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Acid-Base Balance
- in water, acids dissociate in solution to liberate free H+ions
- STRONG acids completely dissociate (HCl--> H+ Cl-)
- WEAK acids have more limited dissociation (H2CO3<---> H+ + HCO3)
- bases bind free H+and remove it from solution
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Acid Production in the body
- H+is continually produced by metabolic activity:
- volatile acids: carbonic anhydrase
- CO2 + H2O <--> H2CO3 <--> H++ HCO3
- non-volatile acids:
- ingested acids
- products of fat, amino acid, and sugar metabolism: phosphate, sulphate, lactate
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H+concentration
- pH is the log of the reciprocal of the free H+ion concentration (negative log)
- pH =
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Plasma pH
- average plasma pH = 7.35-7.45
- most enzymes do not function outside this range
- represents very small H+concentrations: 40 nM
- much higher bicarbonate levels in plasma: 24 mM
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body regulates changes in pH by using:
- 1: buffers
- 2: H secretion
- 3: HCO3 reabsorption
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Buffer Systems
- a buffer system is a combination of two compounds that: minimize pH changes in acids or bases to solution
- BODY BUFFER SYSTEMS:
- in plasma: bicarbinate/carbonic acid (pKa=6.1)
- hemoglobin (unoxygenated/oxygenated) helps buffer plasma
- in urine: phosphate (h2po4 -/h2po4 2-) (pKa=6.8)
- ammonium (NH3 / NH4) (pKa=9.0)
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buffers contain BOTH dissociated and undissociated forms of an acid
- eg. bicarbonate buffer is actually H2CO3 and (HCO3)
- the ratio of these forms is CONSTANT
- K = [H+][HCO3]/[H2CO3]
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Henderson-Hasselbalch equation:
- eq PH=pK+log[HCO3]/[H2CO3] = pK+log [HCO3]/a [HCO2] - a=solubility constant (0.03)
- only the amount of FREE H+determines pH
- more HCO3 than H2CO3 (i.e. CO2) is needed to maintain physiological pH
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in addition to buffering
- bicarbinate buffersystem can alter pH by altering conc of its components
- bicarbonate conc. controlled by kidney ---> HCO3
- CO2 conc controlled by lungs ---> CO2
- alkalosis can be caused by: rise in HCO3 or fall in CO2
- acidosis can be caused by: fall in HCO3 or rise in CO2
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Renal Hydrogen Ion Secretion - Proximal Tubule
- very low (nM) plasma H+conc. , so little is filtered
- instead, H+is secreted by tubular cells and HCO3-is reabsorbed
- large acid load excreted means urine pH is normally about (pH6 slightly acidic)
- Na+concentration gradient created by
- H+moves out of cell using
- H+in filtrate combines with HCO3-to form CO2
- enzyme required
- CO2 diffuses into cell, converted back to HCO3
- HCO3-transported OUT of cell into capillary
- net effect: H+is secreted in order to REABSORB HCO3
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Other Mechanisms of Proximal H+secretion - Phosphate buffering
- H+buffered by HPO42-after filtered HCO3-has been reabsorbed
- H+and HCO3-made in cell using:
- source of HCO3
- H+transported into filtrate using
- net effect: new HCO3-enters blood (i.e. is produced, not just reabsorbed)
- high pCO2 incr H+secretion
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Ammonium secretion - controlling urine pH
- bicarbonate is normally reabsorbed, so it cannot buffer urinary H+
- the kidney can make more HCO3-by: daminating glutamine
- (yeailds ammonia which is lipid soluble, crosses cell membrane easily)
- in the urine ammonium is formed:
- NH3 + H+ NH4
- ammonium is not very permeable
- stays in the urine to act as a buffer
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H+Handling by the Distal Nephron
- intercalated cells secrete H+using H/K ATPase
- (H out - K in)
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Respiratory acidosis =
- reduced pH due to high pCO2
- caused by: inadequeate ventilation
- COMPENSATION: increased renal H secretion and HCO3 reabsorption (causes increased plasma HCO3)
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Metabolic acidosis =
- lower pH with low plasma HCO3
- caused by: diabetic ketoacidosis, lactic acidosis, ethylene glycol or salicylate poisoning, diarhea
- COMPENSATION: hyperventilation (decreased CO2)
- increased renal H secretion and HCO3 absorption
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Metabolic alkalosis =
- Elevated pH due to high plasma HCO3
- caused by: excessive alkali ingestion (antacids)
- COMPENSATION: hypoventilation (increased CO2)
- less renal HCO3 reabsorption
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Respiratory alkalosis =
- elevated Ph due to low pCO2
- caused by: hyperventilation
- COMPENSATION: less renal H secretion, less HCO3 reabsorption
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Analyzing Acid-Base Disorders
- 1. is condition: Acidosis (pH < 7.4) Alkalosis (pH > 7.4)
- 2. what can causethis acidosis/alkalosis? low HCO3 or high pCO2 high HCO3 or low pCO2
- 3. is there a COMPENSATION?low pCO2 high HCO3 high pCO2 low HCO3
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