Test 3 - Acid/Base Physiology Flashcards
1
Q
What aspects of a protein do protons interact with and what are the consequences?
A
- Negative R groups
- Hydrogen bonds
Both of these contribute to the shape of a protein. Changes in proton concentration can alter these interactions and denature the proteins. E.g. enzymes (including those for protein synthesis, DNA replication, etc), transporters, Na/K ATPase, receptors
2
Q
In the case of receptor and enzyme denaturation, what changes?
A
Receptors and enzymes are a specific shape in order to recognize their specific substrates. Denaturation would cause decreased enzymatic rates or decreased effectiveness of hormones/neurotransmitters.
3
Q
How do changes in proton concentration change Na/K ATPase?
A
This changes Na/K ATPase activity. This has implications on:
- Nephron reabsorption/secretion
- Membrane Potential all over the body
4
Q
TRUE/FALSE.
Animals produce more buffer according to its need and it simply accumulates in the body.
A
FALSE.
Cells do manufacture more buffer according to their needs. However, waste is excreted. Acid specifically is removed through the lungs and kidneys.
5
Q
What are the defenses against changes in proton concentration?
A
- Intracellular buffers
- Transporters to send waste into the interstitium and subsequently plasma
- Ultimate Excretion Routes: Breathing and urinating
6
Q
TRUE/FALSE.
Plasma is dead. Therefore, acid/base problems start at living cells.
A
TRUE.
Cells export their waste into plasma as a mode of waste removal.
7
Q
Where are buffers present?
A
Intracellularly
Interstitium
Plasma (this ultimately takes waste to get excreted and we can start all over)
8
Q
What are the major methods of proton removal? Which is the most efficient?
A
- Exhalation of CO2 (thousands of times more efficient than urination).
- Urination
9
Q
What are the main roles of the kidney and lungs specifically in acid/base balance?
A
Kidney - Buffer manufacturing
Lungs - Acid removal through CO2 exhalation
10
Q
Describe the changes in CO2 as it travels in the RBC to the lungs.
A
RBCs convert CO2 to H+ and HCO3-
Once it gets to the lungs, it is converted back to CO2 so that it can diffuse accross the alveloar membrane
11
Q
TRUE/FALSE.
An animal can have more than one acid/base disorder at a time.
A
TRUE.
12
Q
CO2 is a(n) ______ (acid/base) in aqueous solution.
A
ACID
13
Q
What buffers are RBCs full of?
A
Hemoglobin
14
Q
What will cause an animal to become more acidic, kidney or lung damage?
A
Lung Damage
15
Q
What is the concentration of water?
A
55.55… moles/liter
This is treated as a constant
16
Q
______ and _____ are the most abundant anions in plasma.
What does changes in their concentrations elicit?
A
Chloride (#1) and Bicarb (#2)
They are anions of a strong and weak acid, respectively. Changes in their concentrations has significant consequences on pH.
17
Q
More Acidic or basic?
- Add more CO2
- Lose bicarb and gain Cl-
- Lose Cl- and gain bicarb
A
- Acidic
- Acidic
- Bicarb
18
Q
Who adds HCO3 to plasma without adding H?
A
PCT cells
a-intercalated cells
19
Q
How can you tell if an acid is stronger or weaker based on the Ka?
A
A stronger acid has a larger Ka
20
Q
_____ is the most important buffer in extracellular fluid.
A
HCO3-
21
Q
TRUE/FALSE.
If you know the pH of plasma, you know the pH of the fluid bathing the cells/interstitium.
A
TRUE.
22
Q
What pH is optimal for cells?
A
7.4
23
Q
What kind of acid would we want for buffers? Optimally, what state(s) should it exist in under normal conditions?
A
A weak acid would make the best buffer that exists at 50% associated and 50% dissociated states. This gives you the best chances for maintaining proton concentration.
24
Q
What is the pK of a buffer?
A
The particular pH at which a buffer does its best buffering. This is when it exists at 50/50.
25
What is the weak acid that is used to buffer plasma? What is its pK?
Carbonic Acid (H2CO3)
pK = 6.1
26
Explain the pK of carbonic acid and why it works in plasma.
pK = 6.1
We want to defend a pH of 7.4
a pK of 6.1 suffices becauses because HCO3- exists in 20x the amount of carbonic acid.
pH = pK + Log10 ([A-]/[HA])
pH = pK + Log10[20]
pH = 6.1 + 1.3 = 7.4
27
# Define:
- Acidosis
- Acidemia
- Alkalosis
- Alkalemia
- A condition which causes increased [H+]
- The presence of greater than normal [H+] in blood
- A condition which causes a decrease in [H+]
- The presence of less than normal [H+] in blood
28
TRUE/FALSE.
Drug effectiveness can be influence by changes in proton concentration.
Why or why not?
TRUE.
Changes in proton concentration changes the structures that drugs bind to but also because many drugs are acids or bases. Therefore, changes in proton concentration would alter their ability to donate or accepto protons. Their structure would be altered and thire ability to cross cell membranes would change.
29
Discuss the differences between a strong and a weak acid.
A strong acid readily dissociates and exhibits high acidity.
Weak acids do not dissociate as readily. pK is typically used to describe weak acids. The stronger a weak acid, the higher the pK.
30
What is important about pK?
At pK, a weak acid is best able to resist changes in pH in the face of addiition or removal of H+ from solution, i.e., to buffer changes in [H+]. The reason why a buffer does its best buffering at its pK is because it exists abundantly in both the protonated and dissociated forms. This permits it to donate significant amounts of H+ if [H+] decreases and tirate significant amounts of H+ if [H+] increases.
31
Describe the titration curve for phosphoric acid.
The pK = 6.8, where it does its best buffering.
Within 1 pH of its pK it still maintains buffering power but the greater the deviation from the pK, the less it is capable of blunting the changes in [H+]. After a certain point, the same incremental increase in addition causes a more significant change in pH.
32
Who should exist at a higher concentration, CO2 or HCO3-? What happens if one of these is not in this ratio?
HCO3- should exist 20x more than CO2.
If there is more bicarb, then plasma would be alkaline. More CO2 would make plasma acidic.
33
What are the forms of CO2 found in plasma? What gives you TCO2?
CO2 (gas), H2CO3, HCO3-
Addition of these concentrations gives TCO2 (Total concentration of carbon dioxide).
Total CO2 (mM) = [HCO3-] (mM) + (0.3) PCO2 (mmHg)
H2CO3 can be regarded as zero because it exists 400x less than CO2
34
What are the acids produced as a result of metabolism (acidosis)? Where are they produced?
1. Lactic Acid - Skeletal muscle
2. Ketoacids - liver
3. Acids of ethylene glycol metabolism - liver
35
TRUE/FALSE.
Once bicarb is used by the addition of acid, it must be converted to a form such that waste is excreted and bicarb can is recycled.
FALSE.
The kidney will produce more bicarb to replenish what has been used.
36
TRUE/FALSE.
CO2 is a form of bicarb and so it is a weak base in aqueous solution.
FALSE.
It is also a source of proton and so it is a weak acid.
37
What is the best way to get rid of acid?
Through exhalation of CO2.
38
What is the partial pressure of oxygen (PO2) in RBCs going to cells? What is it travelling to the lungs?
Travelling to cells from the lungs PO2 = 100mmHg
Travelling to lungs from cells PO2 = 40 mmHg
39
What is normal [HCO3-]? [CO2]?
[HCO3-] = 24 mmol
[CO2] = 1.2 mmol = 40mmHg
40
How do you convert mmHg to mmol?
Therefore, normal CO2 of 40mmHg = ? mmol
Multiply mmHg x 0.03
40 mmHg x 0.03 = 1.2 mmol
41
What is the solubility coefficient of CO2?
0.03 mmol/mmHg
For every mmHg of CO2, there is 0.03 mmol of CO2 in aqueous solution.
42
TRUE/FALSE.
Metabolic changes alter acid/base equilibrium.
TRUE.
Metabolic waste will change the concentration of proton/bicarb.
43
What are the causes of metabolic acidosis?
Either increased in proton concentration or you are losing bicarb.
Bicarb losing Acidosis
Titration Acidosis
44
What are the causes of metabolic alkalosis?
Decreased proton or increased bicarb.
45
Fill in the table.
NOTICE:
PCO2 and HCO3- always travel in the same direction.
During Respiratory changes, all travel in the same direction.
46
What acid/base disorder is present when [HCO3-]/[CO2] is:
\>20?
\<20?
\>20 is alkalosis
\<20 is acidosis
47
Describe compensatory mechanisms for respiratory acidosis.
The kidneys metabolically compensate by increase bicarb production and secreting it into plasma. However, this will take some time (usually about a day).
48
Why is carbonic acid the most prominent buffer in extracellular fluids?
1. [HCO3-] is relatively high (24mM) - there's a lot of it.
2. CO2 can be exhaled from the animal, and so this allows for rapid corrections to changes in pH via changes in ventilation.
3. Dissociated and associated form (HCO3- & CO2) can be regulated independently by the kidney and lungs, respectively.
49
Describe the components and compensation of metabolic acidosis.
Acidosis means increased [H+].
This causes respiratory compensation to increase ventilation, resulting in decreased PCO2 and decreased HCO3-.
This means that there are 2 reasons that bicarb is low during metabolic acidosis:
There is bicarb loss or increased proton is using it up **AND** respiratory compensation.
50
[HCO3-] = 30 mM
PCO2 = 60 mmHg
What is present?
30/(60x0.03)= 30/1.8 = 16.67
\<20, this means that an acidosis is present.
Both are elevated and so a Respiratory Acidosis is present. e.g. Obstruction of airway.
51
TRUE/FALSE.
During treatment of acid/base disorders, knowing the degree of compensation is not important for therapeutic addition.
FALSE.
It is very important to know what the compensation is. This can be determined by using the nomogram.
52
[HCO3-] = 12mM
PCO2 = 28mmHg
What is present?
12mM/(28\*0.03) = 12/0.84= 14.3
\<20, therefore acidosis is present.
Bicarb and CO2 are less than normal, therefore it is a metabolic acidosis.
53
Can an animal be too acidic if it has too much bicarb?
Too much CO2?
Too Little Bicarb?
No
Yes
Yes
54
Na+ + K+ _____ Cl- + HCO3-
| (\>, \<, =)
Na+ + K+ \> Cl- + HCO3-
ALWAYS
the difference is the anion gap.
Na+K = 140+ 5 = 145
Cl + HCO3- = 105 + 24 = 129
55
What do changes in the anion gap represent?
Increased anion gap means that it is a metabolic acidosis.
56
During disease states, there may be a time when excess acid/base production may exceed the ability of the kidney/lungs to remove the waste. What happens in this situation?
Cells throughout the body will 'hold on' to more acid they produce. This is made possible through the large of amount of intracellular buffer.
Skeletal muscle plays an important role as a buffer organ .
57
How do cells protect themselves against their own metabolism?
Intracellular buffers
Exporting H+/base to maintain intracellular [H+] to maintain it within homeostatic norms. This changes according to the cell's needs.
58
TRUE/FALSE.
Transporters for acid/base across cell membranes is depending on intra/extracellular pH.
TRUE.
Activity increases/decreases in order to maintain pH both intracellular and extracellular within homeostatic norms.
59
TRUE/FALSE.
Anion gap decreases are rare.
TRUE.
One cause is over-administration of isotonic fluid (isotonic overhydration).
60
During diarrhea, what happens to the anion gap? What kind of acid/base disorder is present during diarrhea?
It stays the same because you are losing all of the ions at the same time.
Bicarb losing metabolic acidosis.
However, if it resulted in dehydration because of inadequate water intake, this would lead to hypotension and decreased perfusion. This would to lactic acidosis, which would INCREASE the anion gap.
61
Whenever dehydration is present, you should always be aware of \_\_\_\_\_\_.
Lactic acidosis
62
Define Base Excess/Deficit.
The amount of acid (base) that would restore 1L of blood to normal acid/base composition at PCO2 of 40 mmHg.
Therefore, it is an indicator of the overall non-respiratory acid/base status (i.e. the metabolic component of acid/base disturbance).
63
Base excess/deficit refers to restoring blood to normal composition. Why is it whole blood and not just plasma?
The majority of CO2 goes into RBCs, which convert it to HCO3- and H+. RBCs then exchange HCO3- for Cl-. RBCs are therefore the major contributer of bicarb in plasma.
64
Plasma values from an animal on admission:
PCO2 = 40 mm Hg; pH = 7.3.
Plasma values obtained 45 minutes later:
P CO2 = 30 mm Hg, pH = 7.3.
a) What is the BD/BE on admission?
b) What is the BD/BE 45 minutes later?
c) How do you account for the change in P CO2?
d) What conclusion do you reach after comparing the BD/BE values?
e) Propose a cause for the animal's pH
a) See red line (exact value from calculator
Base excess = -6.4
b) Base excess = -10.8
c) Changes in ventilation would account for changes in PCO2.
d) The animal was undergoing respiratory compensation for the metabolic acidosis.
e) metabolic acidosis
65
What will asking about lactate in an animal that is dehydrated tell you?
It will tell you about cellular perfusion.
Increased lactic acid is a titration metabolic acidosis. This is due to increased anaerobic respiration that resulted from decreased perfusion.
66
A horse is moved to a stable where there is more dust/antigens in the air than it is used to. Describe what happens.
Instantaenous bronchoconstriction, leading to respiratory acidosis because of decreased CO2 exhalation. Bicarb would increase for 2 reasons:
1) Increased CO2 in aq. solution that would produce HCO3-
2) Kidney metabolic compensation.
The horse would obtain a heave-line from respiratory muscle hypertrophy.
67
TRUE/FALSE.
You can have an acidosis and alkalosis but a plasma pH of 7.4.
TRUE.
This would happen if the problems are of equal magnitude.
68
What are some common causes of metabolic acidosis?
1. Renal insufficiency (kidneys are not reabsorbing/manufacturing HCO3-)
2. Ketosis (ketoacidosis; ketones are acids)
3. Hyperkalemia
4. Pancreatic biliary tract obstruction (HCO3-) is sequestered in the GI tract)
5. Diarrhea (secreted HCO3- is lost rather than reabsorbed)
6. Anaerobiosis/Ischemic hypoxia
7. Ingestion of ethylene glycol
69
What happens during GDV?
The abdomen gets so big, that there is decreased ability for the lungs to increase and decrease in size. This results in metabolic and respiratory issues.
Respiratory acidosis because the lungs can no longer contract
Metabolic alkalosis because acid is being secreted into the stomach and not being reabsorbed.
Lactic Acidosis due to decreased perfusion to muscles.
it is caused by the gas in the stomach.
70
TRUE/FALSE.
Ethylene glycol alone is a toxin.
FALSE.
It becomes a toxin because of metabolism in the liver. The amount that does not initially get taken up into the liver travels to the kidney and gets excreted because it is freely filterable (no harm done)
71
Describe ethylene glycol metabolism.
Ethylene glycol --(Alcohol dehydrogenase)--\>
Glycoaldehyde --(Aldehyde dehydrogenase)--\>
Glycolic Acid --(lactic dehydrygenase)--\> Glyoxylic acid --\> Oxalic Acid
72
TRUE/FALSE.
Some of the glyoxylic acid produced in etheylene glycol metabolism is converted to CO2 and excreted in the lungs.
TRUE.
73
What are the main contributors to ethylene glycol poisoning?
Oxalate & oxalic acid. Although the PCT secretes oxalate, it's increased concentration will make it more likely to bind to soluble calcium. This would increase the crystals.
Crystals may also form within the PCT because it will actively transport oxalate in order to let it diffuse out. Once it has entered the PCT, intracellular calcium will bind to the oxalate and form crystals within the PCT cells.
This is another reason pH decreases because PCT is supposed to secrete HCO3 into plasma.
74
How is ethylene glycol poisoning treated?
1. Ethanol: competitive inhibition for alcohol dehydrogenase. May kill the animal, but no way of telling.
2. Methylpyrazole (very expensive)
75
How does hyperkalemia affect acid/base balance?
K+ stimulates principal cells by increasing K+ ports and increases its secretion.
Simultaneously, it inhibits a-intercalated cells, which puts bicarb into the interestitium and H+ into the lumen. This is a **bicarb-losing acidosis.**
K+ also stimualtes insulin secretion to tell skeletal muscle to increase K+, which they trade for proton.
The reciprocal is also true. H+ can lead to hyperkalemia because principal cells would be inhibited and decrease their K+ secretion.
76
\_\_\_\_\_\_ is the enzyme in PCT cells becomes more active during low pH.
Glutaminase
77
How do PCT cells synthesize new bicarb during acidic conditions?
Through metabolism of glutamine
Glutamine is converted to NH3 + glutamate using glutaminase.
Glutamate is converted to a-ketoglutarate and NH3.
a-ketoglutarate can then be oxidized or converted to glucose (both which produce CO2). Then, CO2 is converted to proton and bicarb.
78
The synthesis of bicarb through glutamine metabolism also generates proton. If the PCT were to simply pump it into the lumen, it would be able to diffuse through the tight junction down its concentration gradient. How is this resolved?
Through the secretion of NH3. H+ binds with ammonia to form ammonium (NH4), which cannot diffuse through the tight junctions.
79
For every glutamine molecule metabolised in the PCT, how many bicarbs are put into the interstitium?
2 Bicarbs
80
Who synthesizes bicarb through glutamine metabolism?
PCT
81
What happens to ammonium once it reaches the aLOH?
It can substitute in the Na/K/2Cl symport and then gets deposited into the medullary interstitium.
The medullary interstitium is less acidic and so some of it converts it back to ammonia. Ammonia now diffuses back into the DCT filtrate, where a-intercalated cells are putting H+ into the filtrate. Now, ammonia can soak up the proton that a-intercalted cells have secreted to form ammonium again.
82
Glutamine is a source of _____ and \_\_\_\_\_.
Bicarb and Ammonia
83
How does glutamine synthesis in the liver change in accordance with changes in pH?
Acidic: increased glutamine production
Alkaline: decreased glutamine and increased urea.
84
What are some common causes of respiratory acidosis?
1. Pneumonitis/pneumonia
2. Pulmonary edema
3. Bronchoconstriction
4. CNS Depression
5. Pneumothorax, hydrothorax, hemothorax, chylothroax
6. Neurologic and neuromuscular disorders.
85
The liver synthesizes glutamine by using \_\_\_\_\_.
Amino acids
a-ketoglutarate
(First, glutamate if formed. this soaks up ammonia to form glutamine).
86
TRUE/FALSE.
During respiratory acidosis, elevated bicarb ions is due to metabolic compensation.
FALSE.
Immediately, bicarb becomes elevated simply because of the presence of more CO2. Metabolic compensation through the addition of bicarb by PCT and a-intercalated cells will contribute to the elevation after a day or two.
87
What is the pulmonary safety factor?
There is 3x the distance necessary in the length of the pulmonary capillaries to equilibrate the PCO2 and PO2. This means that in instances where blood is moving faster (e.g. exercise), it still has time to equilibrate completely.
88
CO2 solubility is ____ ( \>, \<, = ) than O2 solubility.
What implications does this have?
\>
This means that hypoxemia develops before hypercapnia. If hypercapnia is seen, then you know you have hypoxia.
89
Describe how congestive heart failure leads to pulmonary edema. How does this cause respiratory acidosis?
If there is a mitral valve defect in the L atrium/L ventricle this will allow back flow. Back flow into the pulmonary veins will then increase CHP and cause edema.
The lungs are full of lymphatics to try to prevent this.
The increase in the distance that O2 and CO2 must diffuse across causes less exchange at alveoli, leading to respiratory acidosis.
90
What are some common causes of metabolic alkalosis?
1. Vomiting of gastric contents (H+ is lost in vomit)
2. Abomasal volvulus (H+ is sequestered in the lumen of the abomasum)
3. Gastric dilitation and volvulus (GDV) (H+ is sequestered in the lumen of the glandular stomach)
4. Hyperadrenocroticism (aldosterone stimulates a intercalated cells)
5. Iatrogenic (too much HCO3- is administerested)
91
What acid/base disorder does vomitting lead to? Explain.
Metabolic alkalosis
Proton and chloride are being lost during vomitting. Parietal cells secrete HCl into the lumen of the stomach.
Chloride is obtained from plasma (in exchange for bicarb) and H+ was produced from CO2.
Therefore, losing chloride causes an animal to become alkaline.
92
How does hyperadrenocorticism cause changes in acid/base status.
More cortisol would be secreted (PU/PD)
More aldosterone would be secreted, which stimulates a-intercalated cells to increase their H+ secretion and cause more bicarb to go into the plasma.
93
Why does aldosterone stimulate a-intercalated cells?
There are 2 major stimuli for release of aldosterone:
1. Hyperkalemia: these inhibit the a-intercalated cells, therefore decreasing their secretions. Aldosterone stimulates them to prevent alkalosis.
2. RAAS: Stimulated when there is decreased blood pressure, which leads to decreased perfusion, which leads to lactic acid production.
94
What metabolic disorder results from hypokalemia and how?
Metabolic alkalosis
Decreased potassium means that more H+ will get secreted from a-intercalated cells.
95
What acid/base disorders can result from GDV?
1. Respiratory acidosis
2. Metabolic Alkalosis
3. Metabolic Acidosis (Lactic acidosis)
96
What are common causes of respiratory alkalosis?
\*Increased respiratory function.
1. CNS lesions
2. CNS inflammation, e.g. encephalitis
3. Pain
4. Severe hypoxemia
97
What metabolic disorder results from changes in altitude?
Respiratory Alkalosis
Less oxygen causes increased ventilation. However, decreased oxygen delivery to the muscles would result in lactic acidosis.
