ACID-BASE BALANCE: IMPLICATIONS FOR THE NEONATE

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1 ACID-BASE BALANCE: IMPLICATIONS FOR THE NEONATE Developed by Lisa Fikac, MSN, RNC-NIC Expiration Date: 12/15/17

2 This continuing education activity is provided by Cape Fear Valley Health System, Training and Development Department, which is an approved provider of Continuing Nursing Education by North Carolina Nurses Association, an accredited approver by the American Nurses Credentialing Center s Commission on Accreditation. 1.8 Contact hours will be awarded upon completion of the following criteria: Completion of the entire activity Submission of a completed evaluation form Completion of a post-test with a grade of at least 85%. The planning committee members and content experts have declared no financial relationships which would influence the planning of this activity. It is expected that there will be no presentation of non-approved use of any FDAapproved product. There is no endorsement of any commercial products displayed in conjunction with this activity by Cape Fear Valley Health System, the American Nurses Credentialing Center, the North Carolina Board of Nursing, or the North Carolina Nurses Association. The author would like to thank Stacey Cashwell for her work as original author.

3 Describe acid-base balance and control mechanisms. Identify the components of an arterial blood gas. Describe the two acid-base imbalances commonly found in the neonate. Describe proper blood sample collection to promote accurate ABG results.

4 Background Information Acid-base balance is a complex concept. There are many ways the body works to keep our ph at a normal level. If you want to be able to treat your patient s acid-base imbalance, it is essential you understand the chemical interactions and our body s control mechanisms. You will see the graphic to the right for Memory Joggers throughout the presentation to highlight important points. Where you see the "baby" graphic to the left, these sections will highlight the differences in the infant s ability vs. the adult s ability to maintain acid-base balance. The picture of a bottle of soap will help you note when the subject is about bases. The warning sign for acid will help you note when we are dealing with acids. Finally, at the end of many sections we have a brief review to help solidify the information for you. This review is designated with the clipboard graphic. Acid-base balance is one of the body s most important homeostatic mechanisms.

5 It represents equilibrium, balance, and a steady state. Without acid-base balance, the cells cannot function properly. The body can tolerate slight deviations in balance for short periods of time Chronic imbalances can result in pronounced, potentially fatal changes in metabolic activity and essential body functions. Let s first make sure we are clear on what are these things we call acids and bases. An acid is called a hydrogen ion (H+) donor." It sheds H+ into solution. A base is a hydrogen ion receiver. It pulls H+ out of solution. You could think of a base like a sponge soaking up a spill (acid). Acids and bases are continually absorbed into the bloodstream from Foods Metabolism of nutrients at the cellular level Extremely high protein diets rich in meats produce an excess of acid mineral residue which challenges the body s ability to maintain acidbase balance. Strictly vegetarian diets produce a surplus of basic mineral residue which also challenges the body s ability to remain in acid-base balance.

6 Memory Jogger The most influential acids are - Carbonic acid (H2CO 3) Dissolved carbon dioxide gas (CO 2). The most influential base is the bicarbonate (HCO3 - ) ion. The infant is in a unique situation when it comes to acid-base balance. The infant s rate of metabolism is twice that of the adult in relation to its body mass. This means the infant produces twice as much acid as the adult. The functional development of the infant s kidneys is not complete until about the end of the first month of life. As a result, the infant concentrates urine to only 1½ times the osmolality of plasma. Whereas the adult can concentrate urine to 3-4 times the osmolality of plasma. o Thus, the infant has a natural tendency toward acidosis. Although both acids and bases are important components of balance, we measure the hydrogen ion (H+) concentration in extracellular body fluids to determine acid-base balance. Even slight variations from normal in the H + concentration can cause marked alterations in the rate of chemical reactions some being slowed, others being accelerated.

7 Control of the H + concentration is one of the most important components of homeostasis. Hydrogen ions are continually entering the body fluids from - Carbonic acid o Formed as a result of aerobic and anaerobic metabolism of glucose Lactic acid o Formed as a result of aerobic and anaerobic metabolism of glucose Sulfuric acid o Created when sulfur-containing amino acids are oxidized Phosphoric acid o Accumulates when certain phosphoproteins and ribonucleotides are metabolized as an energy source Acidic ketone bodies o Acetone, acetoacetic acid, and beta-hydroxybutyric acid accumulate during the incomplete breakdown of fats

8 Control Mechanisms ph Basics The concentration of H + is referred to as the body s ph. The ph is a numeric value (0-14) used to represent the negative logarithm of the number of hydrogen ions present in one (1) liter of a solution This indicates the degree of acidity or alkalinity of the solution. The midpoint (7) indicates a neutral ph in chemical terms. We ll talk about normal ph for humans further on. Since ph is a negative logarithm, think about the H+ and ph as being on the opposite ends of a see-saw - As the H + concentration increases - o ph goes down o Solution becomes more acidic As the H + concentration decreases - o ph goes up o Solution becomes more alkaline A ph of 7.0 indicates chemical neutrality, which means there are equal amounts of hydrogen (H+) and hydroxyl (OH-) ions. Under normal circumstances, body fluids tend to be somewhat alkaline. Blood ph is maintained within a narrow range of Outside this range, cellular activities begin to malfunction. The table below lists some common solutions and body fluids with their ph.

9 Download for free at A favorable ph ( ) is essential to body functions. Without a favorable ph - 1. Structural shapes of proteins and/or protein functions are altered. 2. Enzymatic activity is diminished. 3. Chemical reactions may cease.

10 In addition, acidity or alkalinity may lead to changes in blood vessels or cell membranes. This may jeopardize oxygenation of the myocardium, brain, or other vital organs. The effectiveness of a variety of pharmacological agents may also be altered during times of acid-base imbalance. A sustained ph below 7.0 or above 8.0 is generally considered incompatible with survival. As a result, the body has several mechanisms for neutralizing or eliminating the H+ to keep blood ph is constant and favorable. Memory Jogger These control mechanisms known as buffers act to minimize changes. An acid-base buffer is a solution of chemical compounds that prevent marked changes in the H+ concentration when either an acid or a base is added to the solution. In the premature or sick newborn, buffers may be blunted or insufficient. This places the baby at risk for life-threatening imbalances. Buffers include - Chemical buffers such as carbonic acid, bicarbonate, proteins, phosphates Physiologic buffers such as functioning of the lungs and kidneys Biologic buffers such as blood and cellular activity Before we look at the buffers in the next sections, let's review the Basics of ph. ph is the negative logarithm of the H+ ions (acid) in solution.

11 When the H+ concentration goes up, the ph goes down. ph of 7.0 is neutral, neither acidic or basic. Normal arterial ph for humans is

12 Chemical Buffers Chemical buffers act rapidly to combine with acids or bases entering the body fluids and prevent drastic changes in the H+ concentration and the ph. Buffers combine with the strong acids replacing them with weaker acids, and vice versa. o Buffers do not actually rid the body of H + or CO 2 but combine with them until another system can excrete them from the body. o Depending on whether an acid or base state exists, chemical buffer reactions are reversible. A strong acid easily dissociates, or breaks up. o This frees up more hydrogen ions. o As a result of the buffer s action, a weak acid that contributes fewer hydrogen ions replaces a strong acid with the potential to contribute many hydrogen ions. o The result is that the ph is lowered only slightly (fewer H + ) instead of dramatically (more H + ). The major chemical buffers include - Carbonic acid (H 2CO 3) Bicarbonate (HCO 3- ) Plasma proteins and phosphates Memory Jogger Of the three chemical buffers, the most important are carbonic acid (H2CO3) and bicarbonate (HCO3-). Extracellular fluid normally has a ratio of 1:20 - carbonic acid to bicarbonate. For every 1 part of carbonic acid there must be 20 parts of bicarbonate. This ratio of acid to base is critical in order to keep ph When this 1:20 ratio is maintained, acid-base balance remains near normal despite changes in the absolute amounts of either the carbonic acid or bicarbonate buffer.

13 Depending on whether an acid or base state exists, carbonic acid (H2CO3) can dissociate into bicarbonate (HCO3-) and hydrogen. This process helps to maintain the 1:20 ratio and preserve the body s ph at 7.4. The equation below illustrates it in chemistry terms. A change in the ratio in either direction (increase or decrease) affects the ph by either increasing it (alkalosis) or decreasing it (acidosis). The body s ability to regulate the amount of either or both component(s) to maintain the correct ratio for acid-base balance makes this system one of the most important for controlling the ph of body fluids. The principles of buffering action, as illustrated by the carbonic acid-bicarbonate buffers, can be applied equally to the plasma proteins and phosphate buffers. They are powerful buffers and are capable of functioning as either an acid or base, depending on the existing acidity/alkalinity of body fluids. They are active in the - o Plasma o Intracellular fluids o Extracellular fluids Plasma proteins are the most plentiful buffers in the body. They work both inside and outside the cells. Of the plasma proteins, albumin occurs in the highest concentration and has the greatest buffering capacity of the various plasma proteins. o Other plasma proteins (e.g. immunoglobulins, hemoglobin) are present but in lower concentrations and are less physiologically active. Like the carbonic acid-bicarbonate buffer system, the plasma proteins bind with acids and bases to weaken or neutralize them. The phosphate buffers are active in the intracellular fluids.

14 They also react with either acids or bases forming compounds that result in only slight shifts in the body s ph. Phosphates are the least important of the major non-bicarbonate buffers in the extracellular fluid due to their low concentration levels. Memory Jogger Bicarbonate (HCO3-) and carbonic acid (H2CO3) are the most important buffers in to body. They work fast to neutralize excess acids and bases to keep ph at Before we go on to Physiologic Buffers, let s review what we just covered about Chemical Buffers. The three major chemical buffers are carbonic acid (H2CO3), bicarbonate (HCO3-), and plasma proteins & phosphates. Of these, the most important are carbonic acid and bicarbonate, although plasma proteins are the most plentiful.

15 Physiologic Buffers If the chemical buffers are unable to stabilize the ph, the physiologic buffers - the respiratory and renal systems - respond. The respiratory system alters the rate and depth of breathing to retain or excrete carbon dioxide (CO2), a mild acid. Respiration is the only method of excreting carbon dioxide. The renal system conserves or excretes acids or bases in the urine. Carbon dioxide and other acid waste products are continually formed as a result of cellular metabolism. So both the renal and respiratory systems are essential. Let s look first at the Respiratory System. When the ph falls, CO 2 has increased - Respirations increase to eliminate more CO 2 from the body. As venous blood passes through the lung capillaries, the CO 2 diffuses out of the venous blood into the lungs and is exhaled. This leaves less CO 2 to enter the arterial blood vessels, making it less acidic and raising the ph. Because CO2 and water (H2O) form carbonic acid (H2CO3), ph falls when CO2 increases. Remember, the respiratory system is the only system that can eliminate CO2 from the body. This is how it happens Respirations decrease to retain more CO 2 from the body. As venous blood passes through the lung capillaries, the CO2 diffuses out of the venous blood into the lungs and is exhaled. This leaves less CO2 to enter the arterial blood vessels, making it less acidic and raising the ph.

16 In order for the respiratory system to make these changes, something must stimulate it. Here s how the process works - Neurons located in the respiratory center of the medulla oblongata are sensitive to changes in arterial blood CO 2 and ph. As arterial CO2 increases or arterial blood ph decreases, the respiratory center is stimulated. Respirations increase in rate and depth. More CO 2 is eliminated, and the ph rises. If the situation is reversed - As arterial CO2 decreases or arterial blood ph increases, the respiratory center is stimulated. Respirations decrease in rate and depth. CO2 is retained, and the ph is lowered. But remember, there is a limit to how much we can lower rate and depth of breathing while sustaining life! Especially in the neonate! The respiratory mechanism can maintain acid-base balance twice as effectively as the chemical buffers. It is capable of responding to changes in ph within a matter of minutes. It can handle twice the amount of acids and bases. The lungs can restore normal ph only temporarily. The physiologic buffer, the kidneys, manages the long-term restoration of ph. Memory Jogger Bicarbonate and ph move in the same direction. Think of someone lifting a set of barbells. Both ends should rise and fall evenly. When HCO3- rises or falls, so does the ph.

17 The respiratory system works to eliminate carbon dioxide in a rather rapid manner. On the other hand, the renal system works with bicarbonate and hydrogen ions more slowly, but in a more powerful way. The renal system takes over when the respiratory mechanism is unable to stop the shift in ph. The kidneys respond by conserving varying amounts of acids or bases or by excreting varying amounts of acids or bases into the urine. They also produce bicarbonate to replenish lost supplies. By excreting more or less H + in exchange for reabsorbing more or less sodium ions, the kidneys control urine ph. As a result, they play an important role in blood ph control. Here s an example - o Blood ph decreases. o The renal tubules secrete more H+ from blood into the urine. o The tubules reabsorb sodium ions from urine into the blood - 1 sodium (Na + ) for each H +. o The urine ph decreases, but more importantly - the blood ph increases toward normal. This mechanism depends on the kidneys excreting varying amounts of H + from the body to match the amounts entering the blood. This is a much more effective mechanism in balancing input against output than the respiratory mechanism. However, adjustments to the ph made by the kidneys can take from hours to days to be accomplished. Memory Jogger

18 Remember, the respiratory system eliminates carbon dioxide, an acid. Acids and ph change in opposite directions like a seesaw. The renal system secretes hydrogen ions from the blood into the urine. This lowers serum hydrogen ion concentration and increases serum ph. The renal system also works with bicarbonate, conserving or eliminating it. Bicarbonate and ph change in the same direction. Thus, a loss of bicarbonate causes a decrease in serum ph. It s time for review of Physiologic Buffering Mechanisms before we move on to the Biologic Buffers. The renal and respiratory systems play a major role in adjusting ph. The respiratory system excretes carbon dioxide (acid). The respiratory rate increases in depth and/or volume to eliminate CO2 when the ph rises. The respiratory system works fairly rapidly to bring ph back to normal, but this change is only temporary. The kidneys work more slowly, but are more powerful in their effect. The kidneys excrete or retain H + and bicarbonate to alter ph.

19 Biologic Mechanisms The last of the buffers are the biologic buffers. These are the buffers that shift excess acid or base in and out of the cells. We ve already mentioned that plasma proteins play a role in extracellular regulation as a chemical buffer. One of the major biologic non-bicarbonate buffers is hemoglobin, which is inside all red blood cells (RBC). Strictly speaking, hemoglobin is an intracellular buffer, but due to the permeability of the RBC's membrane it has a relatively rapid and important impact on extracellular fluid. Like all proteins, hemoglobin consists of amino acids linked by peptide bonds, and it is these amino acids that give hemoglobin its buffering capacity. Also, hemoglobin facilitates but does not prevent changes in ph. As we learned in the section on Chemical Buffers - Carbon dioxide and other acid waste products are constantly formed as a result of cellular metabolism. There is a complex system of ion exchange that occurs across the cell membrane to maintain acid-base balance and neutral ionic charge. The illustration below shows this process - Carbon dioxide and water combine to form carbonic acid. Carbonic acid dissociates into bicarbonate and hydrogen ions. Intracellular phosphates combine with the H+. Bicarbonate moves out of the cell in exchange for extracellular chloride ion. This process makes it possible for carbon dioxide to be buffered in the RBC, and carried as bicarbonate in the plasma. These buffers help keep the intracellular ph stable when stressed by cellular processes or by ph changes transmitted from extracellular fluid across cell membranes.

20 Regulating and stabilizing the intracellular environment helps energy transfer and storage. A stable environment is essential for the cellular metabolism to meet the body s immediate and long-term needs. Therefore acid-base imbalance and resulting disruption of enzymatic activity can result in a life-threatening situation. Memory Jogger One control mechanism alone cannot maintain the homeostasis of the ph it requires all three - Chemical buffers - carbonic acid, bicarbonate, proteins and phosphates. Physiologic buffers - renal and respiratory systems Biologic buffers - intracellular and extracellular interaction. Changes in the ph and acid concentration occur in the opposite directions like a seesaw. Changes in bicarbonate and ph occur in the same direction like a bar bell. Now that you understand the basics of acid-base, let s look more closely at how this really comes together in the body.

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22 Correction vs. Compensation As we have said during times of acid-base imbalance, the body s physiologic response is to maintain the ph at or near its normal level. The respiratory and metabolic systems interact to correct or compensate for the imbalance in either of the systems. Correction involves using the same or affected system. If the partial pressure of arterial CO2 (PaCO2) is increased, the respiratory system is the one in which the initial change occurred. In response, the body changes the respiratory rate and/or depth to decrease or blow off CO2 to correct the imbalance. Although correction is the quicker of the two mechanisms taking minutes to effect change it has only a temporary effect. If correction is not effective in bringing the ph back to normal, compensatory mechanisms take over. Compensation involves using the opposite or unaffected system. If CO 2 is increased, the respiratory system is the effected system. The kidneys conserve or retain bicarbonate and excrete more acid to correct the imbalance. o This is the opposite system. Compensation is the slower of the two mechanisms, taking hours to days to effect change, BUT it has a more sustained effect. If compensation has occurred, ph is within the normal range. This is ni in spite of abnormal CO 2 or HCO 3 - values. Memory Jogger Remember that H + and PaCO2 have a direct relationship. Carbon dioxide forms an acid in solution. An increase in the arterial CO2 increases the hydrogen ion concentration This next section reviews two components of the arterial blood gas report, their norms, and their meaning.

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24 Interpretation of blood gases Arterial Blood Gases The term arterial blood gas (a.k.a. - ABG) includes a specific set of tests performed on an arterial blood sample to evaluate acid-base balance, pulmonary function, and oxygenation. An ABG includes the following components - ph - measures the H + concentration in the plasma (negative log of hydrogen ions) o The 1:20 ratio of carbonic acid to bicarbonate maintains a normal ph. PaCO 2 - partial pressure of carbon dioxide dissolved in arterial (a) blood. This indicates the adequacy of pulmonary ventilation. HCO concentration of the bicarbonate ions. This indicates the activity of the kidneys to excrete bicarbonate Base excess/deficit - indicates the concentration of buffer (bicarbonate). o Positive values indicate an excess of base or a deficit of acid. We refer to the positive value as a base excess. o Negative values indicate a deficit of base or an excess of acid. We refer to this as a base deficit. PaO2 partial pressure (P) of oxygen dissolved in arterial (a) blood. SaO2 percent saturation (S) of arterial (a) hemoglobin with oxygen. The last two measures (PaO2 and SaO2) are measures of oxygenation. Factors affecting oxygenation may cause changes in acid-base balance. However, in this module we are concentrating on acid-base balance alone. Memory Jogger The ph, PaCO2, and HCO3 - must all be within normal limits to have a normal acid-base status. Neonatal Arterial Blood Gas Values

25 Component Value ph PCO mmhg PO mmhg HCO meq/l Base Excess -2 to +2 From Verklan, MK & Walden, M.. (2015). Core Curriculum for Neonatal Intensive Care Nursing, 5th Edition. Maryland Heights, MO: WB Saunders Company - Used under license to CFVHS. The ph and the PCO2 values are measured directly from the arterial sample. In contrast, the bicarbonate concentration is calculated, not measured, by the blood gas analysis machine. The machine enters the measured ph and PCO 2 values into the Henderson-Hasselbach equation to make the calculation. Since the bicarbonate is a calculated value, some novice blood gas interpreters assume the value to be inaccurate, and mistakenly disregard it. In truth, the value would be inaccurate only if the measured ph and PCO 2 values were incorrect. While information regarding the PO 2 is useful, it is not directly related to acid-base balance. Blood gas measurement remains the major diagnostic tool for evaluating acid-base balance. The information can be useful in - Diagnosing acid-base disturbances o Acidosis vs. alkalosis o Respiratory vs. metabolic Identifying problems with oxygenation Documenting the infant s response to treatment Evaluation and interpretation of blood gases should follow a consistent and logical sequence. So, let s begin with a basic interpretation -

26 1 st - What is the ph? Is it normal or abnormal? If it is abnormal, is it acidosis (<7.30) or alkalosis (>7.45)? Which system is the origin of the acidosis/alkalosis? 2 nd - Evaluate the respiratory component, the PCO2. Is it normal, low (< 35 mmhg) or high (> 45mmHg)? If so, the problem is probably respiratory in origin. Does the PCO 2 distortion correspond to the change in ph? Memory Jogger ph and PCO2 move in opposite directions like a seesaw. Therefore, if is the PCO2 is high, expect the ph to be low - and vice versa. 3 rd - Now, determine the metabolic status. Look at the HCO3 - (base). Is it normal (19-26 meq/l)? Then there is no metabolic component. Is it low (<19 meq/l)? Then you have metabolic acidosis. Is it high (>26 meq/l)? Then you have metabolic alkalosis.

27 Memory Jogger Bicarbonate (HCO3 - ) and ph increase or decrease in the same direction like two ends of a barbell. Therefore if the bicarbonate ( HCO 3- ) is high, then, expect the ph to be high - and vice versa. The base excess/deficit is a reflection of the calculated HCO 3 - value. 4 th - Does the respiratory or metabolic component match the ph shift? The system whose component matches the ph shift is where the primary disorder occurred. For the following ABG - ph 7.32; PaCO2 75; HCO3-27 The ph is below normal and the PaCO2 is increased a seesaw relationship. This is a primary respiratory acidosis.

28 5 th - Has any compensatory activity occurred? ph begins to shift back to normal The opposite component begins to move out of the normal range. Memory Jogger Interpretation Guide - 1. ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PaCO2 >50? This is most likely due to a respiratory problem. 3. Is the ph <7.30 and the HCO3 <19? This is most likely due to a metabolic problem. 4. Compensatory activity? ph begins to move toward normal with opposite component becoming abnormal. Practice Let s take a few minutes and practice using the interpretation guide with a few ABG results. Your ABG report has the following results - ph 7.34 PCO2 32 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 < Compensatory activity? ANSWER -> Arterial Blood Gases

29 Your ABG report has the following results - ph 7.34 PCO2 32 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? Normal ph 2. Is the ph <7.30 and the PCO2 >50. No 3. Is the ph <7.30 and the HCO3 <19. ph normal with low HCO3-4. Compensatory activity? Compensated metabolic acidosis Your ABG report has the following results - ph 7.23 PCO2 60 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 < Compensatory activity? ANSWER -> Arterial Blood Gases Your ABG report has the following results - ph 7.23 PCO2 60 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? Acidotic 2. Is the ph <7.30 and the PCO2 >50. Yes 3. Is the ph <7.30 and the HCO3 - <19. Yes 4. Compensatory activity? Uncompensated Mixed Acidosis Your ABG report has the following results -

30 ph 7.50 PCO2 42 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 - < Compensatory activity? ANSWER -> Arterial Blood Gases Your ABG report has the following results - ph 7.50 PCO2 42 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? Alkalotic 2. Is the ph <7.30 and the PCO2 >50. No 3. Is the ph <7.30 and the HCO3 - <19. No 4. Compensatory activity? Uncompensated Metabolic Alkalosis Next we will review two major acid-base imbalances common in the neonate, respiratory and metabolic acidosis. We ll look at usual causes and treatment

31 Respiratory Acidosis There are three essential components to the physiologic mechanism we call breathing - Ventilation Perfusion Diffusion Failure or compromise of any one of these components can result in respiratory acidosis. In the premature infant, the most frequent cause of respiratory acidosis is decreased ventilation at the alveolar level. Because of immature lungs, the premature infant is unable to get rid of enough CO 2 to maintain a ph within normal range, leading to respiratory acidosis. Respiratory acidosis is an abnormal increase in the arterial carbon dioxide level (PaCO2). This is also known as hypercapnia or hypercarbia. With the exception of respiratory compensation of metabolic alkalosis, hypercapnia/hypercarbia is abnormal. Frequently, infants with respiratory acidosis are said to be retaining CO 2. o This implies that the production of CO 2 exceeds excretion of CO 2, with the difference being retained. o In fact there is usually a steady state for CO 2 where production and excretion equal one another. o In respiratory acidosis, production and excretion of CO 2 continue to equal one another, and a steady state continues to exist. o o o It's just that the steady state is abnormally high. Although it may be true that early in respiratory acidosis the CO 2 rises so precipitously that production may be greater than excretion, it is not a condition that exists for long. It is only during the early stage of respiratory acidosis that the patient actually retains CO 2. When an infant has inadequate ventilation, CO2 accumulates in the blood, and the ph drops below normal respiratory acidosis. If the respiratory system cannot change or correct the situation, then the body tries to compensate for the drop in ph by retaining more bicarbonate in the kidney.

32 Here s how it works. Step 1 - Pulmonary ventilation decreases. CO 2 levels increase and combine with water (H 2O) to form carbonic acid (H2CO 3- ) in larger than normal amounts. The excess carbonic acid causes the drop in the ph. The carbonic acid dissociates (breaks apart) to release free H+ ions and bicarbonate ions (HCO 3- ). Look for a PaCO2 level >45 mm Hg and a ph of < 7.30 Step 2 - As the ph falls, 2,3-diphosphoglycerate (2,3-DPG) increases in the red blood cell causing changes in the hemoglobin, making it release oxygen. This altered hemoglobin is now strongly alkaline picking up the free H + and CO 2 ions, eliminating some of them. Look for decreasing arterial oxygenation saturation values Step 3 - As PaCO 2 levels continue to increase, CO 2 accumulates in the body tissues and fluids, including cerebrospinal fluid and the respiratory center in the medulla. Like in the blood, the CO 2 combines with H 2O to form H 2CO 3, causing dissociation into H + and HCO 3 - ions. This increase in CO 2 and H+ ions stimulates the respiratory center to increase the respiratory rate (correction) to excrete the excess CO 2 and bring the ph back into normal range. If correction is successful - Look for increased respiratory rates, shallow respirations, a decreasing PaCO2 and an increasing ph

33 Step 4 - If correction is unsuccessful, the ongoing excess CO 2 and H + will ultimately cause dilatation of the cerebral blood vessels. The resulting increased cerebral blood flow can cause cerebral edema and depress central nervous system activity. Look for lethargy/irritably, restlessness, changes in vital signs, temperature instability, and emesis Step 5 - As respiratory mechanisms (correction) fail, the increasing PaCO 2 stimulates the kidneys to retain both HCO 3 - and sodium (Na + ) ions and to excrete H + (compensation) ions. The H + is excreted as free H + and some as ammonium (NH 4). Meanwhile, the Na + and HCO 3 - ions combine to form sodium bicarbonate (NaHCO 3- ), which buffers the non-excreted H + --hopefully raising the ph. Look for more acidic urine, increasing ph and bicarbonate values, slower, possibly shallow, respirations Step 6 - If compensatory mechanisms fail or the original cause of the respiratory acidosis remains unrecognized or untreated, the increasing H + ions move into the cells and potassium ions move out. At the same time, a lack of oxygenation causes an increase in the anaerobic production of lactic acid, further complicating the acid-base balance and critically affecting neurologic and cardiac functions. Look for hyperkalemia, cardiac arrhythmias, increased PaCO2 and decreased PaO2 values, a decreased ph, and changes in neurologic presentation Etiology of Respiratory Acidosis In the neonatal population, respiratory acidosis is usually associated with one of 3 major categories - Central nervous system problems or depression

34 Pulmonary disease Airway obstruction Central Nervous System (CNS) Problems/Depression An intact, functional CNS is required for an effective respiratory mechanism. In order for effective ventilation to occur, it is the CNS responsibility to - Initiate respirations See that the steps are sequential Carry the process through to completion Anything that interferes with CNS function to complete this task potentially interferes with the respiratory mechanism. Steps of the respiratory mechanism include - The neural impulse is initiated by the medulla, the respiratory center. The impulse travels down the spinal cord to the phrenic and intercostal nerves and across the neuromuscular junction. The thoracic muscle and diaphragm, respiratory muscles, are stimulated and contracted. The diaphragm flattens and the chest cage expands The intrapleural pressure drops and the lungs expand as inspiration occurs. If any one of these steps fails, ventilation diminishes. This potentially may result in a disturbance in the acid-base balance and jeopardize the infant s overall physiologic status. Risk Factors may include - Prematurity - related to poor muscle tone and/or CNS immaturity Intracranial bleeds - may interfere with CNS functions Phrenic nerve paralysis/diaphragm paralysis - especially post-pda surgery Asphyxia Infections Central Apnea Drugs - anesthetics, sedatives/hypnotics, narcotics, illegal drugs Post-operative period - related to anesthesia/analgesia depression

35 Pulmonary Disease Although it is the responsibility of the CNS to initiate the process of ventilation, it is the lungs that actually oxygenate the patient through the process of gas exchange giving up CO2 and taking up oxygen. Since the lungs are basically a gas exchange surface, lung disease can be thought of as a gas exchange defect. Lung disease that interferes with the lung s surface area or its ability to perform gas exchange can result in acid-base disturbances and jeopardize the infant s well being. Risk factors may include - Respiratory distress syndrome (RDS) Meconium aspiration syndrome (MAS) Prematurity - related to lung compliance and or decreased muscle tone Pneumothorax - related to loss of lung parenchyma (tissue) to perform the gas exchange Intracardiac shunting through the foramen ovale and/or patent ductus arteriosus (PDA) - bypasses pulmonary circulation Chronic pulmonary insufficiency - bronchopulmonary dysplasia (BPD) Infection - pneumonia Diaphragmatic hernia Atelectasis Hypoventilation due to increased dead space Rib deformities Airway Obstruction Respiratory acidosis may also occur due to obstruction of the upper or lower airways, resulting in accumulation of carbon dioxide. Keep in mind that infants, especially preterm infants, have a very anterior, pliable trachea and are at particular risk for obstruction. Risk Factors may include -

36 Meconium aspiration syndrome (MAS) Infection - pneumonia Pulmonary edema Positioning Choanal atresia Laryngeal/tracheal spasm Accumulation of secretions Mechanical ventilation - related to increased dead space (hypoventilation) ET Tube - related to inappropriate placement or accumulation of secretions Clinical Management of Respiratory Acidosis Intervention and treatment of respiratory acidosis focuses on improving ventilation. The goal is to decrease the PCO 2 level and return the ph to within its normal range. Clinical management may include any or all of the following - o Oxygenation and respiratory support at whatever level necessary to achieve the goal Supplemental oxygen - nasal cannula, oxyhood Continuous positive airway pressure (CPAP) Mechanical ventilation - conventional, neurally adjusted ventilatory assist (NAVA), high frequency oscillatory ventilation (HFOV) o Treatment of the underlying respiratory problem o Fluid/electrolyte/nutritional management o Bronchodilators o Chest physiotherapy o Antibiotic therapy When successful, the PO2, PCO2, ph will return and remain within normal limits. Potential organ damage is avoided, and the infant should improve clinically, depending on the underlying cause and/or other diagnoses. Now that you ve seen the risk factors, progression, and treatment of respiratory acidosis, the next section presents metabolic acidosis.

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38 Metabolic Acidosis Ideally, the excretion of acids and the inflow of bicarbonate from the kidneys would be equal, keeping plasma bicarbonate levels and buffering capabilities constant. Unfortunately, disease processes often disrupt this ideal state, and acid production exceeds renal acid excretion. When a patient has an increase in acids and a loss of base, the bicarbonate level and ph fall metabolic acidosis results. Metabolic acidosis is an abnormally low bicarbonate level, < 18 meq/l. The ph can be normal or low, depending upon whether any compensatory mechanisms have begun. Except for renal compensation for respiratory alkalosis, hypobicarbonatemia is abnormal. In addition, metabolic acidosis depresses the CNS and if left untreated may lead to - o Ventricular arrhythmias o Coma o Cardiac arrest If the metabolic system cannot change or correct the situation, then the body tries to compensate for the fall in ph by increasing the excretion of CO 2. o It does this by altering the respiratory effort. Here s how it works - Step 1 - As H + ions start to accumulate, chemical buffers (plasma bicarbonate and proteins) in the cells and extracellular fluid bind with them in attempt to buffer the acid (H + ). At this early stage, the infant may be asymptomatic. Step 2 - Excess H + ions, that aren t bound to the buffers, decrease the ph and stimulate the chemoreceptor in the brain s medulla. This triggers an increase in respiratory rate, resulting in a decrease in CO 2. This lowers the PCO 2 allowing more H + to bind with the bicarbonate (HCO 3- ) ions.

39 Look for a bicarbonate level < 18 meq/l, a ph of < 7.35, a falling PCO2, and tachypnea. Step 3 - If the kidneys are healthy and mature, they will compensate for the continuing acidosis by secreting excess H + ions into the renal tubules. Once in the tubules, the H + ions are buffered by phosphate or ammonia and excreted into the urine in the form of a weak acid. Look for more acidic urine. Step 4 - Each time a H + ion is secreted into the renal tubule, a sodium (Na + ) and bicarbonate ion are absorbed from the tubule into the circulating blood volume. Look for a slow return of the bicarbonate level and ph to normal. Step 5 - Excess H + ions in the extracellular fluid diffuse across the cell membranes into the cells. To maintain the balance of the ion charge across the cellular membrane, the cells release potassium (K + ) ions into the circulating blood volume (extracellular fluid). Look for diarrhea, emesis/residuals and vomiting, muscle weakness, bradycardia, and EKG changes associated with hyperkalemia a tall T wave, prolonged PR interval, and a wide QRS complex. Step 6 - If metabolic acidosis continues or goes unrecognized or untreated, the influx of intracellular H + ion alters the normal balance of K +, Na +, and calcium (Ca ++ ) ions resulting in reduced excitability of nerve cells and progressive central nervous system depression.

40 Look for changes in vital signs, temperature instability, lethargy, a need for increasing respiratory support, and potentially, seizures. Etiology of Metabolic Acidosis Just as with respiratory acidosis, metabolic acidosis can arise from one of 3 major categories - Increased acid production Decreased acid excretion Loss of bicarbonate from the extracellular fluid Increased Acid Production Metabolic acidosis may be related to overproduction of ketone bodies or lactic acid, as a consequence of increased acid production. Fatty acids are converted to ketone bodies when glucose supplies become depleted, and the body uses fat stores as its source of energy. Metabolism of carbohydrates produces lactate that is metabolized by the liver. During times of decreased tissue perfusion cells are forced to switch from an aerobic to an anaerobic metabolism which produces lactate. o This happens when demands for oxygen exceed the available oxygen supply. Lactate accumulates faster than it can be metabolized, and if accumulates causing or worsening metabolic acidosis. Although this is the most common cause of lactic acid production in the neonate, liver diseases/anomalies can also lead to lactic acidosis since the damaged liver is unable to metabolize lactate. Risk factors may include - Inborn errors of metabolism - disorders of amino acid, organic acid, and carbohydrate metabolism Hypoxia/hypoxemia resulting in anaerobic metabolism and lactic acidosis - RDS, congenital heart disease (CHD), PDA, sepsis, asphyxia Decreased Acid Excretion Metabolic acidosis may also occur when the kidney s ability to excrete acids is compromised due to immaturity, damage, insults, or hypoperfusion. Risk factors may include -

41 Acute renal failure Nephrotoxic drugs Acute tubular necrosis Umbilical arterial catheter (UAC)/umbilical venous catheter (UVC) lines Shock Loss of Bicarbonate While a loss of bicarbonate, or base, resulting in metabolic acidosis most frequently stems from excessive gastrointestinal losses, it can also be associated with other factors. Risk factors may include - GI Losses - diarrhea, excessive GI drainage, excessive/repetitive emesis Failure of kidneys to conserve HCO 3 - Potassium-sparing diuretics - inhibit secretion of acid Rapid extra-cellular expansion Renal tubular necrosis Clinical Management of Metabolic Acidosis As acid accumulates in the blood and the renal system is unable to correct the imbalance, the body compensates for the worsening imbalance by excreting the excess acid, or CO2. The respiratory center in the medulla is stimulated to increase the respiratory rate and depth and/or work of breathing to rid the body of the CO 2. If metabolic acidosis continues to worsen, goes unrecognized, or is inadequately treated major organ system functions can be compromised. As the ph continues to fall - o CNS, as well as myocardial function, is depressed. Cardiac output and blood pressure fall, and if hyperkalemia exists simultaneously, arrhythmias may result. o As the effects on the cardiac system worsen shock, decreased muscle tone, and a loss of deep reflexes will become apparent. o Further deterioration will result in a change in the infant s level of consciousness, and the infant may even progress to a comatose state. Treatment is aimed at correcting presenting symptoms, as well as, the underlying cause(s). Clinical management may include any or all of the following - Respiratory support

42 Bicarbonate replacement therapy Fluid, electrolyte, and nutritional support Antibiotic therapy Of course, the ultimate goal is to return the PO2, CO2, and ph to within normal limits. The final section reviews several important points in collecting the blood sample for ABG analysis. There are several important differences from collecting a venous sample for other diagnostic tests.

43 Collecting the Sample Neonatal nurses frequently obtain blood samples for ABG results. It is important to collect the specimen using the correct equipment and technique. Otherwise, results can be skewed. The specimen may be obtained through an arterial puncture or line draw. When obtaining an ABG specimen, to assure consistent reliable, results, several special handling techniques should be remembered o Heparin is added to the specimen syringe to prevent clotting. Excess heparin should be ejected from the syringe to minimize dilution of the sample that may alter the values. o Low friction syringes that fill easily from arterial pressure should be used. Small suction syringes and/or vacutainers should not be used since they can create a vacuum that causes the dissolved gases to come out of the solution. This reduces both the PCO2 and the PO2 values. o If air bubbles form in the specimen during collection, they should be tapped to the surface and ejected from the specimen. If not, the entrapped air can artificially raise the PO2 and lower the PCO2. o If analysis of the specimen is delayed for more than a few minutes the specimen should be capped, placed in ice, and refrigerated. Refrigerating and icing the specimen slows the red blood cell metabolism and resulting production of lactic acid (due to the anaerobic status of the specimen) which can acidify the specimen. If these guidelines are not followed, inaccurate ABG results may be reported. In addition, if a venous specimen is inadvertently obtained instead of an arterial specimen, the CO2, O2, and ph values will most likely be inaccurate. The Final section puts everything together to help you prepare for your post-test.

44 Putting It All Together This section presents y0u with some common acid-base situations for the neonate. We will present the cases, and then ask you to identify the problem, potential consequences and expected treatment. Baby G is 25 weeks gestation with RDS. He has a UAC and is on bubble CPAP. Your ABG results have just been posted - ph 7.10 PCO2 38 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 < Compensatory activity? ANSWER -> Arterial Blood Gases Your ABG report has the following results - ph 7.10 PCO2 38 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? Acidotic 2. Is the ph <7.30 and the PCO2 >50. No 3. Is the ph <7.30 and the HCO3 <19. Yes 4. Compensatory activity? Uncompensated metabolic acidosis What is the most likely cause of this problem, and how would you expect to treat it? ANSWER-> Metabolic Acidosis Potential causes of metabolic acidosis include -

45 Increased lactic acid production Shock, which leads to inadequate oxygen delivery to the tissues and anaerobic glycolysis Cardiac disease Hypothermia Hypoglycemia Inborn errors of metabolism Treatment must focus on finding the underlying problem and treating it! Strategies should include - Improving oxygenation and ventilation Aggressive treatment of shock Treatment of suspected/known sepsis Treatment of hypothermia and hypoglycemia Ruling out the possibility of inborn errors of metabolism Baby J is a 41 week infant with meconium stained amniotic fluid at delivery. He is non-vigorous and requires ET suctioning below the vocal cords. Your ABG results have just been posted - ph 7.00 PCO2 55 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 < Compensatory activity? ANSWER-> Arterial Blood Gases Your ABG report has the following results - ph 7.00 PCO2 55 HCO ph - acidotic (<7.30) or alkalotic (>7.45)?Acidotic 2. Is the ph <7.30 and the PCO2 >50. Yes 3. Is the ph <7.30 and the HCO3 <19. Yes

46 4. Compensatory activity? Uncompensated mixed acidosis What is the most likely cause of this problem, and how would you expect to treat it? ANSWER-> Mixed Respiratory and Metabolic Acidosis Mixed acidosis has both respiratory and metabolic problems at work. Potential causes of metabolic acidosis include - Increased lactic acid production Shock, which leads to inadequate oxygen delivery to the tissues and anaerobic glycolysis Cardiac disease Hypothermia Hypoglycemia Inborn errors of metabolism Potential causes of respiratory acidosis include - Lung disease such as RDS, aspiration, or pneumonia Pneumothorax Airway obstruction Poor respiratory effort Treatment must focus on finding the underlying problem and treating it! Strategies should include a combination of respiratory and metabolic treatments - Improving oxygenation and ventilation Aggressive treatment of shock Treatment of suspected/known sepsis Treatment of hypothermia and hypoglycemia Ruling out the possibility of inborn errors of metabolism and treating them if identified as a problem

47 Baby S is a term infant whose mother experienced a placental abruption. He is born limp with no respiratory effort. Resuscitation attempts progress quickly from PPV to chest compressions, epinephrine, and a NS bolus. Your ABG results have just been posted - ph 6.90 PCO2 80 HCO ph - acidotic (<7.30) or alkalotic (>7.45)? 2. Is the ph <7.30 and the PCO2 > Is the ph <7.30 and the HCO3 < Compensatory activity? ANSWER-> Your ABG report has the following results - ph 6.90 PCO2 80 HCO ph - acidotic (<7.30) or alkalotic (>7.45)?Acidotic 2. Is the ph <7.30 and the PCO2 >50. Yes 3. Is the ph <7.30 and the HCO3 <19. Yes 4. Compensatory activity? Uncompensated mixed acidosis What is the most likely cause of this problem, and how would you expect to treat it? ANSWER-> Mixed Respiratory and Metabolic Acidosis Mixed acidosis has both respiratory and metabolic problems at work. Potential causes of metabolic acidosis include - Increased lactic acid production Shock, which leads to inadequate oxygen delivery to the tissues and anaerobic glycolysis Cardiac disease Hypothermia Hypoglycemia Inborn errors of metabolism

48 Potential causes of respiratory acidosis include - Lung disease such as RDS, aspiration, or pneumonia Pneumothorax Airway obstruction Poor respiratory effort Treatment must focus on finding the underlying problem and treating it! Strategies should include a combination of respiratory and metabolic treatments - Improving oxygenation and ventilation Aggressive treatment of shock Treatment of suspected/known sepsis Treatment of hypothermia and hypoglycemia Ruling out the possibility of inborn errors of metabolism and treating them if identified as a problem References Askin, D. F. (1997). Interpretation of neonatal blood gases, Part I: Physiology and acid-base homeostasis. Neonatal Network, 16(5), Askin, D. F. (1997). Interpretation of neonatal blood gases, Part II: Disorders of acid-base balance. Neonatal Network, 16(6), Farmand, M. (2009). Blood gas analysis and the fundamentals of acid-base balance. Neonatal Network, 28(2), Gardner, S.L., Carter, B.S., Enzman-Hines, M., & Hernandez, J.A. (2011). Merenstein & Gardner's Handbook of Neonatal Intensive Care. St. Louis: Mosby- Elsevier. Hall, J. (2011). Guyton and Hall Textbook of Medical Physiology, 12th Edition. Philadelphia: Saunders-Elsevier.