LECTURE 14 (Acid-base balance) Flashcards
How does the Acid-base balance maintain normal hydrogen ion concentration in body fluids?
- Utilisation of buffers in extracellular and intracellular fluid
- Respiratory mechanisms that excrete carbon dioxide
- Renal mechanisms that reabsorb bicarbonate + secrete hydrogen ions
What is the difference between an Acid and a Base?
Acid = any compound which forms H+ ions in solution (proton donors)
Base = any compound which combines with H+ ions in solution (proton acceptors)
How is H+ concentration usually expressed as a logarithmic function?
pH = -log10[H+]
EXPLANATION:
- minus sign - as H+ concentration increases, pH decreases (vice versa)
- logarithmic relationship, not linear - equal changes in pH do not reflect equal changes in H+ concentration
What is the normal range of arterial pH?
7.37 to 7.42
- pH < 7.37 = acidemia
- pH > 7.42 = alkalemia
- pH range compatible with life = 6.8 to 8.0
What are the mechanisms maintaining normal pH?
- Buffering of H+ in ECF and ICF
- Respiratory compensation
- Renal compensation
- Buffering and respiratory compensation occur rapidly (minutes to hours)
- Renal compensation is slower (hours to days)
What are the two types of acids produced in the body?
- Volatile acid
[CO2 produced from aerobic metabolism of cells; combines with H2O to form H2CO3 “CARBONIC ACID”, which dissociates into H+ and HCO3- “BICARBONATE ION” (a reversible reaction catalysed by CARBONIC ANHYDRASE)] - Non-volatile acid/”fixed acids”
[e.g sulphuric acid, ketoacids, lactic acid, salicylic acid - produced from catabolism of proteins and phospholipids]
What is the difference in transport and excretion between Volatile acids and Non-volatile acids?
Volatile acids = CO2 produced by cells is added to venous blood, converted to H+ and HCO3- in red blood cells and carried to lungs where CO2 is regenerated and expired
Non-volatile acids = Buffered in body fluids until excreted by kidneys
How are Ketoacids, Lactic acid and Ingested acids produced?
- Ketoacids = B-hydroxybutyric acid and Acetoacetic acid in untreated diabetes mellitus
- Lactic acid = Generated during strenuous exercise or hypoxia
- Ingested acids = Salicylic acid from aspirin overdose, Formic acid from methanol ingestion and Glycolic & Oxalic acids from ethylene glycol ingestion
ADDITIONAL INFO: Overproduction or ingestion of fixed acids leads to metabolic acidosis
What is a buffer?
A mixture of a weak acid and its conjugate base or a weak base and its conjugate acid that prevents a change in pH when H+ ions are added to or removed from a solution
ADDITIONAL INFO: In Bronsted-Lowry, a weak acid is “HA” and is the H+ donor, base is A-. A weak base B and BH+ is the H+ donor.
What is the function of a buffered solution?
To resist a change in pH
[H+ can be added to or removed from a buffered solution but the pH will change only minimally]
What is the Henderson-Hasselbach equation to calculate pH?
pH = pK + log [A-]/[HA]
- A- is the base of the buffer (H+ acceptor)
- HA is the acid of the buffer (H+ donor)
- When the concentrations of A- and HA are equal, the pH of the solution equals pK of the buffer
What is pK and what determines it?
Equilibrium constant is the ratio of the rate constant of the forward reaction divided by the rate constant of the reverse reaction
WHAT DETERMINES IT?
- Strong acids are more dissociated into H+ and A- -> high equilibrium constants -> low pKs
- Weak acids are less dissociated -> low equilibrium constants -> high pKs
Describe what a titration curve shows
- As H+ ions are added to solution, the HA form is produced; as H+ ions are removed, the A- form is produced
- A buffer is most effective in the linear portion of the titration curve
[where addition or removal of H+ causes little change in pH] - When the pH of solution equals the pK, the concentrations of HA and A- are equal (Henderson-Hasselbach equation)
What are the different extracellular buffers?
- HCO3- produced from CO2 and H2O (major extracellular buffer)
[pK of CO2/HCO3- buffer pair is 6.1] - Phosphate (a urinary buffer; excretion of H+ as H2PO4- is “titratable acid”)
[pK of H2PO4-/HPO42- is 6.8]
What are the different intracellular buffers?
- Organic phosphates
- Proteins
(haemoglobin is a major intracellular buffer; in physiologic pH range, deoxyhaemoglobin is a better buffer than oxyhemoglobin)
What are the properties of the Carbonic acid-Bicarbonate buffer system?
- Prevents changes in pH caused by organic acids and fixed acids in ECF
- Cannot protect ECF from changes in pH that result from elevated or depressed levels of CO2
- Functions only when respiratory system and respiratory control centers are working normally
- Ability to buffer acids is limited by availability of bicarbonate ions
What are the properties of the haemoglobin buffer system?
- Helps prevents major changes in pH when plasma PCO2 is rising or falling
- The only intracellular buffer system with an immediate effect on ECF pH
MOA:
1) CO2 diffuses across RBC membrane (no transport required)
2) Carbonic acid dissociates + bicarbonate ions diffuse into plasma in exchange for chloride ions “CHLORIDE SHIFT”
What are the properties of the Phosphate buffer system?
- Consists of anion H2PO4- (a weak acid) + works like the carbonic acid-bicarbonate buffer system
- Important in buffering pH of ICF
LIMITATIONS:
- Provide only a temporary solution to acid-base imbalance
- Do not eliminate H+ ions
- Supply of buffer molecules is limited
What are the properties of the Respiratory acid-base control mechanisms?
- When chemical buffers cannot prevent changes in blood pH -> respiratory system is the SECOND LINE of defence against changes
- Eliminate or retain CO2
- Change in pH are RAPID
- Occur within minutes
What are the properties of the Renal acid-base control mechanisms?
- THIRD LINE of defence against changed in body fluid pH
- Long term regulator of ACID-BASE balance
- May take hours to days for correction
MOA:
- movement of bicarbonate
- retention/excretion of acids
- generating additional buffers
What are the roles of kidneys in Acid-base balance?
- Reabsorption of HCO3- (bicarbonate ions)
- Excretion of H+
[excretion of H+ as titratable acid (buffered by urinary phosphate), excretion of H+ as NH4+ (accompanied by synthesis + reabsorption of new HCO3-)]
Describe the reabsorption of filtered HCO3-
- Almost 99.9% of filtered HCO3- is reabsorbed (ensures conservation of major extracellular buffer)
- Reabsorption primarily occurs in PROXIMAL TUBULE
- Minimal reabsorption in loop of Henle, distal tubule and collecting duct
MOA:
1) Na+-H+ exchanger in luminal membrane
[Na+ moves into cell down its electrochemical gradient + H+ moves into lumen against electrochemical gradient]
2) Catalysed by CARBONIC ANHYDRASE on brush border, H+ combines with HCO3- to form H2CO3 -> H2CO3 decomposes into CO2 and H2O which enter the cell
3) Inside the cell, CO2 and H2O recombine to form H2CO3 catalysed by intracellular CARBONIC ANHYDRASE -> H2CO3 decomposes into H+ and HCO3- -> H+ is secreted by Na+-H+ exchanger to aid in reabsorption of another filtered HCO3- -> HCO3- is transported into the blood via Na+-HCO3- cotransport and Cl- HCO3- exchange
What are the special features of HCO3- reabsorption?
- Net reabsorption of Na+ and HCO3-
- No net secretion of H+
- Little change in tubular fluid pH
What are the factors affecting HCO3- reabsorption?
- Filtered load of HCO3-
[when plasma HCO3 reabsorption mechanism is saturated, excess HCO3 is excreted] - Extracellular fluid (ECF) volume
[ECF volume EXPANSION inhibits isosmotic and HCO3 reabsorption + ECF volume CONTRACTION stimulates isosmotic and HCO3 reabsorption + Involves angiotensin II stimulating Na+-H+ exchange + Explains contraction alkalosis] - Effect of PCO2
[Increased PCO2 increases HCO3- reabsorption (respiratory acidosis compensation) + Decreased PCO2 decreases HCO3- reabsorption (respiratory alkalosis compensation)]
What is the mechanism of excretion of Titratable acid?
Located primarily in the a-intercalated cells of the LATE DISTAL TUBULE and COLLECTING DUCTS
MOA:
1) H+ secretion (active transport by H+ ATPase [stimulated by aldosterone] and H+-K+ ATPase [responsible for K+ reabsorption] -> secreted H+ combines with HPO42- to form H2PO4-
2) Production of H+
[H+ produced from CO2 and H2O forms H2CO3 with CARBONIC ANHYDRASE which dissociates into H+ and HCO3- (reabsorbed into the blood via Cl- HCO3- exchange)
3) Synthesis and reabsorption of HCO3-
[for each H+ excreted, one new HCO3- is synthesised and reabsorbed]
What is the mechanism of excretion of H+ as NH4+?
LOCATION:
- proximal tubule
- thick ascending limb (of loop of Henle)
- a-intercalated cells of the collecting ducts
MOA:
PROXIMAL TUBULE
1) Glutamate is metabolised to a-ketoglutarate, then to CO2 and H2O forming HCO3- -> HCO3- reabsorbed into blood via Na+-HCO3- co-transport
2) NH3 diffuses from cell to lumen -> H+ secreted into lumen on Na+-H+ exchanger -> NH3 and H+ recombine to form NH4+
3) Some NH4+ is excreted into urine, some is reabsorbed by thick ascending limb to be secreted in collecting ducts for final excretion
THICK ASCENDING LIMB
NH4+ reabsorbed by substituting for K+ on Na+-K+-2Cl- co-transporter -> concentrated in interstitial fluid of inner medulla and papilla
COLLECTING DUCT
NH3 diffuses from medullary interstitial fluid into lumen + combines with secreted H+ to form NH4+ which is trapped in tubular fluid and excreted
[H+ is from H2CO3 that dissociates into H+ and HCO3-]
What is the effect of urinary pH on NH4+ excretion?
- Lower urinary pH increases NH4+ excretion
- Acidosis leads to increased H+ excretion
- Lower pH favours NH3 diffusion from medullary interstitial fluid into tubular fluid
What is the effect of acidosis on NH3 synthesis?
- Chronic acidosis increases NH3 synthesis
- Decrease in intracellular pH induces synthesis of glutamine metabolism enzymes
- More H+ excreted as NH4+, more new HCO3- reabsorbed
What is the effect of Hyperkalemia on NH3 synthesis?
- Inhibits NH3 synthesis
- Reduces H+ excretion as NH4+
- Causes type 4 renal tubular acidosis (RTA)
MECHANISM:
K+ enters renal cells, H+ leaves, increases intracellular pH and inhibits NH3 synthesis
What is the effect of Hypokalaemia on NH3 synthesis?
- Stimulates NH3 synthesis
- Increases H+ excretion as NH4+
MECHANISM:
K+ leaves renal cells, H+ enters, decreases intracellular pH, stimulates NH3 synthesis
What is the difference between Acidemia and Alkalemia?
Acidemia = an increase in H+ concentration in blood (decrease in pH) caused by acidosis
Alkalemia = A decrease in H+ concentration in blood (increase in pH) caused by alkalosis
What is the difference between respiratory acidosis and alkalosis?
Respiratory acidosis = caused by hypoventilation which results in CO2 retention, increased PCO2 and decreased pH
Respiratory alkalosis = caused by hyperventilation which results in CO2 loss, decreased PCO2 and increased pH
What are the four basic types of imbalance?
- Metabolic acidosis
- Metabolic alkalosis
- Respiratory acidosis
- Respiratory alkalosis
Describe metabolic acidosis
Overproduction or ingestion of fixed acid or loss of base produces a decrease in arterial [HCO3-]
COMPENSATION:
- hyperventilation (Kussmaul breathing)
- increased excretion of excess fixed H+ as titratable acid and NH4+ and increased reabsorption of HCO3-
- In chronic metabolic acidosis, increase in NH3 synthesis increases excretion of excess H+
Describe metabolic alkalosis
Loss of fixed H+ or gain of base produces an increase in arterial [HCO3-]
COMPENSATION:
- Hypoventilation
- Excretion of HCO3-
ADDITIONAL INFO:
If metabolic alkalosis is accompanied by ECF VOLUME CONTRACTION, the reabsorption of HCO3- increases, worsening the metabolic alkalosis
Describe Respiratory acidosis
Caused by decreased alveolar ventilation and retention of CO2 causes an increase in [H+] and [HCO3-]
COMPENSATION:
- no respiratory compensation
- renal compensation (occurs in CHRONIC respiratory acidosis, not acute) consists of increased excretion of H+ as titratable acid and NH4+ and increased reabsorption of HCO3-
[H+ is aided by increased PCO2]
Describe Respiratory alkalosis
Caused by increased alveolar ventilation and loss of CO2 which causes a decrease in [H+] and [HCO3-] by mass action
COMPENSATION:
- no respiratory compensation
- renal compensation (only occurs in CHRONIC respiratory alkalosis) consists of decreased excretion of H+ as a titratable acid and NH4+ and decreased reabsorption of HCO3-
[process aided by decreased PCo2]
