Respiratory Lecture 8 - Acid-Base Physiology
Normal Range BE
-2 to +2
Ventilatory Compensation for Metabolic Acidosis
(Low HCO3-, BE < -2) Compensatory response = *increase in ventilation* --> Lowers PaCO2 and restores the HCO3-/ PCO2 ratio closer to normal even though the absolute values of both HCO3- and PCO2 are now abnormal
Ventilatory Compensation for Metabolic Alkalosis
(high HCO3-, BE > 2) Compensatory response = *decrease in ventilation* --> Increases PaCO2 andrestores the HCO3-/ PCO2 ratio closer to normal
Metabolic Compensation for Respiratory Alkalosis
(hyperventilation, low PaCO2) Body responds by *decreasing HCO3-,* thereby restoring the [HCO3-]/ PCO2 ratio and pH toward normal - *involves renal excretion of HCO3-*
Metabolic Compensation for Respiratory Acidosis
(hypoventilation, high PaCO2) Body responds by *increasing HCO3-*, thereby restoring the [HCO3-]/ PCO2 ratio and pH toward normal - involves *renal retention of HCO3-* and *physicochemical binding occurring in bone and intracellular proteins*
Lecture Case Study: 55 year old man with dyspnea, fatigue, and confusion ABG and other data: *pH=7.10*, PaO2=38mmHg, *PaCO2=70*mmHg, *HCO3-=21*mM SaO2 = 65 % , A-a PO2 diff: 25 mmHg, hematocrit = 32 % anion gap = 20, carboxyhemoglobin = 7% CXR: right lower lobe pneumonia, emphysema Sputum: pure growth of Hemophilius pneumonia
*1.) acidemic or alkalemic?* Acidemic (pH < 7.35) *2.) Is there a respiratory acid-base disorder?* Yes: PaCO2 > 45 mmHg = respiratory acidosis *3.) Is there a metabolic acid-base disorder? And what type?* Yes: Metabolic acidosis: - HCO3 = 21 = likely metabolic acidosis (HCO3 < 24) BE = - 6 =definitely yes, BE < - 2 4.) *What type*: anion gap acidosis
pH Ranges [Know This]
*Acidemia*: pH < 7.35 *Alkalemia*: pH > 7.45 *Normal range for pH*:7.35-7.45
Acid-Base Derangements: Definitions
*Acidosis or alkalosis*: PROCESS,which if unopposed, lead to a H+ excess or deficit and expected acid-base directional change *Acidemia or alkalemia*: State of Blood pH *If an acidosis and alkalosis co-exist the net effect on pH will be the summation* - thus pH can be high, normal or low depending on the magnitude of each disorder
Two Phases of Respiratory Acidosis
*Acute*: high PCO2, fall in pH, slight increase in HCO3-, *BE = 0 mEq/l* *Chronic*: high PCO2, lower fall in pH (due to renal buffering), much higher HCO3- rise, *BE > 2 mEq/l* - Rise in BE = compensatory metabolic alkalosis a) recruitment of intracellular HCO3-, bone CO3 b) renal excretion of acid and generation of new HCO3-
Two Phases of Respiratory Alkalosis
*Acute*: low PCO2, rise in pH, slight decrease in HCO3-, *BE = 0 mEq/l* *Chronic*: low PCO2, greater fall in pH (due to renal buffering), greater HCO3- fall, *BE < - 2 mEq/l* - Fall in BE = compensatory metabolic acidosis a) movement of HCO3- into intracellular and bone stores b) renal elimination of HCO3-
Respiratory Component (of Acid-Base Status)
*CO2 + H2O <-(CA)-> H2CO3 <--> H+ + HCO3-* Indicated by changes in *PCO2*. - *Increase in PCO2*, and thus [CO2], will drive reaction to the right, increasing [H+] and leading to what is referred to as a *respiratory acidosis* - *Decrease in PCO2* would have the opposite effect, leading to a respiratory alkalosis
Metabolic Component
*CO2 + H2O <-(CA)-> H2CO3 <--> H+ + HCO3-* Indicated by changes of *[HCO3-]* - Addition of H+ from a metabolic source would drive reaction to the left, consuming HCO3- and creating additional CO2, which can be removed via ventilation -->Magnitude of the *metabolic acidosis* would be reflected by the *decrement in [HCO3-]* - With an excess of a metabolic base, H+ will be removed from the right side of the equation and the resultant shift of equilibrium will cause *increased [HCO3 -]* in relation to the magnitude of the *metabolic alkalosis*
Carbonic Acid
*CO2 + H2O <-(CA)-> H2CO3 <--> H+ + HCO3-* aka *Respiratory Acid*, these acids are generated from the reaction above - *volatile acid* produced from CO2 generated by tissue metabolism - Can be effectively removed (excreted) or regulated through the lung as volatile CO2 - Changes in the carbonic acid component, presenting as *changes in PCO2*, are termed *respiratory acid-base abnormalities* - [CO2] (PCO2) set by balance of production of CO2 by tissues and alveolar ventilation
Metabolic Acidosis: Causes
*Develops for one of two reasons*: 1.) Accumulation of excess acid w/ loss of HCO3- via ventilation 2.) Primary loss of HCO3- as CO2 due to defects in renal tubular function or from intestinal secretions. Clinically distinguishing between the 2 helps generate differential dx. *Important difference between these two processes*: 1.) When there is accumulation of excess acid w/ loss of HCO3-, anions accumulate when the excess acid is buffered by the HCO3- system - Unlike Na+ and K+, these anions are unmeasured by lab analyzers (Gap) 2.) When acidosis develops due to loss of HCO3-, the HCO3- losses are balanced by retention of Cl-, which we can easily measure (no accumulation of unmeasured anions). (non-gap)
Importance of H+ Concentration and pH Regulation
*H+ binds to molecules at very low concentrations* *pH affects ionization/charge to alter protein structure/function*: - protein allosteric behavior: e.g. Bohr effect-HbO2 affinity - enzyme activity - membrane potential - membrane ion channel activity - ion activity - ECF/ICF distribution of Mg++, Ca++, K+ and PO4-
Identifying Acid-Base Severity: Summary (Lecture)
*Respiratory acidosis or alkalosis* - deviation of PCO2 above or below normal - quantified directly by magnitude of PCO2 change *Metabolic acidosis or alkalosis* - deviation of HCO3 above or below from normal - not fully quantified or appreciated since other buffers participate if concurrent PCO2 changes exist - Base excess reveals both presence and magnitude
Deviation of CO2 (H2CO3) (*PCO2*) from Normal...
*Respiratory* Acid-Base Derangements *Increased CO2 --> Respiratory Acidosis* - Increased CO2 + H2O <--> Increased H+ + HCO3- *Decreased CO2 --> Respiratory Alkalosis* Decreased CO2 + H2O <--> Decreased H+ + HCO3-
Lecture Case Study: 55 year old man with dyspnea, fatigue, and confusion ABG and other data: *pH=7.10*, PaO2=38mmHg, *PaCO2=70*mmHg, *HCO3-=21*mM SaO2 = 65 % , A-a PO2 diff: 25 mmHg, hematocrit = 32 % anion gap = 20, carboxyhemoglobin = 7% CXR: right lower lobe pneumonia, emphysema Sputum: pure growth of Hemophilius pneumonia *Davenport*
*What is his acid-base status?* - Respiratory acidosis PaCO2 = 70 mmHg Renal compensation: none - would expect HCO3 of 35 mM (3.5 x 3) + 24 = 35 mM - Metabolic acidosis HCO3 = 21 mM: D HCO3 = - 3 mM: possibly (nl HCO3 24 + 3) BE of - 6: definitely, lactate = 8 mM, anion gap = 20
Analyzing Increase in PCO2- (Summary)
*[H+] increases, resulting in an increase in plasma [HCO3-]*. Decrease in *pH is less when this happens in the presence of a physiologic solution with buffering capacity*, as opposed to happening in a simple bicarbonate solution.
Expected Responses to Respiratory Disturbances: Respiratory Acidosis
*acute*: 1 mM [HCO3-] rise per 10 mmHg PCO2 rise from 40 *chronic*: 3.5 mM [HCO3-] rise per 10 mmHg PCO2 rise from 40 - chronic represents kidneys kicking into gear to compensate
Expected Responses to Respiratory Disturbances: Respiratory Alkalosis
*acute*: 2 mM [HCO3-] fall per 10 mmHg PCO2 fall from 40 *chronic*: 4 mM [HCO3-] fall per 10 mmHg PCO2 fall from 40 - chronic represents kidneys kicking into gear to compensate
Davenport Diagram: Metabolic Disorder
- *Vertical displacements above or below the 10-slyke buffer line indicate that a metabolic disorder* (either primary or compensatory) has caused an excess or deficit of base in the extracellular fluid - If there were no respiratory compensation for a primary metabolic disorder the values would follow the line representing PaCO2 = 40mmHg
Common Causes of Respiratory Alkalosis
- Anxiety or severe pain - High Altitude - Asthma exacerbation (early finding)^ - Pulmonary Fibrosis^ - Pulmonary embolism^ ^ Develops due to hypoxemia and neural inputs resulting from the disease process; may not always be present
Causes of Non-Gap Acidosis
- Carbonic anhydrase inhibitors - Diarrhea - Hypoaldosteronism - Renal tubular acidosis - Ureteral diversion procedures
Causes of Gap Acidosis
- Diabetic ketoacidosis and other ketoacidosis (starvation, alcoholic ketoacidosis) - Ethylene glycol ingestion - Lactic acidosis - Methanol ingestion - Salicylate Intoxication - Toluene ingestion - Uremia
Common Causes of Respiratory Acidosis
- Opiate overdose - Severe COPD (chronic or in exacerbation) - Severe asthma exacerbation (late finding) - Neuromuscular Disease (e.g., ALS) - Obesity hypoventilation syndrome
1. A 28 year-old man presents to the Emergency Department complaining of chest tightness and difficulty breathing. He is a life-long non-smoker and has no history of diabetes or hypertension. He endorses multiple recent life stressors in his work as a pharmaceutical salesman. His vitals include a blood pressure of 111/67, HR 105, RR 30 and SpO2 98% breathing air. On exam he is anxious appearing. His breath sounds are clear and he has a normal cardiac exam. Electrocardiography and chest radiography are both unremarkable. On laboratory studies, his creatinine is 0.8 mg/dL, hematocrit 42% and WBC count 8. Which of the following changes would you expect to see in an arterial blood gas on this patient? (BE = Base Excess) A. Increased PaCO2, increased pH, increased HCO3-, BE > 2 B. Increased PaCO2, decreased pH, decreased HCO3-, -2 < BE<2 C. Decreased PaCO2, increased pH, decreased HCO3-, BE>2 D. Decreased PaCO2, increased pH, decreased HCO3-, -2<BE<2 E. Decreased PaCO2, decreased pH, unchanged HCO3-, BE<-2
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2. A patient is seen in the ED with the following arterial blood gas results: pH = 7.20; PaCO2 = 69; PaO2 = 75; HCO3 - = 27. Base Excess = 1. How would you characterize the acid-base status of this patient? A. Acute respiratory acidosis B. Chronic respiratory acidosis C. Metabolic acidosis with respiratory alkalosis D. Metabolic acidosis with respiratory acidosis E. Metabolic alkalosis with respiratory acidosis
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3. An unidentified man is brought into the Emergency Department after being found on the ground with a decreased level of consciousness on the UW Campus. On exam, he has a temperature of 37.0°C, respiratory rate of 8, heart rate of 105, SpO2 of 90% breathing air, and pinpoint pupils that do not react to light. He has clear lung sounds bilaterally and unremarkable cardiac and abdominal exams. A blood gas is drawn and shows: pH 7.25, PaCO2 64, PO2 60, HCO3- 27, Base Excess = 1.5. Which of the following diagnoses would be consistent with this clinical picture? A. Pneumonia B. Heroin overdose C. Cocaine overdose D. Diabetic ketoacidosis E. Septic shock
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7. A 28 year-old medical student is participating in a research project at the Capanna Margherita in the Italian Alps (elevation 4559 m, PB 500 mm Hg). An arterial blood gas is performed and reveals the following: - pH: 7.51 - PCO2: 30 - PO2: 50 - HCO3: 22 - BE: 0.9 Which of the following statements is true at the time the blood was is drawn? A. Hyperventilation is the only cause of her hypoxemia B. Her hypoxemia is due to either shunt or low VA/Q C. She has likely been at high altitude for only 1-2 days D. She has a primary metabolic acidosis E. She has a primary respiratory acidosis
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For question numbers 4-6, match the following arterial acid-base values to the simplest, most probable diagnosis (A through E). A. Metabolic alkalosis with compensatory respiratory acidosis B. Metabolic acidosis with compensatory respiratory alkalosis C. Acute respiratory alkalosis D. Acute respiratory acidosis E. Chronic respiratory acidosis
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Expected Responses to Metabolic Disturbances: Metabolic Alkalosis (Compensation)
0.6-0.7 mmHg rise in PCO2 per 1 mM rise in [HCO3-] below 25 - smaller change w/ metabolic acidosis due to stimulating effect of hypoxemia to limit hypoventilation
Expected Responses Metabolic Disturbances: Metabolic Acidosis (Compensation)
1 mmHg fall in PCO2 per 1 mM fall in [HCO3-] below 25
Importance of CO2-HCO3 Buffer Pair
1.) *CO2 and HCO3- are a major buffer pair* - CO2 is directly regulated by alveolar ventilation - HCO3 is directly regulated by the kidneys 2.) All components easily measured in blood: - PCO2, H+, HCO3- - pH = pK + log ([HCO3-] / [CO2]) - Henderson-Hasselbalch equation 3.) Changes in PCO2 *directly* quantify magnitude of respiratory acid-base disorders and compensation 4.) HCO3- changes measure roughly magnitude of metabolic acid-base disorders
It is convenient to consider *acids produced by the body to be of 2 types*:
1.) *Carbonic Acid* H2CO3 (Respiratory) - CO2 regulated only by the lungs 2.) *Non-Carbonic Acid* (Metabolic - organic and inorganic) - H+ and HCO3 regulated by the kidneys, but liver and other tissues can contribute
Respiratory Acid-Base Derangements
1.) *Respiratory acidosis: hypoventilation* - PCO2 > 45 mmHg - small rise in [HCO3-] from chemical buffering - DHCO3- = -10 x D pH ~1 mEq/l rise per 0.1 pH fall 2.) *Respiratory alkalosis: hyperventilation* - PCO2 < 35 mmHg - small fall in [HCO3-] from chemical buffering - DHCO3- = -10 x D pH ~1 mEq/l fall per 0.1 pH rise *Severity assessment*: size of PCO2 deviation from normal
Davenport Diagram of Changes in Value Over Time in Respiratory Acidosis
1.) Acutely (i.e., before compensation occurs), the individual's values move along the 10-slyke buffer line from the center point to Point 1, telling us that the observed change in HCO3- is due to buffering rather than metabolic compensation 2.) Over time, the kidneys compensate for the respiratory acidosis and the HCO3- value increases above the 10-slyke buffer line, bringing the individual to Point 2 where they have an increased base excess and a higher pH than in the acute phase
7 Steps of Diagnosing Acid-Base Disorders
1.) Determine the reliability of the blood gas data. Do the values fit the Henderson-Hasselbalch and alveolar gas equations? If not, then one must assess their accuracy by rechecking whether the values were transcribed incorrectly or was the sample somehow improperly handled to cause ex-vivo changes (e.g. blood was exposed to air) 2.) Does the patient have a *normal pH, acidemia or alkalemia*? 2.) Determine the *respiratory acid-base status* What is PaCO2? 4.) Determine the *metabolic acid-base status* and evaluate the *anion gap* 5.) Identify the *primary disorder* (Figure 6-3) 6.) Determine if *compensation* is present 7.) Evaluate *other lab values* such as chemistry and liver panels and toxicology screens, which may shed light on the origin of the observed problems
Graphic (Map) Approach to Compensation for Acid-Base Disorders: Davenport Diagram (Lecture)
1.) Locate blood gas values on the map - if in a shaded area: acid-base disorder w/ expected compensation - if outside shaded areas consider either: --> too soon for compensation --> another primary disorder(s)
Time Course of Compensation
1.) Metabolic compensation for *respiratory* disorders: over hours to 3 days - As a result, can subdivide respiratory disorders into *acute processes* (no compensation yet) and *chronic processes* (compensation has occurred) 2.) Metabolic compensation for *ventilatory* compensation: occurs w/in minutes to hours - very rapid and likely occurs before the pt even seeks attention --> do not classify metabolic disorders as acute or chronic because we have no way to distinguish between the two based on the changes in PaCO2
Patient's Acid-Base Status has 2 Components
1.) Respiratory Component 2.) Metabolic Component
Effects of adding metabolic acid to extra-cellular fluid
12 mmol of HCl added to 1L of extracellular fluid, again kept equilibrated to a PCO2 of 40 --> result would be a decrease in [HCO3-] to 14 w/ a pH of 7.2 and an [H+] of 68 nM - pH change is less, as more total buffering has occurred. The *decrement in [HCO3-] is only 10, however, indicating that 2 mmol of H+ have been buffered by the noncarbonic buffers* - Key concept to appreciate is the presence of the buffers and the effect they have on pH changes when metabolic acid or base is added to the system
Normal [HCO3-]
24
Analyzing Decrease in PCO2-
A similar analysis can be performed In this case *[H+] decreases, resulting in a decrease in plasma [HCO3-]*. As was seen with the increase in PCO2, the increase in *pH is less when this happens in the presence of a physiologic solution with buffering capacity*, as opposed to happening in a simple bicarbonate solution.
Primary Acid-Base Disorders
Acid-base derangements usually due to a primary disorder that set these derangements in motion - primary disorder can be respiratory or metabolic in origin and within each of those categories we can define two potential primary processes. - acidemia and alkalemia - acidosis and alkalosis - Possible to have both an acidosis and an alkalosis present simultaneously (e.g., respiratory acidosis + metabolic alkalosis), w/ a pH that is low, high, or normal, depending on the relative magnitude of the different processes. *Acidemia: defined as pH < 7.35* *Alkalemia: defined as pH > 7.45* *Normal range for pH is 7.35-7.45* (Don't Star this card)
Acidosis vs Alkalosis
Acidosis refers to a process which, if left unchecked, leads to acidemia (excess of H+) Alkalosis is a process that if left unchecked leads to alkalemia (deficit of H+ )
Quantifying Metabolic Acid-Base Severity: Effect of Multiple Buffers (Lecture)
Add 12 mEq acid into a solution of 24 mM HCO3- and Hb 12 mEq of acid is buffered by: 10 mEq of HCO3 + 2 mEq of a non-HCO3 buffer (Hb) *Net result*: expected fall in HCO3 of 12 in an unbuffered solution only falls by 10 in this mixed buffer system
Base Excess Concept Rationale
Allows analysis of ECF as a pure HCO3 solution (as if no other buffers present) - change from normal [HCO3-] to the new corrected [HCO3-] - BE gauges and quantifies a metabolic acid-base process Calculation: BE = measured [HCO3-] - (10 x ΔpH) - 24 Can use numerous apps (don't need to know equation!)
Base Excess (BE)
At a pH of 7.4 noncarbonic buffers hold only their normal complement of H+ ions and thus do not contribute to buffering BE calculates any *deviation of [HCO3-]* from 24 that would exist at pH7.4 and thus is *equal in magnitude to the amount of excess metabolic acid or base added to the system* - *Metabolic alkalosis*: present when *BE >2* - *Metabolic acidosis*: present when *BE <-2* (BE <-2 is also called *base deficit*) Simple calculations used to determine BE and many labs report this value along with the blood gas measurements. You will not be responsible for the calculations but do need to know how to interpret BE values given to you in clinical problems.
Buffering of a Metabolic (Non-Carbonic) Acid or Alkali
Buffered by *carbonic acid plus its salt (primarily sodium bicarbonate in extracellular fluid)*. Mechanism demonstrated in the rxn in which hydrochloric acid (HCl) is added to the system. HCl and sodium bicarbonate react to form carbonic acid (H2CO3), which then breaks down into CO2 and H2O. HCl+NaHCO3- <-->H2CO3 +NaCl <--> H+ +HCO3- OR CO2 +H2O
Respiratory Acid (CO2) Handling in Body Fluids (lecture)
Buffering of CO2 changes by non-carbonic buffers results in similar directional *[HCO3-] changes proportional to the concentration of the total non-carbonic buffer* - on average extracellular fluid (bc of 2:1 relationship with interstitial fluid:blood), has slightly different concentrations (e.g. no Hb) - Buffer Value of Blood (Beta) is much higher than water, bicarbonate solution, intersitital fluid (all 0) and extracellular fluid - blood has a high buffer capacity - *extracellular fluid B = 10* - *Blood B = 30*
Metabolic Acids, Buffers, and pH
Buffers have same effect w/ metabolic acid as w/ respiratory acid: they *mitigate the effect on pH when metabolic acid is added to the system*
Buffering of Respiratory Acid (CO2) in Body Fluids (???Not sure we need to know this???)
CO2 changes are buffered by other buffers in the ECF - In case of increasing CO2 from 40 to 80: No buffer: pH falls to 7.1 Buffer of extracellular fluid: pH only falls to &.15
Serum Anion Gap
Calculate the number of unmeasured anions or "anion gap:" Serum Anion Gap = [(Na+)+(K+)] - [(Cl-) + (HCO3-)] - [K+] is usually ignored when we calculate this clinically --> *Serum Anion Gap = [(Na+)] - [(Cl-) + (HCO3-)]* *Normal value ~about 10 +/- 2 mmol* - Based on this, we can then define two distinct forms of metabolic acidosis: Gap and Non-Gap Acidosis
Summary of the Expected Changes in Blood Gas Parameters in the Main Acid-Base Disorders
Chart
Expected Responses to Respiratory and Metabolic Disturbances
Chart Know these????
Clinical pH
Clinically do not use the equation to calculate pH. Instead, pH can be measured directly from an *arterial blood gas (ABG) analyzer*, as can the PCO2. The analyzer will then use the equation to calculate the HCO3 . You will not be asked to calculate values based on this equation for the purposes of this course but should understand the concept and recognize that you can look at blood gas values in light of this equation as a troubleshooting step to *make sure measured values are valid and not the result of measurement error.*
Davenport Diagram Lecture Example
Compensation for respiratory acidosis of PCO2 = 70 *acute buffering* (Star) - HCO3- = 24 + 3 = 27 - pH = 7.15 *chronic compensation (renal)* (oval) - HCO3- = 24 + 10.5 = 34.5 - pH = 7.30
Respiratory Alkalosis
Defined by *Low PaCO2 < 35 mmHg* - indicates that pt has *hyperventilation* which indicates that *alveolar ventilation is in excess of that needed for metabolic demands* Due to buffering processes, the decrease in PCO2 is associated w/ a small *decrease in HCO3-* in which *Δ[HCO3-] ≈ -10 x Δ pH, or 1 mEq/L per 0.1 pH unit rise*
Respiratory Acidosis
Defined by *elevated PaCO2. >45mmHg* - indicates that pt has *hypoventilation* which indicates that *alveolar ventilation is inadequate for metabolic requirements* Due to buffering processes, the increase in PaCO2 is associated w/ a *small increase in HCO3-*, in which *Δ[HCO3-] ≈ -10 x Δ pH, or 1 mEq/L per 0.1 pH unit fall*
How much will the pH change in response to changes in the concentration of the respiratory and/or metabolic acids? [Simplified model in which carbonic acid (as CO2) is added to a solution of *physiologic extracellular fluid*.]
Extracellular fluid Not the same as a simple bicarbonate solution - there are many other molecules present w/ the capacity to "buffer" the change in [H+] that occurs when PCO2 changes acutely and mitigate the change in pH. - to see impact of buffers, add CO2 to a solution of physiologic extracellular fluid PIC: in equation 3 the Potassium salt of Hb (KHb) is used to represent all the non-carbonic buffers e.g. PCO2 increased from 40 to 80, in the extracellular fluid. Some of the newly formed H+ is taken up by Hb. As a result, the reaction continues to the right and HCO3- ions accumulate w/ *plasma [HCO3-] rising by an amount reflecting the number of H+ ions buffered by Hb* - Hb and the other non-carbonic buffers accept ~2.5mmol of H+ and [HCO3-] increases by 2.5 mM. - Notice that pH falls to only 7.15 in this situation demonstrating how the *presence of these of non-carbonic buffers mitigates the pH changes* that would occur in their absence
Buffering Capacity of the Blood vs Total Extracellular Fluid
For *blood with 15gm/100mL Hb, β = 30 slykes*. In the body, the *blood and its plasma are in equilibrium for these ions w/ the extravascular interstitial fluid* (not necessarily w/ the intracellular fluid) 1.) *Interstitial fluid contains no Hb and very little protein* so it contributes little to the noncarbonic buffering, but as H+ are buffered in the blood and HCO3- levels change, these ions come into diffusional equilibrium w/ the interstitial fluid over a time frame of 10-30min. 2.) In effect, *buffering capacity of the blood is diluted by the interstitial fluid and because the blood volume is ~1/3 the total extracellular fluid volume, the buffering capacity of extracellular fluid is ~1/3 that for blood* *For total extracellular fluid then, β ≈ 1/3 x 30 ≈ 10slykes*
Davenport Diagram
Graphic representation of acid-base relationships - diagram is a representation of the Henderson-Hasselbalch equation where *any point shows a potentially coexisting combination of the three variables: pH, PaCO2 and HCO3- * - *pH*:displayed on the x-axis - *HCO3-*: on the y-axis - *PaCO2* values: represented by the curved lines (PaCO2 remains constant if you move along a given line but changes if you move from line to line)
Effect of [Buffer]
Greater the concentration of Hb and other non-carbonic buffers present = Greater buffering of H+ for a given change of pH
Most Important Extracellular Buffer
Hemoglobin (RBCs have a buffering capacity equal to that of the extracellular fluid)
Respiratory Alkalosis (Hpyerventilation)
Hyperventilation - PCO2 < 35 mmHg - small fall in [HCO3-] from chemical buffering - DHCO3- = -10 x D pH ~1 mEq/l fall per 0.1 pH rise *Severity assessment*: size of PCO2 deviation from normal
Respiratory Acidosis (Hypoventilation)
Hypoventilation - PCO2 > 45 mmHg - small rise in [HCO3-] from chemical buffering - DHCO3- = -10 x D pH ~1 mEq/l rise per 0.1 pH fall *Severity assessment*: size of PCO2 deviation from normal
Compensation for Acid-Base Disorders (Lecture)
If an acid-base disturbance continues physiologic compensations occur *Chemical buffering*: (w/in minutes) - Respiratory acid/base disorder: non-bicarbonate buffers (bicarbonate does NOT participate in buffering changes in CO2) - Metabolic acid/base disorder: HCO3- + non-HCO3- buffers *Ventilatory* (w/in hours) compensation for metabolic disorders *Renal* (w/in days) compensation for respiratory disorders General rule: compensations are never fully correcting
Compensation for Acid-Base Disorders
If underlying pathology prevents body from correcting a primary acid-base disorder (e.g. by restoring hypoventilation to normal ventilation) then mechanisms come into play to minimize the deviation of pH from normal - Immediate effects of buffering are aided by series of homeostatic mechanisms termed *physiologic compensation* - Henderson-Hasselbalch equation shows that pH is a function of the ratio of [HCO3-] to PCO2 so pH improves if this ratio is restored toward normal. In general, *compensations for primary acid-base alterations do not completely return pH to 7.40*, and the deviation is greater as the magnitude of the primary disorder increases
Changes in [H+]
Important to note that while the concentration of H+ is far less than that of other ions in bodily fluids, *small changes in the [H+] can produce huge physiologic alterations*. - The body, however, can tolerate wide ranges of [H+] with the range of *viable pH running from about 6.8-7.7*, representing an almost *8-fold change in [H+]* - pH Calculated using Henderson-Hasselbalch Equation
Range of Physiological [H+] and pH
Pic
Basic algorithm for identifying the primary acid-base disorder
KNOW THIS!!!!
Buffering Effect of Non-Carbonic Buffers
Measured as the change in [HCO3-] for a given change in pH Expressed as a buffer value (β): *β = -Δ[ HCO3-]/ΔpH* - Negative sign indicates that the [HCO3-] change is opposite to the change in pH - Units of this ratio (mM/pH) are more simply referred to as *slykes (sl)* You will not be expected to do calculations using this equation but the concept behind this will be important for material on the base excess later in this chapter
Quantifying Metabolic Acid-Base Abnormalities
Metabolic acid-base severity gauged *NON-quantitatively by size of HCO3- change* - because other buffers besides HCO3- participate and reduce the change in HCO3- that would otherwise occur - because HCO3- may be elevated or decreased with PCO2 changes Thus *Δ[HCO3-] from normal can UNDERestimate the metabolic acid-base derangement by 10-50 %*
Causes of Metabolic Alkalosis
Most commonly caused by loss of HCl via gastric secretions with vomiting or suction via a nasogastric tube or by renal HCO3- retention: - Vomiting - Continuous nasogastric suctioning - Diuretic therapy - Hyperaldosteronism - Licorice Ingestion - Excess alkali intake (e.g. milk alkali syndrome)
Can a patient have Respiratory Acidosis and Alkalosis?
NO A pt can have only one of these processes at a given time: it is impossible to have concurrent respiratory acidosis and respiratory alkalosis.
Magnitude of Compensatory Responses in Metabolic Disorders
No distinction made between acute and chronic due to the speed of the ventilatory responses. Keep in mind that the changes in PaCO2 in response to metabolic processes are the "expected" change but other issues such as altered mental status or decreased respiratory drive from medications might limit the expected ventilatory response leading to a smaller than expected change in PaCO2.
Combined Disorders
Not all acid-base disorders fit neatly into the primary and compensatory patterns described above. Combined primary disorders may occur: - e.g. an acute cessation of ventilation (asphyxia) causing both respiratory and metabolic (lactic) acidosis. - e.g. superimposition of acute hypercapnic acidosis or diuretic therapy on a chronic well-compensated respiratory acidosis *Blood pH, PaCO2, HCO3- and BE are sufficient to identify the net components present, but to more fully understand the process requires additional clinical knowledge or prior data*
Once a diagnosis is made...
Once the diagnosis is made and the *acid-base derangements are quantified* - *treat the underlying cause(s)* - determine whether the severity of the acid-base disorder(s) require direct intervention, such as initiation of dialysis for severe ethylene glycol or salicylate intoxication
Effects of adding metabolic acid to water, vs a bicarbonate solution
Quantitatively: *Water*: 12 mmol HCl added to 1L of water --> HCl dissociates and the resultant [H+] is 12 mM, a pH of 1.9 *Bicarb solution*: 12 mmol HCl added to 1L of solution containing 24 mmol NaHCO3- --> the added H+ ions combine with HCO3- ultimately forming CO2 - If the solution is equilibrated to a constant PCO2 of 40mmHg, all the CO2 formed is removed and the reaction continues until the 12mmol of H+ added has reacted w/ 12mmol of HCO3- reducing its concentration from 24 to 12mM - *Based on the Henderson-Hasselbalch Eq* this yields a pH of 7.1, far higher than when the HCl was added to water
Metabolic Acidosis
Recognized by a *decrease in HCO3- greater than that expected for the pH effect alone* (i.e. from any deviation of PCO2 from normal and simple chemical buffering) - Recognized as a *Base Excess (BE) <-2* (referred to as a *base deficit*) *The more negative the BE or larger the base deficit, the greater the magnitude of the acidosis*
Metabolic Alkalosis
Recognized by a *rise in HCO3-* greater than that expected for the pH effect alone - Recognized as a *Base Excess (BE) > 2* The *larger the BE, the greater the magnitude of the alkalosis*
Acidemia vs Alkalemia
Refer to the pH of the blood. (e.g., pH = 7.1 is called acidemia)
Carbonic Acid System
Resp system is closely interrelated to the acid-base status of the body because the *CO2 produced by tissue metabolism dissolves in H2O in tissues or blood and hydrates* to form *carbonic acid*. - In RBCs, the kidneys and the CNS, as well as some other cells of the body relevant to acid-base balance and ventilation, the hydration reaction is greatly accelerated by the enzyme *Carbonic Anhydrase* *CO2 + H2O <-(CA)-> H2CO3 <--> H+ + HCO3-*
Quantifying Respiratory Acid-Base Abnormalities
Respiratory Acid-Base severity gauged by magnitude of PCO2 change (ΔPCO2)
Davenport Diagram: Respiratory Disorder
Respiratory disorder: individual values move from the normal central point to higher or lower values of PaCO2 - sloping line passing through the center shows the 10-slyke buffer value of the non-carbonic buffers and thus indicates the expected values for pH and HCO3- w/ acute changes in PCO2 (i.e., no metabolic compensation yet)
Davenport Diagram showing Range of Values seen in Common Acid-Base Disorders
Showing Range of Values seen in Common Acid-Base Disorders (as reflected in the 95% confidence interval bands) and illustrates the usual limits of compensation. *Although we do not expect you to use these diagrams to interpret blood gas results on tests in this course, it is useful to be aware of these diagrams and their utility.*
How much will the pH change in response to changes in the concentration of the respiratory and/or metabolic acids? [Simplified model in which carbonic acid (as CO2) is added to a *bicarbonate solution* in which [HCO3-] concentration is the same as plasma.]
Simplified model in which carbonic acid (as CO2) is added to a bicarbonate solution in which [HCO3-] concentration is the same as plasma. *Effect of doubling the PCO2 : doubling H+, TRACE rise in HCO3-* PIC: e.g. PCO2 is increased from 40 to 80mmHg --> increase in [CO2] drives equation right - since PCO2 is doubled, final product of reactants on the right must also be doubled --> occurs when 40nM of H+ have been formed, increasing [H+] to 80nM --> causes pH to decrease from 7.40 to 7.10 *Each new H+ formed is associated w/ 1 new HCO3-*, and thus [HCO3-] also increases by 40nmol/L - this is *negligible compared to the 24 mM/L of HCO3- originally present* and as a result [HCO3-] does not change measurably when CO2 is added to a HCO3- solution w/ no other buffers present
FYI
The initial portion of the chapter will take a very basic chemistry-oriented approach to help you understand acid-base regulation. You will not be responsible for applying this basic chemistry on the course examinations (e.g., you will not need to memorize the values such as those in Table 6-1). You should instead focus on using the basic chemistry to understand the key concepts. You should also recognize that the approach laid out in this course might differ in some respects from that in the Urinary System course. There are many ways to "skin the cat" of acid-base interpretation and it is helpful to be aware of the different approaches you will see in the remainder of your training and career.
Magnitude of Compensatory Responses in Respiratory Disorders
There are expected changes in HCO3- and PaCO2 following respiratory and metabolic disorders respectively. Respiratory acidoses: magnitude of change in bicarbonate that results from buffering in acute processes will be smaller than with more chronic processes that allow time for renal compensation.
Bicarbonate vs Other Buffers (Metabolic Acids)
There is some true chemical buffering by other minor buffers such as *plasma proteins, organic acids, and inorganic phosphates*, but the Major buffering in the body is by *bicarbonate* - virtually all the *carbonic acid* thus formed can be* excreted by the lungs as CO2 under conditions of constant PaCO2*, allowing the rxn to proceed without any rate limiting buildup of CO2 - All other nonvolatile buffers lack this characteristic
Metabolic Disorders and [HCO3-]
Typically recognized by abnormal [HCO3-] (Normal value =24) - due to action of the non-carbonic buffers, even a pure respiratory abnormality will be associated w/ *changes in [HCO3-] of +3mM over the pH range 7.1-7.7* (careful to not mistake a small deviation in HCO3 from normal as representing a metabolic acidosis or alkalosis)
Lecture Case Study: 55 year old man with dyspnea, fatigue, and confusion ABG and other data: *pH=7.10*, PaO2=38mmHg, *PaCO2=70*mmHg, *HCO3-=21*mM SaO2 = 65 % , A-a PO2 diff: 25 mmHg, hematocrit = 32 % anion gap = 20, carboxyhemoglobin = 7% CXR: right lower lobe pneumonia, emphysema Sputum: pure growth of Hemophilius pneumonia *Diagnosis*
What is the acid-base disorder (s): acidemia - severe respiratory acidosis: PCO2 = 70 mmHg - metabolic acidosis: ΔHCO3 = - 3, BE of - 6 - lactate = 8 mM, anion gap = 20 *Diagnosis*: primary mixed respiratory and metabolic acidoses a) COPD and pneumonia with acute on chronic CO2 retention b) severe hypoxemia with lactic (anion gap) acidosis - low PaO2, anemia, carboxyhemoglobinemia, sepsis
Normal Values For Components of The Carbonic Acid System
[H+] = 40 nanomolar [HCO3]- = ~24 millimolar [CO2] = 1.2 millimolar
Non-Carbonic Acid
aka *Metabolic Acids*, - These nonvolatile, non-carbonic metabolic acids must be *excreted, primarily through the kidney, metabolized, or buffered by bone and other alkaline stores* - Changes in the handling of these acids or alkalis result in *metabolic acid-base derangements* *Inorganic*: phosphoric, sulfuric, hydrochloric acid *Organic*: amino acids, peptides, proteins, lactic/ketoacids *Drugs/toxins*: e.g. salicylates, methanol
Henderson-Hasselbalch Equation
pH = 6.1 + log[(HCO3-)/(0.03/PCO2)] pH = pK + log ([A-]/[HA])
Elevated Anion Gap Acidosis
resulting from accumulation of excess acid with subsequent loss of HCO3- via ventilation *Serum Anion Gap = >12*
Normal Anion Gap Acidosis
resulting from primary loss of HCO3- due to defects in renal tubular function or from intestinal secretions (diarrhea) *Serum Anion Gap = 8-12*
Quantifying Metabolic Acid-Base Severity: Base Excess (BE) Concept
Δ[HCO3-] can underestimate a metabolic acid-base disorder in a physiologic multi-buffer system *Δ[HCO3-] is affected by three factors* 1.) Changes in HCO3- due to H+ buffering by HCO3- itself 2.) H+ buffering by non-bicarbonate buffers 3.) Changes in HCO3- due to PCO2 changes *Base Excess (or deficit) calculation attempts to deal with the complexity of multiple buffers and CO2 effects on Δ[HCO3-] *
What is β for blood with 15gm/100mL Hb?
β = 30 slykes
What is β for Total Extracellular Fluid
β ≈ 10slykes
