Week 1: Acid Base Regulation Flashcards
Define: Acid Base Strong acid Weak acid
Acid- donates proton Base- proton acceptor Strong acid- fully dissociates in water into its conjugate base and H+ Weak acid- partially dissociates in water forming a buffer pair with its conjugate base that can respond to changes in [H+] by reversibly binding H+.
What is normal pH of the body? What is normal urine pH? What is the normal H + conc in the body?
Normal pH = 7.4 Range : 7.36-7.44 Normal pH urine = 6.0 Normal [H+] range = 36-44 nanomoles /L
What does acid base regulation control? What three things are balanced to maintain homeostasis of this factor?
Why is controlling this factor important?
Acid base regulation controls [H+] within the body.
This via balance of intake, production and excretion to maintain homeostasis.
It is important to control [H+] due to its effect on protein structure and therefore protein function.
Changes in H+ can have systemic effects especially due to effects on enzyme action.
Also due to its effects on ion binding to protein. E.g. decreased H+ can lead to increased Ca2+ binding to albumin. Ions able to bind other proteins in the body which could trick the body into thinking there are low levels of that ion in the body.
Describe what types of acid load the body is faced with and how they are produced. 100mmol
Volatile acid load of 14,000 mmol generated via aerobic metabolism and carbon dioxide production in the tissues. This is excreted as co2/volatile acid via lungs. Non volatile acid load of 70-100 mmol/day produced by other metabolic processes that produce acids like sulphuric acid. Ketoacids and lactic acid produced in certain conditions.
What three main mechanisms control [H+] in the body?
1) buffer system- able to resist changes in pH via reversible binding with [H+]. Prevents sudden pH change but can not control overall [H+]. 2) lungs - rapid adjustment of co2 excretion 3) kidneys- slower adjustment of [H+] via excretion in the urine and reabsorption/synthesis of HCO3-.
Define a buffer What three main buffer systems exist in the body?
A buffer is a substance able to minimise sudden pH change by reversibly binding to H+ ions. 3 main buffer systems: 1) HCO3- buffer system 2) Protein buffer system- haemoglobin in blood and blood protein albumin 3) phosphate buffer system in the urine
What is the Henderson hasslebach equation? What is important about the ratio in this equation?
pH= pK + log10 [HCO3-] / [CO2] where concentration of co2 is partial pressure x solubility Ratio of 20:1 HCO3- to CO2 is important to maintain pH within normal range.
What is the difference between the speeds of response between the lungs and kidneys?
Lungs have a quick response to increase/decrease in pCo2 by increasing or decreasing the ventilation rate and therefore excretion of CO2.
Kidneys have a slower response (hours-days) due to response requiring protein synthesis. Alter acid load by increasing/ decreasing HCO3- synthesis.
Describe the two key processes used by the kidney to maintain EC fluid pH balance
What do both these processes rely on?
Kidneys control EC pH by:
1) reabsorbing all filtered HCO3- (~4500 mmol/day)
2) secreting the non volatile acid load (70-100 mmol/day) (at the same time have HCO3- synthesis).
Therefore urine = acidic pH 6.0
Both processes rely on the ability of the kidneys to secrete H+.
Describe the role of the proximal tubule in acid base balance
- Proximal tubule reabsorbs 85-90% of the HCO3- filtered via the the kidneys.
- Relies on filtered HCO3- combining with H+ ions secreted across the apical membrane via a Na/H+ exchanger (NHE).
- This forms H2CO3 which is then converted to H20 + CO2 under the influence of luminal carbonic anhydrase.
- H20 and CO2 then able to freely diffuse into proximal tubule cell where they are again converted to carbonic acid by intracellular carbonic anhydrase.
- Carbonic acid dissociates into its constituent ions - H+ and HCO3-.
- HCO3- is transported across the BL membrane into the blood via a Na+/HCO3- cotransporter (NBC).
- The H+ ions are recycled across the apical membrane via the Na/H+ exchanger.
- More H+ combines with filtered HCO3-.
- Note: no net change in plasma pH as H+ simply recycled despite secretion across apical membrane.
Describe the role of the late distal tubule/ collecting duct in HCO3- reabsorption and H+ secretion
Describe the cell model (state key cell involved) and proteins involved.
What stimulates it?
The late distal tubule/ early collecting duct reabsorbs around 5% of the filtered HCO3- load via similar mechanisms to the proximal tubule.
Key cell: alpha intercalated cell
How acid secretion mechanism differs and relies on:
1) H+ ATPase 2) H+/K+ ATPase
Co2 from the blood diffuses into the alpha intercalated cell and under carbonic anhydrase is converted to carbonic acid which dissociates into bicarbonate ion and proton.
- Bicarbonate ion reabsorbed into the blood via the bicarbonate/ chloride exchanger on the BL membrane.*
- Chloride is then recycled across the BL membrane via cl channel.*
H+ ion is transported into urine via H+ ATPase and H+/K+ ATPase.
K+ is reabsorbed across the BL membrane via K+ channel.
Acid secretion by alpha intercalated cell is stimulated by aldosterone and hypokalaemia.
Why is the activity of the alpha intercalated cell in late distal/ early collecting duct limited when it comes to controlling EC Fluid pH?
How can we protect its function?
- Alpha intercalated cell is limited in its control of EC fluid pH as it’s ability to secrete acid is limited by the effect acidic pH will have on the function of the H+ ATPase proteins themselves.
- At maximum activity the H+ ATPase proteins will generate an 800 fold concentration gradient and minimum urine pH of 4.5.
- This only equates to 0.03 mmol [H+] which is not sufficient to excrete the daily 70-100 mmol load of nonvolatile acid.
- The way we protect the function of H+ ATPases is by buffering the urine.
Name two urinary buffers
1) ammonia 2) phosphate
What is generated during the secretion of H+ by the kidney?
In conjunction with H+ secretion, HCO3- is generated which is reabsorbed into the blood. This is important as some of the HCO3- is used in the buffering of the 70-100mmol non volatile acid load in the blood plasma.
Describe the urinary phosphate buffer system
Phosphate comes in two forms:
1) monoprotic form HPO4 2-
2) diprotic form H2PO4-
Monoprotic form is in relative excess and will combine with H+ secreted across the apical membrane of tubular cells to form the diprotic form.
The diprotic form combines with tubular Na+ and becomes trapped in the urine and is excreted.
The process of H+ secretion actually forms HCO3- which is reabsorbed across the BL membrane.
Describe the urinary ammonia buffer system: What cells are involved? How does each cell contribute to the buffer system?
Two principal cells involved: 1) Proximal tubule cell 2) Collecting duct cell
In proximal tubule: Glutamine is metabolised by glutaminase to form NH4+ (ammonium).
Glutamine –> glutamate –> a- ketoglutamate–> NH4+
Process actually forms 2HCO3- which are transported across the BL membrane into the blood.
2NH4+ formed in the process are transported across the apical membrane into renal tubule fluid where they combine with Cl- to form NH4Cl.
NH4Cl reabsorbed at the TAL, transported into the interstitium where NH4- becomes NH3. (dont worry about detail here).
Collecting duct cell:
NH3 transported across BL membrane into collecting duct cell where it is transported across the apical membrane along with secreted H+ ions.
H+ and NH3 –> NH4+
NH4+ + Cl- (in tubular fluid) –> NH4Cl
NH4Cl trapped in the urine and excreted.
Process of H+ secretion creates HCO3- which is transported across BL membrane into blood. (CO2 diffuses from blood into cell, combines with H2O under CA, forms H2CO3 –> HCO3- (reabsorbed) + H+ (secreted).
