1. Renal Physiology 1 PART THREE Renal Acid-Base Balance

2. Acid An acid is when hydrogen ions accumulate in a solution. It becomes more acidic [H+] increases = more acidity CO 2 is an example of an acid. 72 pH HCl H + Cl- As concentration of hydrogen ions increases, pH drops

3. Base A base is chemical that will remove hydrogen ions from the solution Bicarbonate is an example of a base. 72 pH H + Cl- NaOH Na+ OH - Acids and basis neutralize eachother

4. 72 pH Na+ Cl- H+ OH - H2OH2O A change of 1 pH unit corresponds to a 10-fold change in hydrogen ion concentration

5. Acids are being created constantly through metabolism Anaerobic respiration of glucose produces lactic acid Fat metabolism yields organic acids and ketone bodies Carbon dioxide is also an acid.

6. Acids must be buffered, transported away from cells, and eliminated from the body Phosphate: important renal tubular buffer HPO 4 - + H + H 2 PO 4 Ammonia: important renal tubular buffer NH 3 + H + NH 4 + Proteins: important intracellular and plasma buffers H + + HbHHb Bicarbonate: most important Extracellular buffer H 2 O + CO 2 H 2 CO 3 H + + HCO 3 -

7. Buffering is good, but it is a temporary solution. Excess acids and bases must be eliminated from the body H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - Lungs eliminate carbon dioxide Kidneys can remove excess non-gas acids and bases gasaqueous

8. Excessive Acids and Bases can cause pH changes---denature proteins Normal pH of body fluids is 7.40 Alkalosis (alkalemia) – arterial blood pH rises above 7.45 Acidosis (acidemia) – arterial pH drops below 7.35 Acidosis: –too much acid –Too little base Alkalosis –Too much base –Too little acid

9. Compensation for deviation Lungs (only if not a respiratory problem) –If too much acid (low pH)—respiratory system will ventilate more (remove CO 2 ) and this will raise pH back toward set point –If too little acid (high pH)—respiratory will ventilate less (trap CO 2 in body) and this will lower pH back toward set point Kidneys –If too much acid (low pH)—intercalated cells will secrete more acid into tubular lumen and make NEW bicarbonate (more base) and raise pH back to set point. –If too little acid/excessive base (high pH)- proximal convoluted cells will NOT reabsorb filtered bicarbonate (base) and will eliminate it from the body to lower pH back toward normal.

10. Acid-Base Balance How would your ventilation change if you had excessive acid? –You would hyperventilate How would your ventilation change if you had excessive alkalosis? –Your breathing would become shallow

11. How can the kidneys control acids and bases? Bicarbonate is filtered and enters nephron at Bowman’s capsule Proximal convoluted tubule –Can reabsorb all bicarbonate (say, when you need it to neutralize excessive acids in body) OR –Can reabsorb some or NONE of the bicarbonate (maybe you have too much base in body and it needs to be eliminated)

12. How can the kidneys control acids and bases? Acidosis Intercalated cells –Secrete excessive hydrogen –Secreted hydrogen binds to buffers in the lumen (ammonia and phosphate bases) –Secretion of hydrogen leads to formation of bicarbonate HPO 4 - NH 3

13. What would happen if the respiratory system had a problem with ventilation? Respiratory Acidosis and Alkalosis Normal P CO2 fluctuates between 35 and 45 mmHg Respiratory Acidosis (elevated CO 2 greater than 45mmHg) Depression of respiratory centers via narcotic, drugs, anesthetics CNS disease and depression, trauma (brain damage) Interference with respiratory muscles by disease, drugs, toxins Restrictive, obstructive lung disease (pneumonia, emphysema) Respiratory Alkalosis (less than 35mmHg- lowered CO 2 ) Hyperventilation syndrome/ psychological (fear, pain) Overventilation on mechanical respirator Ascent to high altitudes Fever

14. What if your metabolism changed? Metabolic acidosis Bicarbonate levels below normal (22 mEq/L) Metabolic alkalosis bicarbonate ion levels higher (greater than 26mEq/L) Ingestion, infusion or production of more acids (alcohol) Salicylate overdose (aspirin) Diarrhea (loss of intestinal bicarbonate) Accumulation of lactic acid in severe Diabetic ketoacidosis starvation Excessive loss of acids due to ingestion, infusion, or renal reabsorption of bases Loss of gastric juice during vomiting Intake of stomach antacids Diuretic abuse (loss of H+ ions) Severe potassium depletion Steroid therapy

15. Acidosis: pH < 7.4 - Metabolic: HCO 3 - - respiratory: pCO 2 Alkalosis: pH > 7.4 - Metabolic: HCO 3 - - respiratory: pCO 2 How can you tell if the acid-base balance is from a kidney disorder or a lung disorder?

16. Compensation If the kidneys are the problem, the respiratory system can compensate. If the kidneys are secreting too much H + (which makes too much bicarbonate, causing metabolic alkalosis), breathing will become slower so that less CO 2 (an acid) is lost. If the kidneys are reabsorbing too much H + (metabolic acidosis), breathing will become faster.

17. Compensation If the respiratory system is the problem, the kidneys can compensate. If breathing is too rapid (too much CO 2, an acid, is lost, leaving the blood in respiratory alkalosis), Kidneys respond by reabsorbing more H +. If breathing is too shallow (not enough CO 2 is lost, leaving the blood in respiratory acidosis), Kidneys respond by secreting more H +.

18. Summary Let’s summarize so we can apply this to clinical conditions! Acidosis –Can be metabolic or respiratory Alkalosis Can be metabolic or respiratory

19. Acidosis Acidosis is excessive blood acidity caused by an overabundance of acid in the blood or a loss of bicarbonate from the blood (metabolic acidosis), or by a buildup of carbon dioxide in the blood that results from poor lung function or slow breathing (respiratory acidosis).

20. Acidosis Blood acidity increases when people ingest substances that contain or produce acid or when the lungs do not expel enough carbon dioxide. People with metabolic acidosis have nausea, vomiting, and fatigue and may breathe faster and deeper than normal. People with respiratory acidosis have headache and confusion, and breathing may appear shallow, slow or both. Tests on blood samples show there is too much acid. Doctors treat the cause of the acidosis.

21. Metabolic acidosis Caused from a decrease in bicarbonate in the blood because of ingestion of an acid (aspirin, ethanol, or antifreeze) or too many acidic waste products have built up (such as from untreated diabetes mellitus or eating too much protein that the kidneys cannot keep up with excreting the acid ), or it could be from loss of bicarbonate from diarrhea. Treatment is give i.v. of sodium bicarbonate.

22. Respiratory acidosis Caused from an increase in CO2 in the blood because the lungs are hypoventilating (seen in asthma, COPD, and overuse of sedatives or narcotics such as valium, heroin, or other drugs which make you sleepy). Treatment is to increase ventilation (oxygen mask).

23. Respiratory acidosis May have no symptoms but usually experience headache, nausea, vomiting, and fatigue. Breathing becomes deeper and slightly faster (as the body tries to correct the acidosis by expelling more carbon dioxide). As the acidosis worsens, people begin to feel extremely weak and drowsy and may feel confused and increasingly nauseated. Eventually, blood pressure can fall, leading to shock, coma, and death.

24. Alkalosis Alkalosis is excessive blood alkalinity caused by an overabundance of bicarbonate in the blood or a loss of acid from the blood (metabolic alkalosis), or by a low level of carbon dioxide in the blood that results from rapid or deep breathing (respiratory alkalosis).

25. Alkalosis People may have irritability, muscle twitching, or muscle cramps, or even muscle spasms. Blood is tested to diagnose alkalosis. Metabolic alkalosis is treated by replacing water and electrolytes. Respiratory alkalosis is treated by slowing breathing.

26. Metabolic alkalosis Caused from an increase in bicarbonate in the blood because of ingestion of excess antacid (Tums), eating excess fruits (vegetarian diets and fad diets*), loss of acid from vomiting, or loss of potassium from diuretics. Treatment is to give an anti-emetic if the problem is from vomiting. If not, give an i.v. of normal saline to increase the blood volume. If potassium is also low, would have to add that to the i.v.

27. FYI *Fruits are the normal source of alkali in the diet. They contain the potassium salts of weak organic acids. When the anions are metabolized to CO2 and removed from the body, alkaline potassium bicarbonate and sodium bicarbonate remain. Metabolic alkalosis may be found in vegetarians and fad dieters who are ingesting a low- protein, high fruit diet.

28. Respiratory alkalosis Caused from a decrease in CO2 in the blood because the lungs are hyperventilating (anxiety, but not panting). Symptoms include irritability, muscle twitching, muscle cramps. Treatment for hyperventilation is to breathe into a paper bag for a while, as the person breathes carbon dioxide back in after breathing it out. For severe cases, need to replace the water and electrolytes (sodium and potassium).

29. Respiratory alkalosis Caused from a decrease in CO2 in the blood because the lungs are hyperventilating (anxiety, but not panting). Treatment is to breathe into a paper bag for a while.

30. Clinical Problem 1a Your patient’s blood pH is too low (acidosis). This can be caused by either respiratory acidosis or metabolic acidosis. Let’s say it was respiratory acidosis (abnormal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If blood carbon dioxide levels are elevated (too much blood acid) and urine bicarbonate levels are elevated (H+ is being secreted to make bicarbonate). That means that the original problem of elevated carbon dioxide (pCO 2 ) is being compensated for by the kidneys, which are secreting more H+ to make more bicarbonate. Since this patient’s bicarbonate levels are also elevated, they are compensating already.

31. Clinical Problem 1b Your patient’s blood pH is too low (acidosis). This can be caused by either respiratory acidosis or metabolic acidosis. Let’s say it was respiratory acidosis (abnormal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If blood carbon dioxide levels are elevated (too much blood acid) and urine bicarbonate levels are decreased (H+ is being absorbed). That means that the original problem of elevated carbon dioxide (pCO 2 ) is NOT being compensated for by the kidneys, which should be secreting more H+ to make more bicarbonate.

32. Clinical Problem 2a Your patient’s blood pH is too high (alkalosis). This can be caused by either respiratory alkalosis or metabolic alkalosis. Let’s say it was respiratory alkalosis (abnormal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If blood carbon dioxide levels are low (too little acid) and bicarbonate levels in the urine are low (too little base). That means that the original problem of decreased carbon dioxide (pCO 2 ) is being compensated for by the kidneys, which need to start reabsorbing more H+ to make more acid in the blood. If they are reabsorbing more H+, they are making less bicarbonate in the urine. Since this patient’s bicarbonate levels in the urine are low, they are compensating.

33. Clinical Problem 2b Your patient’s blood pH is too high (alkalosis). This can be caused by either respiratory alkalosis or metabolic alkalosis. Let’s say it was respiratory alkalosis (abnormal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If blood carbon dioxide levels are low (too little acid) and bicarbonate levels in the urine are high (too much base). That means that the original problem of decreased carbon dioxide (pCO 2 ) is NOT being compensated for by the kidneys, which need to start reabsorbing more H+ to make the blood more acidic. The bicarbonate levels would be low if the kidneys were doing this.

34. Clinical Problem 3a Your patient’s blood pH is too low (acidosis). This can be caused by either respiratory acidosis or metabolic acidosis. Let’s say it was metabolic acidosis (normal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If urine bicarbonate levels are too low (H + is being reabsorbed) and blood carbon dioxide levels are too low (too little blood acid), that means that the original problem of a low bicarbonate level needs to be compensated for by the lungs, which need to hyperventilate, expelling more CO 2 (an acid). Since this patient’s pCO 2 levels are also low, they are compensating already.

35. Clinical Problem 3b Your patient’s blood pH is too low (acidosis). This can be caused by either respiratory acidosis or metabolic acidosis. Let’s say it was metabolic acidosis (normal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If urine bicarbonate levels are too low (H + is being reabsorbed) and blood carbon dioxide levels are too high (too much blood acid), that means that the original problem of a low bicarbonate level needs to be compensated for by the lungs, which need to hyperventilate, expelling more CO 2 (an acid). However, since this patient’s pCO 2 levels are also high (not expelling enough acid), they are NOT compensating.

36. Clinical Problem 4a Your patient’s blood pH is too high (alkalosis). This can be caused by either respiratory alkalosis or metabolic alkalosis. Let’s say it was metabolic alkalosis (normal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If bicarbonate levels in the urine are high (too much base) and blood carbon dioxide levels are high (too much acid), that means that the original problem of increased bicarbonate levels need to be compensated by the lungs, which should take shallower breaths so less acid is lost. Since this patient’s pCO 2 levels are elevated, they are compensating.

37. Clinical Problem 4b Your patient’s blood pH is too high (alkalosis). This can be caused by either respiratory alkalosis or metabolic alkalosis. Let’s say it was metabolic alkalosis (normal breathing rate). We need to look at the patient’s partial pressures of carbon dioxide and bicarbonate to see if they are compensating. If bicarbonate levels in the urine are high (too much base) and blood carbon dioxide levels are low (too little acid), that means that the original problem of increased bicarbonate levels need to be compensated by the lungs, which should take shallower breaths so less acid is lost. Since this patient’s pCO 2 levels are low, they are NOT compensating.

38. ConditionpHRespCO2BicarbCompensating? Resp acidosisLowHypoventilatingHigh Yes Resp acidosisLowHypoventilatingHighLowNo Resp alkalosisHighHyperventilatingLow Yes Resp alkalosisHighHyperventilatingLowHighNo Metab acidosisLowNormalLow Yes Metab acidosisLowNormalHighLowNo Metab AlkalosisHighNormalHighhighYes Metab AlkalosisHighNormalLowHighNo