Kidney Function IV- Regulation of Acid-Base status

• renal compensation for metabolic alkalosis:

  
  

  What occurs in the renal mechanisms during metabolic alkalosis?

  Type B intercalated cells of collecting duct function in metabolic alkalosis to:

  i) Remove bicarbonate into urine.

  ii) Acidify the plasma

  
  

  -> liver reduces glutamine production
• respiratory compensation for metabolic alkalosis

  
  

  What does the brainstem respiratory centre do when there is a metabolic alkalosis?

  pH changes will inhibit respiration, causing additional CO2 to be retained in the body. This and the resulting hypoxia will

  stimulate respiration.
• metabolic alkalosis

  
  

  What do chemical buffers do when there is a metabolic alkalosis?

  There is a decrease in [H+] concentrations so pH increases.

  There will be an increase in plasma [HCO3]. There will not be a significant direct rise in PCO2 as reaction will go to the left.

  H+ + HCO3 -> H2CO3 -> H2O + CO2
• metabolic alkalosis

  
  

  What is metabolic alkalosis?


  It's characterised by pH>7.45 with high plasma [HCO3-], caused by repeated vomiting, excess aldosterone or excess alkali ingestion
• renal compensation for respiratory alkalosis:

  
  

  What occurs in the renal mechanisms during respiratory alkalosis?

  Kidneys respond to fall in pCO2 with reduction in H+ secretion into tubules. There is now insufficient H+ to ensure the reabsorption of all the HCO3¯ in filtrate, and

  HCO3¯ is excreted in the urine, which is alkaline (pH.7.4). The end result is pCO2 is still low, pH high and [HCO3¯] low, but changes smaller than they would otherwise be.

  
  

  -> liver reduces glutamine production
• respiratory compensation for respiratory alkalosis:

  
  

  What does the brainstem respiratory centre do when there is a respiratory alkalosis?

  reduce ventilation
• respiratory alkalosis

  
  

  What do chemical buffers do when there is a respiratory alkalosis?

  [HCO3¯] decreases as some of it reacts with H+ to produce CO2 so both HCO3- and H+ decrease (pH rises).

  H+ + HCO3¯ -> H2CO3 -> H2O + CO2
• respiratory alkalosis

  
  

  What is respiratory alkalosis?

  It's caused by excessive central respiratory drive or hypoxic stimulation and excess CO2 is lost in the lungs and pCO2 falls <5.3kPa (hypocapnia).
• renal compensation for metabolic acidosis:

  
  

  What occurs in the renal mechanisms when there is a respiratory failure?

  - The kidneys increase H+ ion secretion which results in complete reabsorption of filtered bicarbonate.

  
  

  The liver will increase the release of glutamine into the blood and this will be metabolised in the kidney to add bicarbonate to the blood and to excrete acid in the form of ammonium

  --------> this makes the pH reduction smaller than it would have otherwise been but plasma pCO2 and bicarbonate will be elevated & there will still be acidosis.
• respiratory compensation for metabolic acidosis:

  
  

  What does the brainstem respiratory centre do when there is a metabolic acidosis?

  it will increase ventilation which will decrease pCO2
• Metabolic Acidosis

  
  

  What do chemical buffers do when there is a metabolic acidosis?

  the initial blood H+ will cause [HCO3-] to fall and pCO2 to rise.

  (because of the reaction H+ + HCO3- -> H2CO3 -> H2O +CO2)

  
  

  -> so blood H+ increases so PH decreases and this will lead to a reduction in [HCO3-]
• Metabolic Acidosis

  
  

  why do we calculate the anion gap?

  The anion gap helps determine the cause of the metabolic acidosis.
• Metabolic Acidosis

  
  

  How do you calculate anion gap in plasma?

  You assume that the sum of the cations (Na+ and sometimes K+ is used) is the same as the sum of the anions (Cl- and HCO3-) so if it's not, you look at the difference and that is the anion gap
• Metabolic Acidosis

  
  

  What is the anion gap due to?

  The presence of unmeasured anions which include proteins, phosphate, citrate and sulphate
• Metabolic Acidosis

  
  

  What is metabolic acidosis?

  It's characterised by a fall in plasma bicarbonate concentration which can be due to a true HCO3 deficit or by H+ gain
• renal compensation for respiratory acidosis:

  
  

  What occurs in the renal mechanisms when there is a respiratory failure?

  - The kidneys increase H+ ion secretion which results in complete reabsorption of filtered bicarbonate.

  
  

  The liver will increase the release of glutamine into the blood and this will be metabolised in the kidney to add bicarbonate to the blood and to excrete acid in the form of ammonium

  --------> this makes the pH reduction smaller than it would have otherwise been but plasma pCO2 and bicarbonate will be elevated & there will still be acidosis.
• respiratory compensation for respiratory acidosis:

  
  

  What does the brainstem respiratory centre do when there is a respiratory failure?

  The brainstem respiratory centre tries to adjust ventilation to expel CO2 (works in minutes)

  
  

  -> HOWEVER, if ventilation is an issue, then correction CANNOT come from a respiratory change
• respiratory acidosis

  
  

  What do chemical buffers do when there is a respiratory failure?

  
• respiratory acidosis

  
  

  What is something to be mindful of if the patient has respiratory disorders?

  They are likely to be hypoxic (low PaO2) as well because correction cannot come from a respiratory change
• respiratory acidosis

  
  

  What is chronic respiratory acidosis?

  The pCO2 in plasma is elevated >5.3kPa, with a normal/near normal pH, secondary to many disorders, and an elevated serum bicarbonate level >30mM.

  
  

  -> This can be due to airway obstruction, lung damage, chest wall disorder or neuromuscular disorder
• respiratory acidosis

  
  

  What is acute respiratory acidosis?

  The pCO2 is elevated >5.3kPa with an accompanying acidemia which is a result of abrupt failure in ventilation

  
  

  -> This can be due to a drug-induced respiratory depression or airway obstruction
• respiratory acidosis

  
  

  What are the 2 types of respiratory acidosis?

  Acute and chronic
• respiratory acidosis

  
  

  What is respiratory acidosis caused by?

  Insufficient CO2 excretion by the lungs (alveolar hypoventilation), which leads to increase H+ concentration and PH <7.35
• acid-base disturbances

  
  

  What is 'compensation'?

  When a primary acid-base disorder exists, the body attempts to return the pH to normal via compensation
• acid-base disturbances

  
  

  What equation shows the concept of acid-base disorders?

  
• acid-base disturbances

  
  

  What are the 2 forms of acid-base disorders?

  Respiratory and metabolic acidosis/alkalosis-

  respiratory is caused by a respiratory problem and metabolic is caused by a non-respiratory problem

  
• acid-base disturbances

  
  

  What is acidemia and alkalemia?

  Acidemia = blood pH <7.35 (caused by acidosis)

  Alkalemia = blood pH >7.45 (caused by alkalosis)
• Outline all the different mechanisms that maintain a constant pH in the body.

  1. Chemical buffers-

  works in seconds, bicarbonate in ECF, phosphate in ICF, phosphate or ammonia in urine

  
  

  2. Brainstem respiratory centre-

  works in minutes, responds to changes in arterial pCO2, pO2, and/or [H+], adjusts ventilation to retain or expel CO2

  
  

  3. Renal mechanisms-

  works in hours to days, for each H+ secreted, HCO3 is reabsorbed or new bicarbonate is added to plasma
• Hydrogen Excretion using Glutamine

  
  

  how is hydrogen excreted using Glutamine?

  - Glutamine from the tubular lumen or interstitial fluid enters the tubular epithelial cells and is metabolised into ammonium ions (NH4+) and bicarbonate (HCO3-)

  - ammonium ions (NH4+) enter the tubular lumen via a ammonium/sodium counter transporter and is excreted.

  - bicarbonate (HCO3-) goes into the blood.

  
• why does hydrogen excretion requires a buffer to be present?

  because unbuffered hydrogen ions would lower the pH to <5

  (this causes transporters on membranes and enzymes to not function optimally).

  So, PH 5 is the minimum value in which H+ pumps work.
• Hydrogen Excretion using a nonbicarbonate buffer (e.g. monohydrogen phosphate (HPO4 2-)

  
  

  How is hydrogen excreted using HPO4 2-?


  - H+ and HCO3- is formed in the tubular epithelial cells ( HCO3- goes into the blood)

  - H+ is secreted into the tubular lumen

  - H+ combines with HPO4 2- to form H2PO4-

  - H2PO4- is excreted, therefore H+ is excreted.

  
• Hydrogen Excretion

  
  

  what are the two methods of H+ excretion?

  - H+ ion combines with a nonbicarbonate buffer (e.g. monohydrogen phosphate (HPO4 2-)

  - via Glutamine
• Hydrogen Excretion

  
  

  What does the overall process of H+ excretion result in?

  It results in addition of new HCO3- to plasma
• reabsorbing bicarbonate:

  
  

  what happens to the hydrogen ion if there is no HCO3- in the tubular lumen?

  it is excreted
• reabsorbing bicarbonate:

  
  

  how is the H+ ion transported into the tubular lumen?

  By combination of:

  1. Na-H+ countertransporters (NH3)

  2. H+-ATPase pumps

  3. H+-K+-ATPase pumps
• reabsorbing bicarbonate:

  
  

  How is bicarbonate 'reabsorbed' in the kidney?

  H2O and CO2 combine in the tubular epithelial cells to form H2CO3, which dissociates into HCO3- and H+.

  -> the HCO3- (bicarbonate) is absorbed into the peritubular capillary into the blood

  -> the H+ ion is transported into the filtrate and combines with HCO3- (if it is present) to form H2CO3 which dissociates into H2O and CO2, which diffuses into the tubular epithelial cell so that the cycle starts again and no HCO3- is lost (overall it is reabsorbed)

  
• How is bicarbonate renally handled?

  It's freely filtered in the glomerulus but reabsorbed at PCT, ascending loop of Henle and type A intercalated cells of cortical collecting ducts to maintain normal plasma bicarbonate concentration & therefore plasma pH
• What is acid-base balance due to?

  2 related processes:

  1. Matching output (i.e. excretion) to input

  2. Regulating ratio of base to weak acid in buffers systems e.g. bicarbonate to carbonic acid
• why is the bicarbonate buffer short term?

  because sooner of later it will run out of bicarbonate
• How do the kidneys deal with bicarbonate changes?

  1. The kidney can reabsorb bicarbonate

  2. The kidney can rid the body of excess H+