Bod: Renal: Pathophysiology Of Acid-Base Disorders

Front 1

What is normal blood pH?

Back 1

7.38 to 7.42

Front 2

What is the [H+] at a physiologic pH of 7.40?

Back 2

40 nEq/L

Front 3

normal arterial PCO2?

Back 3

36-44 mmHg

Front 4

What is the equation for the carbonic acid buffer system?

Back 4

(lungs) CO2 + H2O <-- --> H2CO3 <-- --> H+ + HCO3- (kidneys).

Front 5

What is a normal plasma [HCO3-]?

Back 5

about 25 mEq/L

Front 6

Where does most bicarbonate reabsorption happen?

Back 6

PCT. The distal nephron has almost no ability to reab HCO3-

Front 7

Explain the process of reabsorption of bicarb at the PCT. Include ions, transporters, etc.

Back 7

1. There is an Na+/K+ ATPase on the anti-lumenal side of the proximal tubule cell. This lowers the [Na+] in the cell.
2. Driven by the gradient above, an Na+/H+ antiporter brings Na+ into the cell and secretes H+ into the tubule lumen.
3. The H+ sec into the lumen combines with bicarb to make H2CO3, which then forms H2O and CO2 with the help of carbonic anhydrase.
4. H2O and CO2 diffuse into the cell, reform H2CO3 --> HCO3- and H+.
5. The H+ is secreted back into the lumen to combine with another molecule of bicarb.
6. The HCO3- in the cell moves into the peritubular fluid via a Na+/HCO3- symporter. This symporter is driven by an ELECTRICAL GRADIENT created by the ATPase and the overall negative charge within the cell.

Front 8

True or false: the kidney will adjust to bicarb levels above 25 mEq/L by increasing reabsorption along the nephron.

Back 8

False. Bicarb reabsorption is saturated at 25 mEq/L. Consequently, the admin of even a large amt of bicarb cannot result in a sustained serum increase.

Front 9

Where along the nephron does acid get secreted? How?

Back 9

Mostly in the collecting tubules, by H+ ATPases (facilitated by aldosterone)

Front 10

What effect does aldosterone have on the cells of the cortical collecting tubule?

Back 10

1. Aldosterone enters principal cell, opening lumenal Na+ channels, and inc Na+/K+ ATPase activity.
2. Na+ moves from the lumen into the principal cells, "leaving behind" a negative charge.
3. This gradient causes K+ to move out of the principal cells into the lumen and H+ to move out of the alpha-intercalated cells into the lumen.
5. Aldosterone also directly stims the H+ ATPase in the alpha-intercalated cell, increasing acid sec. An HCO3- is generated in this process. The bicarb moves into the peritubular fluid via a Cl-/HCO3- antiporter. At a sep location on the antilumenal side, a Cl- moves through a channel into the peritubular fluid to maintain electric neutrality.

Front 11

What is the most important buffer in the urine?

Back 11

Ammonia (NH3).

Front 12

What would be the consequences of failing to make enough urinary ammonia?

Back 12

Reduced renal acid excretion and a fall in blood pH.

Front 13

Where is urinary ammonia synthesized?

Back 13

In the cells of the PCT.

Front 14

What molecule is ammonia synthesized from? What is the other biproduct besides ammonia?

Back 14

Ammonia is synthesized from glutamine. Alpha-ketoglutarate is also formed (and then becomes HCO3- and moves into peritubular fluid)

Front 15

What is the path that urinary ammonia/um takes?

Back 15

1. Sec out of the PCT cells by acting like H+ and hijacking the H+/Na+ antiporter (it becomes a NH4+/Na+ antiporter).
2. Travels to the thick ascending limb and is transported into the medullary interstitum by mimicing K+ on the Na+/K+/2Cl- transporter.
3. Ammonium dissociates to ammonia in the interstitum.
4. Ammonia diffuses down conc grad into the collecting duct.
5. Ammonia combines with H+ to become ammonium.
6. Eventually exc as NH4Cl to maintain electrical neutrality.

Front 16

The quantity of ammonia produced is stimulated by ______emia and _____emia.

Back 16

The quanity of ammonia produced is stimulated by ACIDemia and HYPOKALemia

Front 17

The quantity of ammonia produced is inhibited by ____emia (acid/base) and _____emia (ion).

Back 17

The quantity of ammonia produced is inhibited by ALKALemia and HYPERKALemia.

Front 18

What are the three most common etiologies of metabolic acidosis? (general processes)

Back 18

1. Reduced renal acid excretion.
2. Bicarbonate losses (from kidney or from GI tract).
3. Increased endogenous acid production.

Front 19

What are three cases/situations that may cause a fall in renal H+ excretion?

Back 19

1. Renal failure
2. Type 1 Renal Tubular Acidosis (distal).
3. Type 3 Renal Tubular Acidosis (proximal).
3. Type 4 Renal Tubular Acidosis (hypoaldosteronism).

Front 20

What is the primary cause of reduced H+ excretion in renal failure? (What can worsen this situation?)

Back 20

Inadequate amt of urinary ammonia. (Hyperkalemia can worsen this acidosis).

Front 21

Explain Type 1 Renal Tubular Acidosis. Explain how it affects H+, Na+, and K+.

Back 21

This is a distal RTA. H+ secretion into the collecting tubules is impaired. H+ is not sec, so get metabolic acidosis. Na+ can still be exchanged for K+, however, so often see marked hypokalemia with a urine with a pH of 5.5 to 6.0 (Higher than you'd expect for an acidotic individual. Higher because the patient can't acidify the urine).

Front 22

True or False: The neutral urine pH is 7.4, the same as the blood.

Back 22

False, neutral urine pH is approx 5.3

Front 23

Explain Type 2 Renal Tubular Acidosis. What are two common causes? What is lost in the urine?

Back 23

Proximal tubule bicarbonate reabsorption is impaired. Most often observed when:

1) a carbonic anhydrase inhibitor is given (often when used to treat glaucoma), or

2) a systemic disorder damages PCT cells (Ig light chains due to mutiple myeloma).

Glucose, phosphate, urate may also be lost with the bicarbonate (This is called Fanconi Syndrome).

Front 24

Explain Type 4 Renal Tubular Acidosis. What happens to Na+ and K+? What happens to NH3? What is interesting about the urine?

Back 24

Aldosterone synth/activity is impaired. No Na+ goes into principal cell, therefore no K+ goes out. Hyperkalemia results. Hyperkalemia impairs renal prod of ammonia, and thus H+ exc is also impaired. However, the lack of ammonia means that there is more FREE H+ in the urine, making the pH low at <5.3.

Front 25

What is a physical complication that a pt might worry about wth a Type 1 RTA?

Back 25

Kidney stones.

Front 26

What are four examples of when endogenous acid increases?

Back 26

1. Lactic acidosis
2. Ketoacidosis
3. Rhabdomyolysis
4. Ingestions

Front 27

Explain lactic acidosis. What happens when reperfusion occurs? Rare instances with lactate?

Back 27

Hypotension, sepsis --> ischemia, hypoxia --> lactate. When reperfused, metabolism of lactate restores bicarbonate. BUT, sometimes the body might produce D-lactate instead of L-lactate. (L-lactate will be normal).

Front 28

Explain ketoacidosis. Reaction?

Back 28

glucose metabolism impaired by fasting, insulin def, or insulin resistance --> ketone body overproduction (ketosis): acetoacetic acid --> beta-hydroxybutyric acid --> acetone.

Front 29

Explain rhabdomyolysis. What does it cause?

Back 29

Trauma, infection, drugs. When severe, organic acids can be released into the bloodstream, causing acidosis.

Front 30

What are four common things that, if ingested, can cause metabolic acidosis?

Back 30

1. Salicylates
2. Methanol and ethylene glycol.
3. Toluene.
4. Acetaminophen.

Front 31

Explain the metabolic disturbances due to overingestion of salicylates.

Back 31

First see respiratory alkalosis caused by direct stimulation of the medullary respiratory center. Moderate to severe intoxication presents with a mixed respiratory alkalosis AND a metabolic acidosis.

Front 32

What household items contain toluene? What is toluene metabolized to?

Back 32

From glue/paint thinner. Metabolized to hippuric acid.

Front 33

Explain the relation between acetaminophen and metabolic acidosis.

Back 33

Acetaminophen can cause metabolic acidosis even in some pts who are taking it within the theraputic range, notably pregnant women and malnourished.

Front 34

What is the calculation for the serum anion gap?

Back 34

Anion gap = (Na+ - (Cl- + HCO3-))

Front 35

What is a "normal" anion gap?

Back 35

around 10 mEq/L. (anything below 12)

Front 36

What are three of the most common disorders that cause acidosis with an INCREASED anion gap?

Back 36

1. Advanced renal failure (phosphate).
2. Lactic acidosis (lactate).
3. Ketoacidosis (acac, beta-hydroxy)

Methanol
Uremia
DKA
P (unused medication)
INH
Lactic acidosis
Ethylene glycol
Siacylates

Front 37

What is meant by "hyperchloremic acidosis"?

Back 37

When the fall in serum bicarbonate is matched by a rise in chloride levels. Thus, the chloride levels rise, but the anion gap does not (think: Cl- + HCO3-)

Front 38

What are three of the most common disorders that cause metabolic acidosis with a NORMAL anion gap?

Back 38

1. Diarrhea.
2. Early renal failure.
3. Renal Tubular Acidosis (types 1, 2, 4)

Front 39

What is the formula for the urinary anion gap?

Back 39

Urinary anion gap = (urinary [Na+] + urinary [K+]) - urinary [Cl-]

Front 40

Diarrhea and RTA type 1 both cause metabolic acidosis with a normal anion gap. How can you tell them apart?

Back 40

In pts with diarrhea, urine tends to be acidic (pH <5.3).

In pts with RTA type 1, urine tends to be more alkaline (pH >5.3)

Front 41

What would the urinary anion gap of a pt with diarrhea be if the pH of his urine was alkaline (rare)? Why is his urine alkaline? Would we see the same phenomenon in a pt with RTA type 1?

Back 41

diarrhea --> hypokalemia --> ammonia prod increased --> ammonia inc so much that it is overshoots hydrogen ion secretion --> alkaline urine.

The urinary anion gap would be negative, because ammonia is excreted as ammonium chloride, so there is an increase in the amount of Cl excreted.

A pt with RTA type 1 would have a positive urinary AG because the ammonium chloride excreted is reduced by limited H+ secretion.

Front 42

Kussmal respirations are seen with metabolic ______ and are characterized by an increase in _____ _____ (spirometry), often without an increase in _______ ____ (vitals).

Back 42

Kussmal respirations are seen with metabolic ACIDOSIS and are characterized by an increase in TIDAL VOLUME, often without an increase in RESPIRATORY RATE.

Front 43

What does it indicate if the PCO2 rises (moves in the opposite direction) in response to metabolic acidosis?

Back 43

It indicates the presence of a second primary acid-base disturbance.

Front 44

The appropriate respiratory compensation in metabolic acidosis can be calculated using what formula?

Back 44

The Winter Formula:

Expected PCO2 = 1.5[HCO3-] + 8 +/- 2

For example, if bicarb was 16 mEq/L, then [(1.5 x 16) + 8] = approx 32. (This would indicate that the person was breathing at an increased rate, blowing off CO2)

Front 45

What is a trick of mathematics that can be used to determine if the amount of respiratory compensation in metabolic acidosis is appropriate?

Back 45

The last two digits of the pH should equal the PCO2 if the compensation is appropriate (e.g. 32 mmHg at a pH of 7.32).