Acid/Base Lectures (2) Flashcards
pH measures?
→ H+ concentration
→ in arterial plasma, normally ~0.00004 mEq/L
→ on log scale, 7.40 (slightly alkaline)
→ pH change of 1 unit = 10 fold change in H+ concentration
Normal pH range of plasma/ECF pH (considers whole body pH)
7.38-7.42
Acidosis and alkalosis
→ if pH (H+ concentration) changes, results in H bond disruptions that alter proteins normal 3D structure
ACIDOSIS - low pH
→ CNS depression, confusion, coma
ALKALOSIS - high pH
→ hyperexcitability of sensory neurons/muscles, sustained respiratory muscle contraction
Acid input into body?
→ Diet (FA’s, AA’s)
→ Metabolic products (CO2 from aerobic metabolism, lactic acid from anaerobic metabolism, ketoacids from high amounts of FA metabolism eg. diabetes, starvation)
*carbonic anhydrase converts CO2 into H+ and HCO3-
pH homeostasis depends on 3 mechanisms
→ buffers (HCO3-, proteins, hemoglobin, phosphates, ammonia; all cause small change to pH)
→ ventilation (handles 75% of disturbances, functions in large range of pH)
→ renal regulation of H+ and HCO3- (SLOW!)
Job of a buffer?
Ex?
→ moderates pH changes by combining with or releasing H+
→ combine with strong acid to make weak acid to reduce pH effect
Intracellular buffers: cell’ proteins (hemoglobin), phosphate ions – HPO4-2 and H2PO4-)
What does HCO3- buffer?
phosphates: same process!
HCO3- most important ECF buffer system
→ the 93% of CO2 uptaken into RBC’s: 70% of it is converted to HCO3- and H+
→ H+ buffered by Hb
→ HCO3- leaves cell and enters plasma to combine with any non-respiratory made acids from metabolic processes (lactic acid..)
HCO3- buffer system is so efficient why?
→ plasma HCO3- is almost 600,000x more [ ] than plasma H+ at equilibrium, bc almost all H+ made is buffered by Hb.
→ Any deviation in amount of CO2, HCO3- or H+ in solution will shift reaction until new equil reached
→ inc CO2 shifts eq right: creates more H+ and HCO3-, takes a second for HCO3- [ ] to be greater than H+, then it can begin buffering – this is why pH decreases initially
→ in H+ (via metabolism) shifts eq to left: HCO3- will bind the H+ to create carbonic acid, then CO2 and H2O (inc CO2 and H2O made)
*For HCO3- to change equilibrium, needs to be a huge addition/removal (rare)
Ventilation compensation system
→ kicks in once pH <7.38 or >7.42
→ excess H+: once converted to CO2, inc in plasma CO2 is sensed by peripheral and chemoreceptors
→ signal respiratory control enter to adjust ventilation (inc it to remove excess CO2)
→ less CO2, H+ and HCO3- convert to CO2 to compensate, brings pH down
→ less H+ (i.e. less CO2): chemoreceptors sense, send to RCC, reducing ventilation to retain CO2
→ retained CO2 converted to H+, brings pH back up
Once pH is fixed, breathing rate goes back to normal
What can alterations in ventilation cause?
*these are situations that DON’T arise from corrections
→ disturbances in HA-A- balance
CO2 + H2O → HCO3- + H+
Hypoventilation: inc CO2
→ acidosis (shift eq right)
→ drugs or alcohol
Hyperventilation - dec CO2
→ shifts left
→ panic attacks
Ammonia and Phosphate buffer systems in the Kidney
Handle 25% of pH disturbances SLOWLY (2 days)
→ directly: alter rates of reabsorption/excretion of H+
→ indirectly: alter rate of HCO3- reabsorption/excretion
Acidosis (more H+ around):
H+ not filtered, enters tubule via secretion only
→ kidneys reabsorb more HCO3- so more buffer around
→ ammonia in tubule cells buffers H+
→ phosphate ions and AA’s in lumen buffers H+
Alkalosis (more CO2 around):
→ H+ reabsorption inc
→ HCO3- secretion inc (less buffer around so H+ content inc)
Process:
Proximal tubule secreting H+ and reabsorbing HCO3-
*no apical HCO3- transporter: indirectly moved
→ After Na and HCO3- filtration, NHE secretes H+ into bowman’s capsule in exchange for 1 Na
→ H+ in filtrate combines w filtered HCO3- to form CO2
→ CO2 diffuses out of nephron into tubule cell
→ in tubule cell, CO2 combines with H2O to form HCO3- and H+
→ this is where the H+ thats secreted comes from, so H+ is secreted again (loop)
→ HCO3- in tubule is reabsorbed with Na (that was exchanged with H, from nephron) into peritubular capillary
→ back in tubule cell, glutamine is metabolized to ammonium and a-ketogluterate
→ a-KG then broken into HCO3-
→ HCO3- is reabsorbed in same way as above
→ ammonium is secreted into nephron via Na exchange, and is excreted with H+
Which part of collecting duct is important for acid-base fine regulation?
→ initial portion bc it has principal cells AND intercalated cells
i.e. distal nephron
What are intercalated cells? Why do they do?
Have lots of carbonic anhydrase with 3 transporters that flip membranes to facilitate either H+ secretion and HCO3- reabsorption (type A), or the opposite (type B)
For type A cells, apical memb has H-K ATPase, basolateral memb has HCO3-Cl exchanger
(opposite for type B)
→ Type A function in acidosis to inc H+ secretion and HCO3- reabsorption via taking H+ secreted into them, actively transporting it out and into lumen of collecting duct for excretion. HCO3- then reabsorbed to buffer the acids. However, bc K+ has to be reabsorbed to secrete H+, causes HYPERKALEMIA
→ Type B do opposite. CO2 in cells is converted to H+ and CO3-, H+ then actively reabsorbed into ECF to bring pH down, HCO3- secreted and excreted, however K+ also secreted so results in HYPOKALEMIA
How are type A and B intercalated cells regulated?
→ dunno
→ express angiotensin and renin receptors though so possibly RAS during acidosis
