Acid-Base Balance Lecture # 5 Second class/ 2015
Terms Acid Any substance that can yield a hydrogen ion (H + ) or hydronium ion when dissolved in water Release of proton or H + Base Substance that can yield hydroxyl ions (OH - ) Accept protons or H +
Terms pk/ pka Negative log of the ionization constant of an acid Strong acids would have a pk <3 Strong base would have a pk >9 ph Negative log of the hydrogen ion concentration ph= pk + log([base]/[acid]) Represents the hydrogen concentration
Terms Buffer Combination of a weak acid and /or a weak base and its salt What does it do? Resists changes in ph Effectiveness depends on pk of buffering system ph of environment in which it is placed
Terms Acidosis ph less than 7.35 Alkalosis ph greater than 7.45 Note: Normal ph is 7.35-7.45
Acid-Base Balance Function Maintains ph homeostasis Maintenance of H + concentration Potential Problems of Acid-Base balance Increased H + concentration yields decreased ph Decreased H + concentration yields increased ph
Regulation of ph Direct relation of the production and retention of acids and bases Systems Respiratory Center and Lungs Kidneys Buffers Found in all body fluids Weak acids good buffers since they can tilt a reaction in the other direction Strong acids are poor buffers because they make the system more acid
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Blood Buffer Systems Why do we need them? If the acids produced in the body from the catabolism of food and other cellular processes are not removed or buffered, the body s ph would drop Significant drops in ph interferes with cell enzyme systems.
Blood Buffer Systems Four Major Buffer Systems Protein Buffer systems Amino acids Hemoglobin Buffer system Phosphate Buffer system Bicarbonate-carbonic acid Buffer system
Blood Buffer Systems Protein Buffer System Originates from amino acids ALBUMIN- primary protein due to high concentration in plasma Buffer both hydrogen ions and carbon dioxide
Blood Buffering Systems Hemoglobin Buffer System Roles Binds CO 2 Binds and transports hydrogen and oxygen Participates in the chloride shift Maintains blood ph as hemoglobin changes from oxyhemoglobin to deoxyhemoglobin
Blood Buffer Systems Phosphate Buffer System Has a major role in the elimination of H + via the kidney Assists in the exchange of sodium for hydrogen It participates in the following reaction HPO -2 4 + H + H 2 PO 4 Essential within the erythrocytes
Blood Buffer Systems Bicarbonate/carbonic acid buffer system Function almost instantaneously Cells that are utilizing O 2, produce CO 2, which builds up. Thus, more CO 2 is found in the tissue cells than in nearby blood cells. This results in a pressure (pco 2 ). Diffusion occurs, the CO 2 leaves the tissue through the interstitial fluid into the capillary blood
Bicarbonate/Carbonic Acid Buffer Conjugate base Carbonic acid Excreted by lungs Bicarbonate Excreted in urine
Bicarbonate/carbonic acid buffer system How is CO 2 transported? 5-8% transported in dissolved form A small amount of the CO 2 combines directly with the hemoglobin to form carbaminohemoglobin 92-95% of CO 2 will enter the RBC, and under the following reaction CO 2 + H 2 0 H + + HCO 3 - Once bicarbonate formed, exchanged for chloride
Henderson-Hasselbalch Equation Relationship between ph and the bicarbonate-carbonic acid buffer system in plasma Allows us to calculate ph
Henderson-Hasselbalch Equation General Equation ph = pk + log A - HA Bicarbonate/Carbonic Acid system o ph= pk + log HCO 3 H 2 CO 3 ( PCO 2 x 0.0301)
Henderson-Hasselbalch Equation 1. ph= pk+ log H HA 2. The pco 2 and the HCO 3 are read or derived from the blood gas analyzer pco 2 = 40 mmhg HCO 3- = 24 meq/l 3. Convert the pco 2 to make the units the same pco 2 = 40 mmhg * 0.03= 1.2 meq/l 3. Lets determine the ph: 4. Plug in pk of 6.1 5. Put the data in the formula ph = pk + log 24 meq/l 1.2 meq/l ph = pk + log 20 ph= pk+ 1.30 ph= 6.1+1.30 ph= 7.40
The Ratio. Normal is : 20 = Kidney = metabolic 1 Lungs respiratory The ratio of HCO 3- (salt) to H 2 CO 3 ( acid) is normally 20:1 Allows blood ph of 7.40 The ph falls (acidosis) as bicarbonate decreases in relation to carbonic acid The ph rises (alkalosis) as bicarbonate increases in relation to carbonic acid
Physiologic Buffer Systems Lungs/respiratory Quickest way to respond, takes minutes to hours to correct ph Eliminate volatile respiratory acids such as CO 2 Doesn t affect fixed acids like lactic acid Body ph can be adjusted by changing rate and depth of breathing blowing off Provide O 2 to cells and remove CO 2
Physiologic Buffer Systems Kidney/Metabolic Can eliminate large amounts of acid Can excrete base as well Can take several hours to days to correct ph Most effective regulator of ph If kidney fails, ph balance fails
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Acid-Base Balance Electrolytes that ionize in water and release hydrogen ions are acids; those that combine with hydrogen ions are bases. Sources of Hydrogen Ions Most hydrogen ions originate as by-products of metabolic processes, including: the aerobic and anaerobic respiration of glucose, incomplete oxidation of fatty acids, oxidation of amino acids containing sulfur, and the breakdown of phosphoproteins and nucleic acids. 24
Acidosis Acid-Base Imbalances Two major types of acidosis are respiratory and metabolic acidosis. Respiratory acidosis results from an increase of carbonic acid caused by respiratory center injury, air passage obstructions, or problems with gas exchange. Metabolic acidosis is due to either an accumulation of acids or a loss of bases and has many causes including kidney disease, vomiting, diarrhea, and diabetes mellitus. 25
Acid-Base Imbalances Increasing respiratory rate or the amount of hydrogen ions released by the kidney can help compensate for acidosis. 26
Alkalosis Acid-Base Imbalances Alkalosis also has respiratory and metabolic causes. Respiratory alkalosis results from hyperventilation causing an excessive loss of carbon dioxide. Metabolic alkalosis is caused by a great loss of hydrogen ions or a gain in base perhaps from vomiting or use of drugs. 27
The Bohr effect
The Bohr effect Learning outcome: To describe and explain the effects of raised carbon dioxide concentrations on the haemoglobin dissociation curve. To learn how carbon dioxide is transported in blood.
What determines the loading and unloading of oxygen by haemoglobin? The amount of oxygen that haemoglobin carries is affected by: 1) The partial pressure of oxygen and 2) The partial pressure of carbon dioxide High pc02 Haemoglobin releases oxygen The presence of a high partial pressure of carbon dioxide causes haemoglobin to release oxygen. This is called the Bohr effect
The Bohr effect 1. During respiration, CO 2 is produced. This diffuses into the blood plasma and into the red blood cells. 2. Inside the red blood cells are many molecules of an enzyme called carbonic anhydrase *. 3. It catalyses the reaction between CO 2 and H 2 O. H2O Red cell plasma CO 2 H 2 CO 3 * CO2 + H2O H2CO3 HCO3- + H+. carbon dioxide water 4. The resulting carbonic acid then dissociates into HCO 3- + H +. (Both reactions are reversible). carbonic acid HCO3-
The Bohr effect (continued) 5. Haemoglobin very readily combines with hydrogen ions forming haemoglobinic acid. 6. As a consequence haemoglobin releases some of the oxygen it is carrying. 7. By removing hydrogen ions from the solution, haemoglobin helps to maintain the ph of the blood close to neutral. It is acting as a buffer.
The Bohr effect Three Oxygen Dissociation curves illustrating the Bohr Effect. Increased carbon dioxide in the blood causes a right-shift in the curves, such that the haemoglobin more easily unloads the oxygen it is carrying.
Oxygen Dissociation Curve Curve B: Normal curve Curve A: Increased affinity for hgb, so oxygen keep close Curve C: Decreased affinity for hgb, so oxygen released to tissues
Bohr Effect It all about oxygen affinity!
Why is the Bohr effect useful? High concentrations of carbon dioxide are found in actively respiring tissues, which need oxygen. Due to the Bohr effect, these high carbon dioxide concentrations cause haemoglobin to release its oxygen even more readily than it would do otherwise.
How is carbon dioxide transported? Carbon dioxide is mostly carried as hydrogencarbonate ions in blood plasma, but also in combination with haemoglobin in red blood cells (carbamino-haemoglobin) and dissolved as carbon dioxide molecules in blood plasma.
Carbon dioxide transport About 5% of the CO 2 produced simply dissolves in the blood plasma. About 85% of the CO 2 produced by respiration diffuses into the red blood cells and forms carbonic acid under the control of carbonic anhydrase. The carbonic acid dissociates to produce hydrogencarbonate ions (HCO 3- ) The HCO3- diffuses out of the red blood cell into the plasma Some CO 2 diffuses into the red blood cells but instead of forming carbonic acid, attaches directly onto the haemoglobin molecules to form carbaminohaemoglobin. Since the CO 2 doesn t bind to the haem groups the Haemoglobin is still able to pick up O 2.
References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. Carreiro-Lewandowski, E. (2008). Blood Gas Analysis and Interpretation. Denver, Colorado: Colorado Association for Continuing Medical Laboratory Education, Inc. Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson. 39