1	Acid-Base Physiology N. Anaizi, PhD Associate Professor of Pharmacology & Physiology University of Rochester
2	Learning Objectives Define acid-base balance. Describe the basic mechanisms for acid-base homeostasis. Describe the unique role of HCO₃^- / CO₂ buffer pair in acid-base regulation. Describe the 4 primary acid-base disorders.
3	Objectives of Ventilation Provide enough O₂ for cell metabolism Remove the CO₂ produced in the course of cell metabolism. Also maintain pH within the normal range.
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5	"Relation between PCO₂ and alveolar..." Relation between PCO₂ and alveolar ventilation:
6	Basic Idea of Respiratory Control Maintain relatively constant the levels of:
7	Respiratory Control System Controlled variables: Sensors: central & peripheral chemoreceptors. Central integrator: respiratory centers Effectors: respiratory muscles & lungs
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10	Body Fluids Are Normally Alkaline In a neutral solution at 25°C: [H⁺] = [OH^-] = 100 nmol/L; pH = 7.00 In a neutral solution at 37°C: [H⁺] = [OH^-] = 216 nmol/L; pH = 6.65 Normally, body fluids: [H⁺]_ECF = 40 nmol/L; pH=7.4 [H⁺]_ICF = 100 nmol/L; pH=7.00
11	Endogenous Non-volatile Acid Production Highly dependent on diet. Average meat-eating, adult human: 1 mmol/kg/day. At least twice as high in infants & children <1 yr old.
12	Endogenous Non-volatile Acid Production Sulfur-containing amino acids (methionine, cysteine, and cystine) yield sulfuric acid, Methionine Þ glucose + urea + H₂SO₄ Organic phosphates yield phosphoric acid: R₂-PO₄K + 2H₂O Þ 2ROH + KH₂PO₄
13	Endogenous Non-volatile Acid Production Unusual or Pathological Conditions: Glucose Þ anaerobic glycolysis Þ lactic acid ÝÝ FA b oxidation Þ ÝÝ acetyl-CoA Þ Ketones Methanol Þ formaldehyde Þ formic acid Ethylene glycol Þglycoaldehyde Þ glycolic acid Þ Þ oxalic acid + formic acid + glycine
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15	What Makes A Good Buffer?
16	Biological Buffers The Isohydric Principle In the same solution all buffer systems are in equilibrium with one another: pH = pK₁ + log (A^-/HA) = pK₂ + log (B^-/HB) = 6.1 + log (HCO₃^- / CO₂)
17	Biological Buffers Blood Buffers HCO₃^- / CO₂ Hemoglobin Proteins Phosphate
18	The # 1 Buffer
19	Attributes of the HCO₃^- / CO₂ Despite its < ideal pKa, it has unique properties: It is an open system Its acid component is actually a gas (CO₂) Its components are regulated relatively independently (kidney / lung) It is relatively abundant We can measure it easily.
20	Attributes of an Open System
21	Attributes of an Open System
22	Attributes of an Open System
23	Attributes of an Open System
24	Hemoglobin As A Buffer Relatively abundant (14 - 17 g/dL) Capable of binding both H⁺ and CO₂ Has a dynamic pK_a: HbO₂ is a stronger acid (pK_a = 6.7) than Hb (pK_a = 7.9)
25	Hemoglobin As A Buffer
26	What Happens to CO₂? In Tissues: CO₂ + H₂O Û H₂CO₃ Û H⁺ + HCO₃^-
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30	Basic Definitions Normally: [H⁺]_o = 40 and [H⁺]_i = 100 nmoles/L Acidemia: [H⁺]_o > 44 (pH < 7.36) Acidosis: the process that tends to cause acidemia. Alkalemia: [H⁺]_o < 36 ( pH > 7.44) Alkalosis: the process that tends to cause alkalemia.
31	What is an acid-base “disturbance”?
32	A Rule Without Exception
33	Primary Acid-Base Disturbances
34	The 4 Primary Acid Base Disorders Respiratory acidosis Main Problem: Ý arterial PCO₂ Respiratory alkalosis Main Problem: ß arterial PCO₂ Non-respiratory (metabolic) acidosis Main Problem: ß arterial [HCO₃^-] Non-respiratory (metabolic) alkalosis Main Problem: Ý arterial [HCO₃^-]
35	Secondary Responses Respiratory acidosis Renal Response: Ý [HCO₃^-]_p Respiratory alkalosis Renal Response: ß [HCO₃^-]_p Non-respiratory (metabolic) acidosis Respiratory Response: ß P_aCO2 Non-respiratory (metabolic) alkalosis Respiratory Response: Ý P_aCO2
36	Secondary Responses ... Aim of Secondary Response
37	Evaluating Acid-Base Disorders Conceptual Approach: Patient’s Medical History ABG: PaCO₂, [HCO₃^-]_p, pH Reference to data from whole-body titration studies. Predicted magnitude of the secondary response to a primary ABD
38	Predicted Secondary Responses Metabolic Acidosis P_CO2 falls 1.2 mm Hg per 1 mmol/L drop in [HCO₃^-] or P_CO2 = 1.5 [HCO₃^-] + 8 (P_CO2 » the last 2 digits of pH)
39	Predicted Secondary Responses Metabolic Alkalosis P_CO2 rises 0.7 mm Hg per 1 mmol/L rise in [HCO₃^-] or P_CO2 = 0.9 [HCO₃^-] + 15
40	Predicted Secondary Responses ... Acute Respiratory Acidosis [HCO₃^-] rises 0.12 mmol/L per mm Hg rise in P_CO2 Chronic Respiratory Acidosis [HCO₃^-] rises 0.35 mmol/L per mm Hg rise in P_CO2
41	Predicted Secondary Responses... Acute Respiratory Alkalosis [HCO₃^-] drops 0.2 mmol/L per mm Hg drop in P_CO2 Chronic Respiratory Alkalosis [HCO₃^-] drops 0.4 mmol/L per mm Hg drop in P_CO2
42	Evaluating Acid-Base Disorders Singer & Hastings Method: PaCO₂, [HCO₃^-]_p, pH; and [Hb] or Hct “Whole-blood buffer base” (normal 48 mEq/L)
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46	The Predicted [HCO₃^-] Predicted [HCO₃^-] = 24 + (BC/3) (7.4 - pH)
47	Metabolic Acid-Base Disorders Show Either Positive or Negative Base Excess (BE) Base Excess = [HCO₃^-]_obs - [HCO₃^-]_pred
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56	"Failure to dispose of the..." Failure to dispose of the usual acid load Renal failure; pRTA; RTA₄ Increased acid load Endogenous: lactic; keto-acidosis Exogenous: NH₄Cl, CaCl₂, Lysine HCl Ingestion (salicyl., methanol, e. glycol) Loss of HCO₃^- Via the GIT Via the Kidney
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58	"Net loss of H⁺" Net loss of H⁺through of the GI vomiting, NG suction, antacids, etc. Renal H⁺ Loss diuretics, excess mineralocorticoids, etc. K⁺depletion (à ECF alkalosis) H⁺ - K⁺ exchange Þ á[H⁺]_i Þ áH⁺secretion
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