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0

What does homeostatic control require?

requires recognition of a stimulus as well as a response to it.
We stated that recognition and response require energy, and that cells, organs and eventually organisms die if they do not have adequate energy resources.

1

recognition and response during homeostatic control require energy...how is that energy used?

it is used to generate and conduct electrical messages;
to effect contraction of muscles;
to perform active transport;
to synthesize molecules such as enzymes or transporters.

2

Each of the ways energy is used in homeostatic control is dependent on what? And give examples

on the proper functioning of proteins.
For example, the conduction of electrical messages in neurons and other electrically excitable cells is made possible through the sequential opening and closing of voltage-gated Na+ and K+ channels;
the contraction of muscle requires precise interactions between the proteins actin and myosin; active transport is performed by membrane proteins (either ATPases or antiporters or symporters).

3

the structure of a protein is ultimately dependent on what?

on the sequence of amino acids found within it.

4

As the amino acids are added to a growing polypeptide chain, interactions between constituents of the peptide bonds as well as interactions between constituents of the R groups induce what?

changes in shape until the protein assumes its native conformation.
At this conformation/shape, the protein functions properly as a receptor, transporter, enzyme, etc.

5

Many of the interactions between peptide bond and/or R groups involve what?

polar and/or charged entities.
That is to say that hydrogen bond as well as ionic bond interactions are critical to the generation of a fully functional protein in its native conformation.

6

Since acids are proton donors and bases are proton acceptors, the concentration of these molecules in the ECF and/or ICF is of what?

critical importance

7

What can an excess of protons interfere with?

normal electrostatic interactions between peptide bond/R group constituents

8

a deficiency of protons may result in what?

interactions that otherwise would not take place.
In either case, protein conformation will be altered, and therefore its function will be compromised: receptors may not be respond, transporters may not open (or remain open), ATPase activity may decrease; the cell/organ/organism may die.
Hence the importance of Acid-Base homeostasis.

9

Water as an Acid/Base
a) Water occasionally dissociate

H2O (+) H2O⬅➡H3O+ (+) OH- ⬅➡H2O (+) H+ (+) OH-
or, H2O⬅➡H+ (+) OH-

10

At equilibrium, the concentrations of water, proton and hydroxide are what?

Constant.
As it turns out, dissociation is so infrequent that we can treat [H2O] as a constant = 55.56 M/L, and we can calculate [H+] and [OH-] (which must be equal) by measuring the electrical conductivity of pure water.
Such calculations yield the following concentrations: [H+] = [OH-] = 10-7 M/L

11

pH is defined as what?

–log10[H+]

12

What is the pH of pure water?

–log10[10-7] = 7. Pure water is considered neutral, since the concentrations of H+ and OH- are equal.
In fact, the ion product [H+][OH-] is considered to be constant in aqueous solutions; therefore, an increase in H+ is accompanied by a decrease in OH-, and a lowering of the pH of the solution.

13

A strong acid or base is one which readily does what?

dissociates

14

a weak/acid base is one which does what?

Does not dissociate

15

For example, if one mole of HCl was placed in a small volume of water, it would yield nearly one mole of H+ and Cl-, with only a little HCl remaining at equilibrium; whereas if one mole of lactic acid was placed in an equal volume of water, there would be less H+ at equilibrium, relative to the amount in the HCl system. In other words, HCl is a stronger acid than lactic acid.

.

16

If a solution contains a strong acid such as HCl, the addition of another strong acid (let’s call it HA) will result in a what?

a significant decrease in pH.
This is because H+ generated by the additional acid can associate only with A- or Cl-, and HA and HCl are strong acids.

17

if the solution contains a weak acid (let’s call it HW), the addition of the strong acid HA will result in a what?

a decrease in pH that is not so pronounced.
This is because the H+ generated by the additional acid can associate with A- or W-.
If it associates with W- (thereby forming HW), it may not be released into solution, since HW is a weak acid.

18

We say that the presence of weak acids in solution tends to do what to the solution from changes in pH (Another way of saying this is that weak acids are buffers)?

Buffer.
Given the importance of maintaining pH within a narrow range, it should be clear that buffers are essential constituents of body fluids.

19

To be effective, a buffer must be able to not only “soak up” excess H+ which would lower the pH; it must also be able to what?

“donate” H+ in those conditions where [H+] had decreased for some reason.

20

a good buffer is one that?

at equilibrium, exists both in the protonated (HA) form (which can donate H+ if necessary) and in the dissociated (A-) form (which can “soak up” H+, becoming HA in the process).

21

a weak acid is best able to do what?

buffer when it exists in these two forms in equal concentrations, i.e., when it is
50% HA and 50% A-.

22

The pH at which a buffer is 50% HA and 50% H+ (+) A- is called its what?

pK

23

Each weak acid has its own characteristic pK. For example,

the pK of acetic acid is 4.76 (Figure 1).
Stated another way, acetic acid is best able to defend a pH of 4.76.
Given that plasma should have a pH of approximately 7.4, it is obvious that acetic acid does little to defend plasma pH.
If large amounts of acetic acid were in plasma, plasma pH would be significantly lower than normal (low enough to cause death).

24

Buffers in Body Fluids
a) Intracellular

1) H+ + HPO4-2 ⬅➡ H2PO4-
2) H+ + Protein- ⬅➡HProtein
3) H+ + HCO3- ⬅➡H2CO3

25

Buffers in body fluids
b) Interstitium

1) H+ + HCO3- ⬅➡H2CO3
2) H+ + Protein- ⬅➡ HProtein
3) H+ + HPO4-2 ⬅➡ H2PO4-

26

Buffers in body fluids
c) CSF

1) H+ + HCO3- ⬅➡H2CO3

27

Buffers in body fluids
d) Tubular Filtrate

1) H+ + HCO3- ⬅➡ H2CO3
2) H+ + HPO4-2 ⬅➡H2PO4-
3) H+ +NH3⬅➡NH4+

28

Buffers in body fluids
e) Plasma

1) H+ + HCO3- ⬅➡ H2CO3
2) H+ + Protein- ⬅➡ HProtein
3) H+ + HPO4-2 ⬅➡ H2PO4-

29

carbonic acid is found in?

all body fluids.
It is also specifically generated by many cell types (such as gastric parietal, pancreatic ductular, proximal and distal tubular), each of which is specialized to produce acidic or alkaline secretions.

30

Carbonic acid (H2CO3⬅➡H+ + HCO3-) has a pK of what?

6.1, but the pH of most body fluids is in the vicinity of 7.0 – 7.4 (Although the pH of venous plasma is less than 7.4 and that of arterial plasma is greater than 7.4, one commonly considers “normal” plasma pH to be 7.4).

31

If the carbonic acid system was responsible for maintaining plasma pH at 7.4, there must be some other reaction which in effect lowers the amount of H+. This reaction is:

H2CO3 ⬅➡ H2O + CO2, which is dissolved in plasma and subsequently exhaled at alveoli.

32

At equilibrium, there are approximately how many CO2 molecules per H2CO3 molecule?

400.
Stated another way, most of the proton donor in the carbonic acid system is in the form of CO2 (You should always think of CO2 in aqueous solution as an acid).
Consequently, we are really interested in the relative concentrations of the dissociated form (HCO3-) and the “protonated” form (CO2).

33

Since the concentration of dissolved CO2 is difficult to measure, we make use of an equation which equates the concentration of dissolved CO2 to its solubility and P CO2 (i.e., the partial pressure of CO2):

[CO2] (mM/L) = (0.03 mM/L / mm Hg) x P CO2 (mm Hg)

34

e) “Normal” values in plasma are:

[HCO3-] = 24mM/L and P CO2 = 40mmHg

35

Therefore, [HCO3-] / (0.03) P CO2 should equal 20.

1) If this term is greater than 20, the condition is known as alkalosis
2) If this term is less than 20, the condition is known as acidosis.
3) Alkalosis and acidosis may be classified as metabolic or respiratory (or
mixed) (See sections 7-10 below). A series of simple rules to aid in this classification is as follows:
a) If the term is < 20 and there is no change in P CO2, it is a metabolic acidosis
b) If the term is < 20 and there is no change in [HCO3-], it is a respiratory acidosis
c) if the term is > 20 and there is no change in P CO2 , it is a metabolic alkalosis
d) If the term is > 20 and there is no change in [HCO3-], it is a respiratory alkalosis

36

These rules are a simplification because a change in one of the two entities always causes a compensatory change in the other. For example,

if an organ overproduces a relatively strong acid (such as ketoacids produced by the liver), respiratory compensation takes place in the form of hyperventilation, which removes increased amounts of CO2.
Why? You should always think of CO2 in aqueous solution as an acid.

37

CO2 is the oxidized waste product of the?

aerobic oxidation of carbohydrates, lipids and proteins.

38

The large volumes of CO2 that are produced by aerobic cells could not be removed at the rate they were produced without what?

properly functioning lungs, heart and red blood cells.
The lungs of course are the site of CO2 excretion from the body, while the heart generates the mechanical energy needed to deliver CO2 to these organs.
But why are red blood cells necessary?

39

CO2 produced in cells easily diffuses out into the what?

ECF

40

But since CO2 is not very soluble in aqueous solution, the dissolved gas would?

rapidly rise in the ECF and prohibit continued diffusion out of cells.

41

If CO2 reacts with H2O to form H2CO3 outside cells, CO2 can?

continue to diffuse.
However, the reversible reaction H2CO3 ⬅➡ H2O + CO2 is quite slow.

42

Red blood cells possess the enzyme?

carbonic anhydrase

43

carbonic anhydrase catalyzes?

the reversible hydration of CO2, thereby promoting formation of H2CO3 and uptake of large amounts of CO2 at aerobic tissue.

44

This uptake of CO2 would be slowed if?

if H2CO3 accumulated in the red blood cell, but recall that H2CO3 is an acid: it dissociates into H+ and HCO3-.
And while this dissociation allows for further uptake of CO2, it acidifies the RBC and threatens its normal functioning.

45

The abundant red blood cell protein hemoglobin buffers what?

the H+, while the HCO3- is allowed to diffuse out the red blood cell in exchange for Cl-.
These events are reversed at the lungs, where CO2 diffuses out of the blood down its concentration gradient and into alveolar air spaces (Figure 2)

46

Hemoglobin also is capable of binding some what?

CO2, but about 90% of all CO2 in blood is transported in the form of HCO3- (Figure 3)

47

Total blood CO2 = what?

CO2 transported as HCO3-, dissolved CO2 gas, CO2 bound to hemoglobin, and H2CO3. Since dissolved CO2 is 400 times more abundant than H2CO3, the latter entity is usually ignored.

48

When a plasma or serum sample is collected, CO2 bound to hemoglobin is what?

not present.
Therefore Total plasma (or serum) CO2 (termed T CO2) = HCO3- and dissolved CO2.
For example, if [HCO3-] = 24 mEq/L and P CO2 = 40 mm Hg, T CO2 would equal 24 + (0.03)(40) = 25.2 mM/L. Frequently, laboratories will report T CO2 and P CO2, allowing for calculation of [HCO3-].

49

CO2 is transported in blood in what three forms?

Dissolved CO2 and carbamino compounds are minor forms, while most CO2 is transported as HCO3-, almost all of which is produced by red blood cells.
Note the essentially linear relationship between CO2 content (volume per cent CO2) and P CO2.
See figure 3 pg 83 of notes.

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