1. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid-Base Balance

2. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid-Base Balance  Normal pH of body fluids  Arterial blood is 7.4  Venous blood and interstitial fluid is 7.35  Intracellular fluid is 7.0  Alkalosis or alkalemia – arterial blood pH rises above 7.45  Acidosis or acidemia – arterial pH drops below 7.35

3. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24.5 2 The narrow range of normal pH of the ECF, and the conditions that result from pH shifts outside the normal range The pH of the ECF (extracellular fluid) normally ranges from 7.35 to 7.45. pH When the pH of plasma falls below 7.5, acidemia exists. The physiological state that results is called acidosis. When the pH of plasma rises above 7.45, alkalemia exists. The physiological state that results is called alkalosis. Severe acidosis (pH below 7.0) can be deadly because (1) central nervous system function deteriorates, and the individual may become comatose; (2) cardiac contractions grow weak and irregular, and signs and symptoms of heart failure may develop; and (3) peripheral vasodilation produces a dramatic drop in blood pressure, potentially producing circulatory collapse. Severe alkalosis is also dangerous, but serious cases are relatively rare. Extremely acidic Extremely basic

4. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid–Base Balance - Hydrogen Ions (H + )  Are gained  At digestive tract  Through cellular metabolic activities  Are eliminated  At kidneys and in urine  Must be neutralized to avoid tissue damage  Acids produced in normal metabolic activity  Are temporarily neutralized by buffers in body fluids

5. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://www.nda.ox.ac.uk/wfsa/html/u13/u1312f05.htm

6. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings pH and enzyme function  Hydrogen ion concentration has a widespread effect on the function of the body's enzyme systems.  The hydrogen ion is highly reactive and will combine with bases or negatively charged ions at very low concentrations.  Proteins contain many negatively charged and basic groups within their structure.  Thus, a change in pH will alter the degree ionization of a protein, which may in turn affect its functioning.  At more extreme hydrogen ion concentrations a protein's structure may be completely disrupted (the protein is then said to be denatured).

7. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Sources of Hydrogen Ions  Most hydrogen ions originate from cellular metabolism  Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF  Anaerobic respiration of glucose produces lactic acid  Fat metabolism yields organic acids and ketone bodies  Transporting carbon dioxide as bicarbonate releases hydrogen ions

8. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Volatile acid comes from carbohydrate and fat metabolism  Can leave solution and enter the atmosphere (e.g. carbonic acid – H 2 CO 3 )  Breaks in the lungs to carbon dioxide and water  In the tissues CO 2 reacts with water to form carbonic acid, which dissociate to give hydrogen ions and bicarbonate ions  This reaction occurs spontaneously, but happens faster with the presence of carbonic anhydrase (CA)  P CO2 and pH are inversely related Types of acids in the body CO 2 + H 2 0 H 2 CO 3 HCO 3 - + H +

9. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Types of acids in the body  Fixed acids  Acids that do not leave solution (e.g. sulfuric and phosphoric acids – produced during catabolism of amino acids)  Eliminated by the kidneys  Organic acids  by-products of anerobic metabolism such as lactic acid, ketone bodies

10. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Buffers  Buffers - compound that limits the change in hydrogen ion concentration (and so pH) when hydrogen ions are added or removed from the solution. http://www.nda.ox.ac.uk/wfsa/html/u13/u1312f03.htm

11. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Buffer systems  Two types of buffer in the body  Chemical buffers  Bicarbonate, phosphate and protein systems  Substance that binds H + and remove it from the solution if its concentration rises or release it if concentration decreases  Fast reaction within seconds  Physiological  respiratory (fast reaction – few minutes) or urinary (slow reaction – hours to days)  Regulates pH by controlling the body’s output of bases, acids or CO 2

12. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid-Base Balance  Hydrogen ion and pH balance in the body Figure 20-18 Fatty acids Amino acids CO 2 (+ H 2 O) Lactic acid Ketoacids CO 2 (+ H 2 O) H + input H + output Plasma pH 7.38–7.42 Buffers: HCO 3 – in extracellular fluid Proteins, hemoglobin, phosphates in cells Phosphates, ammonia in urine H+H+

13. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 24 Section 2 1 The major factors involved in the maintenance of acid-base balance Active tissues continuously generate carbon dioxide, which in solution forms carbonic acid. Additional acids, such as lactic acid, are produced in the course of normal metabolic operations. Tissue cells Buffer Systems Normal plasma pH (7.35–7.45) Buffer systems can temporarily store H  and thereby provide short-term pH stability. The respiratory system plays a key role by eliminating carbon dioxide. The kidneys play a major role by secreting hydrogen ions into the urine and generating buffers that enter the bloodstream. The rate of excretion rises and falls as needed to maintain normal plasma pH. As a result, the normal pH of urine varies widely but averages 6.0—slightly acidic.

14. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Chemical Buffer Systems  Three major chemical buffer systems  Bicarbonate buffer system  Phosphate buffer system  Protein buffer system  Any drifts in pH are resisted by the entire chemical buffering system

15. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Bicarbonate Buffer System  A mixture of carbonic acid (H 2 CO 3 ) and its salt, sodium bicarbonate (NaHCO 3 ) (potassium or magnesium bicarbonates work as well)  If strong acid is added:  Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak acid)  The pH of the solution decreases only slightly  If strong base is added:  It reacts with the carbonic acid to form sodium bicarbonate (a weak base)  The pH of the solution rises only slightly  This system is the only important ECF buffer CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 ¯

16. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 27-9 The Basic Relationship between P CO 2 and Plasma pH P CO 2 40–45 mm Hg HOMEOSTASIS If P CO 2 rises When carbon dioxide levels rise, more carbonic acid forms, additional hydrogen ions and bicarbonate ions are released, and the pH goes down. P CO 2 pH H2OH2O  CO 2 H 2 CO 3 HCO 3  HH 

17. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 27-9 The Basic Relationship between P CO 2 and Plasma pH pH P CO 2 When the P CO 2 falls, the reaction runs in reverse, and carbonic acid dissociates into carbon dioxide and water. This removes H  ions from solution and increases the pH. pH 7.35–7.45 HOMEOSTASIS If P CO 2 falls HH  HCO 3  H 2 CO 3 H2OH2OCO 2 

18. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Phosphate Buffer System  Nearly identical to the bicarbonate system  Its components are:  Sodium salts of dihydrogen phosphate (H 2 PO 4 ¯ ), a weak acid  Monohydrogen phosphate (HPO 4 2¯ ), a weak base  This system is an effective buffer in urine and intracellular fluid

19. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Protein Buffer System  Plasma and intracellular proteins are the body’s most plentiful and powerful buffers  Some amino acids of proteins have:  Free organic acid groups (weak acids)  Groups that act as weak bases (e.g., amino groups)  Amphoteric molecules are protein molecules that can function as both a weak acid and a weak base

20. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 27-11 The Role of Amino Acids in Protein Buffer Systems Neutral pH If pH fallsIf pH rises Amino acid In alkaline medium, amino acid acts as an acid and releases H  In acidic medium, amino acid acts as a base and absorbs H 

21. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Buffer Systems in Body Fluids Figure 27.7

22. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physiological Buffer Systems – respiratory system  The respiratory system regulation of acid-base balance is a physiological buffering system  The respiratory buffering system takes care of volatile acids – by-products of glucose and fat metabolism CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 ¯

23. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physiological Buffer Systems – respiratory system  During carbon dioxide unloading, hydrogen ions are incorporated into water  When hypercapnia or rising plasma H + occurs:  Deeper and more rapid breathing expels more carbon dioxide  Hydrogen ion concentration is reduced  Alkalosis causes slower, more shallow breathing, causing H + to increase

24. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings pH Disturbances  The reflex pathway for respiratory compensation of metabolic acidosis Figure 20-19 Respiratory control centers in the medulla Plasma H + ( pH) Plasma P CO 2 Carotid and aortic chemoreceptors Central chemoreceptors Plasma P CO 2 Plasma H + ( pH) by Law of Mass Action Action potentials in somatic motor neurons Muscles of ventilation Rate and depth of breathing Negative feedback Sensory neuron Interneuron

25. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physiological Buffer Systems – kidneys  Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body  The lungs can eliminate carbonic acid by eliminating carbon dioxide  Only the kidneys can excrete the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis  The ultimate acid-base regulatory organs are the kidneys

26. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physiological Buffer Systems – kidneys  The kidney takes care of the non-volatile acid products  By-products of protein metabolism and anaerobic respiration  The kidneys must prevent the loss of bicarbonate ions (re- absorb) that is being constantly filtered from the blood.  Both tasks are accomplished by secretion of hydrogen ions  Only about 10% of the hydrogen ions secreted will be excreted  As a result of the H+ excretion the urine is usually acidic

27. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Renal compensation when pH is low  When H+ or PCO2 in plasma is high – acidosis  The kidneys will:  Secrete H+ in nephron and excretion will increase  All the filtered HCO3- will be reabsorbed  Produce HCO3- to increase its blood levels

28. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Renal Compensation  Hydrogen Ions  Are secreted into tubular fluid along:  Proximal convoluted tubule (PCT)  Distal convoluted tubule (DCT)  Collecting system

29. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Renal Compensation  The ability to eliminate large numbers of H + in a normal volume of urine depends on the presence of buffers in urine  Major Buffers in Urine  Glomerular filtration provides components of:  Carbonic acid–bicarbonate buffer system  Phosphate buffer system  Tubule cells of PCT  Generate ammonia

30. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Reabsorption of Bicarbonate  In a person with normal acid-base balance all the HCO 3 - in the tubular fluid is consumed by neutralizing H + - no HCO 3 - in the urine  HCO 3 - molecules are filtered by the glomerulus and than reabsorbed and appear in the peritubular capillary (most in the PCT).  The re-absorption is not direct – the luminar surface of the tubular cells can not absorb HCO 3 -  The kidney cells can also generate new HCO 3 - if needed

31. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Renal compensation when pH is high  When H+ or PCO2 in plasma is low – alkalosis  The kidneys will:  Inhibit secretion of H+ in nephron and excretion will decrease  Reduced HCO3- reabsorption; will appear in urine and level in plasma decrease

32. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid–Base Balance Disturbances  Respiratory Acid–Base Disorders  Result from imbalance between:  CO 2 generation in peripheral tissues  CO 2 excretion at lungs  Cause abnormal CO 2 levels in ECF  Metabolic Acid–Base Disorders  Result from:  Generation of organic or fixed acids  Conditions affecting HCO 3 - concentration in ECF

33. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Respiratory Acidosis and Alkalosis  Result from failure of the respiratory system to balance pH  P CO2 is the most important indicator of respiratory inadequacy  P CO2 levels  Normal P CO2 fluctuates between 35 and 45 mm Hg  Values above 45 mm Hg signal respiratory acidosis  Values below 35 mm Hg indicate respiratory alkalosis

34. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Respiratory Acidosis and Alkalosis  Respiratory acidosis is the most common cause of acid-base imbalance  Occurs when a person breathes shallowly, or gas exchange is slowed down by diseases such as pneumonia, cystic fibrosis, or emphysema  Respiratory alkalosis is a common result of hyperventilation

35. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Metabolic Acidosis  Metabolic acidosis is the second most common cause of acid-base imbalance  Can be a result of:  Failure of the kidney to excrete metabolic acids  Renal acidosis is either the inability of kidney to excrete H+ or to re- absorb bicarbonate ion  Diarrhea – most common reason of metabolic acidosis  Loss of large amounts of sodium bicarbonate in the feces (which is normal component of the feces)  Diabetes mellitus – results in breakdown of fat that releases acids  Ingestion of acids  Acetylsalicylic acid (aspirin)  Methyl alcohol (forms acid when metabolized)

36. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Metabolic Alkalosis  Is caused by elevated HCO 3 – concentrations  Bicarbonate ions interact with H + in solution  Forming H 2 CO 3  Reduced H + causes alkalosis  Typical causes are:  Vomiting of the acid contents of the stomach  Intake of excess base (e.g., from antacids)  Constipation, in which excessive bicarbonate is reabsorbed

37. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Acid-base imbalances  To be able to assess the type of imbalance:  1. look at the pH – to decide acidosis/alkalosis  2. look at PCO2 and HCO3- to decide respiratory/metabolic  If PCO2 causes the acidosis/alkalosis – it is respiratory  If HCO3- causes the acidosis/alkalosis – it is metabolic

38. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings To determine compensation:  Uncompensated= abnormal pH and change in one blood parameter  Partially compensated= all 3 values of pH, HCO3-, CO2 are abnormal  Fully compensated= pH is normal, both HCO3- and CO2 are abnormal  Corrected= all parameters are normal

39. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The response to acidosis caused by the addition of H  Addition of H  Start (carbonic acid) (bicarbonate ion) HH Other buffer systems absorb H  KIDNEYS Increased respiratory rate lowers P CO 2, effectively converting carbonic acid molecules to water. Lungs CO 2 CO 2  H 2 O Respiratory Response to Acidosis Secretion of H  H 2 CO 3 HCO 3    Na  BICARBONATE RESERVE NaHCO 3 Generation of HCO 3  Renal Response to Acidosis (sodium bicarbonate) Kidney tubules respond by (1) secreting H  ions, (2) removing CO 2, and (3) reabsorbing HCO 3  to help replenish the bicarbonate reserve. CARBONIC ACID-BICARBONATE BUFFER SYSTEM

40. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings BICARBONATE RESERVE Removal of H  HH (carbonic acid) (bicarbonate ion) H 2 CO 3 HCO 3   Other buffer systems release H  Generation of H  Secretion of HCO 3  KIDNEYS H2OH2OCO 2  Lungs Respiratory Response to Alkalosis Decreased respiratory rate elevates P CO 2, effectively converting CO 2 molecules to carbonic acid. Renal Response to Alkalosis HCO 3  NaHCO 3 Na   (sodium bicarbonate) Kidney tubules respond by conserving H  ions and secreting HCO 3 . The response to alkalosis caused by the removal of H  Start CARBONIC ACID-BICARBONATE BUFFER SYSTEM

41. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm

42. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings http://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm