this lecture is an introduction to body pH and the mechanisms that regulate it: the kidneys, the lungs, and chemical buffers. it also talks about the development of kidney stones and the physiology of the bladder.
body pH is largely determined by the balance between the acidic carbon dioxide and the basic bicarbonate. recall from respiratory physiology that carbon dioxide combines with water in cells via carbonic anhydrase to form carbonic acid, which then dissociates into bicarbonate and H+. the body can develop alkalosis or acidosis due to an imbalance of these molecules; acidosis can occur either by hypoventilation (retaining too much CO2) or through metabolic pathways- loss of bicarbonate through diarrhea, renal failure, buildup of lactic acid from exercise, excess ketone body production in the case of diabetes mellitus. alkalosis can occur by hyperventilation (loss of too much CO2 from lungs) or by ingestion of antacids, excess secretion of H+ in the kidneys due to hypertension, or vomiting of acidic HCl.
in order to regulate the pH, the body can increase or decrease the ventilation rate to regulate blood CO2 levels. another main source of pH regulation is in the kidneys via the balance between reabsorption and excretion of bicarbonate and H+. bicarbonate in the blood is filtered in the kidneys and combines with H+ secreted by the epithelial cells of the proximal tubule. this forms carbonic acid, which can be converted back into CO2 and H2O via carbonic anhydrase. the CO2 then diffuses back into the epithelial cells, where it reforms bicarbonate and H+ through the reverse reaction. in this way 99% of bicarbonate filtered through the kidney is reabsorbed.
if the acidity in the blood is too high, then H+ secreted into the lumen will be higher than the bicarbonate in the filtrate, and excess H+ will be bound to ammonia and phosphate buffers and excreted, raising the pH. conversely, if the blood is basic, then there will be more bicarbonate than H+, and the excess will be unable to be reabsorbed as CO2 and thus be excreted, lowering the pH. angiotensin II and aldosterone can both cause excess H+ secretion, resulting in low pH- angiotensin II stimulates the PCT Na+/H+ cotransporters in the tubular epithelia, while aldosterone stimulates the Na+/H+ antiporter, as well as stimulating intercalated cell secretion of H+. this means that the high angiotensinII and aldosterone levels associated with hypertension also result in a lower pH.
a brief look at kidney stones: when there is excess insoluble material in the filtrate or excess water reabsorption, sometimes stones can develop in the kidney and block urine passage. the most common is the calcium oxalate stone, which develops from a hyper-reabsorption of calcium and oxalate from the intestines, which then combine in the kidneys. a second type of kidney stone is struvite, which forms from a bacterial enzyme, urease, which degrades urea into NH3, which raises pH and forms MgNH4PO4 stones.
the urine that forms in the kidney then goes out via the ureters into the bladder. the bladder is surrounded by the detrusor muscle, and has openings that lead out into the urethra, which leads out into the outside world. the urethral sphincter has two layers, the inner sphincter, which is controlled by parasympathetic smooth muscle, and the outer layer, which is controlled by voluntary striated muscle (pudendal nerve, S2,3,4). when the bladder is filling, the detrusor muscle relaxes and the inner sphincter contracts. during the micturition (urination) reflex, the detrusor muscle contracts and the inner sphincter relaxes.
questions
1. what is blood pH regulated by?
2. what is the main chemical buffer in the blood?
3. how do the lungs regulate pH?
4. how do the kidneys regulate pH?
5. what are the pH limits of the body and what occurs beyond the limits?
6. what are the sources of acidity in the body?
7. acidity depends on the ratio between...
8. the reaction that produces bicarbonate from CO2 is catalyzed by...
9. what is the pKa of bicarbonate and what happens at the physiologic pH of 7.4?
10. why is urine continuously acidified?
11. what are the two sources for production of CO2 in the body?
12. describe the ultimate fate of CO2.
13. describe the reabsorption of bicarbonate in the proximal convoluted tubules of the kidney.
14. describe the reabsorption of bicarbonate in the proximal convoluted tubules when there is an acid load.
15. describe acid secretion in the distal convoluted tubules.
16. what is the phosphate buffer? what does it do?
17. what is the major buffer system for excess H+ ions?
18. ammonium buffer produced from...
19. describe the path of the ammonium buffer through the nephron.
20. what is "bicarbonate addition"?
21. how do low potassium levels contribute to an acid urine?
22. what effect does angiotensin II have on H+ secretion?
23. what are the three ways in which aldosterone increases H+ secretion?
24. what is the body's response to respiratory acidosis?
25. what is the body's response to respiratory alkalosis?
26. what are four potential causes of metabolic acidosis?
27. what is the body's response to metabolic acidosis?
28. what are three potential causes of metabolic alkalosis?
29. what is the body's response to metabolic alkalosis?
30. what is the cause of kidney stones?
31. what is the most common type of kidney stone and what is it caused by?
32. what are struvite stones and how are they formed?
33. what is the muscle that contracts in the bladder?
34. what is the trigone?
35. in males, external and internal urethral sphincters are separated by...
36. how long is the urethra in males vs. females?
37. describe the difference between the internal vs. external urethral sphincters in females.
38. bladder filling is mediated by the...
39. baroreceptor sensory neurons in the bladder stimulates...
40. pressure waves are ...
41. what is the nerve that controls the external urethral sphincter?
answers
1. chemical buffers, kidneys, lungs.
2. bicarbonate
3. expiration of CO2 reduces acidity.
4. excess H+ ions are excreted, bound to phosphate and other buffers.
5. a pH below 7.0 results in a depressed CNS state- leading to coma and death. a pH above 7.8 results in an overactive CNS: leading to nervousness, muscle tetany, convulsions.
6. CO2 is derived from metabolism and is a volatile source of acidity. phosphoric, sulfuric, and hydrochloric acids are non volatile sources of acids and are derived from nucleic acid/protein/amino acid metabolism.
7. bicarbonate to carbon dioxide.
8. carbonic anhydrase.
9. pKa of bicarbonate is 6.1- at the body's pH of 7.4, CO2 is constantly removed.
10. because the basic bicarbonate is being selectively reabsorbed to maintain the buffer system, and the excess H+ from the dietary acid loads are being filtered and excreted.
11. metabolism produces CO2. H+ from non volatile acids can also combine with bicarbonate and create CO2.
12. CO2 combines with water to form carbonic acid, which dissociates into bicarbonate and H+ ion. in the kidney, H+ is secreted and bicarbonate is reabsorbed.
13. hydrogen ion is secreted into the lumen, where it combines with bicarbonate to form carbonic acid, which is converted to CO2 and H2O by carbonic anhydrase. CO2 then diffuses through the epithelial membrane and reforms bicarbonate, which is then reabsorbed into circulation.
14. when there is an acid load, there is more H+ than the level of bicarbonate- excess H+ is bound to ammonia and phosphate and excreted. (any excess bicarbonate is simply excreted)
15. bicarbonate has been mostly reabsorbed in the proximal tubules, so H+ is simply secreted by the ATPase pumps in the intercalated cells and lowers the pH of the lumen to approximately 4.5.
16. the phosphate buffer combines with excess H+ secreted into the lumen and aids in its excretion.
17. the ammonia buffer system.
18. glutamine in proximal convoluted tubule
19. ammonia combines with H+ in the proximal tubule, and is reabsorbed in the thick ascending limb, and is then secreted back into the tubule at the distal convoluted tubule and the collecting duct.
20. each H+ ion that is secreted, buffered, and excreted is dissociated from carbonic acid, forming bicarbonate which can then reenter circulation.
21. low blood potassium levels pull K+ ions out via a K+/H+ antiporter, thereby pulling in H+ ions which are then secreted into the urine.
22. angiotensin II stimulates the PCT Na/H contransporters, which facilitate Na reabsorption and H secretion.
23. aldosterone stimulates the intercalated cell secretion of H+, stimulates the Na/H antiporter, and upregulates the Na/K pump (thereby stimulating the Na/H antiporter)
24. the excess H+ that is produced by excess CO2 in the body is secreted and bound to ammonia and phosphate buffers and excreted, thereby raising pH. every H+ ion that is excreted also corresponds to a new bicarbonate ion which can be used to buffer the pH further.
25. less H+ is secreted, allowing excess bicarbonate to be excreted.
26. excess bicarbonate being lost through diarrhea, renal failure (H+ not being secreted fast enough), acidic ketone bodies created from diabetes mellitus, and lactic acid produced from anaerobic respiration.
27. H+ secretion and bicarbonate addition in the kidneys, as well as hyperventilating reducing CO2 levels in the blood.
28. ingestion of antacids, excess H+ loss due to aldosterone or hypokalemia, or loss of HCl through vomiting.
29. less H+ is secreted, allowing excess bicarbonate to be excreted from the kidneys. hypoventilation also raises CO2 levels in the blood.
30. excess insoluble materials or water reabsorption causes stones to precipitate out.
31. calcium oxalate, due to both high calcium levels (from intestinal hyperabsorption or defective renal absorption) and high oxalate levels (intestinal over-absorption)
32. MgNH4PO4, caused by urease action of bacterial infection.
33. detrusor muscle.
34. the triangular area in the bladder between the two ureteric orifices and the urethral opening.
35. the prostate.
36. 20cm in males, 4 cm in females
37. internal urethral sphincter is involuntary, smooth muscle, controlled by autonomic nervous system, and relaxes when bladder is expanded. exteral sphincter is voluntary, striated muscle, controlled by pudendal nerve.
38. sympathetic nervous system
39. relaxation of detrusor muscle and constriction of internal urethral sphincter.
40. parasympathetic micturition reflexes- alternating detrusor contraction and relaxation along with internal urethral sphincter relaxation.
41. pudendal (S2,3,4)
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