SM 201/202 Acid Base Integration Flashcards
(104 cards)
1
Q
Which organ mediates removal of volatile acids in acid-base balance?
A
The lungs, because they expire the volatile acid: CO2
2
Q
Which organ mediates removal of non-volatile acids in acid-base balance?
A
The kidneys, because they excrete non-volatile acids: like the titratable acids, ammonia
3
Q
Does the gut make more acid or base per day?
A
The gut makes more acid, which must be excreted by the kidneys
4
Q
What organ gives rise to metabolic acid-base disorders and what organ compensates for them?
A
Metabolic acid-base orders are caused by the Kidneys and rapidly compensated for by the Lungs
5
Q
What organ gives rise to respiratory acid-base disorders and what organ compensates for them?
A
Respiratory acid-base orders are caused by the Lungs and slowly compensated for by the Kidneys
6
Q
How quickly are respiratory acid-base disorders compensated?
A
Slowly, because the kidneys take days
7
Q
How quickly are metabolic acid-base disorders compensated?
A
Rapidly, because the lungs change breathing rate quickly
8
Q
What are the 4 defenses against acid/base changes?
A
Extracellular buffering (immediate) Respiratory compensation (minutes) Intracellular buffers (hours) Renal excretion (4-6 days)
9
Q
How long does it take for Extracellular Buffering to fix acid/base changes?
A
Extracellular buffering by HCO3 occurs immediately
10
Q
How long does it take for Respiratory Compensation to fix acid/base changes?
A
Respiratory Compensation by hyperventilation and hypoventilation occurs in minutes
11
Q
How long does it take Intracellular Buffers to fix acid/base changes?
A
Intracellular Buffers like proteins and organic phosphate occurs in hours
12
Q
How long does it take for Renal Excretion to fix acid/base changes?
A
Renal Excretion takes 4-6 days
13
Q
What is used for fine tuning of acid/base disorders?
A
Fine tuning occurs via renal excretion of acid and base
14
Q
What are the major intracellular buffers?
A
Histidine, HCO3, Phosphate
15
Q
Is HCO3 primarily an intracellular or extracellular buffer?
A
HCO3 is primarily an extracellular buffer, but there is some inside cells as well
16
Q
Is intracellular pH lower or higher than extracellular pH?
A
Intracellular pH = 7.1 - 7.3 < Extracellular/Plasma pH = 7.4
17
Q
How is the intracellular pH regulated?
A
Acid-base transporters on the cell membrane protect the cell against changes in pH
18
Q
What transporters are found on cell membranes to regulate intracellular pH?
A
Na/H antiporter
Na-dependent Cl/HCO3 Exchanger
Na-independent Cl/HCO3 Exchanger
19
Q
Are Cl/HCO3 exchangers on the cell membrane Na dependent or independent?
A
Both
20
Q
Which cell membrane transporter protects against intracellular acidosis?
A
Na/H antiporter
21
Q
Which cell membrane transporter protects against intracellular alkalosis?
A
HCO3/Cl antiporters (Na dependent and independent)
22
Q
What does the graph of pH vs time look like in response to an acid or base load on a cell?
A
In an acid load, the graph sharply dips and then rapidly recovers due to the Na/H antiporter
In a base load, the graph sharply spikes and then rapidly recovers due to the HCO3/Cl antiporters
23
Q
Do the kidneys excrete acid or base?
A
The kidneys can excrete either, but in the context of a protein heavy Western diet that makes lots of acid, the kidney will primarily excrete acid
24
Q
Describe the relative contributions of different portions of the nephron for bicarbonate reabsorption?
A
All bicarb is filtered at the Glomerulus
PCT reabsorbs 80%
TALH reabsorbs 15%
CCD absorbs 5%
Normally 0% is released into the urine
25
How much bicarb is normally reabsorbed?
100%
26
Which portion of the CD is regulatable?
The collecting duct is regulatable
27
Describe the channels that mediate HCO3 reabsorption in the PCT?
Apical Membrane: Na/H Antiporter, H ATPase, Aquaporins
Basolateral Membrane: Na/K ATPase, Na/3HCO3 symporter
H+ is pumped into the lumen and reacts with HCO3 to form H2CO3, which is acted upon by CA to form H2O and CO2
CO2 diffuses into the cell and is acted upon by CA to form H2CO3, which breaks apart into H+ and HCO3
H+ is secreted into the lumen while HCO3 is reabsorbed into the blood with the Na/3HCO3 channel
28
What is NHE3?
NHE3 is an Na/H antiporter that release H+ into the lumen
29
What is NBCe1A?
NBCe1A releases HCO3 into the bloodstream in the PCT
30
How are H+ secretion and HCO3 reabsorption in the PCT related?
For every 1 H+ secreted into the lumen at the PCT, 1 HCO3 is reabsorbed into the blood
31
How is HCO3 reabsorption different in the TALH, in comparison to the PCT?
HCO3 secretion into the blood uses a HCO3/Cl transporter on the basolateral membrane instead of the Na/3HCO3 channel
32
Is HCO3 reabsorption in the DCT mediated by an Na/H exchanger?
No, an H ATPase is more important here
33
What is the function of Principal Cells in the collecting tubule?
Retain Na and secrete K
34
What is the function of alpha intercalated cells?
Secrete H+ and reabsorb HCO3
35
What is the function of beta intercalated cells?
Secrete HCO3 and reabsorb H+
36
Which proton pump is more important in alpha intercalated cells, H/K antiporters or H+ ATPase?
H+ ATPase is more important for secreting H+ in alpha intercalated cells
37
What does AE1 mediate?
AE1 is an HCO3/Cl exchanger in alpha intercalated cells that facilitates HCO3 reabsorption
38
What does Pendrin mediate?
Pendrin is an HCO3/Cl exchanger in beta intercalated cells that facilitates HCO3 secretion
39
How do alpha and beta intercalated cells interrelate?
Alpha and Beta cells exert opposite effects, and are activated/deactivated by dietary intake of H+/HCO3
40
What buffer is most prevalent in the nephron?
Bicarb acts as the main buffer until the collecting tubule, where phosphate and ammonia are the major urine buffers
41
What is meant by de novo bicarbonate formation in the CD?
Since there is little bicarbonate that reaches the CD, Bicarbonate is formed by:
Absorbing CO2 from the apical side
CO2 + H2O = HCO3 and H+ via CA
H+ is excreted into urine via H/K ATPase and H+ ATPase
HCO3 is reabsorbed into the bloodstream via AE1, a HCO3/Cl antiporter, and is "de novo" because the HCO3 formed is not reabsorbed from the lumen
42
What does titratable acidity refer to?
Weak acids filtered at the glomerulus that act as buffers, with phosphate being the major urinary buffer
43
What is the formula for Net Acid Excretion?
NAE = NH4 + TA - HCO3 (HCO3 is typically very small)
44
What supplies the Ammonia that buffers the urine?
Glutamine, produced by the Liver, is cleaved by Glutaminase and other enzymes to form NH3 that diffuses out of cells and buffers the urine
45
How is Ammonia formed in the PCT?
NH4 is first formed from Glutamine in the PCT after Glutamine is transported into the cell with Na/Glutamine proteins
Glutamine is degraded into NH3 and NH4
NH3 diffuses out of the cell while NH4 hijacks the Na/H transporter to enter the Lumen and flow with the Urine
46
Is NH3 actively or passively transported out of the PCT?
NH3 is passively transported out of the PCT into the Urine, because it diffuses out
47
Is NH4+ actively or passively transported out of the PCT?
NH4 is actively transported by the Na/H transporter because NH4 can mimic H+
48
How is NH4 in the urine altered at the Loop of Henle?
NH4 can be imported by the NKKC channel, which normally transports Na/K/2Cl, into TALH cells
Once in the cell, it can be deprotonated into NH3 and diffuse out into the lumen
Once in the lumen, it can get protonated and trapped outside as NH4
49
What effect does acidosis have on NH4 formation?
Metabolic acidosis increases production of Glutamine to promote secretion of the extra H+ as NH4 in the urine
50
What effect does metabolic acidosis have on acid/base regulation in the Kidney?
Metabolic acidosis stimulates bicarbonate absorption and acid excretion
51
What effect does respiratory acidosis have on acid/base regulation in the Kidney?
Respiratory acidosis stimulates bicarbonate absorption and acid excretion
52
What effect does metabolic alkalosis have on acid/base regulation in the Kidney?
Metabolic acidosis reduces bicarbonate absorption and acid excretion
53
What effect does respiratory alkalosis have on acid/base regulation in the Kidney?
Respiratory acidosis reduces bicarbonate absorption and acid excretion
54
Why do acid/base disturbances effect blood volume?
The Na/H antiporter is involved, which can alter blood volume, because forming bicarbonate requires importing Na to excrete H+, which raises blood volume
55
What effect does volume contraction have on bicarbonate reabsorption and acid excretion?
Volume contraction stimulates bicarbonate reabsorption and acid excretion, because reabsorption of Na to compensate for the volume loss results in H+ excretion and more HCO3 reabsorption
56
What effect does volume expansion have on bicarbonate reabsorption and acid excretion?
Volume contraction inhibits bicarbonate reabsorption and acid excretion, because less reabsorption of Na to compensate for the volume gain results in less H+ excretion and less HCO3 reabsorption
57
What effect do Aldosterone, Hypokalemia, and AngII have on acid base balance in the kidneys?
Stimulates bicarbonate reabsorption and acid excretion
58
What is acidemia?
Acidemia is a decrease in blood pH below normal ranges
59
What is alkalemia?
An increase in blood pH above normal ranges
60
What is acidosis?
A disorder that tends to lower the pH, at any pH
61
What is alkalosis?
A disorder that tends to raise the pH, at any pH
62
How does an acidosis differ from an acidemia?
Acidemia occurs when the actual blood pH is too low, while Alkalosis occurs when the blood pH approaches a low value
63
How does an alkalosis differ from an alkalemia?
Alkalemia occurs when the actual blood pH is too high, while Alkalosis occurs when the blood pH approaches a high value
64
What is the Henderson Hasselbach equation for CO2?
pH = 6.1 +log(HCO3/(0.03*PCO2))
65
Why does compensation occur?
Compensation occurs to prevent the blood pH from rising or falling out of ranges compatible with life
66
What are the expected compensatory responses in metabolic acidosis?
Decrease in pCO2 = 1.2 * DeltaHCO3
| DeltaHCO3 = 24 - Observed HCO3
67
What are the expected compensatory responses in metabolic alkalosis?
Increase in pCO2 = 0.6 * DeltaHCO3
| Delta HCO3 = Measured HCO3 - 24
68
What are the expected compensatory responses in chronic respiratory acidosis?
Increase in HCO3 = 0.4 * DeltapCO2
| DeltapCO2 = Measured pCO2 - 40
69
What are the expected compensatory responses in chronic respiratory alkalosis?
Decrease in HCO3 = 0.5 * DeltapCO2
| DeltapCO2 = 40 - Measured pCO2
70
How do the compensatory responses in metabolic acidosis compare to those of metabolic alkalosis, in terms of the change in pCO2?
The decrease in pCO2 during Metabolic Acidosis is 1.2 * DeltaHCO3, and 0.6 * Delta HCO3 in Metabolic Alkalosis
71
How do the compensatory responses in metabolic acidosis compare to those of metabolic alkalosis, in terms of the change in HCO3?
The DeltaHCO3 is 24 - Observed HCO3 in Metabolic Acidosis, and Observed HCO3 - 24 in Metabolic Alkalosis
72
In the setting of metabolic acidosis, what value(s) should treatment focus on normalizing?
In Met acidosis, treatment should focus on normalizing pH and HCO3
73
What would explain a sharp decrease in pH and a rise in pCO2 for a patient with a metabolic acidosis?
Respiratory fatigue - respiratory compensation occurs during metabolic acidosis, which requires elevating the respiratory rate; if the lungs fatigue and cannot maintain the respiratory rate, the compensation is lost and pH will fall while pCO2 rises as CO2 cannot be excreted
74
What are the 3 general causes of metabolic acidosis?
Loss of HCO3 externally via diarrhea or kidney (RTA)
Failure of the kidneys to excrete acid (Distal RTA/CKD)
Building up acid in circulation due to Acidosis
75
What can cause a loss of HCO3 that leads to metabolic acidosis?
Diarrhea, Vomiting, and Proximal Renal Tubular Acidosis (RTA)
76
What can cause a failure of the kidneys to excrete acid?
Distal Renal Tubular Acidosis (RTA) and CKD
77
What can cause acid to buildup in the circulation leading to metabolic acidosis?
Underperfusion of tissue = lactic acidosis
| Lack of insulin = diabetic ketoacidosis
78
How does a proximal RTA lead to metabolic acidosis?
A proximal RTA causes metabolic acidosis due to failure to reabsorb bicarbonate in the PCT, leading to bicarbonate in the urine
79
What is the hallmark of Proximal RTA?
Bicarbonate in the urine suggests RTA because the kidney is unable to reabsorb bicarbonate
80
What causes Fanconi syndrome?
Proximal RTA, which results in multiple PCT channels being affected and an inability to absorb many ions
81
What are symptoms of Fanconi syndrome?
Bicarbonate wastage in urine
Glycosura
Phosphaturia
Aminoaciduria
82
How does a distal RTA lead to metabolic acidosis?
A distal RTA causes metabolic acidosis due to failure to excrete acid in the principal cells of the collecting duct, causing acid to build up in the bloodstream
83
What are symptoms of a DRTA that accompanies metabolic acidosis?
Hyperchloremia (since alpha cells are defective and can't exchange bicarb for chloride)
Kidney stones
84
What can cause a buildup of acid in the blood that leads to metabolic acidosis?
Increased lactic acid generation from tissue hypoxia
Decreased utilization of lactic acid by the Liver
Low insulin levels leading to DKA
85
What is a normal Anion Gap?
Normal AG = 12 +/- 2 mEq
86
How can a fall in the bicarbonate portion of anions in circulation be filled?
Decreased bicarb can be filled by Chloride (measured in the AG) or other anions (not measured in the AG)
87
What is hyperchloremic metabolic acidosis?
Non-anion gap acidosis; Chloride is part of the normal AG and rises to compensate for the loss in bicarbonate, so the AG is not elevated
88
What does a metabolic acidosis in the setting of a normal anion gap suggest?
Elevated chloride
89
What is a high anion gap metabolic acidosis?
A metabolic acidosis of low bicarb compensated for by an anion other than chloride, which raises the anion gap
90
What can cause an elevated anion gap metabolic acidosis?
CAT MUDPILES
```
Cyanide
Aminoglycosides
Toluene (glue)
Methanol
Uremia
DKA (any acidosis)
Proximal RTA
Isonaizid
Lactic Acidosis
Ethylene Glycol
Salicylic Acid
```
91
What can cause a normal anion gap metabolic acidosis?
USED CAR
```
Utero-bag
Saline administration
Endocrine disorder
Diarrhea
Carbonic Anhydrase inhibitor
Ammonium chloride
Renal Tubular Acidosis
```
92
What is the underlying pathophysiology of a Distal RTA?
Low urinary NH4 and titratable acid excretion
93
What is UAG?
UAG is an inverse approximation of NH4; high urinary NH4 corresponds with a low UAG since UAG = Urinary Anions - Urinary Cations
94
When is UAG relevant?
UAG is relevant in the context of hyperchloremic/non-AG metabolic acidosis
95
What does a positive UAG reflect?
A positive UAG suggests that anions > cations and that NH4 is therefore low in the urine, suggesting distal RTA
96
What does a negative UAG reflect?
A negative UAG suggests that cations > anions and that NH4 is abundant in the urine, which is consistent with diarrhea since more de novo bicarbonate production is occurring to compensate for HCO3 losses
97
Why is respiratory compensation to metabolic alkalosis ineffective?
Respiratory compensation would involve hypoventilation to lower the pH, which would also cause hypoxia and is therefore very limited
98
How do the kidneys respond to metabolic alkalosis?
The kidneys respond by reabsorbing less HCO3 at the PCT and increasing secretion by the beta intercalated cells
99
What can cause metabolic alkalosis?
Loss of H+ due to vomiting
Kidney losses due to Loop/thiazide diuretics
Administration of bicarbonate
100
What the phases of metabolic alkalosis and why is it sustained by the Kidneys?
The generation phase of metabolic alkalosis is when vomiting causes loss of H+ from the stomach
The loss of H+ in stomach drives up Parietal cell secretinon of H+, which is derived from H2CO3, therefore also increasing secretion of HCO3 into the blood
Metabolic alkalosis ensues
Volume loss leads to decreased GFR to the kidney, which stimulates RAAS
RAAS stimulates water/sodium reabsorption, leading to more HCO3 reabsorption at the PCT and CD
101
How does the kidney respond to vomit induced metabolic alkalosis?
The kidney senses lower GFR and responds by activating RAAS to raise fluid volume, which increases Na, Cl, and HCO3 retention while secreting more K
102
What ion is low in urine during vomiting?
Cl, because the kidney attempts to reclaim more of it
103
How can metabolic alkalosis be fixed medically?
Add Normal Saline to expand the volume and correct the chloride deficit
Add KCl if hypokalemia has developed from RAAS activation in an attempt to preserve body volume
104
What ion channels are found in the parietal cells of the stomach and why are they relevant?
The parietal cells of the stomach secrete H+ into the stomach contents
Parietal cells have a Na/H+ exchanger facing the stomach and a Cl/HCO3 exchanger facing the blood
In vomiting, the Na/H exchanger is potentiated due to less H+ in the stomach, demanding more Chloride and resulting in more HCO3 being released into the blood, causing metabolic alkalosis
