Renal Regulation of Acid-Base Balance Flashcards
Why is pH regulation so tightly controlled and important?
Βecause metabolic reactions are highly sensitive to the H+ concentration of the fluid in which they occur
Why are metabolic reactions so sensitive to H+ concentration?
Due to the influence that H+ has on the tertiary structure of proteins, such as enzymes, such that their function can be altered
How can hydrogen regulation be viewed?
Matching gains and losses
What happens when loss exceeds gain in hydrogen ion regulation?
The arterial plasma H+ concentration decreases, and the pH exceeds 7.4, this is known as alkalosis
What is the relationship between H+ and pH?
The greater the H+ concentration –> the lower the pH
What happens if gain exceeds loss in hydrogen ion regulation?
The arterial plasma H+ concentration increases and the pH is less than 7.4, that is known as acidosis
The total-body balance of H+ is a result of what?
Both metabolic production of H+ ions and net gains or losses via the respiratory system, gastrointestinal tract, and urine.
A stable balance is achieved by regulation of urinary losses
What are the sources (gains) of H+?
- Generation of H+ from CO2
- Production of nonvolatile acids from the metabolism of proteins and other organic molecules
- Gain of H+ due to loss of HCO3- in diarrhea or other nongastric GI fluids
- Gain of H+ due to loss of HCO3- in the urine
What are the losses of H+?
- Utilization of H+ in the metabolism of various organic anions
- Loss of H+ in vomitus
- Loss of H+ in the urine (primarily in the form of H2PO4- and NH4+)
- Hyperventilation
Why is there a loss of H+ during vomiting?
Expelling HCl
How does hyperventilation lead to the loss of H+?
CO2 exhalation > CO2 production
What is buffering? How do they achieve that?
A means of minimizing changes in H+ concentration by combining these ions reversibly with anions such as HCO3- and intracellular proteins
What is the general form of buffering reaction?
Buffer + H+ –> HBuffer, H+ ions do not get eliminated but they instead bund them so that they are not free.
What happens when the H+ concentration increases?
The reaction is forced to the right, and more H+ is bound by the buffer to form HBuffer
What happens when the H+ concentration decreases?
The loss of H+ or the addition of alkali, the reaction proceeds to the left ad H+ is released from the HBuffer.
What is the major extracellular buffering system?
CO2/HCO3- system:
CO2 + H2O <–> H2CO3 <–> HCO3- + H+
What is the major intracellular buffer?
Phosphate and proteins, for instance: hemoglobin
What helps the reversible conversion of CO2 + H2O –> H2CO3?
Carbonic anhydrase (CA)
What systems work together to regulate hydrogen ion concentrations?
Kidneys and respiratory
What is the organ that achieves body H+ balance?
The kidneys
What does a decrease in arterial plasma H+ concentration cause?
Reflex HYPOventilation, which increases arterial PCO2, and hence, increases plasma H+ concentration toward normal (pH decreases)
What does an increase in plasma H+ concentration cause?
Reflex HYPERventilation, which decreases arterial PCO2 and, hence, decreases plasma H+ concentration towards normal (pH increases)
When do buffers work?
Within seconds
When does ventilation (respiratory buffers) work?
Within minutes to hours
When does renal buffer system work?
WIthin hours to days
What happens if the respiratory system is the actual cause of the H+ imbalance?
Then the kidneys are the sole homeostatic responder
What happens if malfunctioning kidneys create an H+ imbalance by eliminating too little or too much H+ from the body?
Respiratory response is the only one in control
What is the renal mechanism like?
The kidneys eliminate or replenish hydrogen ions from the body by altering plasma bicarbonate concentration
What is the kidneys’ response to plasma H+ ion concentration decreasing ?
During alkalosis, the kidneys’ homeostatic response is to excrete large quantities of HCO3-
This increases plasma H+ concentration towards normal
What is the kidneys’ response to plasma H+ concentrations increasing?
During acidosis, the kidneys do not excrete HCO3- in the urine rather, kidney tubular cells produce new HCO3- and add it to the plasma.
This decreases the H+ ion concentration towards normal, increases pH
What happens to HCO3- when H+ is secreted into the lumen and combined with filtered HCO3-?
HCO3- is reabsorbed when the H+ generated from tubular cells is secreted and combined with filtered HCO3-
The secreted H+ is NOT excreted in this situation
What happens to the H+ that is generated in the tubular cells that is not secreted?
It combines with the lumen with a filtered HCO3- and generates CO2 and H2O, both of which can diffuse into the cell and be available for another cycle of H+ generation
What is the kidneys’ normal response to HCO3-?
In all cases, except of alkalosis, the kidneys reabsorb all filtered HCO3- and thereby prevent its loss in the urine
What is the mechanism in the case of metabolic acidosis? (H+ ions)
H2O + CO2. –> H2CO3
H2CO3 is broken down into H+ and HCO3-
H+ binds to the HCO3- which is filtered in the tubular lumen to form H2CO3 and break it further down into H2O and CO2
The whole point is to decrease the H+ concentration
What happens when secreted H+ combines with filtered phosphate ions or other non-bicarbonate buffers?
It is excreted and the kidneys contribute to new HCO3- added to he blood
What are examples of non-bicarbonate buffers?
HPO4-
When do H+ ions combine with filtered non-bicarbonate buffers?
Only after the filtered HCO3- has virtually all been reabsorbed, the reason for this is that there is such a large load of filtered HCO3- competing for the secreted H+
What is the mechanism in the case of severe acidosis?
There is no bicarbonate
H2O + CO2 –> H2CO3
H2CO3 –> H+ and HCO3-
The H+ attaches to the HPO4 2- which is filtered into the tubular lumen
HPO4 2- + H+ –> H2PO4- which is then excreted in the urine, and this way, you decrease the H+ ion concentration, neutralizing the pH
When do the kidneys contribute new HCO3- to the blood?
When they produce and excrete ammonium
When is ammonium used as a non-bicarbonate buffer and why?
If the phosphate is not enough, phosphate is not formed in the body so there is a limited supply of it
What is the mechanism of ammonium as a non-bicarbonate buffer like?
Glutamine and sodium enter from the tubular lumen into the tubular epithelial cells
Glutamine is then broken down into NH4+ and HCO3-
The new HCO3- is added to the plasma
The NH4+ is moved into the tubular lumen whilst Na+ is reabsorbed back into the epithelial cells
The NH4+ is then excreted in the urine
What are the classifications of alkalosis/acidosis?
Respiratory or metabolic
What causes respiratory acidosis?
The retention of carbon dioxide (increased CO2)
What causes respiratory alkalosis?
Excessive elimination of carbon dioxide (decreased CO2)
What is the difference between metabolic and respiratory?
In metabolic, it is the reflection of gain or loss of H+ from a source OTHER than CO2
What are the renal responses to acidosis?
- Sufficient H+ is secreted to reabsorb all filtered HCO3-
- Still more H+ is secreted, and this contributes new HCO3- to the new plasma as the H+ is excreted bound to non-bicarbonate urinary buffers such as HPO4 2-
- Tubular glutamine metabolism and ammonium excretion are enhanced, which also contributes new HCO3- to the plasma.
Result: More HCO3- added than usual to the blood and plasma HCO3- is increased, thereby compensating for acidosis. The urine is highly acidic (lowest attainable pH = 4.4)
What are the renal responses to alkalosis?
- The rate of H+ secretion is inadequate to reabsorb all the filtered HCO3-, so significant amounts of HCO3- are excreted in the urine and there is little or no excretion of H+ on non-bicarbonate urinary buffers.
- Tubular glutamine metabolism and ammonium are decreased so that little or no new HCO3- is contributed to the plasma from this source
Result: Plasma HCO3- concentration is decreased, compensating for alkalosis. The urine is alkaline (pH >7.4)
What are the changes in the arterial concentrations of H+, HCO3- and CO2 in respiratory acidosis?
H+ –> high
HCO3- –> high
CO2 –> high
What is the cause of HCO3- change in respiratory conditions?
Renal compensation
What is the cause of CO2 change in respiratory conditions?
Primary abnormality
What are the changes in the arterial concentrations of H+, HCO3- and CO2 in respiratory alkalosis?
H+ –> low
HCO3 –> low
CO2 –> low
What are the changes in the arterial concentrations of H+, HCO3- and CO2 in metabolic acidosis?
H+ –> high
HCO3- –> low
CO2 –> low (compensatory)
What are the changes in the arterial concentrations of H+, HCO3- and CO2 in metabolic alkalosis?
H+ –> low
HCO3- –> high
CO2 –> high (compensatoy)
What is the cause of HCO3- change in metabolic conditions?
Primary abnormality
What is the cause of CO2 change in metabolic conditions?
Reflex ventilatory compensation
