Physiology of Kidney Acid Base Balance Flashcards
What is the normal pH of arterial blood?
7.4
Protons can be bound to protein or acid, however, in order to contribute to pH, what must proton ions be?
Free
What are some of the sources of protons (H+) in the body?
Respiratory acid
Metabolic acid
What is a respiratory acid?
Carbonic acid is formed from carbon dioxide dissolving in water
What does carbonic acid dissociate into?
Carbonates and protons
Why is increased carbon dioxide production in exercise normally not a problem for the body?
It’s compensated for by increased ventilation
What happens if there is impaired lung function in someone who is exercising?
Carbon dioxide builds up as the body cannot fully release and exhale the carbon dioxide, leading to increased respiratory acid production
Metabolic acids are produced via metabolism. What are the two types of metabolic acid?
Inorganic acids
Organic acids
Give an example of an inorganic metabolic acid.
Sulphuric and phosphoric acid due to sulphur/phosphate containing amino acids
Give an example of an organic metabolic acid.
Fatty acids, lactic acid
What is the major source of alkaline in the body?
Oxidation of organic anion such as citrate
Buffers?
Solutions which minimise changes in pH when proton ions are added or removed
What is the most important extracellular buffer?
Bicarbonate buffer
What is the normal pCO2?
40mmHg or 5.3kPa
Protons do not get removed from the body, so how does it work so that these protons don’t contribute to pH thanks to buffers?
Bicarbonate buffers the protons and the respiratory compensation greatly increases the buffering capacity so that free protons ions are prevented from contributing to pH
->basically, just understand that protons are not removed, just buffered so they can’t contribute to pH
What are the two factors which are important when protecting the pH?
Bicarbonate
Carbon dioxide
How is carbon dioxide regulated?
Respiration
How is bicarbonate regulated?
Directly by the kidney
If there is a disruption to the regulation of the bicarbonate, how is this compensated for?
Compensated by ventilation
List some of the primary intracellular buffers.
Proteins, organic and inorganic phosphates
Haemoglobin in erythrocytes
What can buffering of proton ions by ICF buffers cause changes to?
Can cause changes in plasma electrolytes
What is done as compensation when transporting protons into cells to be buffered intracellularly?
Needs to be co-transport of chloride in red cells or potassium
In acidosis, there is movement of potassium out of the cells. What can this cause?
Hyperkalaemia, leading to depolarisation of excitable tissues, ventricular fibrillation and death
What else provides an additional store for buffer?
Bone carbonate
->very important in chronic acid loads in renal failure as can lead to wasting of bones
How can acidosis lead to electrolyte disturbances?
Has to be co-transport of potassium or chlorine which can cause disruption
How many millimoles of protons a day do we get from the diet?
50-100mmoles
If all these protons were free in TBW, this would dramatically reduce pH. However, as long as two organs are working, pH remains constant. Which two organs?
Lungs and kidneys
What is the purpose of buffering?
To give the kidneys time to excrete the proton loading
How does the kidney regulate bicarbonate?
-Reabsorbing filtered bicarbonate
-Generating new bicarbonate
->both of these processes require active proton secretion from the tubule cells into the lumen
Describe the mechanism in which bicarbonate can be reabsroped.
- Active proton secretion from tubule cells
- Coupled to passive Na reabsorption
- Filtered bicarbonate reacts with secreted protons to form carbonic acid
- Carbon dioxide is freely permeable and can enter the cell
- Within the cell, carbon dioxide is converted into carbonic acid in the presence if carbonic anhydrase which then dissociates to form protons and bicarbonate
Where does the bulk of bicarbonate reabsorption take place?
Proximal tubule
Why is bicarbonate converted to carbon dioxide to transport over the membrane?
Bicarbonate is very large and charged so does not pass easily itself
What is the GFR per day?
180L per day
*GFR= glomerular filtration rate
What in the minimum urine pH?
4.5-5.0
What in the maximum urine pH?
8.0
What is the usual net production of protons per day in humans?
50-100mmoles of protons
What would happen if all these protons (H+) where free proton ions in the urine?
pH of 1…ouch!
Luckily, these protons are buffered in the urine
While several weak acids and bases act as buffers, give some examples of the most common in the body.
Dibasic phosphate
Uric acid
Creatinine
Describe the ‘titratable acidity’.
Buffer quantity and pH is measured to work out the amount of NaOH needed to titrate urine pH back to 7.4 during a 24hr urine sample
How does titratable acidity contribute to active proton excretion?
Produces new bicarbonate to compensate for the loss due to buffering and it actively excretes protons from the body
Titratable acidity compensates for the loss by producing new bicarbonate. What is the source of this new bicarbonate?
Indirectly carbon dioxide…it enters the tubule cells and combines with water to form carbonic acid, which in the presence of carbonic anhydrase dissociates into protons and new bicarbonate
What is the site of formation of titratable acidity?
Distal tubule
Is ammonia water or lipid soluble?
Lipid soluble
So, ammonia is lipid soluble, is ammonium?
No
How is ammonia produced?
Deamination of amino acids, primarily glutamine, by renal glutaminase
How is ammonium produced?
Ammonia combines with protons in the tubule lumen
Ammonium secretion allows for additional proton loss in response to chronic acid loading.
How does this work in the proximal tubule?
-Ammonia can cross the membrane freely so does so and combines with protons to form Ammonium.
-Ammonium is excreted
->so the protons joined with the ammonia to form ammonium and then is excreted basically so protons are lost I think
What serves as the source of carbonic acid?
Carbon dioxide in the blood
Ammonium secretion allows for additional proton loss in response to chronic acid loading.
How does this differ in the proximal tubule compared to distal?
In the proximal tubule, there is use of the ammonium transport using the ammonium/sodium exchanger
The activity of renal glutaminase (the enzyme which assists in the production of ammonia) is dependant on what?
pH
->this makes sense lol idk why I made this card as all enzyme depend of pH duhhh
Normally, how many millimoles of protons are lost per day as ammonium?
30-50mmoles
->can increase to 250mmoles/L in severe acidosis
If there is a decrease in body pH, what occurs?
Acidosis
If there is an increase in body pH, what occurs?
Alkalosis
Which two categories of disorders affect the pressure of CO2 in the body?
Resp and renal disorders
What is respiratory acidosis?
Fall in pH due to reduced ventilation causing retention of CO2
In respiratory acidosis, does the pressure of CO2 increase or decrease?
Increase
Give an example of a respiratory condition which can lead to retention of CO2 and therefore respiratory acidosis.
COPD
What are some acute causes of respiratory acidosis?
-Drugs which depress the medullary respiratory centres e.g. barbiturates and opiates
-Obstruction to major airways
What are some chronic causes of respiratory acidosis?
Lung disease e.g. bronchitis, emphysema, asthma
How does the body try to compensate for the CO2 retention in respiratory acidosis?
-Increases secretion of protons and bicarbonate
-Acidic conditions also stimulate renal glutaminase
->By stimulating the renal glutaminase, this means greater production of ammonia and ammonium etc.
Renal compensation of increasing bicarbonate protects the pH but does not correct the original disturbance. What is the only thing that restores the primary disturbance?
Restoration of normal ventilation
This means in chronic respiratory acidosis, blood gas values are never normalised. Give an example of blood gas results for someone with chronic respiratory acidosis.
pH 7.32
PCO2= 65mmHg
Bicarbonate= 38mmoles/L (elevated)
Lung disease patients will always have aberrant PCO2 and bicarbonate but pH can be maintained at a level compatible with life as long as what?
As long kidney function is not impaired
What is respiratory alkalosis?
Fall in pressure of CO2 (PCO2) of respiratory origin due to increased ventilation and CO2 blow-off
What are some acute causes of respiratory alkalosis?
Voluntary hyperventilation
Aspirin
First ascent to altitude
What are some chronic causes of respiratory alkalosis?
Long term residence at altitude
In order to protect pH in patients with respiratory alkalosis, what needs to happen?
Bicarbonate levels need to decrease
How does the body deal with respiratory alkalosis?
Via bicarbonate reabsorptive mechanism
If there is a decrease in the PCO2, what happens to the amount of proton available for secretion?
Less protons available
->this means less of filtered bicarbonate is reabsorbed so is lost in urine
What needs to be done to normalise the disturbance caused by respiratory alkalosis?
Like with respiratory acidosis, ventilation needs to be normalised
What is metabolic acidosis?
An acidosis of metabolic origin due to decrease in bicarbonate levels
What can cause a decrease of bicarbonate, ultimately causing metabolic acidosis?
-Increase buffering of protons
-Direct loss of bicarbonate
To protect the pH in metabolic acidosis, what must be done?
PCO2 must be decreased
->this is typically happening by ventilation
What are the causes of metabolic acidosis?
- Increased proton production
- Failure to excrete the normal dietary load of protons, as in renal failure
- Loss of bicarbonate as in diarrhoea meaning it cannot be reabsorbed
As mentioned, an increase in proton production can cause metabolic acidosis.
In which situations may there be an increase in proton production?
-Ketoacidosis of a diabetic
-Lactic acidosis
Metabolic acidosis stimulates ventilation so PCO2 falls. What is hyperventilation?
Increases in the depth of breathing, rather than the rate
The hyperventilation causing metabolic acidosis can increase to what rate?
What name is given to this?
30L/min compared to normal 5-6L/min
This degree of hyperventilation is known as Kussmaul breathing and is very serious
Kussmaul breathing is an established clinical sign of which conditions?
Renal failure
Diabetic ketoacidosis
How do the kidneys normally resolve decreased bicarbonate?
Restoring bicarbonate levels and getting rid of protons.
Why can’t the bicarbonate levels be lowered by the kidneys in someone with metabolic acidosis?
The source of the protons is from carbonic acid, which comes from CO2.
The respiratory compensation however lowers the PCO2 to protect the pH
How would the body respond if there is increased metabolic protons?
-Immediate buffering in ECF and ICF
2. Respiratory compensation within minutes
3. Renal correction of disturbances by generating new bicarbonate but takes longer to develop e.g. 4-5 days
What happens in metabolic alkalosis?
Increase in bicarbonate so PCO2 rises to protect the pH
What are some of the causes of metabolic alkalosis?
- Proton ion loss e.g. vomiting
- Increased renal proton loss e.g. aldosterone excess or excess liquorice ingestion (!?)
- Massive blood transfusions
- Administration of bicarbonates
->btw liquorice has a similar affect to aldosterone apparently
OKAYYYYY so
Respiratory acidosis/alkalosis are due to problems with which organ?
Lungs
OKAYYYYY and
Metabolic acidosis/alkalosis are due to problems with which organ?
Kidneys
What happens to pH in respiratory acidosis and metabolic acidosis?
pH decreases
What happens to pH in respiratory alkalosis and metabolic alkalosis?
pH increases
What happens to the proton levels in respiratory/metabolic acidosis?
Proton levels increase
What happens to the proton levels in respiratory/metabolic alkalosis?
Proton levels decrease
What is the primary disturbance in respiratory acidosis?
Increase PCO2
What is the primary disturbance in respiratory alkalosis??
Decrease PCO2
What is the primary disturbance in metabolic acidosis?
Decreased bicarbonate levels
What is the primary disturbance in metabolic alkalosis?
Increased bicarbonate levels
In respiratory acidosis, how is the increased PCO2 compensated for?
Increase in bicarbonate levels
In respiratory alkalosis, how is the decreased PCO2 compensated for?
Decrease in bicarbonate levels
In metabolic acidosis, how is the decreased bicarbonate levels compensated for?
Decrease in PC02
In metabolic alkalosis, how is the increased bicarbonate levels compensated for?
Increase in PCO2
In order to determine the acid-base disorder of a patient, what three things need to be measured?
pH
PCO2
Bicarbonate (HCO3)
For a given increase in PCO2, what is the effect on pH in acute respiratory acidosis compared to chronic?
Smaller decrease in pH in chronic than acute
->this is due to mechanism to raise bicarbonate takes 4-5 days to activate ammonia production
Severe acidosis increases risks of what?
Hyperkalaemia
->this is because proton ions are buffered intracellularly in exchange for potassium ions
RECAP- what can hyperkalaemia cause?
Ventricular fibrillation
How is hyperkalaemia treated?
Insulin and glucose combination
In a bad case of vomiting, there would be loss of NaCl and H2O, what does this cause?
Hypovolaemia
In a bad case of vomiting, there would also be loss of HCl, what does this cause?
Metabolic alkalosis
How does the body react to hypovolaemia?
Stimulates the aldosterone mechanism involving distal tubule sodium reabsorption
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got?
pH = 7.32, [HCO-3]= 15 mM, PCO2 = 30mmHg (4kPa)
Metabolic acidosis
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got?
pH = 7.32, [HCO-3]= 33 mM, PCO2 = 60mmHg (8kPa)
Chronic respiratory acidosis
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got?
pH = 7.45, [HCO-3] = 42 mM, PCO2 = 50mmHg (6.7kPa)
Metabolic alkalosis
The following blood gas values were seen in a patient. Which simple Acid/Base Disturbance has he got?
pH = 7.45, [HCO-3]= 21 mM, PCO2 = 30mmHg (4kPa)
Respiratory Alkalosis (acute)
Should of asked this earlier… what is normal bicarbonate levels?
22-29mEq/L
RANDOM BUT GOOD TO KNOW
A PATIENT WITH ELEVATED BIACRBONATE CANNOT BE IN METABOLIC ACIDOSIS SINCE BICARB IS A BASE
