Acid Base Balance Flashcards
What pH must plasma be at?
Plasma pH must be maintained between 7.35 and 7.45.
What is the concentration of H+ in the plasma?
There is a very low but extremely tightly regulated concentration of H+ ions between 44.5-35.5 nmol/l.
What does alkalaemia cause?
Alkalaemia lowers free calcium by causing Ca++ ions to come out of solution increasing neuronal excitability (calcium ions move out of the cells into the plasma and so sodium moves into the cells to maintain electroneutrality). pH greater than 7.45 leads to paraesthesia and tetany. Alkalaemia is extremely serious (45% mortality if pH rises above 7.55 and 80% mortality at pH at 7.65). Tetany is the most serious (respiratory muscles spasm etc.)
What does acidaemia cause?
Acidaemia is less dangerous but still bad. It increases plasma potassium ion concentration effecting excitability particularly cardiac muscles leading to arrhythmias. Increasing [H+] denatures proteins disturbing enzymes (by binding to them and effecting folding), affects muscle contractility, glycolysis and hepatic function. Effects are severe below 7.1 and life threatening below 7.
What determines plasma pH?
Plasma pH is determined by the ratio of [HCO3-]/pCO2. Can be calculated by the Henderson-Hasselbalch equation. There is usually 20 times as much HCO3 as dissolved CO2. pCO2 is determined by respiration which is controlled by chemoreceptors and disturbed by respiratory diseases. HCO3- is determined by the kidneys and is disturbed by metabolic and renal diseases.
What determines the plasma concentrations of CO2 and HCO3?
pCO2 is determined by respiration which is controlled by chemoreceptors and disturbed by respiratory diseases. HCO3- is determined by the kidneys and is disturbed by metabolic and renal diseases.
How do hyper and hypoventilation effect plasma pH?
Hypoventilation - hypercapnia (too much CO2 so high pCO2). This leads to a fall in plasma pH and is termed respiratory acidaemia (acidosis).
Hyperventilation - hypocapnia (too little CO2 so low pCO2). This leads to a rise in plasma pH and is called respiratory alkalaemia (alkalosis).
How is pCO2 normally controlled?
PCO2 is normally controlled within tight limits by central chemoreceptors. They change ventilation rate to correct for respiratory disturbances in pCO2 it is a slower response but accounts for 80% of effect. Peripheral chemoreceptors detect changes in PCO2 and pH of plasma. They respond rapidly but have a smaller effect overall.
How can changes in pH due to changes in pCO2 be compensated for without changing pCO2?
As pH is due to the ratio of HCO3/CO2 then you can compensate for changes in CO2 by changing [HCO3]. Erythrocytes produce hydrogen carbonate but the kidneys control the concentration in blood.
Kidneys can correct metabolic disturbances in pH by excreting or creating more HCO3-.
How does recovery of HCO3 occur in the Proximal tubular
This is driven by the Na+ gradient estalished by the Na-K-ATPase. Movement of Na+ down this graidnet out of the lumen drives the movemment of H+ into the lumen by the Na-H Exchanger. This H+ reacts with HCO3- and breaks down into CO2 and water which diffuse into the tubular cells. Here the CO2 and water react to form HCO3 and H+ via enzyme carbonic anhydrase. The H+ is extrdued and the HCO3 is absorbed into the ECF. This allows the kidneys to absorb a large amount of the HCO3 that is excreted.
How is HCO3 produced in the proximal tubule?
Glutamine Alpha-ketoglutarate. This reaction produces HCO3 and ammonium. HCO3 enters ECF whilst NH4+ breaks down into NH3 and H+, NH3 diffuses through membrane whilst H+ is pumped out via Na-H exchanger in the lumen it reforms into NH4+.
How is HCO3 produced in the distal tubule?
By the distal tubule usually all the HCO3 has been recovered. Metabolic activity of Kidneys is extremely high, the CO2 produced reacts with water to form HCO3 and H+. However, the Na+ gradient is no longer strong enough to drive secretion of H+ so a H+ ATPase is used instead. In the Lumen H+ is buffered by filtered HPO42- and excreted NH3 from the PCT.
What is the minimum pH of urine and why is it so acidic?
Minimum pH of urine is 4.5. No HCO3 in the urine as it has all been recovered. Some H+ is buffered by phosphate which is titratable (Meaning that it can freely gain H+ ions in an acid/base reaction). Some has reacted with ammonia to form ammonium ions. Total acid excretion = 50-100mmol of H+ per day. This is needed to keep HCO3- normal.
How is H+ secretion controlled in the kidneys?
Control of H+ secretion
H+ secretion is controlled by the kidneys. It is thought that tubular cells detect changes in intracellular pH. If ECF [HCO3] is low more HCO3- moves out of the cells to ECF so more H+ is secreted from the cells.
How do the kidney cells respond to a drop in pH?
Decrease pH enhances the activity of: Na-K-ATPase, ammonium production in the proximal tubule and activity of H+ ATPase (proton pump) in distal tubule. This increases the capacity to export HCO3- from tubular cells to ECF.
