Mechanisms of Acid-Base Balance Flashcards
What is the normal extracellular concentration of H+?
40 nmol/L
What is the normal plasma pH range?
7.35-7.45
Outside what range of plasma pH is considered incompatible with life?
<6.8
>7.8
What is the urine pH range?
5 - 8.5
What controls the PCO2?
Alveolar ventilation
What controls plasma HCO3- concentration?
Renal excretion of H+ and reabsorption of HCO3-
What are the two main buffers: intracellular and extracellular?
Intracellular: H2PO4- —–> H+ + HPO42-
Extracellular: H2CO3 —–> H+ + HCO3-
Describe where most of the buffering takes place in the four kinds of acid-base imbalance.
Metabolic Acidosis - 80-85% intracellular
Metabolic Alkalosis - 30-35% intracellular
Respiratory Acidosis + Alkalosis - almost ALL intracellular
In which three regions of the nephron does renal H+ excretion take place?
Proximal convoluted tubule
Thick ascending limb of the loop of Henle
Alpha intercalating cell of the outer medullary collecting duct
What transporters are involved in the renal excretion of H+ and reabsorption of HCO3- in the proximal convoluted tubule and in the collecting duct?
PCT
Na+/H+ exchanger, H+ ATPase (apical membrane)
HCO3-/Na+ cotransporter, Na+/K+ ATPase, HCO3-/Cl- exchanger (basolateral membrane)
Collecting Duct
Alpha cell:
Na+/H+ exchanger, H+ ATPase, K+/H+ ATPase (apical membrane)
Cl-/HCO3- exchanger (basolateral membrane)
Beta cell:
Same transporters on the opposite membranes
Describe the process of excretion of H+ and retention of HCO3-.
Bicarbonate is unable to enter the cell.
H+ goes out of the cell into the filtrate.
H+ reacts with HCO3- in the filtrate to form H2CO3.
Carbonic anhydrase converts H2CO3 to H2O + CO2.
H2O + CO2 can then diffuse into the tubular cell and react to form H2CO3.
Carbonic anhydrase in the cell converts H2CO3 —-> H+ + HCO3-.
H+ moves out again into the filtrate and HCO3- is reabsorbed into the blood
Where does bicarbonate reabsorption take place and which areas reabsorb more bicarbonate?
80% takes place in the proximal convoluted tubule
10% takes place in the thick ascending limb of the loop of Henle
6% takes place in the distal convoluted tubule 4% takes place in the outer medullary collecting duct
State two primary stimuli for increase in H+ secretion.
Decrease in plasma bicarbonate concentration
Increase in PaCO2
State two secondary stimuli for an increase in H+ secretion.
NOTE: secondary means that it is not directed at maintaining acid-base balance
Angiotensin II secretion Aldosterone secretion Decrease ECF volume Hypokalaemia Increase in filtered load of bicarbonate
How are the stimuli for a decrease in H+ secretion different?
They are the opposite
Describe bicarbonate production by cells.
Amino acids are broken down in the liver to produce glutamine and urea
Glutamine is taken to the kidneys and broken down to produce ammonium and alpha ketoglutarate.
Alpha-ketoglutarate is then converted to HCO3-.
What happens to the ammonia produced in the tubular cells from the breakdown of glutamine?
It moves into the tubular fluid either as ammonium or as NH3 + H+
Further down the nephron, H+ will enter the tubular fluid and react with the NH3 to form NH4+
What could cause metabolic acidosis?
Addition of non-volatile acids
Loss of non-volatile alkalis - uncontrolled diabetes
What is the most common cause of metabolic alkalosis?
Loss of non-volatile acids (e.g. vomiting)
What are the acute and chronic compensatory mechanisms for respiratory acidosis and alkalosis?
Acute = intracellular buffering. Chronic = altered bicarbonate reabsorption and ammonium excretion.
What is the significance of bicarbonate?
It is a high capacity chemical buffer which can respond rapidly to changes in metabolic acid and can be produced from volatile respiratory acid
Henderson-Hasselbach equation
pH = pKa + log10[HCO3-]/[CO2]
