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Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

Table 27-3 A Review of Important Terms Relating to Acid–Base Balance. 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

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Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

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  1. Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

  2. 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. 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 from7.35 to 7.45. When the pH of plasma falls below7.5, acidemia exists. Thephysiological state that results iscalled acidosis. When the pH of plasma risesabove 7.45, alkalemia exists.The physiological state thatresults is called alkalosis. Extremelyacidic Extremelybasic pH Severe acidosis (pH below 7.0) can be deadlybecause (1) central nervous system functiondeteriorates, and the individual may becomecomatose; (2) cardiac contractions grow weak andirregular, and signs and symptoms of heart failuremay develop; and (3) peripheral vasodilationproduces a dramatic drop in blood pressure,potentially producing circulatory collapse. Severe alkalosis is alsodangerous, but serious casesare relatively rare.

  4. 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).

  5. 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

  6. CO2 + H20 H2CO3 HCO3- + H+ Types of acids in the body • Volatile acidcomes from carbohydrate and fat metabolism • Can leave solution and enter the atmosphere (e.g. carbonic acid – H2CO3) • Breaks in the lungs to carbon dioxide and water • In the tissues CO2 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) • PCO2 and pH are inversely related

  7. 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

  8. Acid-Base Balance • Hydrogen ion and pH balance in the body CO2 (+ H2O)Lactic acidKetoacids Fatty acidsAmino acids H+ input Plasma pH7.38–7.42 Buffers:• HCO3– in extracellular fluid• Proteins, hemoglobin, phosphates in cells• Phosphates, ammonia in urine CO2 (+ H2O) H+ output H+ Figure 20-18

  9. 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

  10. 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 CO2

  11. Figure 24 Section 2 1 The major factors involved in the maintenanceof acid-base balance The respiratory systemplays a key role byeliminatingcarbon dioxide. The kidneys play a majorrole by secretinghydrogen ions into the urine and generatingbuffers that enter thebloodstream. The rate ofexcretion rises and fallsas needed to maintainnormal plasma pH. As a result, the normal pH ofurine varies widely butaverages 6.0—slightlyacidic. Active tissuescontinuously generatecarbon dioxide, which insolution forms carbonicacid. Additional acids,such as lactic acid, areproduced in the course ofnormal metabolicoperations. Normalplasma pH(7.35–7.45) Tissue cells Buffer Systems Buffer systems cantemporarily store Hand thereby provideshort-term pHstability.

  12. 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

  13. Bicarbonate Buffer System • A mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3) (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 CO2 + H2O  H2CO3 H+ + HCO3¯

  14. Figure 24.6 4 BICARBONATE RESERVE The reactions of the carbonic acid–bicarbonate buffer system Body fluids contain a large reserve ofHCO3, primarily in the form of dissolvedmolecules of the weak base sodiumbicarbonate (NaHCO3). This readilyavailable supply of HCO3 is known asthe bicarbonate reserve. CARBONIC ACID–BICARBONATEBUFFER SYSTEM NaHCO3(sodium bicarbonate) CO2 H2CO3(carbonic acid) H CO2 H2O  HCO3 HCO3  Na (bicarbonate ion) Lungs The primary function of the carbonicacid–bicarbonate buffer system is toprotect against the effects of the organicand fixed acids generated throughmetabolic activity. In effect, it takes the Hreleased by these acids and generatescarbonic acid that dissociates into waterand carbon dioxide, which can easily be eliminated at the lungs. Addition of Hfrom metabolicactivity Start

  15. Figure 27-9 The Basic Relationship between PCO2 and Plasma pH H2O CO2 H2CO3 H HCO3   PCO2 40–45 mm Hg HOMEOSTASIS If PCO2rises When carbon dioxide levels rise, more carbonic acid forms, additional hydrogen ions and bicarbonate ions are released, and the pH goes down. PCO2 pH

  16. Figure 27-9 The Basic Relationship between PCO2 and Plasma pH H HCO3 H2CO3 H2O CO2   pH 7.35–7.45 HOMEOSTASIS If PCO2falls When the PCO2 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 PCO2

  17. Phosphate Buffer System • Nearly identical to the bicarbonate system • Its components are: • Sodium salts of dihydrogen phosphate (H2PO4¯), a weak acid • Monohydrogen phosphate (HPO42¯), a weak base • This system is an effective buffer in urine and intracellular fluid

  18. 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

  19. Figure 27-11 The Role of Amino Acids in Protein Buffer Systems Neutral pH If pH rises If pH falls 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

  20. Buffer Systems in Body Fluids Figure 27.7

  21. Figure 27-10 Buffer Systems in Body Fluids Buffer Systems occur in Extracellular fluid (ECF) Intracellular fluid (ICF) Carbonic Acid– Bicarbonate Buffer System Phosphate Buffer System Protein Buffer Systems Protein buffer systems contribute to the regulation of pH in the ECF and ICF. These buffer systems interact extensively with the other two buffer systems. The phosphate buffer system has an important role in buffering the pH of the ICF and of urine. The carbonic acid– bicarbonate buffer system is most important in the ECF. Amino acid buffers (All proteins) Hemoglobin buffer system (RBCs only) Plasma protein buffers

  22. 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 CO2 + H2O  H2CO3 H+ + HCO3¯

  23. 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. 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

  25. 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

  26. Reabsorption of Bicarbonate • In a person with normal acid-base balance all the HCO3- in the tubular fluid is consumed by neutralizing H+ - no HCO3- in the urine • HCO3- 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 HCO3- • The kidney cells can also generate new HCO3- if needed

  27. Reabsorption of Bicarbonate Figure 26.12

  28. Buffers in Urine • The ability to eliminate large numbers of H+ in a normal volume of urine depends on the presence of buffers in urine • Carbonic acid–bicarbonate buffer system • Phosphate buffer system • Ammonia buffer system

  29. Figure 27-13a Kidney Tubules and pH Regulation The three major buffering systems in tubular fluid, which are essential to the secretion of hydrogen ions Cells of PCT, DCT, and collecting system Carbonic acid–bicarbonate buffer system Phosphate buffer system Ammonia buffer system Peritubular fluid Peritubular capillary KEY  Countertransport  Reabsorption  Active transport  Secretion  Exchange pump  Diffusion  Cotransport

  30. Renal Responses to Acidosis • Secretion of H+ • Activity of buffers in tubular fluid • Removal of CO2 • Reabsorption of NaHCO3–

  31. Renal Responses to Alkalosis • Rate of secretion at kidneys declines • Tubule cells do not reclaim bicarbonates in tubular fluid • Collecting system transports HCO3– into tubular fluid while releasing strong acid (HCl) into peritubular fluid

  32. Figure 27-13c Kidney Tubules and pH Regulation The response of the kidney tubule to alkalosis Tubular fluid in lumen Carbonic anhydrase KEY  Countertransport  Reabsorption  Active transport  Secretion  Exchange pump  Diffusion  Cotransport

  33. Acid–Base Balance Disturbances • Respiratory Acid–Base Disorders • Result from imbalance between: • CO2 generation in peripheral tissues • CO2 excretion at lungs • Cause abnormal CO2 levels in ECF • Metabolic Acid–Base Disorders • Result from: • Generation of organic or fixed acids • Conditions affecting HCO3- concentration in ECF

  34. Respiratory Acidosis and Alkalosis • Result from failure of the respiratory system to balance pH • PCO2 is the most important indicator of respiratory inadequacy • PCO2 levels • Normal PCO2 fluctuates between 35 and 45 mm Hg • Values above 45 mm Hg signal respiratory acidosis • Values below 35 mm Hg indicate respiratory alkalosis

  35. 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

  36. Figure 27-15a Respiratory Acid–Base Regulation Responses to Acidosis Respiratory compensation: Stimulation of arterial and CSF chemo- receptors results in increased respiratory rate. Increased PCO2 Renal compensation: Combined Effects H ions are secreted and HCO3 ions are generated. Decreased PCO2 Respiratory Acidosis Elevated PCO2 results in a fall in plasma pH Buffer systems other than the carbonic acid–bicarbonate system accept H ions. Decreased H and increased HCO3 HOMEOSTASIS RESTORED HOMEOSTASIS DISTURBED HOMEOSTASIS Hypoventilation causing increased PCO2 Plasma pH returns to normal Normal acid–base balance Respiratory acidosis

  37. Figure 27-15b Respiratory Acid–Base Regulation HOMEOSTASIS HOMEOSTASIS DISTURBED HOMEOSTASIS RESTORED Normal acid–base balance Plasma pH returns to normal Hyperventilation causing decreased PCO2 Respiratory Alkalosis Combined Effects Responses to Alkalosis Lower PCO2 results in a rise in plasma pH Increased PCO2 Respiratory compensation: Inhibition of arterial and CSF chemoreceptors results in a decreased respiratory rate. Increased H and decreased HCO3 Renal compensation: H ions are generated and HCO3 ions are secreted. Decreased PCO2 Buffer systems other than the carbonic acid–bicarbonate system release H ions. Respiratory alkalosis

  38. 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)

  39. Metabolic Alkalosis • Is caused by elevated HCO3–concentrations • Bicarbonate ions interact with H+ in solution • Forming H2CO3 • 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

  40. Figure 24.7 1 The responses to metabolic acidosis Additionof H Start CARBONIC ACID–BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE HCO3  Na CO2 H2O CO2 H2CO3(carbonic acid) H NaHCO3(sodium bicarbonate)  HCO3 (bicarbonate ion) Lungs Generationof HCO3 Otherbuffersystemsabsorb H KIDNEYS Respiratory Responseto Acidosis Renal Response to Acidosis Increased respiratoryrate lowers PCO2,effectively convertingcarbonic acid moleculesto water. Kidney tubules respond by (1) secreting Hions, (2) removing CO2, and (3) reabsorbingHCO3 to help replenish the bicarbonatereserve. Secretionof H

  41. Figure 24.7 3 The responses to metabolic alkalosis Removalof H Start CARBONIC ACID–BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE Lungs HCO3  Na H2CO3(carbonic acid) H NaHCO3(sodium bicarbonate) CO2 H2O  HCO3 (bicarbonate ion) Generationof H Otherbuffersystemsrelease H Respiratory Responseto Alkalosis KIDNEYS Decreased respiratoryrate elevates PCO2,effectively convertingCO2 molecules tocarbonic acid. Renal Response to Alkalosis Kidney tubules respond byconserving H ions and secreting HCO3. Secretionof HCO3

  42. Table 27-4 Changes in Blood Chemistry Associated with the Major Classes of Acid–Base Disorders

  43. Acid-Base Balance Table 20-2

  44. The response to acidosis caused by the addition of H Addition of H Start CARBONIC ACID-BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE H2CO3 HCO3 Na CO2 CO2 H2O HCO3  NaHCO3  H (bicarbonate ion) (carbonic acid) (sodium bicarbonate) Lungs Generation of HCO3 Other buffer systems absorb H KIDNEYS Respiratory Response to Acidosis Renal Response to Acidosis Increased respiratory rate lowers PCO2, effectively converting carbonic acid molecules to water. Kidney tubules respond by (1) secreting H ions, (2) removing CO2, and (3) reabsorbing HCO3 to help replenish the bicarbonate reserve. Secretion of H

  45. The response to alkalosis caused by the removal of H Removal of H Start CARBONIC ACID-BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE Lungs  HCO3 Na CO2 H2O H2CO3 HCO3 NaHCO3  H  (bicarbonate ion) (sodium bicarbonate) (carbonic acid) Generation of H Other buffer systems release H Respiratory Response to Alkalosis KIDNEYS Decreased respiratory rate elevates PCO2, effectively converting CO2 molecules to carbonic acid. Renal Response to Alkalosis Kidney tubules respond by conserving H ions and secreting HCO3. Secretion of HCO3

  46. http://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm

  47. http://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm

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