Homeostasis

1. Homeostasis

2. Section 2: Acid-Base Balance Acid-base balance (H+ production = loss) Normal plasma pH: 7.35–7.45 H+ gains: many metabolic activities produce acids CO2 (to carbonic acid) from aerobic respiration Lactic acid from glycolysis H+ losses and storage Respiratory system eliminates CO2 H+ excretion from kidneys Buffers temporarily store H+

3. 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.

4. Section 2: Acid-Base Balance Classes of acids Fixed acids Do not leave solution Remain in body fluids until kidney excretion Examples: sulfuric and phosphoric acid Generated during catabolism of amino acids, phospholipids, and nucleic acids Organic acids Part of cellular metabolism Examples: lactic acid and ketones Most metabolized rapidly so no accumulation

5. Section 2: Acid-Base Balance Classes of acids (continued) Volatile acids Can leave body by external respiration Example: carbonic acid (H2CO3)

6. Module 24.5: Buffer systems pH imbalance ECH pH normally between 7.35 and 7.45 Acidemia (plasma pH <7.35): acidosis (physiological state) More common due to acid-producing metabolic activities Effects CNS function deteriorates, may cause coma Cardiac contractions grow weak and irregular Peripheral vasodilation causes BP drop Alkalemia (plasma pH >7.45): alkalosis (physiological state) Can be dangerous but relatively rare

7. Figure 24.5 1

8. 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.

9. Module 24.5: Buffer systems CO2 partial pressure effects on pH Most important factor affecting body pH H2O + CO2 H2CO3  H+ + HCO3– Reversible reaction that can buffer body pH Adjustments in respiratory rate can affect body pH

10. Figure 24.5 3 The inverse relationship between the PCO2 and pH PCO240–45mm Hg pH7.35–7.45 HOMEOSTASIS If PCO2 rises If PCO2 falls H2CO3 H2CO3 H2O  CO2 H2O  CO2 H HCO3 H HCO3 When the PCO2 falls, the reaction runs in reverse, andcarbonic acid dissociates into carbon dioxide andwater. This removes H ions from solution andincreases the pH. When carbon dioxide levels rise, more carbonic acidforms, additional hydrogen ions and bicarbonate ionsare released, and the pH goes down. pH PCO2 PCO2 pH

11. Module 24.5: Buffer systems Buffer Substance that opposes changes to pH by removing or adding H+ Generally consists of: Weak acid (HY) Anion released by its dissociation (Y–) HY  H+ + Y– and H+ + Y–  HY

12. Figure 24.5 4 H HY H H Y HY H Y H Y H HY H The reactions that occur when pH buffer systems function Adding H to thesolution upsets the equilibrium and resultsin the formation ofadditional molecules ofthe weak acid. Removing H from thesolution also upsets theequilibrium and results in the dissociation ofadditional molecules ofHY. This releases H. A buffer system in body fluids generallyconsists of a combination of a weak acid (HY) and the anion (Y) released by its dissociation.The anion functions as a weak base. In solution,molecules of the weak acid exist in equilibriumwith its dissociation products.

13. Module 24.5 Review a. Define acidemia and alkalemia. b. What is the most important factor affecting the pH of the ECF? c. Summarize the relationship between CO2 levels and pH.

14. Module 24.6: Major body buffer systems Three major body buffer systems All can only temporarily affect pH (H+ not eliminated) Phosphate buffer system Buffers pH of ICF and urine Carbonic acid–bicarbonate buffer system Most important in ECF Fully reversible Bicarbonate reserves (from NaHCO3 in ECF) contribute

15. Module 24.6: Major body buffer systems Three major body buffer systems (continued) Protein buffer systems (in ICF and ECF) Usually operate under acid conditions (bind H+) Binding to carboxyl group (COOH–) and amino group (—NH2) Examples: Hemoglobin buffer system CO2 + H2O  H2CO3  HCO3– + Hb-H+ Only intracellular system with immediate effects Amino acid buffers (all proteins) Plasma proteins

16. Figure 24.6 1 The body’s three major buffer systems Buffer Systems occur in Intracellular fluid (ICF) Extracellular fluid (ECF) Carbonic Acid–Bicarbonate Buffer System Phosphate BufferSystem Protein Buffer Systems Contribute to the regulation of pH in the ECF and ICF;interact extensively with the other two buffer systems Has an importantrole in buffering thepH of the ICF andof urine Is most important in theECF Amino acidbuffers(All proteins) Plasmaproteinbuffers Hemoglobinbuffer system(RBCs only)

17. 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

18. Figure 24.6 2 The events involved in the functioning of the hemoglobin buffer system Lungs Tissuecells Plasma Plasma Red blood cells Red blood cells Releasedwithexhalation H2O H2O CO2 H2CO3 CO2 H HCO3 Hb H2CO3 Hb H HCO3

19. Figure 24.6 3 The mechanism by free amino acids function inprotein buffer systems Start Increasing acidity (decreasing pH) Normal pH(7.35–7.45) At the normal pH ofbody fluids (7.35–7.45), the carboxylgroups of most amino acids have releasedtheir hydrogen ions. If pH drops, the carboxylate ion (COO)and the amino group (—NH2) of a freeamino acid can act as weak bases andaccept additional hydrogen ions, forming acarboxyl group (—COOH) and an aminoion (—NH3), respectively. Many of theR-groups can also accept hydrogen ions,forming RH.

20. Module 24.6: Major body buffer systems Disorders Metabolic acid-base disorders Production or loss of excessive amounts of fixed or organic acids Carbonic acid–bicarbonate system works to counter Respiratory acid-base disorders Imbalance of CO2 generation and elimination Must be corrected by depth and rate of respiration changes

21. Module 24.6 Review a. Identify the body’s three major buffer systems. b. Describe the carbonic acid–bicarbonate buffer system. c. Describe the roles of the phosphate buffer system.

22. Module 24.7: Metabolic acid-base disorders Metabolic acid-base disorders Metabolic acidosis Develops when large numbers of H+ are released by organic or fixed acids Accommodated by respiratory and renal responses Respiratory response Increased respiratory rate lowers PCO2 H+ + HCO3–  H2CO3  H2O + CO2 Renal response Occurs in PCT, DCT, and collecting system H2O + CO2 H2CO3  H+ + HCO3–  H+ secreted into urine  HCO3– reabsorbed into ECF

23. 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

24. Figure 24.7 2 The activity of renaltubule cells in CO2removal and HCO3production Steps in CO2 removal andHCO3 production Tubularfluid ECF Renal tubule cells CO2 generated by the tubulecell is added to the CO2diffusing into the cell fromthe urine and from the ECF. CO2 CO2H2O CO2 Carbonicanhydrase Na Carbonic anhydraseconverts CO2 and water tocarbonic acid, which then dissociates. H H2CO3 H H HCO3 HCO3 Cl The chloride ions exchangedfor bicarbonate ions areexcreted in the tubular fluid. H HCO3 Cl Na Bicarbonate ions andsodium ions are transportedinto the ECF, adding to thebicarbonate reserve.

25. Module 24.7: Metabolic acid-base disorders Metabolic alkalosis Develops when large numbers of H+ are removed from body fluids Rate of kidney H+ secretion declines Tubular cells do not reclaim bicarbonate Collecting system transports bicarbonate into urine and retains acid (HCl) in ECF

26. Module 24.7: Metabolic acid-base disorders Metabolic alkalosis (continued) Accommodated by respiratory and renal responses Respiratory response Decreased respiratory rate raises PCO2 H2O + CO2 H2CO3  H+ + HCO3– Renal response Occurs in PCT, DCT, and collecting system H2O + CO2 H2CO3  H+ + HCO3– HCO3– secreted into urine (in exchange for Cl–) H+ actively reabsorbed into ECF

27. 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

28. Figure 24.7 4 CO2 generated by the tubulecell is added to the CO2diffusing into the cell from thetubular fluid and from the ECF. The events in thesecretion of bicarbonateions into the tubularfluid along the PCT, DCT,and collecting system Tubularfluid ECF Renal tubule cells CO2H2O CO2 CO2 Carbonic anyhydrase convertsCO2 and water to carbonic acid, which then dissociates. Carbonicanhydrase H2CO3 The hydrogen ions are activelytransported into the ECF,accompanied by the diffusionof chloride ions. HCO3 H H HCO3 Cl Cl HCO3 is pumped into thetubular fluid in exchange forchloride ions that will diffuseinto the ECF.

29. Module 24.7 Review a. Describe metabolic acidosis. b. Describe metabolic alkalosis. c. lf the kidneys are conserving HCO3– and eliminating H+ in acidic urine, which is occurring: metabolic alkalosis or metabolic acidosis?

30. CLINICAL MODULE24.8: Respiratory acid-base disorders Respiratory acid-base disorders Respiratory acidosis CO2 generation outpaces rate of CO2 elimination at lungs Shifts bicarbonate buffer system toward generating more carbonic acid H2O + CO2 H2CO3  H+ + HCO3– HCO3– goes into bicarbonate reserve H+ must be neutralized by any of the buffer systems Respiratory (increased respiratory rate) Renal (H+ secreted and HCO3– reabsorbed) Proteins (bind free H+)

31. Figure 24.8 1 The events in respiratory acidosis CARBONIC ACID–BICARBONATEBUFFER SYSTEM BICARBONATE RESERVE CO2 H2CO2(carbonic acid) NaHCO3(sodium bicarbonate) H HCO3  Na  HCO3 CO2 H2O (bicarbonate ion) Lungs To limit the pH effects ofrespiratory acidosis, the excess H must either be tied up byother buffer systems or excreted at the kidneys. The underlyingproblem, however, cannot beeliminated without an increase inthe respiratory rate. When respiratory activity does not keeppace with the rate of CO2 generation,alveolar and plasma PCO2 increases.This upsets the equilibrium and drivesthe reaction to the right, generatingadditional H2CO3, which releases Hand lowers plasma pH. As bicarbonate ions and hydrogen ionsare released through the dissociation ofcarbonic acid, the excess bicarbonateions become part of the bicarbonatereserve.

32. Figure 24.8 2 Responses to Acidosis The integrated homeostatic responsesto respiratory acidosis Respiratory compensation Stimulation of arterial and CSFchemoreceptors results inincreased respiratory rate. IncreasedPCO2 Renal compensation H ions are secreted andHCO3 ions are generated. Combined Effects Respiratory Acidosis Decreased PCO2 Buffer systems other than thecarbonic acid–bicarbonatesystem accept H ions. Elevated PCO2 resultsin a fall in plasma pH Decreased H andincreased HCO3 HOMEOSTASISRESTORED HOMEOSTASISDISTURBED HOMEOSTASIS Hypoventilationcausing increased PCO2 Plasma pHreturns to normal Start Normal acid-base balance

33. CLINICAL MODULE24.8: Respiratory acid-base disorders Respiratory alkalosis CO2 elimination at lungs outpaces CO2 generation rate Shifts bicarbonate buffer system toward generating more carbonic acid H+ + HCO3–  H2CO3  H2O + CO2 H+ removed as CO2 exhaled and water formed Buffer system responses Respiratory (decreased respiratory rate) Renal (HCO3– secreted and H+ reabsorbed) Proteins (release free H+)

34. Figure 24.8 3 The events in respiratory alkalosis CARBONIC ACID–BICARBONATEBUFFER SYSTEM BICARBONATE RESERVE H2CO2(carbonic acid) HCO3  Na CO2 H  HCO3 NaHCO3(sodium bicarbonate) CO2 H2O (bicarbonate ion) Lungs If respiratory activity exceeds the rate of CO2generation, alveolar and plasma PCO2 decline,and this disturbs the equilibrium and drivesthe reactions to the left, removing H and elevating plasma pH. As bicarbonate ions and hydrogenions are removed in the formation ofcarbonic acid, the bicarbonate ions—but not the hydrogen ions—arereplaced by the bicarbonate reserve.

35. Figure 24.8 4 The integrated homeostatic responses torespiratory alkalosis HOMEOSTASIS Start HOMEOSTASISDISTURBED HOMEOSTASISRESTORED Normal acid-base balance Plasma pHreturns to normal Hyperventilationcausing decreased PCO2 Combined Effects Respiratory Alkalosis Responses to Alkalosis Increased PCO2 Lower PCO2 resultsin a rise in plasma pH Respiratory compensation Inhibition of arterial and CSFchemoreceptors results in adecreased respiratory rate. Increased H anddecreased HCO3 Renal compensation H ions are generated and HCO3 ions are secreted. DecreasedPCO2 Buffer systems other than thecarbonic acid–bicarbonate systemrelease H ions.

36. CLINICAL MODULE24.8 Review a. Define respiratory acidosis and respiratory alkalosis. b. What would happen to the plasma PCO2 of a patient who has an airway obstruction? c. How would a decrease in the pH of body fluids affect the respiratory rate?