of carbon dioxide (PaCO 2 ).
Energy Production
• Three sub-pathways of metabolism – Glycolysis – Tricarboxylic acid (TCA) cycle – Cytochrome (oxidative phosphorylation) system
Energy Production
•
Glycolysis
and the
Krebs cycle
both generate the high energy compound adenosine triphosphate (
ATP
) directly, by
substrate
-level phosphorylation, but this represents only a small fraction of the energy in each
glucose
that passes through these pathways. • Much more of the energy in glucose is conserved in the form of high-energy electrons carried in pairs by the electron "shuttles" NADH and FADH 2 , which are generated in glycolysis and the Krebs cycle.
Energy Production
• Glycolysis – Enzymes break down glucose into
pyruvic acid
,
hydrogen ions
, and
adenosine triphosphate (energy) ATP
– When no oxygen is present (anaerobic conditions),
lactic acid
is product – http://www.youtube.com/watch?v=3GTjQTqUuOw
Energy Production
• Glycolysis – C 6 H 12 O 6 2CH 3 O COOH + 4 H C 6 H 12 O 6 is glucose and CH 3 is pyruvic acid + where – CH 3 lactic acid CHOH COOH + energy (heat) – http://www.youtube.com/watch?v=bz5 T4p8WEQ&feature=related
Energy Production
• Tricarboxylic acid (TCA) cycle – Also known as
Krebs cycle
– In the presence of oxygen, pyruvic acid yields adenosine triphosphate (ATP) and carbon dioxide, and hydrogen molecules – 2 CH 3 = C = COOH + O 2 2 H 2 + 2 CO 2 + Acetyl CoA – http://www.youtube.com/watch?v=WcRm3MB3OKw
Energy Production
• Cytochrome (oxidative phosphorylation) system – Proceeds from TCA cycle in presence of sufficient oxygen – Produces the most energy of the three pathways
Energy Production
• Cytochrome (oxidative phosphorylation) system – Oxygen and hydrogen molecules produce water and energy –
O 2 + H 2 H 2 O + ATP (energy)
Glucose
Pyruvic Acid Acetyl CoA 2 H 2
2 ATP Lactic acid
+ O 2 2 H 2 2 CO 2 Cytochrome System
2 ATP 4 CO 2 6 H 2 O 34 ATP Final Products
Acid-Base Balance
• The dynamic equilibrium that exists between the substances in the body that are proton (H + ) donors and those that are proton acceptors • "Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions." H.L. MENCKEN
Acid-Base Balance
• Hydrogen ions are protons and do not exist in the naked state in body fluids; instead they react with water (H20) to form hydronium ions, such as H30 + and H5O 2 + . For clinical purposes H + used to represent these hydrated protons. can be Because [H + ] is so critical to enzyme function yet the absolute concentration is small and difficult to manipulate, the concept of pH was developed and is now universally used to represent [H + ].
*
Acid-Base Balance
• Normally maintained within very fine, but slightly alkaline range • Has two key mechanisms –
Lungs – regulation of CO 2 .
–
Kidneys – regulation of HCO 3 ˉ
Acid-Base Balance
Blood (H + ) H + Non-Bicarbonate Buffer System (Closed) + Buf ˉ Buf H + + HCO 3 ˉ Bicarbonate Buffer System (Open) H 2 CO 3 Eliminated Through Ventilation H + + CO 2
Acid-Base Balance
Open= removed/ exhaled
Acid-Base Balance
• Buffering System – A chemical solution consisting of a weak acid and its salt, which has the ability to minimize changes in pH when adding acid or alkali
Acid-Base Balance
• Buffering System: • A buffer system counteracts the effects of adding acid or alkali to the blood. The resulting pH change is less than if the buffer were not present.
• Blood contains two basic buffer systems: bicarbonate and nonbicarbonate. Each consists of a weak acid or acids and their conjugate base or bases.
Acid-Base Balance
• The bicarbonate system buffers the effects of fixed acids and alkalies that are added to the blood; the acid component is H2CO3 and the base is HCO 3 • The nonbicarbonate system consists mainly of proteins and phosphates and serves to buffer changes in carbon dioxide. • Since the nonbicarbonate system is a heterogeneous group of compounds, the acid component is represented by HBuf and the base by Buf. Note that carbon dioxide is part of an open system, since any buildup in plasma (aqueous or dissolved CO 2 ) can be excreted by healthy lungs.
Acid-Base Balance
• The bicarbonate and nonbicarbonate buffer systems are in equilibrium with each other. Measuring the components of either system will give the hydrogen ion concentration ([H + ]) or the pH of the blood. • However, since the nonbicarbonate system is a heterogeneous group of molecules, it is easier to measure the bicarbonate buffer components in order to determine pH. An extremely small quantity of H2C03 is present in the blood compared with dissolved CO 2 (approximately 1 to 400). Since H2CO3 is in equilibrium with dissolved CO 2 , the latter (measured as PaCO 2 ) can be used as the acid component in calculating pH. Therefore measurement of HCO 3 and PaCO 2 will provide the pH.
Henderson-Hasselbalch Equation
• Describes the relationship between pH, bicarbonate, and PCO 2 • pH = 6.1 +
log HCO 3 PCO 2 X 0.03
• Blood gas analyzers measure pH and P a CO 2 , but calculate HCO 3 ˉ
Henderson-Hasselbalch Equation
• carbonic acid has the value 6.1. • The pH of the blood is equal to the bicarbonate buffer system plus the logarithm of the following ratio bicarbonate concentration ([HCO 3 ]) over 0.03 times the arterial partial pressure of carbon dioxide (PaCO 2 ). • The constant 0.03 converts PaCO 2 from mm Hg to mmoles/L. Inserting normal values gives 7.4, the normal blood pH.
HendersonHasselbalch equation
• It is not necessary to memorize the full HendersonHasselbalch equation to intelligently manage acidbase disorders.
It is important to understand that pH reflects a ratio of HCO 3 to PaCO 2 .
• The bicarbonate buffer system is the most important of the body's buffer systems for several reasons.
This system provides the major way to buffer the additions of fixed acid and alkali to the blood. Since one of its components is carbon dioxide, the system is open, i.e., the respiratory system allows for excretion of huge amounts of carbon dioxide. Also, since carbon dioxide is readily diffusible across all cell membranes, the results of buffering can be reflected quickly in intracellular compartments.
• The body preferentially wants to maintain normal pH and does so by altering the numerator (HCO 3 ) or denominator (PaCO 2 ) of the HendersonHasselbalch equation as necessary.
Short Cut
• Rule of 8’s (a rule of thumb when determining what the HCO3 will be given an pH and CO2) • pH Factor example: When pH is 7.40 and PCO2 is 40 the 7.60 8/8 PCO2 HCO3- will be?
7.50 6/8 PCO2 5/8 (40) = 25 meq/ml 7.40 5/8 PCO2 7.30 4/8 PCO2 7.20 3/8 PCO2
DOES THE PATIENT HAVE AN ACID BASE DISORDER?
• It is important to recognize when a patient has an acidbase disorder since that recognition is the first step toward diagnosis and therapy. If any of the three variables in the HendersonHasselbalch equation are abnormal, the answer to this question is yes. Any acidbase derangement will be reflected in one or more components of the bicarbonate system: pH, PaCO 2 , HCO 3 • A single abnormal component, even without knowledge of the other two, always indicates an acidbase disorder.
DOES THE PATIENT HAVE AN ACID BASE DISORDER?
• This is particularly important since an abnormal HCO 3 is often found in venous blood (as part of the serum electrolytes measurement) without a concomitant blood gas measurement. An abnormal HCO 3 value alone cannot define or diagnose an acidbase disorder but nonetheless points to its presence. For example, an elevated HCO 3 suggests either metabolic alkalosis or respiratory acidosis.
DOES THE PATIENT HAVE AN ACID BASE DISORDER?
• Assess your patients thoroughly to determine possible cause of acid base disturbance • Look for possible metabolic causes (Renal failure, liver failure, dehydration/hypotension, verse respiratory disorders: COPD)
CALCULATED VS. MEASURED HCO
3 -
• Incorrect therapeutic decisions can occur if blood gas values are accepted at face value. They should always be examined for physiologic correctness, particularly when considering acid base disorders, which seem prone to misdiagnosis. For example, a PaCO 2 Hg, pH of 7.35, and HCO 3 of 49 mm of 16 mEq/L may be interpreted as a metabolic acidosis (low pH and low HCO 3 ) when in fact there is a transcription error: the HCO 3 should be 26 and cannot possibly be 16 if the pH is 7.35 and the PaCO 2 is 49 mm Hg.
CALCULATED VS. MEASURED HCO
3 -
• Such errors can be avoided if it is remembered that HCO 3 , PaCO 2 , and pH must satisfy the Henderson Hasselbalch equation. If PaCO 2 and pH have been measured, arterial HCO 3 can be calculated and does not have to be measured. The HCO 3 is routinely measured as one of the serum electrolytes (on venous blood), and this measurement can pose a problem when a comparison is made with the blood gas HCO 3 . Often, the measured venous HCO 3 does not agree with the arterial HCO 3 - that has been calculated from the HendersonHasselbalch equation.
POSSIBLE REASONS FOR MEASURED VENOUS HCO 3 AGREEING WITH CALCULATED ARTERIAL HCO 3 NOT
•
PHYSIOLOGIC REASONS
1. The venous HCO 3 measurement is actually the total CO 2 plasma HCO 3 content and is not identical to the calculated from the Henderson Hasselbalch equation. • Total CO 2 content includes all the acidlabile forms of carbon dioxide, of which plasma HCO 3 constitutes approximately 85%; hence the normal value for measured venous HCO 3 (total CO 2 content) is approximately 2 to 3 mEq/L higher than calculated arterial HCO 3 -
POSSIBLE REASONS FOR MEASURED VENOUS HCO 3 AGREEING WITH CALCULATED ARTERIAL HCO 3 NOT
•
PHYSIOLOGIC REASONS
2. In critically ill or unstable patients, the pK of the bicarbonate buffer system may not be 6. 1, thus rendering calculation of HCO 3 inaccurate 3. The venous sample may be drawn at a time different from that of the arterial sample used for blood gas analysis, and thus reflect a true change in acidbase status.
POSSIBLE REASONS FOR MEASURED VENOUS HCO 3 AGREEING WITH CALCULATED ARTERIAL HCO 3 NOT
•
TECHNICAL REASONS
1. The blooddrawing technique may alter venous HCO 3 , e.g., tourniquet placement may create a transient lactic acidosis, lowering the HCO 3 .
• 2. The blood gases are usually measured within minutes after the arterial sample is obtained, whereas the serum electrolytes may not be measured for an hour or more after the venous sample is drawn. The venous sample's HCO 3 , may change if the blood is not stored anaerobically or if its measurement is delayed .
POSSIBLE REASONS FOR MEASURED VENOUS HCO 3 AGREEING WITH CALCULATED ARTERIAL HCO 3 NOT
•
TECHNICAL REASONS
3. If pH and PaCO 2 are inaccurately measured, the calculation of HCO 3 will be inaccurate as well.
4. The venous HCO 3 or the arterial HCO 3 be transcribed incorrectly.
may
ACIDEMIA AND ALKALEMIA
• In terms of pH, the blood can reflect either acidemia or alkalemia. Acidemia indicates an acid pH (less than 7.35), and alkalemia indicates an alkaline pH (greater than 7.45). • The terms acidemia and alkalemia provide no specific information about acidosis vs. alkalosis, metabolic disorder vs. respiratory disorder, or the underlying clinical causes. To characterize a patient's blood as having acidemia or alkalemia, only one value is needed: pH.
ACIDEMIA AND ALKALEMIA
• Since pH is determined by a ratio of HCO 3 to PaCO 2 , the HendersonHasselbalch equation may be conveniently reduced for clinical use to
ACIDEMIA AND ALKALEMIA
• The kidneys are responsible for maintaining HCO 3 , and the lungs are responsible for maintaining PaCO 2
ACIDEMIA AND ALKALEMIA
• Since the kidneys affect HCO 3 changes slowly (from hours to days) and since the lungs may affect changes in PaCO 2 quickly (within minutes), the ratio determining pH is viewed as slow over fast • Important when considering the compensatory changes for acidbase disturbances. For example, a compensation that involves altering the HCO 3 occurs relatively slowly. Understanding acidbase disorders depends on knowing how the kidneys and the lungs act and react to the acidbase disorder.
ACIDEMIA AND ALKALEMIA
•
DISORDERS IN THE BLOOD Acidemia.
A low blood pH (less than 7.35)
Alkalemia.
A high blood pH (greater than 7.45)
Hypocapnia.
Hypercapnia.
A low PaCO 2 A high PaCO (less than 35 mm Hg) 2 (greater than 45 mm Hg)
ACIDEMIA AND ALKALEMIA
•
DISORDERS IN THE PATIENT Metabolic acidosis.
A primary physiologic process that causes a decrease in the serum bicarbonate and, when not complicated by other acidbase disorders, lowers the blood pH.
Metabolic alkalosis.
A primary physiologic process that causes an increase in the serum bicarbonate and, when not complicated by other acidbase disorders, raises the blood pH.
ACIDEMIA AND ALKALEMIA
•
DISORDERS IN THE PATIENT Respiratory acidosis.
A primary physiologic process that leads to an increased PaCO 2 and, when not complicated by other acidbase disorders, lowers the blood pH.
Respiratory alkalosis.
A primary physiologic process that leads to a decreased PaCO 2 and, when not complicated by other acidbase disorders, raises the blood pH.
Compensatory process.
Not a primary acidbase disorder, but a change that follows a primary disorder. A compensatory process attempts to restore the blood pH to normal and is not appropriately termed acidosis or alkalosis.
Examples
• Metabolic Alkalosis – 7.55, 40, 40 • Metabolic Acidosis – 7.25, 40, 16 • Respiratory Alkalosis – 7.55, 25, 22 • Respiratory Acidosis – 7.25, 55, 22 All of these are uncompensated blood gases
Uncompensated (ACUTE)
• ABG’s that have one of the following variables which is in normal range (PaCO2 of HCO3) while the pH is out of range is considered uncompensated • Simple means the body has not yet attempted to correct the blood gas • Example: • 7.25, 60, 24 • This patient has a uncompensated respiratory acidosis since the HCO3 has not been increased to increase the pH
ACIDEMIA AND ALKALEMIA
Primary disorder Compensatory process
Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis Hyperventilation (lower PaCO 2 ) Hypoventilation (raise PaCO 2 ) Renal HCO3 retention Respiratory Alkalosis Renal HCO 3 excretion
Acidosis and Alkalosis
• In contrast to acidemia and alkalemia, which refer to the in vitro determination of blood pH, acidosis and alkalosis refer to the physiologic processes occurring in the patient. Acidosis and alkalosis cannot be fully characterized without reference to the patient's history, physical examination, serum electrolyte values, and other relevant laboratory data. Acidosis and alkalosis cannot be defined by reference to blood changes only.
Acidosis and Alkalosis
• The numerator of the HendersonHasselbalch equation, HCO 3 , is called the metabolic component, and the denominator, PaCO 2 , is called the nonmetabolic or respiratory component (the term respiratory is used henceforth instead of nonmetabolic). • There may be both metabolic and respiratory causes of acidbase disorders. The primary change determines the type of disorder
• http://www.youtube.com/watch?v=i_pTaTveCCo& feature=related • http://www.youtube.com/watch?v=eK2dBdBRvC U&feature=related • http://www.youtube.com/watch?v=HrUvft2d8Zo&f eature=related
ABG Practice
• http://www.vectors.cx/med/apps/abg.cgi
Interpret the gas
•
Practice Problem 1
• pH 7.31 PCO 2 55 mm Hg HCO 3 • And give a possible cause 26 mEq/L
ABG practice
•
Practice Problem 2
• ABG's: pH 7.31 PCO 2 mEq/L 55 mm Hg HCO 3 35
ABG practice
•
Practice Problem 3
• ABG's: pH 7.31 PCO 2 mEq/L 35 mm Hg HCO 3 20
ABG practice
•
Practice Problem 4
• ABG's: pH 7.31 PCO 2 mEq/L 25 mm Hg HCO 3 20
ABG practice
•
Practice Problem 5
• ABG's: pH 7.48 PCO 2 mEq/L 25 mm Hg HCO 3 28
Acidosis and Alkalosis
• Compensatory processes are secondary changes; as such, they occur after the primary process has begun and occur solely as an attempt to correct the pH change brought about by the primary disorder. • Compensatory changes are not termed acidosis or alkalosis.
Acidosis and Alkalosis
• Acidosis and alkalosis refer to what is happening in the patient, not necessarily to what is manifested in the blood.
• For example, a low pH may reflect an acidosis alone or may indicate an acidosis plus an alkalosis. • If the physiologic process causing the disorder is uncomplicated by other acidbase disorders, then the blood is appropriately acidemic (low pH) from an acidosis or alkalemic (high pH) from an alkalosis. • However, if another acidbase disorder is present, the resulting pH may be high or low. Socalled mixed acidbase disorders are common in patients with respiratory disease
CLINICAL CAUSES OF THE PRIMARY ACIDBASE DISORDERS
•
METABOLIC ALKALOSIS
• Potassium loss (from diruretics) Corticosteroids Diuretics Vomiting or nasogastric suction •
RESPIRATORY ACIDOSIS
• Depression of central nervous system respiratory center Severe impairment of chest bellows Severe lung and/or airways disease
CLINICAL CAUSES OF THE PRIMARY ACIDBASE DISORDERS
•
RESPIRATORY ALKALOSIS
• Anxiety Sepsis Central nervous system lesions Aspirin overdose Liver failure Hypoxemia Interstitial lung disease Acute lung and airways disease
CLINICAL CAUSES OF THE PRIMARY ACIDBASE DISORDERS
METABOLIC ACIDOSIS Increased anion gap
• Uremia Ketoacidosis Lactic acidosis Intoxicants Aspirin overdose Methanol Ethylene glycol Paraldehyde
METABOLIC ACIDOSIS No increased anion gap
• Renal HCO 3 loss Renal tubular acidosis Interstitial nephritis Early renal failure Gastrointestinal HCO 3 Diarrhea loss Ureteral diversion procedures Carbonic anhydrase inhibitors Acids containing chloride (e.g., HCl, NH4Cl) Hyperalimentation
CLINICAL CAUSES OF THE PRIMARY ACIDBASE DISORDERS
• Refer to handouts for all causes of ACID BASE abnormalities
ANION GAP
• A useful aid in diagnosing both simple and mixed acidbase disorders • The AG is the difference between measured cations and anions. • The measured cations are sodium (Na + ) and potassium (K + ), and the measured anions are chloride (Cl) and bicarbonate (HCO 3 ). Since potassium is of relatively low concentration, it is usually ignored when calculating the AG.
Anion Gap
Anion Gap
• The normal AG is 12 -16 mEq/L and is a result of the presence of anion proteins, sulfates, and other molecules that are not routinely measured with the serum electrolytes. • An elevated AG is caused by metabolic acidosis.
• Not all cases of metabolic acidosis manifest an elevated AG. • The AG is elevated when the metabolic acid added to the blood contains an "unmeasured" anion, such as lactate or ketones. States of metabolic acidosis that add no unmeasured anion to the blood do not elevate the AG and are called hyperchloremic metabolic acidosis. In hyperchloremic metabolic acidosis the reduced HCO 3 is replaced by chloride, which is measured as part of the serum electrolytes.
PRIMARY VS. COMPENSATORY PROCESSES
• A metabolic acidosis or metabolic alkalosis is a physiologic acidbase disorder in which the primary change is in the HC0 3 -. • A respiratory acidosis or respiratory alkalosis is one in which the primary change is in the PaCO 2 . • The key word is primary, meaning first change. If HCO 3 changes first and then PaCO 2 changes as a compensatory event, the basic process is metabolic, not respiratory, and the patient has a metabolic acidosis or metabolic alkalosis with respiratory compensation. Similarly, if the primary event is a change in PaCO 2 HCO 3 and changes as compensation, the basic process is either respiratory acidosis or respiratory alkalosis with metabolic compensation.
PRIMARY VS. COMPENSATORY PROCESSES
• From the basic relationship expressed by the Henderson Hasselbalch equation, what is the primary change and the compensatory response for metabolic acidosis? • The body wants to keep pH in the normal range so that, given a primary event, the compensatory response should be predictable. • In
metabolic acidosis
, the primary event leads to reduction of HCO 3 . This reduction may arise from an actual loss of HCO 3 (renal or gastrointestinal) or from the buffering of fixed acid (e.g., lactic acid).
PRIMARY VS. COMPENSATORY PROCESSES
•
Primary event
• As HCO 3 decreases, pH falls. The body responds by decreasing the denominator (i.e., by hyperventilating) as much as possible. This decrease in the denominator alters pH back toward normal: •
Primary event plus compensatory response
PRIMARY VS. COMPENSATORY PROCESSES
• • A common clinical cause of metabolic acidosis is lactic acidosis. For example, suppose a patient in shock produces enough lactic acid to lower his HCO 3 to 12 mEq/L or half of normal. Before any compensatory response occurs, i.e., when the PaCO 2 pH will be 7.10. is still normal, the
Primary event
PRIMARY VS. COMPENSATORY PROCESSES
• • The compensatory response of hyperventilation, e.g., lowering the PaCO 2 a ratio of HCO 3 to PaCO 2 to 30 mm Hg results in that elevates pH to 7.30.
Primary event plus compensatory response
PRIMARY VS. COMPENSATORY PROCESSES
• A pH of 7.30 is not normal, but it is a lot safer than 7.10. The compensatory response in this example is hyperventilation and the response should not be termed respiratory alkalosis.
• Alkalosis implies a primary physiologic process; hyperventilation is only a secondary or compensatory phenomenon. This differentiation is not just an exercise in semantics; the terminology helps to distinguish between single acidbase disorders and mixed acidbase disorders, an area that is often confusing.
BASE EXCESS
• Base excess is an in vitro measurement that was introduced to characterize the metabolic component of acidbase disorders. Base excess was widely used before studies showed the human response to primary acidbase disorders • Base excess is still calculated and reported in many blood gas laboratories. However, for the novice base excess is a confusing concept and probably impedes understanding of acidbase problems.
BASE EXCESS
• To calculate base excess, the blood sample is equilibrated at two CO 2 tensions different from the patient's PaCO 2 , the pH is measured at both CO 2 levels, and the interpolated pH at PaCO 2 of 40 mmHg is used to calculate a standard bicarbonate (normal 24 mEq/L). • Any change from this standard bicarbonate represents the metabolic component of the acidbase problem. The actual base excess (reported in mEq/L) is a derived value; the deviation from the standard bicarbonate is multiplied by a factor that takes into account hemoglobin content. If the patient's bicarbonate (calculated from blood gas measurements) is above the derived value, a positive base excess is present (i.e., a component of metabolic alkalosis); if the patient's bicarbonate is below the derived value, a negative base excess is present (i.e., a metabolic acidosis component).
ACUTE VS. CHRONIC RESPIRATORY DISORDERS
• Acute vs Chronic: In acidbase terminology these terms are synonymous with compensated and uncompensated; these terms apply only to respiratory acidosis and respiratory alkalosis. • Acute respiratory acidosis occurs when carbon dioxide is retained acutely; it is the state of affairs before the kidneys have had a chance to compensate by retaining any HCO 3 .
ACUTE VS. CHRONIC RESPIRATORY DISORDERS
• Chronic respiratory acidosis occurs when the retained carbon dioxide has been, to some degree, buffered by the kidney's retention of HCO 3 . The pH is higher than in acute respiratory acidosis, but it is still below 7.4. The HCO 3 retention does not begin for at least a few hours and may take up to 3 days for maximal compensation. • Acute respiratory alkalosis occurs when carbon dioxide is blown off acutely, before the kidneys have had a chance to compensate by excreting HCO 3 . As with acute CO 2 retention, this change can occur quickly (within minutes) and may last for hours before there is any compensation.
ACUTE VS. CHRONIC RESPIRATORY DISORDERS
• Chronic respiratory alkalosis occurs when the reduction of carbon dioxide is compensated for by the renal excretion of HCO 3 . The pH is lower than in acute respiratory alkalosis, but it is still above 7.4. The HCO 3 excretion does not begin for at least a few hours and takes up to 3 days for maximal compensation. • The terms chronic and compensation do not imply "normal pH" Maximal compensation simply means that the body has done everything it can to return the pH toward normal. Rarely does compensation return pH to normal. A normal pH in the face of an acidbase disorder strongly suggests a mixed picture, with two or more primary disorders balancing each other. Occasionally patients can have a pH in the normal range when they have chronic respiratory acidosis or metabolic alkalosis, but the pH still does not return to the patient's true normal pH. For example, if a patient's normal pH is 7.40, compensation for respiratory acidosis might return it to 7.37 or 7.38 but not to 7.40.
ACUTE VS. CHRONIC METABOLIC DISORDERS
• The compensation for metabolic acidosis occurs much more quickly than the compensation for respiratory disorders; in response to an acute reduction of HC0 3 , the maximal reduction of PaCO 2 occurs within 12 to 24 hours.
ACUTE VS. CHRONIC METABOLIC DISORDERS
• Not much is known about how long it takes for the maximal compensation of metabolic alkalosis. Except when massive amounts of HC0 3 are given to a patient, acute metabolic alkalosis is practically unknown in clinical practice. Also, not all patients seem to compensate for metabolic alkalosis with hypoventilation • Otherwise healthy people do not usually retain carbon dioxide to compensate for metabolic alkalosis, whereas patients suffering from severe lung disease or dehydration commonly retain carbon dioxide to compensate for this disorder.
MIXED ACIDBASE DISORDERS
• Patients with pulmonary disease often have two or more acidbase disorders occurring at the same time • they are called mixed, acidbase disorders. As a general rule, the more severe an acidbase disorder, the more likely it will be accompanied by another primary acidbase disturbance. • For example, patients with severe respiratory acidosis (e.g., a PaCO 2 of 80 mm Hg) are more likely to manifest accompanying metabolic acidosis than when the respiratory acidosis is mild to moderate (e.g., a PaCO 2 of 50 mm Hg). This is simply because they are more likely to be severely hypoxemic or have cardiovascular impairment. The acidbase map is especially useful in sorting out these combined disorders.
MIXED ACID-BASE DISORDERS
• Example: • pH • PaCO2 • HCO3 • BE • PaO2 7.20
79 16 -5 60
CLINICAL APPROACH TO ACIDBASE DIAGNOSIS
• The means to diagnose acidbase disorders, both simple and complicated, have been explained. Acidbase disorders refer to what is happening in the patient and represent physiologic processes, not just blood gas values. This concept allows diagnosis and management of difficult acidbase disorders. A rational approach to acidbase diagnosis and management is suggested below: • 1. Find the acidbase disorderserum HCO 3 measurement. or arterial blood gas • 2. Based on a full clinical assessment (history, physical examination, detailed laboratory review), explain the blood gas values in terms of physiologic processes and underlying clinical conditions. • 3. Correct the pH if it is outside the range of 7.307.52. • 4. Treat the underlying clinical condition.
Clinical Problem 1
• A 72yearold man is admitted in shock with a blood pressure of 70 mm Hg measured by palpation. He has a history of chronic obstructive pulmonary disease and is also receiving treatment for a heart condition. An initial arterial blood gas analysis while he was breathing 40% oxygen shows PaCO 2 , 70 mm Hg; pH, 7.1; PaO 2 , 35 mm Hg; and SaO 2 , 58%. He is intubated, and a subsequent blood gas analysis also while breathing 40% oxygen reveals pH, 7.3; PaCO 2 , 40 mm Hg; and PaO 2 , 87 mm Hg. The anion gap is elevated at 22 mEq/L. What is the patient's acidbase status?
Clinical Problem 2
• An 18yearold girl is admitted to the intensive care unit because of an acute asthma attack that is unresponsive to treatment received in the emergency room. Her blood gas values while breathing room air show pH, 7.45; PaCO 2 , 25 mm Hg; PaO 2 , 55 mm Hg; and SaO 2 , 87%. Her peak expiratory flow rate is 95 L/min (predicted normal, 520 L/min). She continues to receive asthma medication (intravenous aminophylline and corticosteroids).
Clinical Problem 3
• A 52yearold woman has been artificially ventilated for 2 days following a drug overdose. Her blood gas values have been stable for the past 12 hours at pH, 7.45 and PaCO 2 , 25 mm Hg. Serum electrolytes studies reveal Na + , 142 mEq/L; HCO 3 , 18 mEq/L; Cl 100 mEq/L; and K + , 4 mEq/L. How would you access her acidbase status?
Clinical Problem 4
• A 53yearold man initially presented to the emergency room where he was found to have the following blood gas values while breathing room air: pH, 7.51; PaCO 2 , 50 mm Hg; PaO 2 , 40 mm Hg; and HCO 3 , 39 mEq/L. His acidbase disorder is best characterized as which of the following? • a. Metabolic alkalosis • b. partially compensated Metabolic alkalosis with moderate hypoxemia • c. Respiratory acidosis with metabolic compensation • d. Indeterminable without more information
Clinical Problem 5
• This patient was found to have congestive heart failure. (His initial blood gas values are given in Part A.) He was treated with low F I O 2 and diuretics. Three days later his pH was 7.38, PaCO 2 was 60 mm Hg, HCO 3 and PaO 2 was 34 mEq/L, was 73 mm Hg while he was breathing 24% inspired oxygen, and he was clinically improved. How would his acidbase status be characterized at this point?
Regulation of Carbon Dioxide Tension
• Anatomic structures contributing to regulation – Medulla oblongata – Pons – Central chemoreceptors – Vagus nerve – Peripheral chemoreceptors
Regulation of Carbon Dioxide Tension
• Anatomic Structures Contributing to Regulation – Central Chemoreceptors – Peripheral Chemoreceptors
Regulation of Carbon Dioxide Tension
• Anatomic Structures Contributing to Regulation – Medulla Oblongata – Pons
Anatomic Structures Contributing to Regulation
• Medulla oblongata – Houses the respiratory control center – CO 2 and HCO 3 ˉ pass through the blood-brain barrier and stimulate chemoreceptors in the medulla – These afferent impulses are transmitted to the medullary center located in the brain stem – Maintains the normal, rhythmic pattern of breathing
Anatomic Structures Contributing to Regulation
• Pons – has two distinct centers – Pneumotaxic center • Fine tunes ventilatory rhythmicity by inhibiting length of inspiration • Maximum stimulation limits inspiration to 0.5 seconds (≥ 40 breaths/minute); weak stimulation reduces respiratory rate to 3 to 5 breaths/minute
Anatomic Structures Contributing to Regulation
• Pons – has two distinct centers – Pneumotaxic center • Destruction of the center causes apneustic breathing (long, sustained inspirations)
Anatomic Structures Contributing to Regulation
• Pons – has two distinct centers – Apneustic center • Causes sustained inspiratory pattern with only short expiratory phases • Stimulation of apneustic center unclear; vagus nerve must be impaired for the apneustic center to be active • Destruction of apneustic and pneumotaxic centers leads to a rapid, irregular, gasping respiratory pattern
Pons
Anatomic Structures Contributing to Regulation
• Central chemoreceptors – Located on the ventrolateral surface of each side of the medulla oblongata – In contact with cerebral spinal fluid (CSF) and arterial blood
Anatomic Structures Contributing to Regulation
• Central chemoreceptors – Stimulated by H + concentration in CSF – CO 2 is the only readily diffusible substance across the blood-brain barrier
Anatomic Structures Contributing to Regulation
• Central chemoreceptors – H + and HCO 3 ˉ move across the barrier, but much more slowly – Changes in arterial CO 2 result in changes in CO 2 in the CSF
Anatomic Structures Contributing to Regulation
• Central chemoreceptors – The change in H + stimulates or inhibits ventilation (↑H + leads to ↑ in ventilation; ↓H + leads to ↓ in ventilation) – Factors affecting CSF CO 2 include cerebral blood flow, CO 2 production, CO 2 content of arterial and venous blood, and alveolar ventilation
Anatomic Structures Contributing to Regulation
• Vagus Nerve – Transmits afferent impulses from two centers • Baroreceptors (located in the aortic arch) • Pulmonary reflexes
Regulation of Carbon Dioxide Tension
• Anatomic Structures Contributing to Regulation – Vagus Nerve
Vagus Nerve
• Baroreceptors – Primarily stimulated by variations in blood pressure – Hypotension may lead to hyperventilation – Hypertension may lead to hypoventilation
Vagus Nerve
• Pulmonary reflexes – Pulmonary stretch receptors (Hering-Breuer reflex) • Located in smooth muscle of conducting airways • Stimulated by lung inflation and increase in transpulmonary pressure
Vagus Nerve
• Pulmonary reflexes – Pulmonary stretch receptors (Hering-Breuer reflex) • Stimulation results in increase in inspiratory time, increase in respiratory rate, bronchodilation, tachycardia, and vasoconstriction • Used to provide input regulating rate and depth of breathing
Vagus Nerve
• Pulmonary reflexes – Deflation reflex • Stimulated by lung collapse • Stimulation leads to increase in force and frequency of inspiratory effort • May be responsible for hyperpnea in pneumothorax • Specific point of stimulation unknown
Vagus Nerve
• Pulmonary reflexes – Irritant receptors • Located in epithelium of trachea, bronchi, larynx, nose, and pharynx • Stimulated by irritants: inspired irritants (e.g., ammonia), mechanical irritants (e.g., particulate matter), anaphylaxis, pneumothorax, pulmonary congestion
Vagus Nerve
• Pulmonary reflexes – Irritant receptors • Stimulation results in bronchoconstriction, hyperpnea, laryngospasm, closure of glottis, cough
Vagus Nerve
• Pulmonary reflexes – Type J (juxtapulmonary-capillary) receptors • Located in walls of pulmonary capillaries • Stimulated by increase in interstitial fluid volume, pulmonary congestion, chemical irritants, And microembolism • Stimulation results in rapid, shallow breathing; severe expiratory constriction of larynx; hypoventilation; bradycardia; and inhibition of spinal reflexes
Regulation of Carbon Dioxide Tension
• Anatomic Structures Contributing to Regulation – Central Chemoreceptors – Peripheral Chemoreceptors
Anatomic Structures Contributing to Regulation
• Peripheral chemoreceptors – Aortic bodies • Located in the arch of the aorta • Innervated by vagus nerve • Stimulated by decrease in P a O 2 , decrease in pH, and increase in P a CO 2
Anatomic Structures Contributing to Regulation
• Peripheral chemoreceptors – Carotid bodies • Located at the bifurcation of the common and carotid arteries • Innervated by glossopharyngeal nerve • Stimulated by decrease in P a O 2 , decrease in pH, and increase in P a CO 2
Peripheral Chemoreceptors
Peripheral Chemoreceptors
• Effects of P a O 2 – Maximum stimulation occurs at P a O 2 60 mmHg – When P a O 2 ≤ 30 mmHg, stimulation is decreased
Peripheral Chemoreceptors
• Effects of P a O 2 – Only stimulated by dissolved oxygen – Also stimulated by decrease in blood flow and increase in temperature – Not stimulated by anemia or carbon monoxide
Peripheral Chemoreceptors
• Effects of P a CO 2 and H + concentrations – Affected directly only by increases in H + concentrations – P a CO 2 causes change in H + concentration, stimulating the receptor
Peripheral Chemoreceptors
• Effects of P a CO 2 and H + concentrations – Decrease in H + concentration has minimal effect – Increase in H+ Stimulation causes increase in respiratory rate and tidal volume
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory acidemia – Increase in arterial P a CO 2 leads to increase in CSF P a CO 2 – Increase in CSF P a CO 2 leads to decrease in CSF pH, stimulating central chemoreceptors
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory acidemia – When body cannot increase ventilation, as in COPD, elevation of P a CO 2 persists in the CSF – This stimulates kidney to retain HCO 3 ˉ
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory acidemia – As HCO 3 ˉ increases in the serum, active transport mechanisms and diffusion increase the level of HCO 3 ˉ in the CSF – The CSF pH returns to normal
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory acidemia – When the CSF pH is normal, the body then responds to changes in the P a CO 2 at the newly elevated level
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory acidemia – When chronically elevated, the central chemoreceptor drive to ventilate is diminished and there is decreased sensitivity to carbon dioxide changes
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory alkalemia – Decrease in arterial P a CO 2 leads to decrease in CSF PCO 2 – Decrease in CSF PCO 2 raises CSF pH, inhibiting central chemoreceptors
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory alkalemia – When the stimulus causing hyperventilation persists, the kidney excretes HCO 3 ˉ – As HCO 3 ˉ in the serum decreases, active transport and diffusion decrease the level of HCO 3 ˉ in the CSF
Regulation of Carbon Dioxide Tension
• Response of the medulla in respiratory alkalemia – When the CSF pH is normal, the body then responds to changes in the PCO 2 at the newly decreased level
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic acidemia – Decreases in pH in the plasma stimulate the peripheral chemoreceptors; H + ions do not readily cross the blood-brain barrier
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic acidemia – The decrease in pH is interpreted as an increase in P a CO 2 by the peripheral chemoreceptors which increase the level of ventilation, decreasing the P a CO 2
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic acidemia – The decrease in P a CO 2 increases the CSF pH, resulting in inhibition of ventilation via the central chemoreceptors
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic acidemia – Peripheral chemoreceptors increase ventilation while central chemoreceptors decrease ventilation; however, the peripheral chemoreceptors predominate
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic acidemia – Maximum response to metabolic acidemia does not occur until CSF is normalized
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic alkalemia – Neither H + nor HCO 3 ˉ readily cross the blood-brain barrier – The peripheral chemoreceptors respond poorly to metabolic alkalemia
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic alkalemia – Significant increase in pH causes inhibition of the peripheral chemoreceptors, inhibiting ventilation – The increase in arterial P a CO 2 increases CSF PCO 2 causing stimulation of the central chemoreceptors, increasing ventilation
Regulation of Carbon Dioxide Tension
• Response of the medulla in metabolic alkalemia – The peripheral chemoreceptors predominate – Rare for the P a CO 2 to rise above 50 mmHg in order to compensate for a metabolic alkalemia • If the P a CO 2 increases, arterial PO 2 decreases, resulting in hypoxemia, which stimulates ventilation via the peripheral chemoreceptors
Regulation of Bicarbonate (HCO
3
ˉ) Levels
• Classified as an open system – End product of CO 2 is exhaled
Regulation of Bicarbonate (HCO
3
ˉ) Levels
• HCO 3 ˉ combines with H + to form H 2 CO 3 which dissociates to form H 2 O and CO 2 – CO 2 eliminated as long as ventilation occurs – Removal of CO 2 prevents reaction from reaching equilibrium with reactants
Regulation of Bicarbonate (HCO
3
ˉ) Levels
• Bicarbonate and hypoventilation – Unable to buffer carbonic acid (H 2 CO 3 ) in states of hypoventilation – Closed non-bicarbonate buffer systems act as buffers in cases of hypoventilation
Regulation of Bicarbonate (HCO
3
ˉ) Levels
•
Role of the kidney
– H + secreted into the filtrate • From H 2 CO 3 • From fixed acids
Regulation of Bicarbonate (HCO
3
ˉ) Levels
• Role of the kidney – Generally excrete less than 100 mEq./day • Retention of HCO 3 ˉ • If blood PCO 2 is high, then more H + is excreted and HCO 3 ˉ is reabsorbed • If blood PCO 2 is low, then more HCO 3 ˉ is excrete and less H + is secreted
Non-Bicarbonate Buffering Systems
• Closed systems so ability to buffer are limited • Hemoglobin (Hb) most important because it is most abundant • Intracellular protein accounts for most of intracellular buffering – 60 to 70% of all buffering in the body is intracellular
Non-Bicarbonate Buffering Systems
• Sum of HCO 3 ˉ plus protein buffers equals the buffer base – Normal total buffer base is 54 mEq./L.
– Actual buffer base minus normal buffer base equals base excess/deficit – Normal BE/BD is 0 ± 2 mEq./L