Acid-Base Balance Flashcards
What are the blood buffering systems?
Bicarbonate
Bicarbonate ions will ‘mop up free hydrogen ions to create carbonic acid which is held in equilibrium with carbon dioxide and water
H+ + HCO3- ->
How does each buffer act pH wise?
Notice how the curve for bicarbonate is to the left of that for phosphate
Bicarbonate buffers within a range that is below the physiological pH where as phosphate’s is closer to the physiological pH
So each has its effective ranges
What do all buffers obey?
All buffers obey the Henderson-Hasslebalch Equation
Most important is the [HCO3–]:[CO2] ratio
Plasma [CO2] proportional to the partial pressure of CO2 (pCO2) in plasma
Mathematical constant to convert pCO2 (mmHg) to [CO2] mmol/L is 0.03, hence:
» measured clinically a ratio of ~20:1
» measure pH with arterial blood gases (ABG)
What are the pros and cons of bicarbonate buffering?
What we would want from a good buffer:
-pK = equilibrium constant of reaction
-Buffer solutions resist change in pH when [base] = [acid]
-Buffer is most effective “1 pH” on either side of pK
At 6.1 the pK of CO2-HCO3 buffer not close to desired plasma pH of 7.4
From a purely chemical point-of-view, it is not a great choice!
However:
An abundant source – CO2 from metabolism
Independent regulation:
Alveolar ventilation controls PCO2
Kidneys control [HCO3–]ECF
How are acid-base levels controlled on a renal level?
Kidneys control acid-base levels by excretion of acidic or basic urine
Primary renal mechanisms involved in this are:
-“Re-absorption” and secretion of HCO3-
-Formation of “new” HCO3-
-Secretion of [H+] into tubular fluid
Buffer systems within tubule that react with secreted [H+] are:
HCO3-:H2CO3 ratio
HPO42-:H2PO4- ratio
NH3: NH4+ ratio
What happens to each buffer once they enter the kidneys?
Three main buffers in plasma enter protein
The protein does not pass the glomerulus so stays in the plasma
Phosphate ions reabsorbed from tubule
Bicarbonate ions will be “reabsorbed” from the tubule
The kidney also generates new HCO3- which is then released into plasma at a controlled rate
The kidney also produces ammonia which contributes to buffering within the tubule
Ultimately this comes together to produce urine that is acidic
How is [H+] controlled via [HCO3-] in the kidneys?
The most important reaction is the reaction between water and CO2 producing carbonic acid, catalysed by carbonic anhydrase whose activity depends on the [H+] in ECF
This carbonic acid dissociates into a bicarbonate ion and a hydrogen ion
The hydrogen ion is removed to the lumen either using a sodium hydrogen antiporter or pumped out through ATP proton pumps which enters the urine and acidifies it
At the same time, molecules of bicarbonate are excreted via a sodium bicarbonate symporter
Acetazolamide and other thiazide diuretics would inhibit carbonic anhydrase
What happens to HCO-3 in the proximal tubule?
85-90% of filtered HCO3- “reabsorbed”
Great capacity to secrete [H+]
There will be bicarbonate crossing the glomerulus and entering the tubular fluid
This bicarbonate reacts with a hydrogen ion creating carbonic acid and via the activity of carbonic anhydrase creates carbon dioxide and water
The water goes out with the urine but the carbon dioxide can pass transcellularly into the ECF
But it can also feed in again to react with water molecules to create carbonic acid then bicarbonate to be exported into the ECF
How do phosphate buffers work in the kidneys?
Further H+ secreted into lumen buffered by HPO42-
Very effective buffer because pK=6.8 (close to pH of filtrate)
In this case protons are pumped out via an ATPase that is aldosterone sensitive
The dihydrogen phosphate molecule reacts with the proton to create dihydrogen phosphate which is excreted into the urine
In these cells the bicarbonate ions are removed form the cell via an antiporter that uses chloride that diffuses out via a channel
How does the ammonia buffer work?
Tubular epithelium produces NH3 from glutamine with the enzyme glutaminase
That produces alpha-ketoglutarate and 2 ammonia molecules
The alpha-ketoglutarate is metabolised into 2 carbonic acid molecules which breaks down into 2 protons and 2 bicarbonate ions
The protons will combine with the 2 ammonia molecules to produce 2 ammonium ions which traverse into the lumen via a sodium-based antiporter and excreted as ammonium salts in the urine
The bicarbonate is secreted into the ECF via a sodium-dependent symporter
So one glutamine molecule gives rise to 2 molecules of bicarbonate
Excretion of ammonium salts increases tenfold during metabolic acidosis
What happens if there is a disturbance in the acid-base balance?
Role of the respiratory system
Chemo-sensitive area in medulla oblongata regulates respiration
Monitors [H+] of plasma indirectly, via CSF
Charged ions can not cross BBB, but CO2 can diffuse across and react with water through the action of carbonic anhydrase form carbonic acid which will dissociate to give hydrogen ions and bicarbonate ions
The chemo-sensitive area of the medulla oblongata will sense the concentration of hydrogen ions
If we have an increase in partial pressure of carbon dioxide in the plasma this will lead to both a decrease in plasma pH and in CSF pH detected by the medulla oblongata sending a signal to increase respiratory ventilation
At the same time changes in blood pH can also be detected by peripheral chemoreceptors present in the aortic arch and carotid arteries also causing you to breathe more
These will decrease plasma PaCO2 and returning the ECF to a normal pH
What is metabolic acidosis?
Characterised by low pH as a result of
Increased ECF [H+] or decreased ECF [HCO3-]
Caused by:
severe sepsis or shock ⇒ excess lactic acid production
uncontrolled diabetes ⇒ overproduction of 3-OH-butyric acid & other ketoacids
diarrhoea ⇒ loss of HCO3- from GI tract
How do the lungs and kidneys work together to compensate during acidosis?
Increased levels of hydrogen levels first trigger ICF and ECF buffering but eventually, the bicarbonate molecules are all used up
One thing is that we will have increased ventilation in the lungs decreasing the partial pressure of carbon dioxide ultimately. Increasing ECF pH
At the same time, the kidney will increase hydrogen ion secretion, increasing ammonium secretion and bumping up the production of bicarbonate and bicarbonate reabsorption
All this leads to compensatory raise of ECF pH
What is metabolic alkalosis?
Characterised by high pH caused by
Increased ECF [HCO3-] or decreased ECF [H+]
Caused by:
Excessive diuretic (thiazide) use ⇒ chronic loss of Cl-, Na+ & K+ ⇒ increase H+ secretion
Vomiting ⇒ loss of H+ from GI tract
Ingestion of alkaline antacids
Hypokalaemia
How do the lungs and kidneys compensate for alkalosis?
In this case a high concentration of bicarbonate leads to protons buffering but eventually those run out
In the lung there will be a decrease in ventilation increasing pCO2
In the kidney there will be decreased H+ secretions by decreasing ammonium ion secretion as well as decreasing bicarbonate ion formation and reabsorption and increasing bicarbonate excretion
