2 Section 2: Acid-Base Balance Acid-base balance (H+ production = loss)Normal plasma pH: 7.35–7.45H+ gains: many metabolic activities produce acidsCO2 (to carbonic acid) from aerobic respirationLactic acid from glycolysisH+ losses and storageRespiratory system eliminates CO2H+ excretion from kidneysBuffers temporarily store H+
3 The major factors involved in the maintenance of acid-base balance 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.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.Normal plasma pH (7.35–7.45)Tissue cellsFigure 24 Section 2.1 Acid-Base BalanceBuffer SystemsBuffer systems can temporarily store H and thereby provide short-term pH stability.Figure 24 Section3
4 Section 2: Acid-Base Balance Classes of acidsFixed acidsDo not leave solutionRemain in body fluids until kidney excretionExamples: sulfuric and phosphoric acidGenerated during catabolism of amino acids, phospholipids, and nucleic acidsOrganic acidsPart of cellular metabolismExamples: lactic acid and ketonesMost metabolized rapidly so no accumulation
5 Section 2: Acid-Base Balance Classes of acids (continued)Volatile acidsCan leave body by external respirationExample: carbonic acid (H2CO3)
6 Module 24.5: Buffer systems pH imbalanceECH pH normally between 7.35 and 7.45Acidemia (plasma pH <7.35): acidosis (physiological state)More common due to acid-producing metabolic activitiesEffectsCNS function deteriorates, may cause comaCardiac contractions grow weak and irregularPeripheral vasodilation causes BP dropAlkalemia (plasma pH >7.45): alkalosis (physiological state)Can be dangerous but relatively rare
7 Figure 24.5.1 Potentially dangerous disturbances in acid-base balance are opposed by buffer systems 7
8 Extremely acidic Extremely basic The narrow range of normal pH of the ECF, and the conditions that result from pH shifts outside the normal rangeThe pH of the ECF (extracellular fluid) normally ranges from 7.35 to 7.45.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.Extremely acidicExtremely basicpHFigure Potentially dangerous disturbances in acid-base balance are opposed by buffer systemsSevere 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.Figure8
9 Module 24.5: Buffer systems CO2 partial pressure effects on pHMost important factor affecting body pHH2O + CO2 H2CO3 H+ + HCO3–Reversible reaction that can buffer body pHAdjustments in respiratory rate can affect body pH
10 The inverse relationship between the PCO2 and pH PCO2 40–45 mm HgpH 7.35–7.45HOMEOSTASISIf PCO2 risesIf PCO2 fallsH2O CO2H2CO3H HCO3H HCO3H2CO3H2O CO2When carbon dioxide levels rise, more carbonic acid forms, additional hydrogen ions and bicarbonate ions are released, and the pH goes down.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.Figure Potentially dangerous disturbances in acid-base balance are opposed by buffer systemsPCO2pHpHPCO2Figure10
11 Module 24.5: Buffer systems 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 The reactions that occur when pH buffer systems function A buffer system in body fluids generally consists 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 equilibrium with its dissociation products.Adding H to the solution upsets the equilibrium and results in the formation of additional molecules of the weak acid.Removing H from the solution also upsets the equilibrium and results in the dissociation of additional molecules of HY. This releases H.H YHH HYH HYHH YHYH YFigure Potentially dangerous disturbances in acid-base balance are opposed by buffer systemsFigure12
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 systemsAll can only temporarily affect pH (H+ not eliminated)Phosphate buffer systemBuffers pH of ICF and urineCarbonic acid–bicarbonate buffer systemMost important in ECFFully reversibleBicarbonate 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 systemCO2 + H2O H2CO3 HCO3– + Hb-H+Only intracellular system with immediate effectsAmino acid buffers (all proteins)Plasma proteins
16 Buffer Systems The body’s three major buffer systems occur inIntracellular fluid (ICF)Extracellular fluid (ECF)Phosphate Buffer SystemProtein Buffer SystemsCarbonic Acid– Bicarbonate Buffer SystemContribute to the regulation of pH in the ECF and ICF; interact extensively with the other two buffer systemsHas an important role in buffering the pH of the ICF and of urineIs most important in the ECFFigure Buffer systems can delay but not prevent pH shifts in the ICF and ECFHemoglobin buffer system (RBCs only)Amino acid buffers (All proteins)Plasma protein buffersFigure16
17 CARBONIC ACID–BICARBONATE BUFFER SYSTEM The reactions of the carbonic acid–bicarbonate buffer systemBICARBONATE RESERVEBody fluids contain a large reserve of HCO3, primarily in the form of dissolved molecules of the weak base sodium bicarbonate (NaHCO3). This readily available supply of HCO3 is known as the bicarbonate reserve.CARBONIC ACID–BICARBONATE BUFFER SYSTEMCO2CO2 H2OH2CO3 (carbonic acid)H HCO3HCO3 NaNaHCO3 (sodium bicarbonate)(bicarbonate ion)LungsThe primary function of the carbonic acid–bicarbonate buffer system is to protect against the effects of the organic and fixed acids generated through metabolic activity. In effect, it takes the H released by these acids and generates carbonic acid that dissociates into water and carbon dioxide, which can easily be eliminated at the lungs.Figure Buffer systems can delay but not prevent pH shifts in the ICF and ECFAddition of H from metabolic activityStartFigure17
18 Released with exhalation The events involved in the functioning of the hemoglobin buffer systemTissue cellsPlasmaPlasmaLungsRed blood cellsRed blood cellsReleased with exhalationH2OH2OCO2H2CO3HCO3 HbHHbH HCO3H2CO3CO2Figure Buffer systems can delay but not prevent pH shifts in the ICF and ECFFigure18
19 The mechanism by free amino acids function in protein buffer systems StartIncreasing acidity (decreasing pH)Normal pH (7.35–7.45)At the normal pH of body fluids (7.35– 7.45), the carboxyl groups of most aminoacids have released their hydrogen ions.If pH drops, the carboxylate ion (COO) and the amino group (—NH2) of a free amino acid can act as weak bases and accept additional hydrogen ions, forming a carboxyl group (—COOH) and an amino ion (—NH3), respectively. Many of the R-groups can also accept hydrogen ions, forming RH.Figure Buffer systems can delay but not prevent pH shifts in the ICF and ECFFigure19
20 Module 24.6: Major body buffer systems DisordersMetabolic acid-base disordersProduction or loss of excessive amounts of fixed or organic acidsCarbonic acid–bicarbonate system works to counterRespiratory acid-base disordersImbalance of CO2 generation and eliminationMust 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 acidosisDevelops when large numbers of H+ are released by organic or fixed acidsAccommodated by respiratory and renal responsesRespiratory responseIncreased respiratory rate lowers PCO2H+ + HCO3– H2CO3 H2O + CO2Renal responseOccurs in PCT, DCT, and collecting systemH2O + CO2 H2CO3 H+ + HCO3– H+ secreted into urine HCO3– reabsorbed into ECF
23 NaHCO3 (sodium bicarbonate) Other buffer systems absorb H The responses to metabolic acidosisAddition of HStartCARBONIC ACID–BICARBONATE BUFFER SYSTEMBICARBONATE RESERVECO2CO2 H2OH2CO3 (carbonic acid)H HCO3HCO3 NaNaHCO3 (sodium bicarbonate)(bicarbonate ion)LungsGeneration of HCO3Respiratory Response to AcidosisOther buffer systems absorb HKIDNEYSRenal Response to AcidosisIncreased respiratory rate lowers PCO2, effectively converting carbonic acid molecules to water.Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systemsKidney tubules respond by (1) secreting H ions, (2) removing CO2, and (3) reabsorbing HCO3 to help replenish the bicarbonate reserve.Secretion of HFigure23
24 The activity of renal tubule cells in CO2 removal and HCO3 production Tubular fluidRenal tubule cellsECFSteps in CO2 removal and HCO3 productionCO2 generated by the tubule cell is added to the CO2 diffusing into the cell from the urine and from the ECF.CO2CO2 H2OCO2Carbonic anhydraseNaCarbonic anhydrase converts CO2 and water to carbonic acid, which then dissociates.HH2CO3HHHCO3HCO3ClThe chloride ions exchanged for bicarbonate ions are excreted in the tubular fluid.HClHCO3NaBicarbonate ions and sodium ions are transported into the ECF, adding to the bicarbonate reserve.Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systemsFigure24
25 Module 24.7: Metabolic acid-base disorders Metabolic alkalosisDevelops when large numbers of H+ are removed from body fluidsRate of kidney H+ secretion declinesTubular cells do not reclaim bicarbonateCollecting 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 responsesRespiratory responseDecreased respiratory rate raises PCO2H2O + CO2 H2CO3 H+ + HCO3–Renal responseOccurs in PCT, DCT, and collecting systemHCO3– secreted into urine (in exchange for Cl–)H+ actively reabsorbed into ECF
27 NaHCO3 (sodium bicarbonate) Other buffer systems release H The responses to metabolic alkalosisRemoval of HStartCARBONIC ACID–BICARBONATE BUFFER SYSTEMBICARBONATE RESERVELungsCO2 H2OH2CO3 (carbonic acid)H HCO3HCO3 NaNaHCO3 (sodium bicarbonate)(bicarbonate ion)Generation of HRespiratory Response to AlkalosisOther buffer systems release HKIDNEYSDecreased respiratory rate elevates PCO2, effectively converting CO2 molecules to carbonic acid.Renal Response to AlkalosisFigure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systemsKidney tubules respond by conserving H ions and secreting HCO3.Secretion of HCO3Figure27
28 CO2 generated by the tubule cell is added to the CO2 diffusing into the cell from the tubular fluid and from the ECF.The events in the secretion of bicarbonate ions into the tubular fluid along the PCT, DCT, and collecting systemTubular fluidRenal tubule cellsECFCO2CO2 H2OCO2Carbonic anyhydrase converts CO2 and water to carbonic acid, which then dissociates.Carbonic anhydraseH2CO3HCO3HCO3HHThe hydrogen ions are actively transported into the ECF, accompanied by the diffusion of chloride ions.ClClFigure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systemsHCO3 is pumped into the tubular fluid in exchange for chloride ions that will diffuse into the ECF.Figure28
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 MODULE 24.8: Respiratory acid-base disorders Respiratory acidosisCO2 generation outpaces rate of CO2 elimination at lungsShifts bicarbonate buffer system toward generating more carbonic acidH2O + CO2 H2CO3 H+ + HCO3–HCO3– goes into bicarbonate reserveH+ must be neutralized by any of the buffer systemsRespiratory (increased respiratory rate)Renal (H+ secreted and HCO3– reabsorbed)Proteins (bind free H+)
31 CARBONIC ACID–BICARBONATE BUFFER SYSTEM NaHCO3 (sodium bicarbonate) The events in respiratory acidosisCARBONIC ACID–BICARBONATE BUFFER SYSTEMBICARBONATE RESERVECO2CO2 H2OH2CO2 (carbonic acid)H HCO3HCO3 NaNaHCO3 (sodium bicarbonate)(bicarbonate ion)LungsWhen respiratory activity does not keep pace with the rate of CO2 generation, alveolar and plasma PCO2 increases. This upsets the equilibrium and drives the reaction to the right, generating additional H2CO3, which releases H and lowers plasma pH.To limit the pH effects of respiratory acidosis, the excess H must either be tied up by other buffer systems or excreted at the kidneys. The underlying problem, however, cannot be eliminated without an increase in the respiratory rate.As bicarbonate ions and hydrogen ions are released through the dissociation of carbonic acid, the excess bicarbonate ions become part of the bicarbonate reserve.Figure Respiratory acid-base disorders are the most common challenges to acid-base balanceFigure31
32 HOMEOSTASIS Responses to Acidosis The integrated homeostatic responses to respiratory acidosisRespiratory compensationStimulation of arterial and CSF chemoreceptors results in increased respiratory rate.Increased PCO2Renal compensationH ions are secreted and HCO3 ions are generated.Combined EffectsRespiratory AcidosisDecreased PCO2Buffer systems other than the carbonic acid–bicarbonate system accept H ions.Elevated PCO2 results in a fall in plasma pHDecreased H and increased HCO3HOMEOSTASIS DISTURBEDHOMEOSTASIS RESTOREDFigure Respiratory acid-base disorders are the most common challenges to acid-base balanceHOMEOSTASISHypoventilation causing increased PCO2Plasma pH returns to normalStartNormal acid- base balanceFigure32
33 CLINICAL MODULE 24.8: Respiratory acid-base disorders Respiratory alkalosisCO2 elimination at lungs outpaces CO2 generation rateShifts bicarbonate buffer system toward generating more carbonic acidH+ + HCO3– H2CO3 H2O + CO2H+ removed as CO2 exhaled and water formedBuffer system responsesRespiratory (decreased respiratory rate)Renal (HCO3– secreted and H+ reabsorbed)Proteins (release free H+)
34 CARBONIC ACID–BICARBONATE BUFFER SYSTEM NaHCO3 (sodium bicarbonate) The events in respiratory alkalosisCARBONIC ACID–BICARBONATE BUFFER SYSTEMBICARBONATE RESERVECO2CO2 H2OH2CO2 (carbonic acid)H HCO3HCO3 NaNaHCO3 (sodium bicarbonate)(bicarbonate ion)LungsIf respiratory activity exceeds the rate of CO2 generation, alveolar and plasma PCO2 decline, and this disturbs the equilibrium and drives the reactions to the left, removing H and elevating plasma pH.As bicarbonate ions and hydrogen ions are removed in the formation of carbonic acid, the bicarbonate ions— but not the hydrogen ions—are replaced by the bicarbonate reserve.Figure Respiratory acid-base disorders are the most common challenges to acid-base balanceFigure34
35 The integrated homeostatic responses to respiratory alkalosis HOMEOSTASISHOMEOSTASIS DISTURBEDStartHOMEOSTASIS RESTOREDNormal acid- base balanceHyperventilation causing decreased PCO2Plasma pH returns to normalCombined EffectsRespiratory AlkalosisResponses to AlkalosisIncreased PCO2Lower PCO2 results in a rise in plasma pHRespiratory compensationInhibition of arterial and CSF chemoreceptors results in a decreased respiratory rate.Increased H and decreased HCO3Figure Respiratory acid-base disorders are the most common challenges to acid-base balanceRenal compensationDecreased PCO2H ions are generated and HCO3 ions are secreted.Buffer systems other than the carbonic acid–bicarbonate system release H ions.Figure35
36 CLINICAL MODULE 24.8 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?
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