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Questions and Answers
What pH level indicates acidosis?
What pH level indicates acidosis?
Which buffer system is mentioned as important despite having low buffering capacity?
Which buffer system is mentioned as important despite having low buffering capacity?
What is the consequence of a pH level exceeding 7.55?
What is the consequence of a pH level exceeding 7.55?
Which condition is associated with a high risk of mortality when the pH reaches 7.65 or greater?
Which condition is associated with a high risk of mortality when the pH reaches 7.65 or greater?
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What is the pH level associated with severe metabolic or mixed acidemia within the first 24 hours of ICU admission?
What is the pH level associated with severe metabolic or mixed acidemia within the first 24 hours of ICU admission?
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Which systems help control arterial pH?
Which systems help control arterial pH?
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What is the reference value for arterial blood pH?
What is the reference value for arterial blood pH?
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Which of the following conditions can result from alterations in H+ values?
Which of the following conditions can result from alterations in H+ values?
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What is the primary function of the kidneys in regulating blood pH?
What is the primary function of the kidneys in regulating blood pH?
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In which condition do the kidneys excrete HCO3- to help regulate blood pH?
In which condition do the kidneys excrete HCO3- to help regulate blood pH?
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How do the kidneys prevent excessive acid gain in the blood?
How do the kidneys prevent excessive acid gain in the blood?
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What common process occurs as the body excretes H+ ions?
What common process occurs as the body excretes H+ ions?
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What is a key characteristic of the process of bicarbonate reabsorption?
What is a key characteristic of the process of bicarbonate reabsorption?
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How much acid does the body typically produce each day that the kidneys must excrete?
How much acid does the body typically produce each day that the kidneys must excrete?
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What is the role of sodium (Na) in kidney function related to pH regulation?
What is the role of sodium (Na) in kidney function related to pH regulation?
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Which substance is a key component in buffering H+ ions in the tubular lumen?
Which substance is a key component in buffering H+ ions in the tubular lumen?
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What term describes a condition where the blood pH is less than the reference range due to excess acid concentration?
What term describes a condition where the blood pH is less than the reference range due to excess acid concentration?
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Which of the following compensatory mechanisms is immediate but short in duration?
Which of the following compensatory mechanisms is immediate but short in duration?
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In the context of acid-base disorders, what distinguishes primary respiratory acidosis from nonrespiratory disorders?
In the context of acid-base disorders, what distinguishes primary respiratory acidosis from nonrespiratory disorders?
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What is the typical bicarbonate to carbonic acid ratio maintained to keep pH within normal limits?
What is the typical bicarbonate to carbonic acid ratio maintained to keep pH within normal limits?
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What characterizes mixed respiratory and nonrespiratory disorders?
What characterizes mixed respiratory and nonrespiratory disorders?
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What happens during renal compensation in response to altered pH?
What happens during renal compensation in response to altered pH?
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Which factor is primarily altered to compensate for metabolic/renal causes of pH imbalance?
Which factor is primarily altered to compensate for metabolic/renal causes of pH imbalance?
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What is a fundamental characteristic of compensatory mechanisms in acid-base homeostasis?
What is a fundamental characteristic of compensatory mechanisms in acid-base homeostasis?
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What is the primary purpose of blood gas measurements?
What is the primary purpose of blood gas measurements?
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When might blood gas measurements be ordered?
When might blood gas measurements be ordered?
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Which condition is NOT indicated for blood gas measurement?
Which condition is NOT indicated for blood gas measurement?
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What is a common use for checking blood gases from a newborn's umbilical cord?
What is a common use for checking blood gases from a newborn's umbilical cord?
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What does a cooximeter measure in relation to blood gas analysis?
What does a cooximeter measure in relation to blood gas analysis?
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What factor is crucial before collecting a blood sample for gas measurement?
What factor is crucial before collecting a blood sample for gas measurement?
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Which of the following statements about spectrophotometric determination is correct?
Which of the following statements about spectrophotometric determination is correct?
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What is the primary purpose of calculating base excess or deficit in a patient?
What is the primary purpose of calculating base excess or deficit in a patient?
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Which hemoglobin species is commonly measured to assess oxygen saturation?
Which hemoglobin species is commonly measured to assess oxygen saturation?
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What temperature is conventionally used for measuring pH, PCO2, and PO2 in blood gas analysis?
What temperature is conventionally used for measuring pH, PCO2, and PO2 in blood gas analysis?
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What is considered a best practice for minimizing preanalytic errors in blood gas analysis?
What is considered a best practice for minimizing preanalytic errors in blood gas analysis?
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Which of the following preanalytic considerations is crucial during blood gas sample collection?
Which of the following preanalytic considerations is crucial during blood gas sample collection?
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What is included in the blood gas analysis quality assurance cycle?
What is included in the blood gas analysis quality assurance cycle?
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What type of electrode is used to measure pCO2?
What type of electrode is used to measure pCO2?
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Which of the following is a source of error when using a pH electrode?
Which of the following is a source of error when using a pH electrode?
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What is the main function of a semipermeable membrane in a modified pH electrode?
What is the main function of a semipermeable membrane in a modified pH electrode?
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What is the purpose of the Henderson-Hasselbalch equation in blood gas measurement?
What is the purpose of the Henderson-Hasselbalch equation in blood gas measurement?
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Which type of sensors are described as miniaturized macroelectrodes?
Which type of sensors are described as miniaturized macroelectrodes?
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How is the pH electrode calibrated?
How is the pH electrode calibrated?
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Total carbon dioxide content in blood can be calculated by combining which components?
Total carbon dioxide content in blood can be calculated by combining which components?
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What is a characteristic of self-calibrating instruments?
What is a characteristic of self-calibrating instruments?
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Study Notes
Clinical Chemistry I - Unit III: Blood Gases and Buffer Systems
- Unit covers the interrelationship of buffering mechanisms (bicarbonate, carbonic acid, and hemoglobin).
- Clinical significance of: pH and blood gas parameters
- Methods for determining metabolic/respiratory acidosis/alkalosis (using the Henderson-Hasselbalch equation and blood gas data)
- Identification of common causes of nonrespiratory and respiratory acidosis/alkalosis, and mixed abnormalities.
- Body's compensatory mechanisms (kidneys and lungs) for various pH conditions.
- Significance of the hemoglobin-oxygen dissociation curve and impact of pH, 2,3-DPG, temperature, and pCO2 on oxygen release to tissues.
- Measurement principles of pH, pCO2, pO2, and hemoglobin species.
- Problems and precautions in collecting and handling samples for pH and blood gas analysis.
- Instrumental approaches to measure hemoglobin species and pH/blood gas parameters
- Quality assurance approaches, including quality control and proficiency testing.
Introduction
- Clinical biochemistry provides information on a patient's acid-base balance and blood gas homeostasis.
- Data assists in assessing patients in life-threatening situations, identifying medical conditions like: kidney failure, heart failure, uncontrolled diabetes, hemorrhage, metabolic disease, head/neck injuries affecting breathing, chemical poisoning, and drug overdose/shock.
Definitions: Acid, Base, Buffer
- Acid: substance yielding H+ or H3O+ ions in water.
- Base: substance yielding OH- ions in water.
- Dissociation constant (K): describes relative strengths of acids and bases.
- pK: negative log of ionization constant at pH where protonated/unprotonated forms are equal.
- pH: -log[H+]
- Buffer: weak acid and its salt/conjugate base; resists pH changes. Bicarbonate-carbonic acid system (pKa 6.1) is a primary blood plasma buffer. Reference value for blood plasma pH is 7.40.
Acid-Base Balance: Maintenance of H+
- Normal H⁺ concentration in extracellular fluid is 36-44 nmol/L (pH 7.34-7.44).
- Intracellular pH is ~7.1.
- Mechanisms that maintain blood pH homeostasis: blood buffers, lungs, kidneys.
- Values outside the 7.34-7.44 range lead to chemical reactions, metabolism disfunction, consciousness changes, neuromuscular irritability, tetany, coma, and death.
Acid-Base Balance: Maintenance of H+, cont.
- Extreme metabolic alkalemia (pH > 7.65) correlates with high mortality risk (up to 80%).
- Immediate intervention & correction is crucial when arterial blood pH exceeds 7.55.
- Severe metabolic or mixed acidemia (pH <7.20) within 24 hours of ICU admission is correlated with 57% mortality risk.
Acid-Base Balance: Buffer Systems
- Buffers (weak acid and its salt/conjugate base) are body's first defense against extreme pH changes.
- Bicarbonate-carbonic acid system, although with limited buffering capacity, plays a vital role in homeostasis for 4 reasons: the dissociation of into water, adjusting ventilation rate, kidney's role in HCO3- regulation, and countering nonvolatile acids.
- Other buffer systems include: phosphate system and plasma proteins.
- Lungs and kidneys regulate blood pH.
Regulation of Acid-Base Balance: Lungs
- CO2 diffuses from tissues to blood and readily enters/leaves blood as a dissolved gas or as a carbamino-compound, and most importantly, combines with water to form carbonic acid (H₂CO₃).
- H₂CO₃ dissociates into H+ (hydrogen ions) and HCO3- (bicarbonate ions).
- HCO3- diffuses out of red blood cells into plasma to maintain electrical neutrality (chloride shift).
- Plasma proteins and buffers combine with the released H+ to stabilize pH.
- Lungs reverse this process by removing CO2 through exhalation.
- Change in CO2 levels directly modifies ventilation speed.
Regulation of Acid-Base Balance: Kidneys
- Kidneys play a critical role in regulating acid-base balance, excreting acids or bases.
- Under normal conditions, the body produces excess amounts of acid daily (50-100 mmol/L.)
- Kidneys regulate pH through: Reabsorbing bicarbonate, excreting ions and as phosphate and ammonium ions.
Reabsorption of Bicarbonate
- Bicarbonate reabsorption process is not direct. It involves the exchange of Na+ in the filtrate for H+ in tubular cells.
- This process results in the recovery of HCO3- which helps maintain pH.
Excretion of H+ ions
- For maintaining normal blood pH, daily excretion of excess H+ (acid) by the kidneys is critical, with normal levels between 50 and 100 mmol/L.
- This involves exchange of Na + for H+ ions in the tubular cell, creating carbonic acid (H2CO3), which then dissociates into CO2 and water, allowing the CO2 to be removed from the body.
Excretion of H+ ions As Phosphate
- H+ ions are buffered using the phosphate buffer system in tubular fluid. The amount of HPO4-2 available for combing with H+ is fairly constant.
- NaH2PO4 is transported into the tubular lumen, and excreted into urine.
Excretion of Ammonium Ions
- This process happens primarily in the distal convoluted tubules.
- Daily H+ excretion within the urine greatly depends on NH4+ formation.
- Excess glutamine is converted to ammonia (NH3), which then combines with H+ to produce ammonium (NH4+) that can then be excreted in urine.
Assessment of Acid-Base Homeostasis
- Bicarbonate buffering system & Henderson-Hasselbalch equation:
- Measurement of bicarbonate components, helps with information regarding other buffers & systems contributing to acid/base production/retention/excretion.
- Inferences about systems producing, retaining and excreting acids/bases.
- Henderson-Hasselbalch equation relates pH, pK', and concentrations of acid/base.
- In plasma (at body temperature), pK' of the bicarbonate buffer is 6.1.
- HCO3- concentration is proportional to the partial pressure of dissolved CO2 in the blood.
Acid-Base Disorders: Acidosis and Alkalosis
- Acidosis: Low pH (e.g., metabolic or respiratory acidosis).
- Alkalosis: High pH (e.g., metabolic or respiratory alkalosis).
- Disruptions can be due to pathological conditions or imbalances in bicarbonate levels.
- Ventilatory, renal, diabetic ketoacidosis, starvation ketoacidosis, lactic acidosis.
- Respiratory acidosis is due to reduced alveolar ventilation resulting in increased CO2 levels.
- Causes include diseases like bronchopneumonia, chronic obstructive lung disease, bronchial asthma, pulmonary edema, hypoventilation linked to drug use. Compensated through increased renal bicarbonate reabsorption, or elevated excretion of H+ and NH4+.
Compensation of Metabolic Acidosis
- Acute metabolic acidosis is often compensated through respiratory mechanisms (hyperventilation).
- Hyperventilation increases CO2 elimination from the body which helps reverse the effect of H2CO3.
Compensation of Metabolic Acidosis - continued
- Kussmaul's breathing is a pattern of rapid, deep breathing observed in diabetic ketoacidosis as a compensatory mechanism.
- Respiratory compensation is quick, but short-lived.
- Secondary compensation is realized when the other compensatory organs (kidney) start actively retaining bicarbonate and increasing H+ and NH4+ excretion.
- Renal compensation typically occurs within 3-4 days.
Acid-Base Disorders: Acidosis and Alkalosis, cont.
- Respiratory acidosis is caused by decreased alveolar ventilation, leading to buildup of CO2 and resulting in a rise in carbonic acid (H2CO3).
- Respiratory alkalosis is caused by increased alveolar ventilation, decreased CO2 levels and a resulting decrease in carbonic acid (H₂CO₃).
- Causes include, but are not limited to, hypoxia, hysteria, drug stimulation, elevated temperatures, over-ventilation related to mechanical devices, pulmonary embolism, fibrosis, pulmonary function decrease and anxiety.
- Compensated through renal mechanisms involving an increase in bicarbonate reabsorption and H+ and NH4+ secretion.
Acid-Base Disorders: Nonrespiratory (Metabolic) Alkalosis
- Metabolic alkalosis has as a defining feature an increased concentration of bicarbonate.
- Common causes include; excessive alkali intake, severe vomiting, prolonged nasogastric suction, & prolonged diuretic use.
- Kidney-mediated compensation through excretion of bicarbonate and increases in H+ reabsorption.
- Respiratory depression can increase CO2 retention which contributes to an increase in H₂CO₃ levels.
Acid-Base Disorders: Respiratory Alkalosis
- Increased alveolar ventilation and excess CO2 elimination.
- Common causes include, but are not limited to, hypoxia, hysteria, drug-induced stimulation, environmental factors such as elevated temps & use of mechanical ventilation devices, respiratory system issues like pulmonary emboli and fibrosis, and anxiety.
- Renal mechanisms compensate by decreasing bicarbonate reabsorption and increasing H+ secretion.
Oxygen and Gas Exchange
- Oxygen is essential for cellular metabolism; electrons are transferred to molecular oxygen in the mitochondria for ATP synthesis.
- Proper tissue oxygenation depends on: available atmospheric oxygen, gas exchange between lungs and arterial blood, adequate ventilation, oxygen loading onto hemoglobin, adequate hemoglobin levels and transport, & release of oxygen to tissues.
- Common factors influencing the amount of oxygen reaching tissues: destruction of alveoli, pulmonary edema, airway blockage, inadequate blood supply, and CO2/O2 diffusion.
Oxygen Transport
- Most oxygen in arterial blood is transported by hemoglobin.
- Hemoglobin in the blood can bind to up-to 4 oxygen molecules.
- Availability of O2, oxygen concentration and type of hemoglobin present, presence of interfering substances, blood pH and temperature, levels of 2,3-DPG (Diphosphoglycerate) are all critical to adequate transport and functionality.
Oxygen Dissociation
- Oxygen must be released from hemoglobin at tissues.
- The oxygen dissociation curve shows the relationship between oxygen partial pressure and the percentage of hemoglobin saturation.
- Factors affecting hemoglobin's affinity for oxygen include hydrogen ion activity, partial pressure of CO2, body temperature, and 2,3-DPG levels..
- Dyshemoglobin formations can also affect oxygen transport.
Measurement of Blood Gases
- Blood gas measurements provide key information on lung function, acid-base balance. Procedures include checking for respiratory problems, effectiveness of treatments, detecting acid/base imbalances, determining electrolyte imbalances, or during surgical procedures.
- Blood gas measurement is sensitive to temperature.
- Instruments used to assess Blood Gases include but are not limited to Spectrophotometry; using an instrument to determine amount of oxyhemoglobin. Methods often involve using wavelengths of light to measure the absorbance or transmission of light through the sample.
- Measurement of pH, pCO2, pO2, commonly requires electrochemical sensors (macro/microelectrodes). Amperometric method: measures oxygen levels by current flow. Potentiometric method: changes in voltage indicate analyte activity, like pCO2 and pH.
- Measurement of blood gases typically involves using 2 electrodes and a voltmeter. The use of two electrodes & a voltmeter helps measure the potential difference which can be related to the concentration of ions.
- Calibration and quality assurance are critical for accuracy and reliability of blood gas analysis.
Quality Assurance
- Preanalytic considerations: Correct patient identification, proper labeling of specimen, experienced personnel, proper collection and handling of blood gas samples, transport time.
- Analytic assessment: quality control (QC) and proficiency testing using surrogate liquid control materials, tonometry, duplicate assays, and non-surrogate QC which includes an interpretation of results.
- A quality assurance cycle is important and helps ensure accuracy. The cycle includes preanalytic stages (including patient prep, sample collection, and transportation), analytic measurements (including instrument performance and quality control) and post-analytic stages (including reporting and data review).
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