1. Acid Base Balance Mike Clark, M.D.

2. Acid - proton H + donor Base – proton H + acceptor Buffer – a chemical that resists a change in pH

3. Acid-Base Balance Normal pH of body fluids – Blood pH range 7.35 – 7.45 – 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 (physiological acidosis)

4. pH Buffer A substance that resists a change in pH Composition: A weak acid in equilibrium with its conjugate base Weak Acid Conjugate Base [H 3 A] [H 2 A - ] + [H + ] A weak acid does not completely dissociate -liberate its H + whereas a strong acid completely or almost completely dissociates Add outside acid to buffer it combines with the base H 2 A - to make more weak acid – add base it combines with the acid H + to make more weak acid

5. Chemical Buffer Systems Three major chemical buffer systems 1.Bicarbonate buffer system – main extracellular buffer – Two non-bicarbonate buffer systems 2.Phosphate buffer system 3.Protein buffer system – most abundant – main intracellular buffer Any drifts in pH are resisted by the entire chemical buffering system

7. What Is the Problem with the wrong pH in the Human Body? Improper pH denatures (bends out of shape) proteins. When proteins bend too far out of shape they cease to function. Functions of Proteins- Contractile, Regulatory, Enzymatic, Structural, Transport, Hormones Most important function of all “Enzymes” Why? They direct the pathway of all biochemical reactions.

8. What are the mechanisms in the human body that regulate blood pH? Concentration of hydrogen ions is regulated sequentially by: – Chemical buffer systems – act within seconds – The respiratory center in the brain stem – acts within 1-3 minutes – Renal mechanisms – require hours to days to effect pH changes

9. Why is the regulation of blood pH so important? Don’t we have other fluids and tissues to protect also? Since blood transports throughout the entire human body (except dead areas like the top of the skin) – it keeps the pH of the other body areas proper – if its pH is proper.

10. pH Scale Goes from 0 – 14 with 7 being neutral Below seven is acidic Greater than 7 is basic (alkaline)

11. What is pH and how is it determined? pH – stands for the powers of hydrogen It is calculated using a mathematical formula pH = - Log [H + ] This is the universal formula used in all of chemistry to determine pH However – the biochemical community uses another formula derived from the universal pH formula (Henderson-Hesselbach formula)

12. Henderson-Hasselbach pH = pKa + Log [Base] / [Acid] The equation was derived from the universal pH equation. The equation uses the reaction H 2 CO 3 HCO 3 - + H + as its basis Using this reaction the pKa is 6.1 The Base is HCO 3 - The Acid is H 2 CO 3

13. In an arterial blood gas – one does get the HCO 3 - (bicarbonate) value but not the H 2 CO 3 (carbonic acid value). But the amount of Carbonic acid in the blood depends on Henry’s law – thus the partial pressure of the gas times the solubility coefficient. Thus.03 x PaCO 2 is used. The arterial blood gas does give the value of PaCO 2. pH = pKa (6.1) + Log [HCO 3 - ] /.03 x [PaCO 2 ]

14. The ideal arterial pH of the blood should be 7.4 So if 7.4 = 6.1 + Log [HCO 3 - ] /.03 x [PaCO 2 ] The Log of Base of Acid needs to equal to 1.3 The Log of 20 is 1.3 – thus the ratio of base to acid needs to be 20 (20 more times base than acid)

15. [Total Acid] = [Volatile Acid] + [Fixed Acid] The total [H + ] (Acid) in the blood is measured when you calculate pH – it makes no difference where the H + came from There are two acid types in the body Fixed Acids and Volatile Acids There is only one type of Volatile Acid – Carbonic acid – created from carbon dioxide mixing with water All the other Acids in the body are termed “fixed acids” like lactic acid, hydrochloric acid and others Homeostasis – if the fixed or volatile acid concentration goes up because of a problem the acid concentration without the problem should go down to compensate

16. Normal Arterial Blood Gas Values pH – 7.35 – 7.45 PaO 2 - 80 to 100 mm Hg. HCO 3 - - 22 to 26 mEq/liter PaCO 2 - 35-45 mm Hg

17. When Acid/Base Balance in the Blood Goes Wrong Respiratory Acidosis – Lungs caused the acidosis Metabolic Acidosis – there is blood acidosis, but the lungs did not cause – something else in the body caused it Respiratory Alkalosis – Lungs caused the alkalosis Metabolic Alkalosis - there is blood alkalosis, but the lungs did not cause – something else in the body caused it

18. Respiratory Acidosis and Alkalosis Result from failure of the respiratory system to balance pH P CO2 is the single 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

19. pH = 6.1 + Log [HCO 3 ]/PaCO 2 x.03 Must keep a ratio of 20 to 1 Base to Acid for pH to be 7.4. Respiratory Acidosis If PaCO 2 goes up then the ratio drops and the blood becomes acidic – unless the kidney holds on to more bicarbonate to compensate Respiratory Alkalosis If PaCO 2 goes down then the ratio increases and the blood becomes basic – unless the kidney removes (urinates out) more bicarbonate to compensate

20. pH = 6.1 + Log [HCO 3 ]/PaCO 2 x.03 Must keep a ratio of 20 to 1 Base to Acid for pH to be 7.4. Metabolic Acidosis If PaCO 2 is normal or low and the blood is acidotic then the lungs are not the problem since they are not causing more carbonic acid to be made – thus the acidosis is due to something else in the body “metabolic” - the lungs maybe blowing off more CO 2 than usual to help – thus compensate. Examples Lactic Acidosis or Diabetic Ketoacidosis Metabolic Alkalosis If PaCO 2 is normal or elevated and the blood is alkalotic then the lungs are not the problem since they are not causing less carbonic acid to be made – thus the alkalosis is due to something else in the body “metabolic” - the lungs maybe holding on to more CO 2 than usual to help – thus compensate. Example Milk alkali sydrome

21. Compensatory Actions Complete compensation – though a metabolic or respiratory problem – the compensatory mechanism is so good it completely compensates – thus pH stays completely normal (this very, very rarely occurs – for the most part never) Partial compensation- though a metabolic or respiratory problem – the compensatory mechanism tries to keep the pH normal – and does to some extent. Respiratory Acidosis (completely or partially) compensated by a metabolic alkalosis Metabolic Acidosis (completely or partially) compensated by a respiratory alkalosis This also occurs for respiratory or metabolic alkalosis

23. Davenport Curves

24. pH Problems Arrhythmias can result when the pH falls below 7.25, and seizures and vascular collapse can occur when pH rises above 7.55.

25. PLAY InterActive Physiology ®: Acid/Base Homeostasis, page 34 Reabsorption of Bicarbonate Carbonic acid formed in filtrate dissociates to release carbon dioxide and water Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ion secretion Figure 26.12

26. Copyright © 2010 Pearson Education, Inc. CO 2 combines with water within the type A intercalated cell, forming H 2 CO 3. H 2 CO 3 is quickly split, forming H + and bicarbonate ion (HCO 3 – ). H + is secreted into the filtrate by a H + ATPase pump. For each H + secreted, a HCO 3 – enters the peritubular capillary blood via an antiport carrier in a HCO 3 – -CI – exchange process. Secreted H + combines with HPO 4 2– in the tubular filtrate, forming H 2 PO 4 –. The H 2 PO 4 – is excreted in the urine. Nucleus Type A intercalated cell of collecting duct Filtrate in tubule lumen Peri- tubular capillary H + + HCO 3 – Cl – HPO 4 2– H 2 PO 4 – out in urine H 2 O + CO 2 H 2 CO 3 H+H+ Primary active transport Simple diffusion Secondary active transport Facilitated diffusion Carbonic anhydrase Transport protein Ion channel Cl – HCO 3 – (new) ATPase Figure 26.13 New HCO 3 – is generated via buffering of secreted H + by HPO 4 2 – (monohydrogen phosphate). Slide 1 1 2 4 5 3a 3b 1 2 4 5 3a 3b

27. Figure 26.14 Nucleus PCT tubule cells Filtrate in tubule lumen Peri- tubular capillary NH 4 + out in urine 2NH 4 + Na + 3Na + Glutamine Tight junction Deamination, oxidation, and acidification (+H + ) 2K + NH 4 + HCO 3 – 2HCO 3 – HCO 3 – (new) ATPase 1 PCT cells metabolize glutamine to NH 4 + and HCO 3 –. 2a This weak acid NH 4 + (ammonium) is secreted into the filtrate, taking the place of H + on a Na + - H + antiport carrier. 2b For each NH 4 + secreted, a bicarbonate ion (HCO 3 – ) enters the peritubular capillary blood via a symport carrier. 3 The NH 4 + is excreted in the urine. Primary active transport Simple diffusion Secondary active transport Transport protein 1 2a2b 3