Clinical Chemistry - 13 Blood Gases and pH

CLINICAL CHEMISTRY BLOOD GASES AND PH OUTLINE • Plasma pH • Lines of Defense against pH Change • Regulation of Acid-Base Balance • Blood Buffers • Henderson-Hasselbalch Equation • Parameters of Interest in Acid-Base Balance • Four Basic Abnormal States • Compensation • Case Studies ACID & BASES • Acid - a substance that can yield hydrogen/hydronium ions when dissolved in water • Base - a substance that can yield hydroxyl ions when dissolved in water • Plasma - serves as water, suspends acids & bases • Plasma pH - determined by level of acid & base present/dissolved in plasma • Acidosis - processes in body that causes decreased pH • Acidemia - product of acidosis, increased levels of acid in the blood • Alkalosis - processes that causes increased plasma pH • Alkalemia - product of alkalemia, increased base in blood PLASMA pH • Normal plasma pH: 7.43-7.45 o Arterial - 7.4 • Plasma pH - one of the parameters that have narrow range; essential for normal metabolic activity and physiologic responses • Disruption in plasma pH can surely affect normal processes inside the body • <7.35 - acidosis o <6.8 - incompatible with life (fatal) • >7.45 - alkalosis o >8 - incompatible with life (fatal) • Sources of H+ in the body o Acids taken with foods (exogenous source) o Carbonic acid formation (in cell & plasma) - constant o Inorganic acids produced during breakdown of nutrients (associated with diet) o Organic acids resulting room intermediary metabolism LINES OF DEFENSE AGAINST pH CHANGE • Chemical Buffers o First line of defense o Fastest and first to respond to change in plasma pH o Responds within seconds to minutes after fluctuation/occurrence abnormality in pH o Bicarbonate-Carbonic Acid Buffer System - major chemical buffer in the blood • Respiratory Mechanisms o Second line of defense o Second to respond to change in plasma pH through ventilation processes o Responds within minutes to hours after pH change • Renal Mechanisms o Third line of defense o Through reabsorption/excretion o Responds within hours to days after pH change REGULATION OF ACID-BASE BALANCE CA • CO 2 + H2O ↔ H 2 CO 3 ↔ HCO 3 + H o CO 2 - released during cellular respiration, regulated by the lungs through ventilation o Bicarbonate - controlled by the kidneys • CO 2 combines with H 2 O to produce H 2 CO 3 (carbonic acid) • Formation of carbonic acid is catalyzed by carbonic anhydrase (CA) • Carbonic acid can further dissociate to produce HCO 3 & H o Bicarbonate will diffuse out of the cell which decreases negative charge within the cell ▪ To compensate for HCO 3 loss, chloride will enter cell to maintain electroneutrality (chloride shift) o Hydrogen will combine with deoxyhemoglobin/ reduced Hgb LUNGS • Regulates CO2 & H+ ion concentration o CO2 & H has directly proportional relationship o ↑ CO2 = ↑ H+ • Inspired O 2 will diffuse from the alveoli to the blood o When O 2 is available, reduced Hgb will release H ions to accommodate/bind with O 2 ▪ Hgb prioritizes affinity to O 2 • The H + that was carried on the reduced Hgb in the venous blood is released to recombine with HCO 3 to form H 2 CO 3 o H 2 CO 3 will dissociate to produce H 2 O and CO 2 o H 2 O is retained while CO 2 will be expelled from the lungs by exhalation • CO 2 diffuses into the alveoli and is eliminated through ventilation o Rate of removal of CO2 determines the level of H ion concentration in the body o Slow removal/non-removal of CO2 will result to accumulation of CO2 causing increased H+ ion concentration

o Rapid/fast elimination of CO2 by the lungs will result to decreased H+ ion concentration o Hypoventilation - slow respiration o Hyperventilation - fast/rapid respiration • Respiratory Adjustments to Acidosis and Alkalosis and Alkalosis Induced by Non-respiratory Causes Acid-Base Status Normal (pH 7.4) Nonrespiratory (metabolic) acidosis (pH 7.1) Nonrespiratory (metabolic) Alkalosis (pH 7.7) Ventilation Normal ↑ ↓ Rate of CO2 Removal Normal ↑ ↓ Rate of H2CO3 Formation Normal ↓ ↑ Rate of H+ Generation from CO2 normal ↓ ↑ o Acidosis - promote hyperventilation to conserve CO2 o Alkalosis - promote hypoventilation to accumulate CO2 and increase H+ generation and increase pH KIDNEYS • Regulates HCO3 • Excrete considerable amounts of acid and base for acid-base regulation • Kidney will conserve essentials and excrete wastes • Kidneys have threshold that limits the amount of substances reabsorbed in the blood o Anything in excess will be removed • Main role of kidney is to reclaim bicarbonate from the glomerular filtrate • Also responsible for excreting excess acid or base • CO2 diffuses into the tubule and reacts with H2O to reform H2CO3 and then HCO3 o 50-100 mmol/L of acid/day o 26-30 mmol/L of HCO3 • Increased HCO3 o IV infusion (Lactate, actate, and HCO3) ▪ When lactate & acetate are infused intravenously, they are converted into HCO3 • Decreased HCO3 o Diuretics o Reduced reabsorption o Chronic nephritis • Summary of Renal Responses to Acidosis and Alkalosis Acid-Base Abnormality Acidosis ( ↓ pH) Alkalosis ( ↑ pH) H+ Secretion ↑ ↓ H+ Excretion ↑ ↓ HCO3 Reabsorption and Addition of New HCO3 to Plasma ↑ ↓ HCO3 Excretion Normal (zero; all filtered is reabsorbed) ↑ pH of Urine Acidic Alkaline Compensatory Change in Plasma pH Alkalinization toward normal Acidification toward normal BLOOD BUFFERS • Bicarbonate and carbonic acid • Plasma proteins • Hemoglobin (deoxyhemoglobin/ reduced Hgb) • Inorganic phosphate HANDERSON-HASSELBACH EQUATION • Expresses acid-base balance relationship and relationship and relates the pH of a solution to the dissociation properties of the weak acid • pH = pK o pKa = equvalent to 6.1 • • Ratio of to HCO3 to CO2 maintain pH: 20:1 o Acid-base disturbance occurs when PARAMETERS OF INTEREST IN ACID-BASE BALANCE • pH • pCO2 • pO2 • HCO3 pH • Normal pH: 7.35 - 7.45 • pH 7.40: optimum value for arterial blood • An increase in H+ concentration decreases pH • When the kidneys and lungs are properly functioning, a normal ratio is maintained (HCO3:CO2::20:1) pCO2 • Evaluates ventilation of lungs • Index of efficiency of gas exchange • Lungs regulate the pH through CO2 by ventilation • Normal pCO2 = 35 - 45 mmHg • <35 mmHg = Respiratory Alkalosis • >45 mmHg = Resportatory Acidosis • Barbiturates, morphine or alcohol affect pCO2 • Heparin can have an increasingly marked effect on measured pCO2 • pO2 is lower in venous blood when oxugen had been released to the capilalries • Total CO2 = 19-24 mmol/L (arterial); 22-16mmol/L (venous)

HCO3 • Evaluates metabolic processes • Kidneys regulate pH by reabsorbing HCO3 and excreting excess acid/base • Normal HCO3 = 21 - 28 mEq/L • <21 mEq/L = Metabolic Acidosis • >28 mEq/L = Metabolic Alkalosis pO2 • Evaluates the degree of oxygenation • Reflects the availability of the gas in the blood • Normal pO2 = 81 - 100 mmHg • <81 mmHg = Hypoxemia o Mild Hypoxemia = 61 - 80 mmHg o Moderate Hypoxemia = 41 - 60 mmHg o Severe Hypoxemia = 40 mmHg or less • The degree of association or dissociation of oxygen with hemoglobin is determined • Excessive oxygen supply can cause acidosis o More O2 present cause deoxyhgb releases H ions to increase binding to O2 which causes increased H ions in plasma leading to acidosis ( ↓ pH) • Healthy persons living in high altitudes will show lower range of arterial pO2 o Due to reduced O2 levels in high altitudes FOUR BASIC ABNORMAL STATES • R = Respiratory • O = Opposite (pCO2, HCO3 vs pH) • M = Metabolic • E = Equal (pCO2, HCO3 vs pH) Acidosis (↓ pH) Alkalosis (↑ pH) pCO 2 (respiratory) ↑ ↓ HCO 3 (metabolic) ↓ ↑ METABOLIC ACIDOSIS • ↓ pH, ↓ HCO3, ↓ pCO2 • Caused by bicarbonate deficiency • Seen in conditions w/ production of excess amount of acid o DKA o Lactic Acidosis o Renal Failure o Diarrhea o (+) Hyperkalemia and Hyperchloremia • Compensatory mechanism o Breathing reate increases (hyperventilation) • Low HCO3 + Low pCO2 + pH < 7.40 METABOLIC ALKALOSIS • ↑ pH, ↑ HCO3, ↑ pCO2 • Caused by bicarbonate excess • Reversal of the levels of metabolic acidosis o Vomitiitng with the loss of chloride from the stomach • Compensatory mechanism o Breathing decreases to accumulate/increase CO2 • (+) Hypokalemia and Hypochloridemia • High HCO3 + High pCO2 + pH > 7.40 RESPIRATORY ACIDOSIS • ↓ pH, ↑ pCO2, ↑ HCO3 • Caused by excessive carbon dioxide accumulation • Seen in o COPD o Myasthenia gravis o CNS disease o Drug overdose o Pneumonia • Compensatory mechanism o Kidneys retain HCO3 because of increased pCO2 (alkalinization) • High pCO2 + High HCO3 + pH < 7.40 RESPIRATORY ALKALOSIS • ↑ pH, ↓ pCO2, ↓ HCO3 • Caused by excessive carbon dioxide loss • Seen in o Anxiety o Sever pain o Aspirin overdose o Hepatic cirrhosis o Gram negative sepsis • Compensatory mechanism o Decreased reabsorption of HCO3 (acidification) • (+) Hypokalemia • Low pCO2 + Low HCO3 + pH > 7.4 COMPENSATION • Respiratory Acidosis/Alkalosis o Issues in the lungs o Compensated by kidney through HCO3 release/retain o Acidosis (↑ pCO 2 ): ↑ HCO 3 by ↑ HCO 3 retention o Alkalosis ( ↓ pCO 2 ): ↓ HCO 3 by ↑ HCO 3 excretion o Compensation: Complete within 2-4 days (Kumpleto) • Metabolic Acidosis/Alkalosis o Issues with the kidney o Compensated by lungs through ventilation/respiration o Acidosis ( ↓ HCO 3 ): ↓ pCO 2 by hyperventilation o Alkalosis ( ↑ HCO 3 ): ↑ pCO 2 by hypoventilation (to conserve CO 2 ) o Compensation: incomplete but immediate (kuLUNG) • Uncompensated o Metabolic - pCO 2 is still normal, HCO 3 is abnormal o Respiratory - bicarbonate is still normal o Metabolic Acidosis ( ↓ HCO3) ▪ normal pCO2 = no action from lungs • Partially Compensated o Everything is abnormal (pH, bicarbonate, CO 2 ) o pH = <7.35 or >7.45 o pH is not yet within the range but the compensatory mechanism is working o Metabolic Alkalosis = ↑ pH, ↑ pCO2, ↑ HCO3 • Compensated/Fully Compensated o pH is normal, the rest is abnormal (CO 2 and HCO 3 ) o pH = 7.35 - 7.45 ▪ <7.40 - from acidosis ▪ >7.40 - from alkalosis o Not all normal value indicate compensation o Eg. ↑ pH, ↓ pCO2, ↑ HCO3 = mixed alkalosis (uncompensated)

CASE STUDIES • Case 1 o Test Results : ▪ Blood pH = 7.30 ▪ pCO2 = 70 mmHg ▪ HCO3 = 24 mmol/L o Finding : Respiratory Acidosis, Uncompensated o Rationalization : pH pCO2 HCO3 ↓ (acid) ↑ = (normal) ▪ Low pH = acidosis ▪ High pCO2 = acidosis ▪ Normal HCO3 = kidney is not compensating • Case 2 o Test Results : ▪ Blood pH = 7.48 ▪ pCO2 = 20 mmHg ▪ HCO3 = 40 mmol/L o Finding : Mixed Alkalosis, Uncompensated o Rationalization : pH pCO2 HCO3 ↑ ↓ ↑ ▪ High pH = alkalosis ▪ Low pCO2 = respiratory alkalosis ▪ High HCO3 = metabolic alkalosis ▪ Both kidney & lungs contribute • Case 3 o Test Results : ▪ Blood pH = 7.36 ▪ pCO2 = 25 mmHg ▪ HCO3 = 15 mmol/L o Finding : Metabolic Acidosis, Fully Compensated o Rationalization : pH pCO2 HCO3 ↓/= ↓ ↓ ▪ Slightly low pH = slightly acidic • pH is within normal range ▪ Low pCO2 = blood should be alkaline ▪ Low HCO3 = metabolic alkalosis, decreased pCO2 is compensatory mechanism • Lungs attempts to alkalinize blood pH •