Role of The Kidneys in The Regulation of Acid-Base Balance
Richard Thomas P. Lim, MD Assistant Professor I Department of Physiology Jonelta Foundation School of Medicine January 22, 2013
I. The Bicarbonate Buffer System II. Overview of Acid-Base Balance III. Net Acid Excretion by The Kidneys
A. Bicarbonate Reabsorption Along the Nephron B. Regulation of H Secretion C. Formation of New Bicarbonate
IV. Response to Acid-Base Disorders
A. Extracellular and Intracellular Buffers B. Respiratory Compensation C. Renal Compensation
V. Simple Acid-Base Disorders
A. Types of Acid-Base Disorders
1. 2. 3. 4. Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis Respiratory Alkalosis
B. Analysis of Acid-Base Disorders
Acids and Bases
• Diet • Cellular metabolism • Kidney, lungs, liver
• Acid – adds H to body fluids • Alkali – removes H from body fluids
Each day, we ingest a variety of acidic and basic substances. Also, cellular metabolism produces acids and bases. Without proper regulation of the pH of the body, many biochemical reactions necessary for life might not occur. For this lecture, we will be focusing on how the kidneys regulate the body’s pH. However, aside from the kidneys, the lungs and liver also help in maintaining a normal pH of the body. An acid is defined as any substance that adds H to body fluids while alkali or bases remove H from the body fluids.
It can potentially buffer up to 350meq of H. The enzyme carbonic anhydrase speeds up this reaction. and is the rate-limiting step.
. such as the phosphate. The first reaction is slow.Bicarbonate Buffer System
• Buffer of ECF • Regulated by both kidneys and the lungs
The bicarbonate buffer system is an important buffer of ECF. The dissociation of carbonic acid occurs instantaneously. It is different from the other buffer systems in the body. because it is regulated by both the kidneys and the lungs.
Suffice it to say at this point that any change in PCO2 or any change in bicarbonate will alter the pH or the H concentration of the body.Change in bicarbonate – metabolic acid-base disorder Change in PCO2 – respiratory acid-base disorder Kidneys – bicarbonate Lungs – PCO2
This equation is derived from the HH equation. The kidneys are responsible for regulating the bicarbonate while the lungs regulate the PCO2
. this is called a respiratory acid-base disorder. When the alteration in pH is due to a change in bicarbonate. this is called a metabolic acid-base disorder. When the alteration in pH is due to a change in PCO2.
Ingestion of acidic comounds. aklasis will occur.Acid Balance
Acid production/ingestion = acid excretion Acidosis – addition > excretion Alkalosis – addition < excretion
As we have discussed repeatedly in the past. acidosis results.
. If excretion is more than the addition of H. regulation of any compound in the body depends on the amount ingested or produced and the amount excreted. If addition of H is greater than the excretion. or the production of acids from cellular metabolism must be equal to the amount of acid excreted in order to maintain a normal body pH.
eliminated immediately. CO2 does not impact acid-base balance. It is the only volatile acid.
. All the other acids produced in the body are non-volatile acids. Because of this. does not impact acid-base balance • Non-volatile acid – not derived from CO2s
Carbon dioxide is eliminated immediately from the lungs. These are acids not derived from CO2. It is called as such because it has the potential to generate H from the hydration of CO2.Volatile and Non-volatile
• Volatile acid – derived from CO2.
• Dietary intake – meat • Cellular metabolism • Feces – bicarbonate loss • Net addition of nonvolatile acid
the kidneys must be able to replenish the bicarbonate needed. the body gets a net addition of nonvolatile acids from different processes. These nonvolatile acids are immediately neutralized by bicarbonate.Normally. Our bicarbonate stores. if not replenished would only last us 5 days. Metabolism of certain amino acids yield acids. composed of protein – amino acids yield a net production of acids. while only a few result to production of a basic compound. To continually neutralize these acids. Cellular metabolism also result to a net production of acids.
. All of these processes result in a net addition of volatile acids. The acids formed from these processes are neutralized by bicarbonate. Remember that volatile acids are acids not derived from the hydration of carbon dioxide. Bicarbonate is also lost in the feces. thereby forming Na salts and consuming bicarbonate in the process. Thus dietary intake of meat yield acids. Intake of meat.
while only 100meq of HCO3 are needed to neutralize the production of nonvolatile acids.Net Acid Excretion by Kidneys
• Acid excretion = acid production • Prevent bicarbonate loss in urine • 4320 meq HCO3 – filtered load • 100meq HCO3 – needed for nonvolatile acids
Normally. the kidneys must also prevent loss of bicarbonate in the urine.
. In addition. The reabsorption of HCO3 is quantitately more important because we can potentially lose so much HCO3 from the urine. because we need the bicarbonate to neutralize the production of nonvolatile acids. The filtered load of bicarbonate is about 4320 meq/day. the acid excreted by the kidneys is equual to the amount of acid production.
. These include phosphate.Titratable Acids
• Way of excreting H • Urinary buffers – phosphate.0.0 already. aside from being secreted as H in the urine is via titratable acids. if the urine has a pH of 4. creatinine
• Maximum urine pH 4. Therefore.0 • Way of excreting excess H beyond maximum pH
The kidneys are unable to excrete urine with a pH of less than 4. These collective term refer to compounds found in the urine which bind H and serve as another means of excreting H. how will the kidneys excrete the excess H? Another way of excreting H. creatinine and other urine constituents.
• Way of excreting H • Ammonium lost = bicarbonate returned
Remember that there is an overall excess of H in the body produced from the processes discussed earlier. We talked about titratable acids earlier as one way of excreting H. However.
. Ammonium serves another way of excreting H in the urine. this method is not enough to handle the load from production of nonvolatile acids.
Net Acid Excretion NEA
Rate of ammonium excretion Rate of titratable acid excretion Amount of bicarbonate lost in urine
• Maximized when little bicarbonate lost • Bicarbonate freely filtered and almost entirely reabsorbed
This is the equation for net acid excretion. This is actually normally the case because bicarbonate is freely filtered is almost entirely reabsorbed. we can see that NAE is maximized when little or no bicarbonoate is lost in the urine. From the equation.
. Net acid excretion is equal to the rates of excretion of ammonium and titratable acid minus the amount of bicarbonate lost in the urine.
Almost no bicarbonate is lost in the urine. The PT reabsorbs most of the bicarbonate and the other segments are able to reabsorb what is left of the filtered bicarbonate.This figure shows how much bicarbonate is reabsorbed by the different segments of the nephron.
Proximal Convuluted Tubule
H goes out via the NaH antiporter. H will combine with bicarbonate to form carbonic acid.once in the tubular fluid. CA present in the brush border catalyzes the dehydration reaction to yield CO2 and H2O which then diffuse back to the tubular cell. H is secreted out via the mechanisms discussed earlier while bicarbonate is reabsorbed back to the blood via either a Na3HCO3 symporter or a Cl-HCO3 antiporter. As Na gets in. they again react via carbonic anhydrase which will yield H and bicarbonate. This creates a gradient for Na to be transported from the tubular fluid into the tubular cell. Inside the cell.
.H is actively tranported out of the tubular cell via a NaH antiporter or a H ATPase. The NaK ATPase maintains the intracellular concentration of Na low. This is the predominant pathwya for H secretion. The H ATPase directly uses ATP to transport H out of the tubular cell.
DT and CD
• Two types of intercalated cells
– Alpha – secrete H/reabsorb bicarbonate – Beta – secrete bicarbonate
Distal tubule and collecting duct
For the other protein. The secreted H combines with bicarbonate to form carbonic acid which then dissociates to CO2 and H2O.
.H is secreted from the alpha cell via two pathways: HK antiporter and an HATPase. Carbonic anhydrase form bicarbonate and H. H is secreted again via the two mechanisms described above while bicarbonate is reabsorbed back to the blood via a Cl-HCO3 antiporter. These then diffuse back to the cell. Movement of K into the cell is coupled with the movement of H out of the cell. ATP is used to pump H out of the cell.
Distal tubule and collecting duct
. secrete bicarbonate. The Cl-HCO3 antiporter is located at the apical side while the H ATPase is located in the basolateral side. The key difference in this cell compared to the alpha or H secreting/ bicarbonate reabsorbing cell is the location of the H ATPase and the Cl HCO3 antiporter. instead of reabsorbing bicarbonate.The beta cells.
5 because H is reabsorbed. because H is not reabsorbed and persists in the urine. The DT and CD are not very permeable to H. ph 4. The urine in this segment will then be less acidic pH 6. • Which segment is the most acidic of them all?
The segments of the nephron have different permeabilities to H and bicarbonate.
.0. thus it is able to reabsorb more H and bicarbonate. The proximal tubule is the most permeable to H and bicarbonate.Most acidic of them all
• PT has higher permeability to H and HCO3 than DT and CD. Thus the urine at this segment will be very acidic.
Regulation of H Secretion
• Acidosis – stimulate H secretion • Alkalosis – reduce H secretion
Acidosis or an excess of H will promote secretion of H while alkalosis will reduce the secretion of H. Gets agad.
. O di ba etong part na to madali lang intindihin.
• Immediate – decrease in intracellular pH
– Cell-to-tubular fluid H gradient – Allosteric changes in transport proteins – More transporters shuttled to the membrane
• Long term
– Increased synthesis of transport proteins
– Endothelin – Cortisol
Hormones also mediate these changes in H transport proteins. the tubual cells synthesize more transport proteins for H secretion.
When metabolic acidosis becomes prolonged. Another immediate result of a decrease in pH is the transport of more transport proteins into the membranes of these cells.Depending on how long metabolic acidosis has been occuring. there may be immediate and long term changes occurring in the cells of the nephron. This will create a more favorable cell-to-tubular fluid gradient for H secretion. which result to enhancing their ability to secrete more H. More transport proteins means more H can be secreted out of the cell. The increase in acidity also causes allosteric changes in the transport proteins in these cells. These are endothelin and cortisol. Metabolic acidosis causes the pH inside the tubular cell to decrease.
• Produced from endothelial and proximal tubule cells • Stimulated by acidosis • Insertion of NaH and Na-3HCO3 into the apical and basolateral membranes
Endothelin is produced from the endothelial cells and in the proximal tubule cells. Secretion of this hormone is stimulated by acidosis. This hormones promotes insertion of transport proteins in the tubular cells which facilitate secretion of H
• Produced from adrenal cortex • Stimulated by acidosis • Increases transcription and translation of NaH antiporter and Na-3HCO3 symporter genes
Secretion of coritsol is also stimulated by acidosis from the adrenal cortex. This homone increases the transcription and translation of genes coding for transport proteins which will facilitate H secretion
• Increase in intracellular pH • Inhibits H secretion • Mechanisms reversed for acidosis
In alkalosis, the changes we have discussed are reversed. Alkalosis will increase intracellular pH. A decrease in the H concentration inside the tubular cells will inhibit secretion of H because of a less favorable gradient for H transport out of the cell.
Na affects H and HCO3
• Na affects H secretion • NaH antiporter
• Glomerulotubular balance – GFR and PCT reabsorption • ↑ GFR - ↑ filtered Na and HCO3 - more bicarbonate reabsorbed
In the proximal tubule and the loop of Henle, the NaH antiporter is involved in H secretion. Since this is an antiporter, change in Na will also affect H secretion. This will also translate to a change in bicarbonate reabsorption since H secretion is also linked to bicarbonate reabsorption. Glomerulotubular balance matches the reabsorption at the PCT with the GFR. Thus when the GFR increases, there will be more fluid reaching the PCT, and thus it will also reabsorb more fluid, containing Na and HCO3.
or a Na deficit.Volume Contraction
• Negative Na balance • H secretion is enhanced via activation of RAAS • ↓Peritubular capillary hydrostatic pressure
H secretion is also enhanced when there is volume contraction. There is a decrease in peritubular capillary hydrostatic pressure. This condition activates the RAAS.
. which enhances Na and water reabsorption. we talked about the changes occuring in volume contraction. whose overall effect is to retain water by reabsorbing more Na. In our previous lecture.
Aldosterone on the other hand acts on the DT and CD. It stimulates the NaH antiporter and Na-HCO3 symporter.
. the lumen becomes more electro negative or it hyperpolarizes the transepithelial voltage. Increasing the activity of these proteins will reabsorb more Na and secrete more H. This will then facilitate the secretion of positively charged H into the lumen.Volume Contraction
• Angiotensin II – PCT – Stimulate NaH antiporter and Na-HCO3 symporter – Insertion of more transporters • Aldosterone – DT and CD – Hyperpolarizes transepithelial voltage – Stimulate Na reabsorption in principal cells – Stimulate H secretion by intercalated cells
Angiotensin II acts on the PCT. It also inserts more of these transport proteins in the cells of the PT. When it stimulates Na reabsorption in the principal cells.
Proximal Convuluted Tubule
. The NaK ATPase maintains the intracellular concentration of Na low. H is secreted out via the mechanisms discussed earlier while bicarbonate is reabsorbed back to the blood via either a Na3HCO3 symporter or a Cl-HCO3 antiporter.once in the tubular fluid. H will combine with bicarbonate to form carbonic acid. This is the predominant pathwya for H secretion. CA present in the brush border catalyzes the dehydration reaction to yield CO2 and H2O which then diffuse back to the tubular cell. The H ATPase directly uses ATP to transport H out of the tubular cell. Inside the cell.H is actively tranported out of the tubular cell via a NaH antiporter or a H ATPase. H goes out via the NaH antiporter. As Na gets in. they again react via carbonic anhydrase which will yield H and bicarbonate. This creates a gradient for Na to be transported from the tubular fluid into the tubular cell.
Late distal tubule and collecting duct
H2O Cl Cl H2O
it maintains a low intracellular sodium. Again.
. the principal cell and the intercalated cell. and chloride. since positively charged sodium ions are removed from it. This will then form a gradient for Chloride to be passively reabsorbed through the gap junctions via the paracellular pathway. The reabsorption of sodium. In the intercalated cell. We have now discussed how sodium. Potassium uptake from the blood is done by the NaKATPase. The reabsorption of Na. water is also reabsorbed in the principal cells via aquaporin channels located both in the apical and basolateral membranes of the tubular cells.The late distal tubule is composed of two cells. This will be further discussed in the succeeding lectures. creates a relative negative charge on the tubular fluid. and secretion of K depends on the activity of the NaK ATPase. Aside from sodium. chloride and water are reabsorbed by the principal cells. This increases the K inside the principal cells. Sodium then enters the blood via the action of the NaKATPase. K is reabsorbed via a K-H ATPase. creating a gradient which allows Na to be reabsorbed passively through Epithelial Na-selective channels or ENaC in the apical membrane. Let’s first discuss what the principal cell does. thus it is important in regulating acid-base balance. K then moves out of the cell via diffusion.
Now we move on to how potassium is secreted in the principal cell. It secretes either bicarbonate or H. down its concentration gradient via apical cell membrane K channels.
An increase in peritubular capillary hydrostatic pressure will inhibit Na reabsorption during volume expansion. or positive Na balance.
. The RAAS will not be activated thus there will be low angiotensin and aldosterone which promote Na reabsorption and H secretion in the tubules.Volume Expansion
• • • • Positive Na balance H secretion is reduced Low angiotensin and aldosterone ↑ Peritubular capillary hydrostatic pressure
During volume expansion. Less Na is reabsorbed from the tubules thus less H will be secreted via the NaH antiporter. Inhibition of Na reabsorption will also inhibit secretion of H. H secretion is reduced.
During acute acidosis.PTH
• Acute – inhibits H secretion
– Inhibits NaH antiport – Endocytosis
• Chronic – stimulates H secretion
– TAL. This constitutes the renal response to acidosis which is to secrete H. PTH will stimulate the kidney to secrete H.
. During chronic acidosis. DT – Renal response to acidosis
PTH has both as stimulatory and an inhibitory role in secretion of H. PTH will inhibit secretion of H by inhibiting the action of the NaH antiporter and promoting endocytosis of transport proteins in the apical membranes.
Aside from this mechanism. which inhibits H secretion. Hypokalemia acidifies the cells of the tubules. hypokalemia also increases the experssion of HKATPase at the intercalated cells.inhibts H secretion • K-induced cellular changes
Changes in K also alter H secretion. K-induced cellular changes are thought to influence the secretion of H from the tubular cells. Hyperkalemia. alkalinizes the tubular cells. which promote H secretion.K
• Hypokalemia – acidifies tubular cells promotes H secretion.
. on the other hand. increased HKATPase expression in intercalated cells • Hyperkalemia – alkalinizes tubular cells .
and also to maintain acid-base balance. the kidneys reabsorb bicarbonate. The kidneys must form new bicarbonate to replenish the bicarbonate lost. However. this is not enough to replenish the bicarbonate lost from neutralizing the nonvolatile acids.
.Formation of New Bicarbonate
• Reabsorption of HCO3 not enough • Formation of HCO3 needed • Excretion of titratable acid • Excretion of NH4
To maintain acid-base balance. Generation of new bicarbonate is done by excreting titratable acid and excretion of ammonium.
or urinary buffers such as phosphate. Formation of titatable acid is not sufficient to generate the appropriate amount of bicarbonate.
. Thus the tubular fluid reaching the DT and CD have very little amounts of bicarbonate available to neutralize the secreted H. formation of H also forms bicarbonate which is reabsorbed back into the blood. Instead of combining with bicarbonate. Since the secreted H is formed inside the cell. This is augmented by the formation and excretion of ammonium.Titratable Acid
• HCO3 reabsorbed in PT and loop of Henle • Little HCO3 reach DT and CD • Secreted H combines with nonHCO3 buffers (P)
• Insufficient to generate required amount of HCO3
The proximal tubule and the loop of Henle reabsorb bicarbonate. H will combine with non-HCO3 compounds.
. which occurred inside the cell. also generates bicarbonate via the action of CA. which is needed to neutralize the formation of nonvolatile acids. This bicarbonate is reabsorbed back into the blood. The generation of H. Since the tubular fluid reaching the DT and CD have low amount of bicarbonate. the secreted H will combine with urinary buffers such as phosphate.This slide shows how the formation of a titratable acid is able to generate bicarbonate. The combined H-buffer is then excreted into the urine.
secreted in the CD • 1 ammonium excreted = 1 bicarbonate returned
The synthesis and excretion of ammonium result to addition of bicarbonate to the ECF. a process called ammoniagenesis. reabsorbed in TAL. Ammonium is synthesized and secreted from the PCT.
. It is then reabsorbed in the TAL. secreted again in the CD before getting excreted into the urine.Ammonium
• Synthesis and excretion result to addition of bicarbonate to ECF • Produced from glutamine – ammoniagenesis • Secreted from PCT. Ammonium comes from the breakdown of glutamine. Excretion of 1 molecule of ammonium will result to a return of 1 molecule of bicarbonate to the ECF.
let’s talk about how ammonium is excreted and why it is important. we already have returned molecules of bicarbonate back to the ECF.
. Now. First let’s look at the cell of the PCT.This slide shows the complicated synthesis and excretion of ammonium. and how this process is able to generate bicarbonate. Glutamine is degraded into ammonium and an anion (2-oxoglutarate). This is where ammoniagenesis occurs. At this point. Metabolism of this anion will yield 2 molecules of bicarbonate which will be reabsorbed back into the peritubular capillary.
it will be converted to urea by the liver. Thus if ammonium is not excreted or is reabsorbed. because if not. The formation of bicarbonate and ammonium from glutamine is not enough. Ammonium still has to be excreted. which will then be needed to be neutralized by consuming another bicarbonate. it will be reabsorbed. When it is reabsorbed. we will not be able to generate bicarbonate but instead will consume another bicarbonate. NH4+ → urea
– Generates H – Consumes bicarbonate
The excretion of ammonium involves a complex process. as we will discuss later.
.Excretion of Ammonium
• Complex • If not excreted. This process will yield an additional H.
Ammonium secreted from the PT
It may also be deprotonated to ammonia. with ammonium substituting for H.Now let’s discuss how ammonium is excreted. ammonia is then protonated again because of the secreted H from the PT. which can then diffuse out of the PT.
. Once in the tubular fluid. We have formed ammonium from the metabolism of glutamine. Ammonium can be secreted from the PT by a NaH antiporter. We have now secreted ammonium from the PT.
Majority of the ammonium secreted from the PT gets reabsorbed in the TAL.
Ammonium reabsorbed in the TAL
-Na-K-2Cl symporter -Positive transepithelial luminal voltage
. the ammonium moves to the medullary interstitium. The reabsorption of ammonium at this segment is mediated by the NaK2Cl symporter and a positive transepithelial luminal voltage. From the TAL.
Secretion of Ammonium from CD
• From interstitium to CD • First mechanism
– Nonionic diffusion – NH3 diffuses into CD – Diffusion trapping – CD less permeable to NH4+
• Second mechanism
– NH4-H antiporters
Secretion of ammonium moves ammonium from the interstitium back into the lumen of the CD.
. Secretion of ammonium involves two mechanisms: noniondic diffusion and diffusion trapping and via NH4-H antiporters.
Secretion of NH4+ in the CD
-nonionic diffusion -diffusion trapping
From the medullary interstitium. This will then form ammonium again. The CD is les permeable to ammonium than ammonia because ammonium has a charge. Once inside the lumen of the CD. ammonium is excreted out into the urine. ammonia will be protonated by H secreted from the intercalated cell of the CD. ammonium diffused into the CD as ammonia. This is nonionic diffusion. ammonium will not be reabsorbed back into the interstitium.
. This is diffusion trapping. Once trapped in the tubular lumen.The first mechanism for the secretion of ammonium involves two processes: nonionic diffusion and diffusion trapping. Once in the tubular fluid.
The secreted ammonium is then excreted in the urine. This antiporter secretes ammonium out of the cell and transfer H back into the cell.
.Secretion of NH4+ in the CD
The second mechanism for the secretion of ammonium in the CD involves this antiporter.
45.Response to Acid base Disorders
• pH 7.45 • Extracellular and intracellular buffering • Respiratory compensation • Adjustments in renal net acid secretion • Minimize change in pH
The body’s pH is maintained at a very narrow range. When there is a change in the body’s pH. at pH 7.
.35 to 7. the body employs several mechanisms to defend against the changes in pH. These mechanisms do not correct the pH but just minimizes the change in pH imposed the a certain condition.35 to 7. The body pH changes when there is any alteration in either the pCO2 or the bicarbonate.
• First line of defense • Extracellular – instantaneous • Intracellular – slower.
. buffering pH in minutes. minutes
Intracellular and extracellular buffers are the first line of defense against any changes in pH. Effects of extracellular buffers are instanteneous while intracellular buffers are slower.
. or proteins inside the cell.Buffer Mechanism
• Extracellular – Acid added – neutralized by HCO3 – HCO3 consumed – Alkali added – neutralized by H – more HCO3 produced from H2CO3 • Intracellular – acid added – H moves into the cell – alkali added – H moves out of the cell
In extracellular buffers. when acid is produced or added into the body. This process will consume H. this will promote movement of H into the cells. The H inside the cell will then be buffered by bicarbonate. it will be neutralized by H. In intracellular buffering. When alkali is added. which is produced from carbonic acid. this will promote H to move out of the cell so it can buffer the H outside. This consumes the bicarbonate thus lessening the bicarbonate concentration in the ECF. When alkali is added. when acid is added. but will also produce more bicarbonate as well. phosphate. this acid is neutralized by bicarbonate in the ECF.
Phosphate and plasma proteins provide additional buffering capacity. B.Bida ang Bicarbonate
• Bicarbonate buffer system – principal buffer of ECF • Phosphate and plasma proteins provide additional ECF buffering
The principal buffer in the ECF is the bicarbonate buffer system.bicarbonate = Bida
HCO3 in Respiratory acid-base
↓ PCO2 ↓ CO2 inside cell ↑ PCO2 ↑ CO2 moves inside cell
↓ bicarbonate goes out ↓ ECF bicarbonate
↑ bicarbonate goes out ↑ECF bicarbonate
When there is an increase in PCO2 or respiratory acidosis. less CO2 will be inside the cell. more CO2 will move inside of the cell. there will be less bicarbonate which will go out of the cell.
. This will then increase the ECF bicarbonate and thus decrease the change in pH induced by the increase in pCO2. This will shift the reaction towards the formation of more H and HCO3. And the ECF bicarbonate will decrease. Thus.This is how bicarbonate buffers the ECF during respiratory acid-base disturbances. The formed H is buffered intracellularly while the bicarbonate goes out of the cell. if the pCO decreases.
On the other hand. This will shift the reaction towards the dissociation of carbonic acid to CO2 and H2O.
↑RR • ↓H .↓ pH .Respiratory Compensation
• 2nd line of defense • Response occurs in hours • Chemoreceptors in brainstem.↑ pH .↓RR
. aortic bodies sense changes in pCO2 and H • ↑ H . carotid.
carotid and aortic bodies sense changes in pCO2 and H.Based on the HH equation. the respiratory rate will be decreased so that more CO2 will be retained. These will then determine the ventilatory rate. or a decrease in H. any change in pCO2 will alter the body’s pH. the respiratory rate is increased so that more CO2 will be blown off and the pCO2 will decrease. When there is metabolic acidosis. Chemoreceptors found in the brainstem.
. Adjustments in ventilatory may be initiated immediately but full compensation might require several hours to complete. or an increase in H. This will then decrease the H. If there is metabolic alklaosis. This will then increase the H.
• 3rd line of defense • Response takes several days to complete
Renal adjustment to acid base disorders is the 3rd line of defense. It takes several days for the kidneys to adjust so that the pH is maintained at normal values.
. Since there is excess of H. When these compounds are formed. ↑ production and excretion of NH4. bicarbonate is also formed and is reabsorbed into the blood. the tubules will secrete more H. ↑ bicarbonate production – ↑ ECF bicarbonate
When there is acidosis. The entire filtered load of bicarbonate is also reabsorbed. excretion of titratable acid and NH4 will increase as well. This will then increase the ECF bicarbonate and restore the pH back to normal.Renal Adjustment
– ↑H secretion – entire filtered HCO3 reabsorbed – ↑excretion of titratable acid.
there will be an increase in the filtered load of bicarbonate since there is an excess of bicarbonate in the blood.Renal Adjustment
– ↑filtered load of HCO3. A decrease in H secretion will also decrease synthesis and excretion of titratable acid and ammonium resulting a decrease in net acid excretion. ↓H secretion – ↑ HCO3 excretion. Bicarbonate excretion will increase and thus bicarbonate will be found in the urine. ↓ net acid excretion – ↓ ECF bicarbonate
When there is alkalosis. All these processes will decrease ECF bicarbonate to restore pH back to normal. ↓ titratable acid and NH4 excretion – HCO3 in urine.
. Secretion of H in the collecting duct will be inhibited.
but does not correct the underlying cause of the acid base disorder
.Acid Base Disorders
• Compensation only reduces the change in pH.
the 3 defense mechanisms we discussed earlier are used. In respiratory acid base balance. To compensate for this. this is buffered by the ICF and the kidneys by decreasing net acid excretion. there is a decrease in pCO2. There is hyperventilation to decrease the pCO2 and increase in renal net acid excretion to balance out the increase in pH. only two mechansims are involved for compensation. to try to maintain the pH at values which will still allow for life to continue without any problems. Once these mechanisms are overwhelmed. the primary problem is an excess of bicarbonate. If you have alkalosis. since the respiratory system is already the problem. In metabolic acidosis.
. In metabolic alkalosis. there is a decrease in pH. When you have acidosis. there is an increase in pCO2. this is buffered by the ICF and the kidneys by increasing net acid excretion..Acid base disorders include the following 4 disorders. same mechanisms are involved to decrease the change in pH. you have an increase in your pH. The compensation does not correct the underlying cause of the acid base disorder. the primary problem is a deficiency in bicarbonate in the ECF. The compensations we discussed only reduce the change in pH. There will be hyperventilation and a decrease in net acid excretion to compensate for the increase in pH. the acid base disorder will still persist unless the underlying cause has been resolved. In respiratory acidosis. In respiratory alkalosis. Again.
↓PCO2 – ↑NEA
The causes of metabolic acidosis include addition of acid such as in diabetic ketoacidosis. and the compensation for the change in pH is mediated by the buffers.
. The primary problem here is a deficiency in bicarbonate. loss of base as in diarrhea and failure to excrete H when you have renal failure.diabetic ketoacidosis – Loss of base – diarrhea – Failure to excrete H – renal failure
• Compensation – Buffering in ICF and ECF – ↓pH – stimulates respiratory center .↑RR . and increasing secretion of H by the kidneys.• Causes – Addition of acid . decreasing the pCO2 by increasing the RR.
this is buffered by the ICF and ECF.↑ PCO2
Metabolic alkalosis is caused by addition of base such as in ingestion of antacids.
.↓RR .Metabolic Alkalosis
• Causes – Addition of base – ingestion of antacids – Volume contraction – hemorrhage – Loss of acid – vomiting
• Compensation – Decreased HCO3 reabsorption – ↑pH – inhibits respiratory center . The primary problem here is an excess of bicarbonate. the respiratory rate is decreased to increase the pCO2 and the kidneys decrease the secretion of H. volume contraction such as in hemorrhage and loss of acid during vomiting. To offset this.
Respiratory acidosis is primarily caused by a decrease in gas exchange. The compensation in respiratory acidosis is done by the kidneys by reabsorbing more HCO3 and excretion of more titratable acid and NH4.
. the buffering of the ICF maintain the pH at accetable levels. or impairment in gas diffusion such as in pulmonary edema. NH4 . probably from depression of the respiratory center. however.• Decreased gas exchange – Inadequate ventilation (drug induced depression of respiratory center) – Impaired gas diffusion (pulmonary edema)
• Compensation – Acute – ICF buffering – Chronic – renal . This is usually caused by inadequate ventilation. this response will take several days so in the acute setting.Stimulate HCO3 reabsorption and excretion of titratable acid.
the ICF does the buffering while in the chronic phase. and the excretion of titratable acid and NH4 are also reduced. NH4 .Respiratory Alkalosis
• Increased gas exchange – Increased ventilation (stimulation of respiratory centers. In the acute phase. anxiety or pain. such as when the respiratory centers are stimulated or by hyperventilation caused by fear.
. the reabsorption of HCO3 is inhibited. hyperventilation)
• Compensation – Acute – ICF buffering – Chronic – inhibit HCO3 reabsorption.↓ NEA
Respiratory alkalosis is caused by an increase in gas exchange. This may occur when there is increase in ventilation. These events will lead to a decrease in net acid excretion to compensate for the alkalosis. reduce excretion of titratable acid.
Analysis of Acid-Base Disorders
• pH 7.35-7.45) • HCO3 = 16 (24) • PCO2 = 30 (40)
• Interpret this ABG result.
acidosis • 2. metabolic • 3.Answer
• 1. compensated
• The kidneys also prevent the loss of HCO3.Key Concepts
• The kidneys maintain acid-base balance through the excretion of an amount of acid equal to the amount of nonvolatile acid produced by metabolism and the quantity ingested in the diet.and excretion of acid are accomplished via secretion of H+ by nephrons
. • Both reabsorption of the filtered HCO3.in urine by reabsorbing virtually all the HCO3filtered at the glomeruli.
Acid is excreted by the kidneys in the form of titratable acid (primarily as Pi) and NH4+.
• . which replenishes the ECF HCO3. • Excretion of both titratable acid and NH4+ results in the generation of new HCO3-.lost during the neutralization of nonvolatile acids.
• The body uses three lines of defense to minimize the impact of acid-base disorders on body fluid pH: (1) ECF and ICF buffering. (2) respiratory compensation. and (3) renal compensation.
• An increase in ECF [HCO3-] causes alkalosis. which decreases PCO2.Key Concepts
• Metabolic acid-base disorders are caused by primary alterations in ECF [HCO3-]. pulmonary ventilation is increased.
. Renal net acid excretion is also decreased. This response may take several days. • In response to metabolic acidosis. which elevates PCO2. This decreases pulmonary ventilation. which in turn result from the addition of acid to or loss of alkali from the body. • The pulmonary response to metabolic acid-base disorders occurs in a matter of minutes. and renal net acid excretion is increased.
• Respiratory acid-base disorders result from primary alterations in PCO2.
. a reduction in PCO2 produces alkalosis. • Conversely. and renal net acid excretion is reduced. and the kidneys respond with an increase in net acid excretion. • Elevation of PCO2 produces acidosis. • The kidneys respond to respiratory acid-base disorders over a period of several hours to days.