1. Regulation of acid base balance Regulation of H+ concentration balance Measuring the acidity and alkalinity of a solution in the units of pH, which is the measurement of the concentration of free H+ in solution The H+ concentration of the body fluids normally is kept at a low level, which averages only 0.00004 mEq/L in the extracellular fluids

2. Acids and bases definitions Molecules containing hydrogen atoms that can release hydrogen ions in solutions are referred to as acids. HCl, which ionizes in water to form hydrogen ions (H+) and chloride ions Cl- A base is an ion or a molecule that can accept an H+. For example, HCO3- is a base

3. Alkalosis refers to excess removal of H+ from the body fluids Acidosis refers to excess addition of H+

4. Strong and Weak Acids and Bases Strong acid: rapidly dissociates and releases especially large amounts of H+ in solution. An example is HCl Weak acids have less tendency to dissociate their H+ ions in solution. An example is H2CO3 Strong base is one that reacts rapidly and strongly with H+ and, therefore, quickly removes these from a solution, (NaOH). Weak base is HCO3- it binds with H+ much more weakly than does OH-. Most of the acids and bases in the extracellular fluid that are involved in normal acid-base regulation are weak acids and bases. The most important ones are H2CO3 and bicarbonate base.

5. pH is inversely related to the H+ concentration Low pH corresponds to a high H+ concentration, and a high pH corresponds to a low H+ concentration.

6. Normal pH of arterial blood is 7.4, a person is considered to have acidosis when the pH falls below 7.4 and to have alkalosis when the pH rises above 7.4 The lower limit of pH at which a person can live more than a few hours is about 6.8, and the upper limit is about 8.0

7. pH and H+ concentration of body fluids

8. Defenses against changes in hydrogen ion concentration There are three primary systems that regulate the H+ concentration in the body fluids to prevent acidosis or alkalosis: (1) the chemical acid-base buffer systems of the body fluids (2) the respiratory center (3) the kidneys, which can excrete either acid or alkaline urine, thereby readjusting the extracellular fluid H+ concentration toward normal during acidosis or alkalosis

9. Buffer system A chemical substance that minimizes changes in pH by releasing or binding hydrogen ions

10. Buffer system Most buffers composed of weak acid and weak base The purpose of the buffer is to help the body maintain pH Three important buffer system: H2CO3/HCO3 buffer system H2PO4-/HPO4-2 buffer system Protein buffers

11. Respiratory control of pH Within body fluids, CO2 and H2O coming together to form H2CO2 which breaks down into HCO3- and H+ HCO3- and H+ are constantly forming H2CO3 which can split apart to form CO2 and H2O

12. Respiratory control of pH When we breathe more quickly, more CO2 leaves the body When we breathe more slowly, less CO2 leaves the body

13. Renal control of pH The kidneys control acid-base balance by excreting either an acidic or a basic urine Excreting an acidic urine reduces the amount of acid in the extracellular fluids Excreting a basic urine removes base from the extracellular fluids

14. Under normal conditions, almost all HCO3- are reabsorbed from the tubules, thereby conserving the buffer system of the extracellular fluid This reabsorption of HCO3- are accomplished through the process of H+ secretion by the tubules

15. Renal control of acid base balance The kidneys regulate extracellular fluid H+ concentration through three mechanisms: Secretion of H+ Reabsorption of filtered HCO3- Production of new HCO3-

16. About 80 to 90 per cent of the bicarbonate reabsorption (and H+ secretion) occurs in the proximal tubule In the thick ascending loop of Henle, another 10 per cent of the filtered bicarbonate is reabsorbed The remainder of the reabsorption takes place in the distal tubule and collecting duct

17. Secretion of Hydrogen Ions CO2 arrive at the kidney tubules cells Within tubular cells, CO2 combine with H2O to form H2CO3 by carbonic anahydrase Then H2CO3 split to HCO3 and H+ The H+ is secreted from the cell into the tubular lumen by Na-H counter transport The HCO3- generated in the cell moves into the peritubular capillary blood The epithelial cells in PCT, thick ascending limb and DCT all secrete H+ into the tubular lumen

18. Reabsorption of HCO3- from filtrate HCO3- that is filtered by the glomerulus combines with H+ to form H2CO3 which eventually becomes CO2 and H2O The H2CO3 formed dissociate into CO2 and H2O CO2 diffuses into tubular cell where it recombine with H2O under the influence of CA to generate H2CO3 Then H2CO3 split to HCO3 and H+ The HCO3- generated in the cell moves into the renal interstitial fluid and the peritubular capillary blood

19. Generating new HCO3- H+ combined with HCO3- in the tubular fluid which results in reabsorption of HCO3- If high H+ (as in acidosis), the kidneys generate new HCO3- by phosphate and ammonia buffers mechanisms

20. Phosphate buffer system carries excess H+ into the urine and generate new bicarbonate Phosphate buffer composed of HPO4= and H2PO4- Excess H+ can combine with HPO4= After H+ combines with HPO4= to form H2PO4 , it can be excreted as a NaH2PO4 carrying with it the excess H+

21. Excretion of excess H+ and generation of new HCO3- by ammonia buffer system The glutamine delivered to the kidneys is transported into the epithelial cells of the proximal tubules, thick ascending loop of Henle, and distal tubules Glutamine is metabolized to form two NH4+ and two HCO3- The HCO3 is transported across the basolateral membrane along with reabsorbed Na+ into the peritubular capillaries In chronic acidosis the dominant mechanism by which acid is eliminated is excretion of NH4+