3. www.biology.arizona.edu, a) Acids and Bases b) Clinical correlates of pH levels,

Question 2: What is pH? The pH of a solution is equal to:

A. the hydrogen ion concentration, [H +] B. log [H +] C. -log [H +] D. ln [H +] E. -ln [H +] ANSWER: C pH is defined as the negative log of the H + concentration.

respiratory acidosis

apnea or impaired lung capacity, with a build-up of CO2 in the lungs

Question 4: Calculating pH What is the pH of a 10 - 3 M solution of HCl?

-log [10 - 3] = 3

Question 3: Physiological pH Physiological pH is 7.4. What is the hydrogen ion concentration of a solution at physiological pH?

A. -7.4 M B. 0.6 M C. 0.6 x 10 - 8 M D. 1 x 10 - 8 M E. 4 x 10 - 8 ANSWER: E To be exact, 10 raised to the power of -7.4 = 3.98 x 10 - 8.

Question 6: Relation between H + and OH - concentrations If the concentration of H + in a solution is 10 - 3 M, what will the concentration of OH - be in the same solution at 25° C?

A. 10 - 3 M B. 10 - 11 M C. 1011 M D. 2 x 10 - 11 M E. 10 - 14 M ANSWER: B [H +] [OH - ] = 10 - 14

Question 7: Neutralizing a basic solution How many ml of a 0.4 M HCl solution are required to bring the pH of 10 ml of a 0.4 M NaOH solution to 7.0 (neutral pH)? Note: HCl and NaOH both completely dissociate in water (i.e., no pKa calculation is necessary).

A. 4 B. 40 C. 10 D. 20 E. 2 ANSWER: C Because both the acid and the base are at the same concentration and both completely dissociate in water, a neutral pH can be achieved by adding an equal amount of the acid solution to the base solution.

Question 8: Neutralizing an acidic solution How many ml of a 0.2 M NaOH solution are required to bring the pH of 20 ml of a 0.4 M HCl solution to 7.0?

A. 4 B. 40 C. 10 D. 20 E. 5 ANSWER: B Because the acid has twice the concentration of the base, a neutral pH can be achieved by adding twice the amount of the base solution to the acid solution.

Problem 2: Bicarbonate as a biological buffer Bicarbonate is a crucial buffer in the body and is usually present in body fluids as sodium bicarbonate (sodium being the main positive ion in extracellular fluids). What features of sodium bicarbonate contribute to its effectiveness as a biological buffer?

A. The bicarbonate ion (HCO3-) can combine with a proton (H+) to form carbonic acid (H2CO3), thus absorbing protons from solution and raising blood pH. B. Carbonic acid, which can be formed from CO2 and water, can dissociate into H+ and HCO3- in order to provide H+ and lower blood pH. C. Carbonic acid, which can be formed from bicarbonate, is converted to CO2 and water via a very fast enzymatic reaction. D. CO2, being volatile, can be rapidly expelled from the body at varying rates by respiration. ANSWER: A,B,C,D

Question 1: Water as a solvent

A. The high surface tension of water, which is due to the formation of hydrogen bonds between adjacent water molecules. B. The ability to serve as a buffer, absorbing the protons given off by acetic acid. C. The ability to orient water molecules so that their polarities neutralize the ions formed when the acid dissociates. D. The ability to form hydrogen bonds with the carbonyl and the hydroxyl groups of acetic acid. ANSWER: C & D Because acetic acid is a weak acid, its dissociation in water is incomplete. That portion which does ionize, however, is neutralized in solution when the water molecules orient their partially charged atoms around the ions. The un-ionized portion of acetic acid is also soluble due to its polar character as well as via hydrogen bonds. Thus, multiple solvent properties of water are important to solubilize acetic acid.

Question 9: Acids & pKa Acids are defined as compounds with pKa values below 7.0.

A. True B. False ANSWER: B Acids are defined as compounds which can reversibly lose protons to the solution.

Problem 5: Diagnosing acidosis/alkalosis The normal range for blood pH is 7.35-7.45. Patients with acidosis or alkalosis will have pH values outside of this range.

A. True B. False ANSWER: B Patients are often encountered who significantly deviate from normal bicarbonate values for blood, yet nonetheless maintain blood pH within a range compatible with life. Such patients have compensated for circumstances that would normally produce acidosis or alkalosis.

Question 10: Relationship between pKa and pH The correct operational relationship between pKa and pH is that:

A. both are log functions. B. both are always <7 for acids, and >7 for bases. C. These two concepts are not operationally related in any way since biological fluids contains mixtures of too many acids and bases. D. When pH = pKa , the compound in question will have a charge of +0.5. E. When pH = pKa , the ionizable compound in question (whether acid or base) will be half protonated and half deprotonated. ANSWER: E This is in fact the very definition of pKa.

Problem 8: Chronic compensation for diet rich in acid Your patient presents with the following blood gases. When questioned about his diet, he admits to binging on citrus fruits in the past few weeks, and his favorite drinks are grapefruit and tomato juice. Patient's Value Normal Value pH 7.32 7.35-7.45 pCO2 25 mm Hg 35-45 mm Hg [HCO3-] 15 mmol/liter 24-28 mmol/liter What condition does this patient appear to have?

A. compensated respiratory acidosis B. compensated metabolic acidosis C. uncompensated respiratory acidosis D. uncompensated metabolic acidosis ANSWER: B Decreased HCO3- together with decreased pH signals a metabolic acidosis. The lowered pCO2 is due to compensation in the lung, which nearly normalizes blood pH.

Problem 3: Rapid response to mild acidosis The bicarbonate buffering system of blood can respond quickly to mild metabolic acidosis (between pH 7.15 and 7.35) by:

A. expelling CO2 in the lung. B. retaining HCO3- in the kidney. C. excreting H+ in the kidney. D. direct buffering action of the H2CO3 central intermediate. E. retaining CO2 in the lung. ANSWER: A This removal of CO2 from the system then elicits a shift in the bicarbonate equilibrium, consuming H+ and HCO3- to replace the vanished CO2 (with water as the other product). Since H+ ions are consumed, pH is raised. (HCO3- is also consumed, but this is not a problem with mild acidosis, since the CO2 is constantly produced via the processes of normal metabolism and will gradually balance the bicarbonate reaction back the other way, restoring equilibrium.)

Problem 6: Compensation for chronic metabolic alkalosis For chronic metabolic alkalosis, effective compensation by the body involves:

A. expelling H+ in the kidney. B. retaining CO2 in the lung. C. expelling HCO3- in the kidney. D. retention of NH4+Cl- in the kidney. E. expelling OH- in the kidney. ANSWER: B. By mass action, an increase in CO2 in the lungs triggers an increase in the H2CO3 intermediate, which, in turn, dissociates to bicarb and H+, thus lowering pH.

Problem 7: Chronic compensation for collapsed lung Suppose a patient has a collapsed lung and cannot expel CO2 at a normal rate. Chronic compensation would involve:

A. increased activity of carbonic anhydrase. B. kidney retention of H+. C. kidney retention of HCO3-. D. kidney expulsion of HCO3-. E. switching to anaerobic metabolism. ANSWER: C Decreased renal resorption of bicarbonate will increase the blood levels of this species. This will effectively match the increased CO2 caused by the pneumothorax and maintain the ratio of bicarbonate to CO2, thus maintaining a normalized pH.

Question 11: pH and buffering capacity of a mixed solution If equal volumes of 0.05 M NaH2PO4 and 0.05 M H3PO4 are mixed, which of the following best describes the resulting solution? (pKa's for phosphoric acid are 2.0, 6.8 and 12.0)

A. pH 2 and poorly buffered. B. pH 2 and well buffered. C. pH 6.8 and well buffered. D. pH 12 and well buffered. E. pH 6.8 and poorly buffered. ANSWER: B Equal amounts of phosphoric acid (H3PO4) and monosodium phosphate (NaH2PO4) will be present at a pH of 2.0, which is the pKa for phosphoric acid. Because both components of the mixture have 50mM phosphate and the solution is poised at the pKa of the first ionization, the solution will be able to absorb as much as 25mM of either acid or base before its buffering capacity is exhausted. The solution is thus judged to be "well buffered."

Problem 4: Additional rapid response to acidosis Continuing with the previous question, an additional rapid response to metabolic acidosis kicks in at or below pH 7.14, which is:

A. retention of OH- in the kidney. B. retaining HCO3- in the kidney. C. excreting H+ in the kidney. D. direct buffering action of the H2CO3 central intermediate. E. retaining CO2 in the lung. ANSWER: D In tissues at pH values below 7.14 (i.e., within one pH unit of the pKa), H+ ions are instantaneously absorbed by bicarbonate ion.

Problem 1: What is blood bicarbonate? Blood bicarbonate can be thought of as:

A. the ionized (deprotonated) form of carbonic acid, which is derived from CO2 and water. B. the protonated form of carbon dioxide. C. a transient species that cannot be measured in body fluids. D. being formed from hydrogen peroxide via the action of catalase. ANSWER: A This is true, despite the fact that carbonic acid is itself a transient species.

Problem 9: Hyperventilation A 19-year-old male presents to the emergency room with the following blood gases: Patient's Value Normal Value pH 7.55 7.35-7.45 pCO2 25 mm Hg 35-45 mm Hg [HCO3-] 22 mmol/liter 24-28 mmol/liter His companions report that he was "trying to set the world record for holding his breath underwater", but had fainted after hyperventilating for 15 minutes. What condition does this patient appear to have?

A. uncompensated respiratory alkalosis B. uncompensated metabolic alkalosis C. partially compensated respiratory alkalosis D. partially compensated metabolic alkalosis ANSWER: C The pCO2 value, which varies from normal in the opposite direction to pH, is the cue to a respiratory problem. The lowered HCO3- represents an attempt by the kidney to compensate, which is only partial in this case.

Production of Bicarbonate

Cells generate and excrete large quantities of carbon dioxide (CO2) during aerobic metabolism of glucose and fats. CO2 is subsequently converted to carbonic acid (H2CO3), which serves as the basis for the bicarbonate buffering system. Hence, the body is not dependent on ingestion of exogenous compounds or complex syntheses to maintain this buffering system.

TREATMENT

For respiratory problems caused by alterations in CO2, the best treatment involves ventilation. If bicarbonate is used to raise the pH in cases of respiratory acidosis, the result can be fatal, since compensation is also working to increase the blood bicarbonate concentration. For metabolic problems that involve HCO3-, the best treatment is either bicarbonate infusion (for acidosis) or NH4Cl infusion (for alkalosis). NH4Cl dissociates into NH4+ and Cl-. The NH4+ (ammonium ion) is in equilibrium with NH3 (ammonia) and H+. Because ammonia is volatile, it is respired through the lungs, leaving behind H+ and Cl- or hydrochloric acid, which lowers the pH. Often, metabolic acidosis is found in combination with respiratory alkalosis (e.g. compensated). This is a fragile situation because the buffering power is significantly reduced.

Movement into and out of cells

The acid components of the bicarbonate system (i.e. H+ and CO2) cross biological membranes rapidly, thus do not depend on complex transport kinetics. The base component (HCO3-), on the other hand, is transported rapidly in all cells via anion exchange. Consequently, the bicarbonate buffering system helps to maintain both intracellular and extracellular pH.

Role of other blood components

The acid components of the bicarbonate system are transported from the tissues to the lungs by hemoglobin. Thus, this important protein participates in both the production and removal of metabolic acid.

Removal of Bicarbonate

The bicarbonate buffering system is in volatile equilibrium (via breathing) with the external environment (lungs and air). Thus it is able to respond rapidly to endogenous alterations. It can also be affected, either positively or negatively, by environmental manipulation.

Question 5. More pH Calculations What is the pH of a 10 - 10 M solution of HCl?

The correct answer is: 7 Although -log [10 - 10] = 10, common sense dictates that a very small amount of acid does not make a solution basic. Rather, such a small concentration of H + ions (10 - 10 M) is far below the H + concentration for water (10 - 7 M), thus the pH remains at 7.

Clinical Correlates of pH Levels: Bicarbonate as a buffer

The major buffering systems in the body are proteins, particularly those with the amino acids histidine and cysteine exposed to the outside environment, phosphate, and bicarbonate. All three of these are weak acids with pKa values lower than physiological pH. As a consequence, buffering capacity increases as the pH is lowered from the physiological range. This meets the needs of most organisms because physiological pH excursions generally occur in the acid direction. Hence, the low pKa of these buffering systems is poised to respond to metabolic acidosis. Of these three, only the bicarbonate system, which is critical for buffering extracellular fluids such as blood, is in steady-state between production and removal. Thus, pH changes via this dynamic bicarbonate system are taking place on a background provided by the more static protein and phosphate systems.

respiratory alkalosis

hyperventilation, with a net loss of CO2 from the blood.

metabolic acidosis

ingestion of acid, production of ketoacids in uncontrolled diabetes, or kidney failure Note: These conditions all result in build-up of H+ from sources other than excess CO2.

metabolic alkalosis

ingestion of alkali, prolonged vomiting leading to a loss of HCl, or extreme dehydration leading to kidney retention of bicarbonate. Note: The common thread here is the loss of H+ for reasons other than depletion of CO2.