W05: Physiology Cont. - ACID/BASE BALANCE Flashcards
Define the relationship between [HCO3-] and pCO2 which determines the pH.
(respiratory acids form carbonic acids)
CO2 + H2O ⟷ H2CO3 ⟷ H+ + HCO3-
⇧CO2 shifts equilibrium => ⇧H+ + HCO3- = acidification
thus, H2CO3 quantity depends on amount of CO2 dissolved in plasma in turn depends on CO2 solubuility and P(CO2)
therefore pH is relative to [HCO3-]/PCO2
Describe the mechanisms employed by the kidney in the maintenance of [HCO3-].
- REABS OF HCO3- (mainly at proximal tubule)
• H+ secretion into lumen (Na coupling)
• HCO3- reacts wtih H+ in lumen = HCO3 = CO2 + H2O (presence of carbonic anhydrase)
= CO2 freely enters the cell and reverse dissociates within the cell = intracellular H+
•HCO3- pass into peritubular capillaries with Na+
- HCO3- GENERATION
> via tirating acid @ distal tubule; new HCO3- derived from blood CO2 is liberated as well as the excretion of accompanying H+
>
both require H+ secretion from tubule cells into lumen;
⇧HCO3 =
⇩HCO3 =lead to ⇩pH and compensated by increased vent. and ⇩P(CO2)
Define respiratory acidosis and suggest possible causes & reactions
CO2 retention
Compromised respiratory function to blow off CO2 from the system and thus dampen the ability of HCO3- buffer and lead to increased H+ thus decreasing pH.
acute causes
- BARBITUATES & OPIATES (depress medullary resp centres)
- obstruction of airways
chronic:
* lung diseases
response:
- ⇧[HCO3-]
- ⇧pH = ⇧renal glutaminase = ⇧NH3
Define respiratory alkalosis and suggest possible causes & reactions
Fall in PCO2 due to ⇧⇧ventilation
acute:
* voluntary hypervent., aspirin, first ascent to altitude
chronic:
* LT high altitude = ⇩PO2 stimulates ⇩ventilation thus ⇩[HCO3-] to protect pH
response:
⇩[HCO3-] via urine and less reabsorption
Sources of H+
- resp = carbonic acid (in health CO2 blown off and not retained therefore not a net contributor to acid)
- metabolic acids; inorganics (S containing A.A); organic acids: FA, lactic
Sources of alkalis
Organic anions such as citrate = ⇧pH
Normal pCO2 and HCO3-] range
pCO2
4.8-5.9kPa
36-44mmHg
[HCO3-]
22-26mmols/l
Intracellular buffering
H+ fluctuations are met by Cl- movement or exchange for K+
*!high acidosis = hyperkalaemia = ventricular fibrillation
Bone carbonate buffers
Chronic acid loads in chronic renal failure = bone wasting d/t release of carbonates in attempt to buffer
Define metabolic acidosis and suggest possible causes & reactions
d/t ⇩[HCO3-]
d/t ⇧H+ buffering or HCO3- LOSS
= ⇩P(CO2) to protect pH
causes:
- ⇧H+ production (ketoacidosis/ lactic acidosis)
- failure to excrete normal dietary load d/t renal failure
- diarrhoeal loss of HCO3- (failed reabs of intesinal HCO3-)
typical reaction:
- Kussmaul breathing
- pH attempted to balanced but not fully restored (still a lack of HCO3- as resp compensation is in action not lower CO2
- PLASMA HCO3 REDUCED THUS LESS TOTAL H+ NEEDED FOR HCO3- REABS THUS GREATER PROPORTION AVAILABLE FOR EXCRETION (titratable acid + ammonia mechs)
=
⇩ H+ secretion = ⇩HCO3- reabsorption + ⇧new HCO3- generated
Define metabolic alkalosis and suggest possible causes.
⇧[HCO3-] and thus ⇧P(CO2) to protect pH
= ⇧[H+] in body
causes:
- ⇧H+ loss via vomiting (gastric secretions)
- ⇧renal loss via aldosterone excess (liquorice ingestion)
- renal impairment plus XS HCO3- administration
- massive blood transfusions = influx of exogenous citrate converted to HCO3-
reaction:
urine loss alongside resp compensation
Describe the mechanisms used for the secretion of organic acids such as PAH.
actively secreted by the proximal tubules
- measure renal plasma flow
Describe the principles involved in renal replacement therapy and state the social, economic and psychological implications of dialysis and renal transplantation.
a
Where does buffering primarily occur?
METABOLIC ACID: 43% in plasma, HCO3- in cells
RESPIRATORY ACID: 97% within cells, rest in plasma protein
Significance of buffering urine
primarily occurs in DISTAL TUBULE
carried out by dibasic phosphate HPO4, also uric acid and creatinine within urine
production of titratable acid produces new HCO3- and actively excretes H+ (as H2PO42-)
- significant for acid loading via consumption
1) Na2HPO4 in lumen, Na+ reabs in exchange for H+ thus removing H+ from body
2) HCO3- is indirectly from CO2 (blood), dissociates within tubular cell, and HCO3- goes back to peritubular whilst H+ is excreted
- highly dependent on P(CO2)
- titratable acid forms in distal tubule d/t highly concentrated phosphate at this stage d/t removal of filtrate volume
Adaptive response to high and chronic acid loading (ammonium)
NH4+ is not lipid soluble thus perfect form of excretion
1) NH3 (glutamine deamination in tubule cells)
2) NH3 combines with H+ (blood CO2) = NH4+
3) NH4+ combines with Cl- (NaCl) = NH4Cl excreted @ distal tubule vs NH4+ in proximal
= NET EXCRETION OF H+ ACHIEVED
*new HCO3- passes with Na+ into peritubular capillaries
Significance of renal glutaminase
activity of renal glutaminase is pH dependent, with the falling of pH = ⇧glutaminase activity therefore ⇧NH4+ production
- ## ⇧protein synthesis significant impact to ensure maximal effect over 4-5 days
Significance of respiratory acidosis blood gas values vs pH
Although pH is being protected via renal compensation, pCO2 will still be deranged as well as [HCO3-]
thus problems arise when patients develop renal dysfunction
Significance of Kussmaul breathing
Deep slow breathing, sign of renal failure or dka, in attempt to reduce P(CO2)
⇧pH, ⇩P(CO2), ⇩[HCO3-] whats the disorder?
Respiratory Alkalosis with HCO3- loss as compensation
The pH differences between acute and chronic resp acidosis
for a given increase in Pco2, there is a smaller decrease in pH in chronic respiratory acidosis than in acute respiratory acidosis.
in mechanisms used to raise [HCO3-]. NH3 production takes 4-5 days to be fully turned on. So initially can only raise [HCO3-] by titratable acid, so limited. With time, can use NH3 production which has a considerable capacity to raise [HCO3-].
Mixed A/B disorder
Mixed disorders such as DKA, bronchitis, and haemorrhagic loss will bring significant acidosis.
Risk of hyperkalaemia as H+ are buffered and K+ exchanged and released into cell = risk of VFibrillation
> Insulin
Calcium Resonium = fixes hyperkalaemia d/t Ca2+ exchange
Ca gluconate to counter calcium resonium d/t risk of hyperpolar. of cardiac muscles.
Serious vomiting risk
Aggravated metabolic alkalosis
d/t loss hypovolaemia (NaCl loss) and resulting HCl loss (alkalosis)
= ⇧aldosterone to ⇧Na+ reabs in exchange for H+
= H+ secretion alongside resp compensation of ⇧P(CO2) brings pH higher (with more plasma HCO3-)
*H+ drawn out d/t aldosterone will drive equilibrium in cell to bring in more CO2 to balance
+!hypokalaemia
*Aldosterone stimulates secretion of H+ via the H+/ATPase in the intercalated cells of the cortical collecting tubules
> NaCl to restore volume
