Acid-Base Balance and Gases

Metabolic reactions → Acids and CO2

• Arterial blood pH = 7.35 - 7.45

• Maintained by Blood Buffers

• Respiratory System

• Renal System

Blood buffers:

• First line of defense against pH changes

• Weak acid + Conjugate base

• Acts as an acid when base is added

• Acts as a base when acid is added

Bicarbonate-Carbonic acid:

• Principle plasma buffer

  • Responds in respiratory and renal acid-base regulation

• H+ + HCO3- ←→ H2CO3 ←→ CO2 + H2O

Phosphate Buffers:

• Renal Mechanisms

  • HPO2²-, H2PO4- (involved in exchange of sodium ion in the urine filtrate, plus H+)

Hemoglobin:

• Major RBC buffer

Plasma Proteins:

• Negatively charged, bind H+

Isohydric Shift:

• H+ is shifted among acid-base pairs so that [H+] remains essentially unchanged

Isohydric shift: Plasma phase:

• Some CO2 combines with H2O:

  • CO2 + H2O ←→ H2CO3 ←→ H+ + HCO3

  • H+ is buffered by plasma buffers, i.e., proteins

Isohydric shift: RBC phase:

• Most CO2 enters RBC and combines with H2O

• CO2  + H2O ←→ H2CO3 ←→ H+ + HCO3-

  • CO2 + H2O ←→ H2CO3

    • Carbonic anhydrase

  • H+ is buffered by oxyhemoglobin (HbO2-)

  • Oxyhemoglobin is transported to the tissues

  • Oxygen diffuses to the tissue cells

  • CO2 diffuses from the tissue into the RBC (deoxyhemoglobin)

• Isohydric and Chloride Shift — RBC

Chloride Shift (RBC):

• HCO3- builds up in RBC, and diffuses into plasma

• Cl- diffuses into RBC for electroneutrality

Renal Acid-Base Balance:

• Final defense against changes in body pH

  • Excretes acid produced by metabolism

  • Excretes variable amounts of acid/base

Renal Acid-Base Balance Mechanisms:

• Acid excretion

  • Na+ H+ exchange

  • H+ reacted with buffer base: PO3, NH3

• HCO3- reabsorption (reclamation)

  • Vital to maintain plasma buffering

  • Generally proportional to Na+ reabsorption

Renal Acid Excretion: Na+ - H+ Exchange:

• H+ secretion

• Na+ reabsorption (active exchange)

• K+ and H+ compete for exchange

  • Hyperkalemia

    • More H+ in RBCs, more K+ in plasma

    • Metabolic acidosis

  • Hypokalemia

    • More K+ in RBCs, more H+ in plasma

    • Metabolic alkalosis

Renal buffers: Phosphate

• H+ + Na2HPO4 (dibasic Na phosphate) → NaH2PO4 (monobasic Na phosphate)

• Excreted in urine

Renal buffers: NH3:

• H+ + NH3 —> NH4+

• Excreted in urine as ammonium salt, NH4Cl

Henderson-Hasselbalch Equation:

• Bicarbonate-Carbonic acid Buffer System

  • Blood pH = 6.1 + log[HCO3-]/[H2CO3]

  • pH controlled by [HCO3-]/[H2CO3] ratio

    • Ratio normally 20/1

    • Increased ratio = Increased pH

    • Decreased ratio = Decreased pH

• Bicarbonate (HCO3-) “Metabolic”

  • Kidney

• Carbonic acid (H2CO3) “Respiratory”

Acid Base Imbalance: Respiratory disorders (CO2):

• Increased CO2 (acidosis)

• Decreased CO2 (alkalosis)

• Renal system compensates

Acid Base Imbalance: Metabolic disorders (HCO3-):

• Decreased HCO3- (acidosis)

• Increased HCO3- (alkalosis)

• Respiratory system compensates

Acid Base Imbalance: Acidosis:

• Decreased pH

• Decreased ratio

  • Make umeratory HCO3- smaller; OR make denominator (pCO2) larger

Acid Base Imabalance: Acidosis: Respiratory factor altered:

• n [HCO3-]/INCREASED pCO2

Acid Base Imbalance: Acidosis: Metabolic factor altered:

• DECREASED [HCO3-]/ n pCO2

Acid Base Imbalance: Alkalosis:

• Increased pH

• Increased Ratio

  • Make numerator (HCO3-) larger; OR make denominator (pCO2) smaller

• Respiratory factor altered: pCO2

  • n HCO3- / decreased pCO2

• Metabolic factor altered: HCO3-

  • Increased HCO3-/ n pCO2

Acid-Base Imbalance: Compensation:

• Opposite factor moves in same direction as the primary problem to normalize pH (Bring back to 20:1 ratio)

  • Example: Primary problem is Respiratory factor: pCO2

  • n HCO3- / decreased pCO2

• For compensation, HCO3- goes down to normalize ratio

• pH becomes normal, BUT both factors now abnormal!!

  • Primary problem is the more abnormal result

  • Decreased HCO3-/ VERY DECREASED pCO2

Respiratory Compensatory Mechanisms:

• Immediate, short-term, often incomplete

Respiratory Compensatory Mechanisms: Metabolic alkolosis:

• Increased CO2 retention

  • Hypoventilate

Respiratory Compensatory Mechanisms: Metabolic acidosis:

• Decrease CO2 (eliminate it)

  • Hyperventilate (“blow off” CO2)

Renal Compensatory Mechanisms:

• Slower, (a few days to maximize), long-term, potentially complete

Renal Compensatory Mechanisms: Respiratory alkalosis:

• Increased H+ retention

• Decreased HCO3- retention

Renal Compensatory Mechanisms: Respiratory acidosis:

• Decreased H+ retention

• Increased HCO3- retention

Metabolic Acidosis:

• 1 degree Bicarbonate deficit

  • Decreased [HCO3-/[H2CO3] ratio → decreased pH

• Increased anion gap

Metabolic Acidosis: Normochloremic type:

• Endogenous acids:

  • Ketoacidosis, Lactic acidosis

• Exogenous acids:

  • Isopropanol, Salicylate toxicity (Late)

  • Decreased acid excretion: Increase renal failure

Metabolic Acidosis: Hyperchloremic type:

• Direct HCO3- loss

• Increase in Cl- for electroneutrality

Metabolic Acidosis disorders:

• Renal tubular acidosis (RTA)

• Diarrhea

Metabolic Acidosis: Lactic Acidosis:

• Glycolysis: Glucose → Pyruvate

  • Pyruvate converts to Lactate in anaerobic conditions instead of acetyl Co A

Lactic acidosis: Physiologic:

• Strenuous exercise: increased blood lactate and pyruvate

• Lactate/pyruvate ratio unchanged

Lactic acidosis: Pathologic:

• Often leads to coma and death

• Hypoxic: Shock, volemia, heart failure

• Increased lactate/pyruvate ratio

Lactic Acid/Pyruvate Specimen:

• Must minimize in vivo and in vitro glycolysis

  • Leads to false increased lactate; Pyruvate - unstable

• Patient prep

  • Fasting, resting for >2 hours; No tourniquet/fish

• Whole blood

  • Collect in heparnized tube, on ice, gray top

  • Transfer blood to TCA (trichloroacidic acid) or perchloric acid tube

• Plasma

  • Collect in NaF, K oxolate tube, gray top, on ice

  • Separate from cells within 15 minutes

Metabolic Acidosis Compensation Mechanisms:

• Respiratory

  • Blow off CO2 to raise ratio toward normal

• Renal

  • Increased acid excretion

  • Increased HCO3- reabsorption (reclamation)

Metabolic Acidosis: Lab findings:

• Decreased pH, decreased HCO3-

  • After compensation: decreased pCO2

  • Other findings: Cl- might be increased (Hyperchloremic)

Metabolic Alkalosis:

• 1 degree bicarbonate excess

  • Increased [HCO3-]/[H2CO3] ratio → increased pH

Metabolic Alkalosis: Disorders:

• Antacid or bicarbonate overdose

  • Increased H+ excretion/loss

  • Prolonged vomiting, nasogastric suctioning

  • Increased K+ depletion

    • Increased Na+ retention (hyperaldosteronism)

    • Diuretics

Metabolic Alkalosis: Compensation:

• Respiratory

  • Increased CO2 retention

    • Hypoventilation

• Renal

  • H+ retention

  • Decreased HCO3- retention

Metabolic Alkalosis: Lab Findings:

• Increased pH, increased HCO3-

  • After compensation: increased pCO2

  • Other findings: alkaline urine pH

Respiratory Acidosis:

• 1 degree CO2 excess (Hypercapnia)

  • Decreased [HCO3-]/[H2CO3]  ratio → decreased pH

  • Hypoventilation

Respiratory Acidosis: Disorders:

• Chronic obstructive pulmonary disease (COPD)

  • Asthma, pulmonary emphysema

• Chemoreceptor depression

  • Drugs, i.e. heroin, morphine

• Rebreathing exhaled air

Respiratory Acidosis: Compensation mechanisms:

• Renal: Increased acid excretion, increased bicarb

• Respiratory: blow off CO2

Respiratory Acidosis: Lab findings:

• Decreased pH

• Increased pCO2

• Decreased O2

• After compensation: Increased HCO2- (retained since kidney is primary compensation)

• Other findings: Cl- may be decreaed

Respiratory Alkalosis:

• 1 degree CO2 deficit (Hypocapnia)

  • Increased [HCO3-]/[H3CO3] ratio → increased pH

  • Hyperventilation

Respiratory Alkalosis: Disorders:

• Phsychogenic, i.e. anxiety, hysteria

• Hyperstimulation of respiratory center

  • Hypoxia

  • Drugs, i.e. salicylate toxicity (Early)

Respiratory Alkalosis: Compensation mechanisms:

• Renal: Increased H+ retention, decreased bicarb. retention

• Respiratory: Increased CO2 retention

Respiratory Alkalosis: Lab findings:

• Increased pH, decreased pCO2

  • After compensation: decreased HCO3-

  • Other findings: Alkaline urine pH

Oxygen Significance: Increased pO2

• O2 administration

• Hyperventilation

Oxygen Significance: Decreased pO2

• Hypoxemia

• Hypoventilation

Case: A 13-year-old male was brought to the

emergency room in a comatose state.

His mother stated that he was nauseated

earlier that day. Upon physical

examination, it was noted that the patient

was breathing deeply and rapidly, his

breath had a fruity odor, and the skin and

mucous membranes were dry.

• Pt has diabetic ketoacidosis

  • Due to increased glucose, acetone in urine

• BUN is increased in DM due to dehydration, since urea moves with water and is retained, leading to a buildup of NPNs

• Loss of body water is indicated by osmolality and decreased Na+

• Glycosuria is due to being past the renal threshold

• Metabolic acidosis

• ABG and pH test results:

  • pH decreased

  • pCO2 decreased

  • pO2 increased

pH and Blood Gas Analysis: Measured analytes include:

• pH, pO2, and pCO2

pH and Blood Gas Analysis: Derived parameters include:

• H2CO3, HCO3-, Base excess (BE), TCO2, %SO2

• H2CO3 directly related to pCO2

  • H2CO3 calculation:

    • pCO2 × 0.031

  • HCO3- calculation:

    • Blood pH = 6.1 + log[HCO3-]/[pCO2 × 0.031]

Titratable Base Excess (BE):

• Estimates Metabolic component of Acid-Base disorder

• Positive values (base excess)

  • Suggests metabolic alkalosis

• Negative values (base deficit)

  • Suggests metabolic acidosis

• Numerical values indicate theoretical amount of acid/base (mmol/L) to correct blood pH

  • Less given in practice, b/c of compensation

pH and Blood Gas Specimen: Whole blood:

• Arterial (ABG), venous, capillary

pH and Blood Gas Specimen:

• Heparinized syringe!

  • Anaerobic technique

  • Air exposure causes: increased pH, increased pO2, decreased pCO2

  • Mix well to avoid clots

• Transport on ice, analyze immediately (<30 min)

  • Excessive metabolism causes:

    • Decreased pH, decreased pO2, increased pCO2

ABG Reference ranges: pH:

• 7.35-7.45

ABG Reference ranges: pO2:

• 80-90 mmHg

ABG Reference ranges: pCO2:

• 35-45 mmHg

ABG Reference ranges: O2 saturation:

• 95-99%

pH and Blood Gas Analysis:

• Whole blood mixed well

• Sample aspirated, warmed to 37 C

• Electrodes protrude into sample chamber

pH and ABG Electrodes:

• H+ gas

• pH Reference electrode: calomel/sat.KCl or Ag-AgCl2/sat. KCl

  • Salt bridge (contracts sample)

• pCO2 electrode: gas permeable membrane, e.g. silicone

  • Modified pH electrode

• pO2 electrode: gas permeable membrane, i.e. polypropylene

  • Platinum cathode → Current (Amperometric)

ABG Instrument Calibration:

• Frequent verification (every 30 minutes)

• pH

  • pH standards (High + Low)

• pO2 and pCO2

  • pO2 and pCO2 gases (high + low)

ABG Errors: Pre-analytical:

• Sample collection, transport, poor mixing before sampling

• Patient temperature

  • Need actual temperature to correct result

  • Especially important for accurate pO2

ABG Errors: Calibration:

• Wrong set points

ABG Errors: Instrument Temperature control (> ± 1 C)

• pO2 electrode

ABG Errors: Dirty sample chamber/sample path:

• Flushed between samples to avoid blood/fibrin clot build-up

• Interferes with electrode contact (including salt-bridge) with calibrators, samples

• Incomplete specimen sampling

ABG Instrument Troubleshooting: All analytes out-of-control:

• Recalibrate

ABG Instrument Troubleshooting: All analytes out-of-control and calibration fails:

• Check sample chamber/sample path, electrode for dirt, blood build-up, or clots

• Check calibrator materials/set points

ABG Instrument Troubleshooting: Specific analyte(s) out-of-control:

• Check specific electrode(s), replace membranes as needed

• pO2 flucuation

  • Check instrument temperature

Oximetry: Co-oximeter:

• Measures oxygen saturation (SO2), carbon monozid (COHb), methemoglobin (MetHb)

• Spectrophotometry

  • Characteristic absorption wavelengths of various hemoglobin species

Oximetry: Pulse oximeter:

• Attaches to finger, toe, or earlobe

• Measures SO2 trends

  • Spectrophotometry

Case 2: A 5-year-old girl was admitted to the ER in a

comatose state. The following laboratory

results were found:

• Decreased total CO2

• Increased Anion Gap

• Ethylene glycol poisoning