Clinical Chemistry 2 - Blood Gases, PH, Buffer Systems PDF

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LEC BLOOD GASES, PH, BUFFER SYSTEMS The information on the patient’s acid-base balance and blood gas homeostasis are used to assess patients in life-threatening situations.Definitions: Arrhenuis’s definition : + Acid: a substance that increases the concentration of hydrogen ion/H+ when dissolved in ...

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Blood Gases, pH, & Buffer System LEC

4/16/21

BLOOD GASES, PH, BUFFER SYSTEMS The information on the patient’s acid-base balance and blood gas homeostasis are used to assess patients in life-threatening situations. Definitions: Arrhenuis’s definition: + Acid: a substance that increases the concentration of hydrogen ion/H+ when dissolved in water + Base: a substance that increases the concentration hydroxyl ions/OH- when dissolved in water.

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Body produces much greater quantities of H+, but the body controls and excretes H+ in order to maintain pH homeostasis. ○ Any values of H+ outside of normal range cause alterations in rates of chemical reactions and metabolic processes leading to alterations in consciousness, neuromuscular irritability, tetany, coma, death Sources of H+ ions: ✓ Breakdown of phosphorus-containing proteins releases phosphoric acid ✓ Anaerobic respiration of glucose produces lactic acid ✓ Fat metabolism produces fatty acids and ketones ✓ Loading and transport of carbon dioxide in the blood as bicarbonate release H+

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The logarithmic pH scale expresses H+ concentration

Bronsted & Lowry’s definition: most widely accepted and most clinically relevant × Acid: a substance that donates a proton in a reaction × Base: a substance that accepts a proton in reaction Lewis definition: ↣ Acid: molecule or ion that accepts a pair of electrons to form a covalent bond ↣ Base: a molecule that donates a pair of electrons to form a covalent bond The relative strengths of acids and bases, their ability to dissociate in water, are described by their dissociation constant/ionization constant/ K value. ------------------------------------pKa ∶ Defined as the negative log of the ionization constant ∶ Is also the pH in which the protonated and unprotonated forms are present in equal concentrations ∶ Strong acids have pKa values less than 3.0; strong bases have pKa values greater than 9.0 ∶ For acids, raising the pH above the pKa will cause the acid to dissociate and yield a H+ (hydrogen) ∶ For bases, lowering the pH below pKa will cause the base to release OH- (hydroxyl ion) Buffer ∾ ∾ ∾

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Is a combination of a weak acid or a weak base and its salt; a system that resists changes in pH The effectiveness of a buffer depends on the pKa of the buffering system and the pH of the environment The bicarbonate-carbonic acid system with a pKa of 6.1 is one of the principal buffers in the body(H2CO3 ⟷ HCO3- + H+) The reference value for blood plasma pH is 7.40 If pH of 100 ml of water is 7.35 and one drop of 0.05 mol/L of HCl is added, pH will change from 7.35 to 7.0 To change 100ml of blood to form pH of 7.35 to 7.0, 25ml of 0.05 mol/L of HCl is needed; for 5.5L of blood in the average body, more than 1,300 ml of HCl is needed.

Acid-Base Balance Maintenance of H+ ⊟ Normal concentration of H+ in the ECF (extracellular fluid) is 36-44 nmol/L (pH 7.34-7.44)

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pH = log 1/concentration of H+ = -log concentration of H+ ⊸ ⊸ ⊸

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Arterial blood pH is 7.4; equivalent to an H+ concentration of 40 nmol/L Venous blood pH is 7.35 Because pH is a negative log of H+ concentration, an increase in H+ decrease pH and a decrease in H+ increases pH Acidosis: pH below 7.34 Alkalosis: pH above 7.44 Chemically speaking, pH of 7.35 is not acidic if one considers a neutral pH is 7.0 ⊹ However, at pH 7.35 concentration is higher than optimal for most cells; this is called physiologic acidosis.

Suffixes ⊸ -osis refers to a process in the body ⊸ -emia refers to corresponding state in the blood (alkalemia, acidemia) ⊸ pH controlled by systems that regulate the production & retention of acids and bases; this include: ⊹ buffers ⊹ respiratory centers and lungs ⊹ kidneys ⊹ buffer systems (chemical buffer system) act faster than lungs & kidneys (physiological buffering system); physiological buffers have more buffering power. Buffer System: Regulation of H+ ⊙

Body’s first line of defense against extreme changes in H+ concentration; resist changes in pH when a strong base or acid is added (bind H+ when pH drops, release H+ when pH rises)

Bicarbonate-Carbonic Acid Buffer System ⋮ Consist of a weak acid (carbonic acid/ H2CO3) and its salt or conjugate base (bicarbonate/ HCO3-)

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⋮ H2CO3 (carbonic acid) is a weak acid since it does not completely dissociate into H+ and HCO3⋮ When a strong acid is added, the HCO3- (bicarbonate) will combine H+ to form H2CO3 HCl + NaHCO3 ⇢ H2CO3 + NaCl ⋮ When a strong base is added, H2CO3 will combine with OH- to form H2O and HCO3NaOH + H2CO3 ⇢ NaHCO3 + H2O ⋮ A smaller change of pH result from adding acid or base ⋮ Buffering power of this system is directly related to the concentration of buffering substances ○ When all available HCO3- (carbonic acid) (referred to as alkaline reserve) is used up, the buffer system becomes ineffective and blood pH changes ○ HCO3- concentration in ECF (extracellular fluid) is 25 mEq/L Buffer system is important because: 1. H2CO3 dissociate into H2O and CO2 allowing CO2 to be eliminated by lungs and H+ as H2O 2. Changes in CO2 modify ventilation/ respiratory rate 3. HCO3- concentrations can be altered in the kidneys 4. Counter effects of non-volatile acids (H+A-) by binding the dissociated hydrogen ion (H+A- + HCO3 + A-) ; resultant H2CO3 then dissociates and H+ is neutralized by the buffering system of hemoglobin. Phosphate Buffer System ⟡ Consists of sodium salts of HPO4 – (monohydrogen phosphate) and H2PO4- (dihydrogen phosphate) ⟡ NaH2PO4 acts as a weak acid, Na2HPO4 acts as a weak base HCl + Na2HPO4 ⇢ NaH2PO4 + NaCl NaOH + NaH2PO4 ⇢ Na2HPO4 ⟡ Play a role in plasma and RBC; involved in the exchange of sodium ion in the urine H+ filtrate Plasma Proteins (esp. imidazole group of histidine): ⟡ Buffer system in plasma ⟡ Most circulating proteins have a net negative charge and are capable of binding H+ Lungs and Kidneys: regulation of Acid-base balance ⤌ Carbon dioxide, the end product of aerobic metabolism, diffusion out of tissues and enters plasma and RBC ⤌ In the plasma, small amounts of CO2 is dissolved or combined with proteins to form carbamino compounds ⤌ Most of CO2 combines with H2O to form H2CO3, which quickly dissociates to H+ and HCO3- ; reaction accelerated by carbonic anhydrase in RBC membranes CO2 + H2O ⇠ ca ⇢ H2CO3 ⟷ H+ + HCO3⤌ Chloride shift: HCO3- concentration increase in RBC and diffuse into plasma; to maintain electroneutrality (same

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number of positive and negative ions on each side of RBC membrane), chloride diffuses into RBC. In the lungs, process is reversed: ⤏ Inspired O2 diffuses from alveoli into blood and is bound to hemoglobin forming oxyhemoglobin or O2Hb ⤏ The H+ that was carried on the reduced hemoglobin is released to recombined with HCO3- to form H2CO3, which dissociates into H2O and CO2; CO2 diffuses into alveoli and is eliminated through ventilation ⤏ Net effect is a minimal change in H+ concentration between venous and arterial blood ⤏ Ventilation affects pH of blood: ⤏ When lungs do not remove CO2 at the rate of its production (ex: decreased ventilation or disease), CO2 accumulates causing an increase in H+ concentration ⤏ When lungs remove CO2 faster than production (ex: hyperventilation), H+ concentration is decreased. ⤏

A change in H+ concentration of blood that results from non-respiratory disturbances cause the respiratory centers to respond by altering rate of breathing to restore blood pH ○ When pCO2 or when blood H+ concentration rises, respiratory rate and depth increases ○ When blood pH rises, respiratory rate drops and respiration becomes shallower ○ Thus, lungs and the buffer system are the first line of defense to change acid-base status.

Kidneys: ⤷ Acts slowly but surely (takes hours to days) to compensate for acid-base imbalances ⤷ Can rid body of acids generated by cellular metabolism/nonvolatile acids (uric acid, phosphoric acid, lactic acid, ketones) ⤷ Also regulates blood levels of alkaline substances and renew chemical buffers ⤷ Main role is to reabsorb HCO3- from the glomerular filtrate (if HCO3- is lost in urine, excess acid gain in the blood results) ⟡ Glomerular filtrate contains same HCO3- levels as plasma ⟡ Reabsorption takes place in proximal tubules ⟡ HCO3 is not directly transported across tubular membrane; instead, Na+ in the glomerular filtrate is exchanged for H+ in tubular cells; H+ combines with HCO3- in the filtrate to form H2CO3 which is converted to H2O and CO2 by carbonic anhydrase; CO2 diffuses into tubular membranes and reacts with H2O to reform H2CO3, which dissociates into HCO3- and H+; HCO3- is reabsorbed into blood together with Na+ ⤷ Maximum urine pH is 4.5 ⟡ Kidney excretes little unbuffered H+ ⟡ Most of urinary H+ is combined with ammonia (NH3) and monohydrogen phosphate (HPO4-)

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and is excreted as ammonium (NH4) and dihydrogen phosphate (H2PO4--) Factors that affect reabsorption of (bicarbonate) HCO3-: ⟡ Blood plasma HCO3- levels > 26-30 mmol/L; occurs when HCO3- is given Intravenously, excess amounts of lactate or acetate; HCO3 will be excreted by kidneys ⟡ Low plasma levels of HCO3- : occurs with diuretic use, chronic nephritis; HCO3reabsorbed by kidneys.

Assessment of Acid-Base Homeostasis ⟡ To assess acid-base homeostasis, components of the bicarbonate buffering system are measured and calculated; inferences can be made pertaining to other buffer systems ⟡ In the bicarbonate buffer system, the dissolved CO2 (dissolved CO2) is in equilibrium with CO2 gas which can be expelled by the lungs; thus the bicarbonate buffer system is referred to as an open system and the dissolved CO2 is the respiratory component. ⟡ Lungs participate rapidly in regulation of the blood pH through hypo- and hyperventilation. ⟡ Kidneys, the non-respiratory / metabolic component, controls the bicarbonate concentration. Henderson-Hasselbalch Equation ⟡ Expresses acid-base relationship in a mathematical formula pH = pKa + log cA-/cHA ○ pKa is the pH at which there is equal concentrations of protonated and unprotonated species ○ A- the proton acceptor or base (HCO3-) ○ HA is the proton donor or weak acid (H2CO3) ⟡ In the plasma at 37oC body temperature, pKa of the bicarbonate buffering system is 6.1 ⟡ The equilibrium between H2CO3 (carbonic acid) and CO2 in plasma is 1:800 ⟡ Concentration of H2CO3 is proportional to the partial pressure exerted by the dissolved CO2 ⟡ In plasma at 37oC, the value for the combination of the solubility constant for pCO2 and the factor to convert mmHg to mmol/L is 0.0307 mmol/L/mm Hg ○ Temperature and solvent affect the constant; if either changes, the solubility constant also changes ⟡ pH and pCO2 are measured in blood gas analysis ⟡ HCO3- can be calculated as: pH = pKa + log cHO3- / (0.0307 x pCO2) ⟡ Substituting normal values, the equation in healthy individuals reads: pH = 6.1 + log 24 mmol/L / (0.0307 mmol/L/mm Hg x 40 mm Hg) = 6.1 + log (24 / 1.2) = 6.1 + log (20) = 6.1 + 1.3 = 7.40

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Acid-Base Disorders ⧺ Acidemia – when blood pH is less than the reference range; reflects excess acid or H+ concentration ⧺ Alkalemia – when blood pH is greater than reference range; excess base ⧺ Primary respiratory acidosis or alkalosis – disorder caused by ventilatory dysfunction / changes in the pCO2 or carbon dioxide pressure (respiratory component) ⧺ Non-respiratory acidosis or alkalosis – disorder resulting from change in the bicarbonate levels (renal / metabolic component) ⧺ ⧺

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Whenever an imbalance occurs, the body tries to restore acid-base homeostasis by compensation Compensation is done by altering the function or component that is not primarily affected by the pathological process. ○ If imbalance is of non-respiratory origin, body compensates by altering ventilation ○ For disturbances of the respiratory component, kidneys compensate by selectively excreting or reabsorbing anions and cations. ○ Lungs can compensate immediately but response is short-term and often incomplete ○ Kidneys are slower to respond (2-4 days) but response is long-term and complete Fully compensated – implies that pH has returned to normal range (20:1 ratio has been restored) Partially compensated – implies pH is approaching normal

1. Primary Non-Respiratory Acidosis /Metabolic Acidosis ⟡ Decrease in (bicarbonate) HCO3- (+2)

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Respiratory alkalosis: patient who are alkalotic with a PaCO2...