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51 Cards in this Set

  • Front
  • Back
• What is an acid? What is a base?
BRONSTED-LOWRY DEFINITION

An acid is any substance that is able to give a hydrogen ion (H+) to another molecule or ion (i.e. acids are “proton donors”)

In an acidic molecule, the acidic H atoms are those bonded to electronegative atoms like oxygen or chlorine and not those bound to carbon

A base is a substance that accepts a hydrogen ion from an acid

An acid-base reaction, then, is one in which a proton is transferred

ARRHENIUS DEFINITION:

Limited to those reactions that occur in aqueous solutions, but useful when thinking about pH

An acid is a substance that produces hydrogen ions [H+] when dissolved in water

A base is a substance that produces hydroxide ions [OH-] when dissolved in water

Recognize that the hydroxide ions “produced” by the base can come from one of two sources:

1) Ionic compounds that already contain OH- and merely release those ions when they dissolve in water (e.g. NaOH)

2) Substances that react with water in such a way as to produce OH- (hydroxide comes from water)
What is pH?
pH is a measure of a solution’s H+ concentration.

pH is equal to the negative common logarithm of the H+ concentration.

The common logarithm of a number is the power to which 10 must be raised to equal that number.

log (100) = ?
10? = 100
10 x 10 = 100
log (100) = 2
pH = -log [H+]

[H+] = 10 tothepowerof -pH

Acidic solutions have a pH of less than 7.

Neutral solutions have a pH of 7.

Basic solutions have a pH of more than 7.
• For the clinician, what is the significance of the fact that pH is an expression of [H+] on a logarithmic scale?
o The logarithmic scale involves powers of ten, so the clinician must be aware that small changes in pH actually represent large fluctuations in [H+]
• What is the average pH of blood?
Blood plasma: 7.4

[H+] = 1 x 10-7.4 M
• What is the pH of the interstitial fluid?
Interstitial fluid: 7.4

[H+] = 1 x 10-7.4 M
• What is the pH of the cytosol?
Cytosol: 7.0

[H+] = 1 x 10-7 M
• Why is it important for organisms to regulate the pH of their fluids so tightly?
o The 3-dimensional shape of proteins is very sensitive to pH.
• What is chemical equilibrium?
o Chemical equilibrium is a state in which the rates of the forward and reverse reactions are the same.

o In other words, in chemical equilibrium, reactants are forming products at same rate as products are forming reactants.

o At equilibrium the concentration of reactants and products are constant but not equal.

o It is the reaction rates of the forward and reverse reactions that are equal.
• What is Le Châtelier’s principle?
o When a stress is applied to a system at equilibrium, the equilibrium shifts to relieve that stress.

o By “stress” it is understood any change in concentration, pressure, volume, or temperature that disturbs the original equilibrium and causes the rates of the forward and reverse reactions to become temporarily unequal.

o Chemical equilibrium implies equal reaction rates between the forward and reverse reactions, so a change in one of these reaction rates bumps the system out of equilibrium.

o Le Châtelier’s principle simply states that the system will shift in such a way as to restore equilibrium, or the equality of forward and reverse reaction rates.

o What happens when you increase concentration of one of the reactants?

o The forward reaction rate increases, pushing reaction towards products until reverse reaction rate also increases and the two are equal.
• What is a buffer?
o A buffer is a combination of substances that work together to prevent dramatic changes in pH.

o A buffer usually consists of a weak acid and a roughly equal concentration of its conjugate base.
• How do buffers work?
o A buffer consists of a weak acid and roughly equivalent amounts of its conjugate base. For example:

o HA <--> H+ + A-

o These species are in equilibrium with one another.

o If we add a strong acid, it’s the same as adding a bunch of protons to the situation because strong acids dissociate 100%. These protons would drop the pH quite markedly.

o If the protons can be bound up in the weak acids, however, they won’t be free in solution because weak acids by definition do not dissociate very much.

o According to Le Chatelier’s principle, increasing the concentration of the products (in this case protons) will simply cause the equation to shift to the left in favor of the production of more reactants (weak acid).

The extra protons will get burned up in the production of more reactants, becoming part of the weak acid and thus preventing any steep change in pH.
• What are the three mechanisms by which the body regulates changes in the ECF pH?
o Buffering, respiratory response, and renal response
• In a human being, buffering occurs both intracellularly and extracellularly. What percentage of buffering occurs intracellularly?
o 60%
• Why might a sudden acid load be associated with an increase in ECF potassium concentration?
o When entering cells for intracellular buffering, H+ ions are exchanged for normally intracellular K+ ions to maintain electrical balance.
• Name a skeletal sequela of long-term acidosis.
o Osteomalacia
• Why does long-standing systemic acidosis cause osteomalacia?
o Hydrogen ions enter bony tissue in exchange for calcium ions.
• What are the most important intracellular buffers?
o Proteins
• Give an example of an intracellular protein buffer.
o Hemoglobin
• Give an example of an extracellular buffer that is not bicarb.
o Phosphate

o But didn’t we say a buffer was a weak acid and a roughly equivalent amount of its conjugate base? How is phosphate a buffer?

o Phosphate is the conjugate base of the weak acid dihydrogen phosphate.
• Name the most important extracellular buffer.
o Bicarbonate and its conjugate acid carbonic acid
• Describe the reaction of bicarbonate and hydrogen ions in the presence of carbonic anhydrase.
o H+ + HCO3- ←→ H2C03 ←→ CO2 and H20
• Why is the value of bicarbonate as a buffer in the ECF unique?
o The situation with bicarbonate is unique because the end products (CO2 and H20) can be dissipated by the lungs and kidneys, respectively.

o This means that the reaction will be constantly shifted to the right favoring the production of products, with free H+ ions being used up in the process.
• Give the formula that relates pH to [HCO3-] and PCO2
o pH is directly proportional to [HCO3-] / PCO2

This is a simplified version of the Henderson-Hasselbach equation.
• According to the Henderson-Hasselbach equation, what effect will removing bicarbonate or raising the PCO2 have on ECF pH?
o Decrease in pH
• According to the Henderson-Hasselbach equation, what effect will adding bicarbonate or lowering the PCO2 have on ECF pH?
o Increase in pH
• Describe the role of the respiratory system in maintaining pH homeostasis.
o Recall the reaction describing the buffering of protons by bicarb:

o H+ + HCO3- ←→ H2C03 ←→ CO2 and H20

o To eliminate excess protons the body wants the equation running from left to right.

o In order for the reaction to continue running from left to right, two conditions must be met.

o First, there must be enough bicarbonate for the protons to react with. The provision of bicarbonate is the job of the kidney.

o Second, CO2 must continue to be eliminated. This is the job of the lungs.
• If you could summarize the role of the lungs in the maintenance of ECF in 2 words, what would they be?
Eliminate CO2
• What is the respiratory response to rising [H+]?
o Increased ventilation
• What is the proximate stimulus of increased ventilation?
o Rising [H+] sensed by cells in the brain stem
• What is the role of the kidney in maintaining ECF pH?
o The kidney is concerned with producing bicarbonate to supply the extracellular buffering system.
• How do renal cells produce bicarbonate?
o Back to our favourite reaction:

o H+ + HCO3- ←→ H2C03 ←→ CO2 and H20

o In the plasma, the body wants this equation running left to right, with H+ being used up and converted to CO2 and H20 that can, in turn, be eliminated.

o In the kidneys, the objective is to produce bicarbonate, so the reaction needs to run from right to left, with CO2 and H20 coming together to form HCO3- and H+.
• Which enzyme catalyzes the formation of carbonic acid from CO2 and H20?
o Carbonic anhydrase
• Where along the nephron does bicarbonate production and proton secretion occur?
o Virtually all parts of the nephron, with the exception of the THIN descending and ascending loops of Henle
• If you could summarize the renal role in the maintenance of ECF pH in 3 words, what would they be?
o Replenish HCO3- stores
• What is the “price the kidney must pay” for making new bicarbonate?
You can't make bicarbonate in the way that the kidney does without making a proton at the same time.

Recall the reaction:

H+ + HCO3- ←→ H2C03 ←→ CO2 and H20
• What are the only two regions of the nephron not involved in bicarbonate production and proton secretion?
o THIN descending and ascending loops of Henle
The kidney produces protons as a byproduct of bicarbonate production and subsequently secretes them into the lumen.

How are these protons disposed of once they reach the lumen?
Three principle mechanisms:

1) Bicarbonate trapping

2) Ammonia production

3) Titratable acidity
• The proton produced as a byproduct of the bicarbonate production is secreted into the tubular lumen, but this secretion occurs in different ways at different points in the nephron. Describe the different methods of proton secretion and where along the nephron they occur.
o Proximal tubule, thick ascending loop of Henle, and early distal tubule:

o Secondary active transport via Na+/H+ antiporter

o Late distal tubule and collecting ducts:

o Primary active transport via H+ pump
Describe the phenomenon of bicarbonate trapping.
A small amount of bicarb is filtered at the glomerulus and present in the renal lumen.

This bicarb reacts with secreted H+ in the usual fashion:

H+ + HCO3- ←→ H2C03 ←→ CO2 and H20

The CO2 produced diffuses back into the renal cells, where it is converted into bicarb and a hydrogen ion.

Thus, in effect, for every bicarb. ion that is trapped by a hydrogen ion, another bicarb. ion is generated by the tubular cell.
• Where in the nephron are protons secreted using a Na+/H+ antiporter?
o Proximal tubule, thick ascending loop of Henle, and early distal tubule
HCO3- can't be reabsorbed from the lumen.

How does the kidney make up for this?
When filtered bicarb traps a secreted proton, the following reaction occurs:

H+ + HCO3- ←→ H2C03 ←→ CO2 and H20

The CO2 then diffuses across the membrane into the tubular cell, where the reverse reaction occurs, resulting in the production of a bicarb molecule.

The original filtered bicarb is not reabsorbed. It does, however, result in the production of another bicarb ion that enters circulation.

Thus we could say the bicarb trapping in the renal tubule, in addition to eliminating H+ ions, results in the effective reabsorption of bicarb.
• Where in the nephron are protons secreted using primary active transport in the form of an H+ pump?
o Intercalated cells of the late distal convolute tubules and collecting ducts
• Why does the kidney synthesize ammonia?
o Ammonia is produced to buffer tubular protons, which renal cells must secrete as a byproduct of bicarbonate production.

Ammonia is a highly diffusible substance. As soon as it is produced it diffuses completely into the tubular lumen, where it meets with a secreted proton to become ammonium.

Ammonium, on the other hand, cannot diffuse through the membrane and as such is trapped in the lumen.
• Which type of cell possesses the proton pump for primary active transport of protons into the tubular lumen?
o Intercalated cells of late tubule and collecting duct
• What is the chemical formula for ammonia? What is the chemical formula for ammonium? Which is the acid and which is the base?
o Ammonia: NH3

o Ammonium: NH4+

o Ammonia is a base while ammonium is an acid
How do renal cells synthesize ammonia?
?
• What determines the rate at which renal ammonia is synthesized?
o Ultimately, the amount H+ secreted by the tubular cells determines how much urea is produced.

o The ammonia produced by tubular cells will only diffuse into the lumen to become ammonia if there is a concentration gradient allowing them to do so.

o If there are a lot of protons in the lumen, this gradient is maintained because ammonia is converted to ammonium upon entering the tubule.

o If there are few protons in the lumen, then ammonia will accumulate in the tubule and eventually begin to diffuse back into the tubular cells, shutting down ammonia production.
• What is meant by titratable acid production?
o ?

o It has something to do with the buffering of protons in the lumen by buffers other than bicarbonate, principally phosphate.
• What is quantitatively the most important urinary buffer?
o Phosphate
• What is the chemical formula of phosphate?
o HPO4 2-
• Phosphate is a weak base. What is the name and chemical formula of its conjugate acid?
o Dihydrogen phosphate
o H2PO4-