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David's- Renal Exam 2 > Renal Control of Acid-Base Balance > Flashcards

Renal Control of Acid-Base Balance Flashcards

1
Q

Extracellular pH must be: ____

A

pH= 7.4

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2
Q

Why must we maintain a constant pH?

A

We must maintain a pH of 7.4 because changes in pH change the function and structure of proteins. It affects the electrostatic charge that impacts protein folding, interaction and drug binding.

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3
Q

Regulation of H+ and CO2 is regulated by what?

A
  1. Kidneys
  2. Lungs
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4
Q

What are our metabolic acid sources that are volatile, which can be eliminated by the lungs?

A

Oxidation of [glucose] and [fat].

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5
Q

How much H+/CO2+ can our lungs blow out a day?

A

24,000 mEq/day

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6
Q

What are our metabolic acid sources that are eliminated by our kidneys?

A
  1. Glucose –(anaerobic)–> H+ + lactate
  2. Cysteine + O2–> H+ and sulfate
  3. Phosphoproteins + O2–> H+ + Phosphate

Oxidation of cysteine and phosphoproteins and [glucose- anaerobic]

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7
Q

How much H+/CO2+ are eliminated by our kidneys/ day?

A

50mEq/day

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8
Q

A decrease of 0.3 pH–> ______ H+ concentration

A

DOUBLES

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9
Q

A increase of 0.3 pH–> ______ H+ concentration

A

HALVES

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10
Q

What is the pH range of intracellular fluid?

A

pH= 6.0-7.4

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11
Q

What is the pH range of urine?

A

4.5 - 8.0

-this allows us to concentration and dilute the urine-

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12
Q

Why does urine have such a big pH range?

A

Urine has such a big range to accomodate for large changes in H+ and HCO3- excretion.

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13
Q

What are the 4 major buffers of the body?

A

1. Bicarb (HCO3-)

2. Hemoglobin (Hb-)

3. Phosphate (HPO4-)

4. Plasma proteins

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14
Q

What is the rate of the 4 major buffers of the body?

A

Instantaneous

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15
Q

What is the pK value of bicarb, Hb, phosphate and plasma proteins?

A

bicarb= 6.1

hb= 7.3

phosphate= 6.8

plasma proteins= 6.7

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16
Q

What are the organs involved in buffering?

A

1. Lungs

2. Ionic shift

3. Kidneys

4. Bones

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17
Q

How do the lungs buffer the body?

A

Lungs regulate the retention or elimination of CO2, and therefore, the H2CO3 concentration. It is prompted within minutes-hours.

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18
Q

How does the ionic shift buffer the body?

A

Ionic shift exchanges [intracellular K+ & Na+] for [H+] within 2-4 hours.

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19
Q

How do the kidneys buffer the body?

A

1. Bicarb reabsorption and regeneration

2. Form ammonia

3. Use phosphate to buffer

Rate: hours-days

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20
Q

How do the bones buffer the body?

A
  1. Buffer Ca2+ and P and the release of carbonate occurs slowly, from hours- days.
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21
Q

What happens if we add a weak acid to water (acetic acid)?

A

It will not completely dissociate. Thus, in water it will exist as [CH3COOH and CH3COO- and H+].

Thus, the amount of free H+ will not be as high and pH will not be as low as a strong acid.

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22
Q

What happens if we add a strong acid to water (HCl)?

A

[Strong acid]–> completely dissociate–> increase H+ in the water, decreasing the pH, making a more acidic fluid.

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23
Q

CH3COONa+ in water will produce CH3COO- and Na+ with a pH of 14.

What happens when we add HCl?

A

HCl–> H+ + Cl—> H+ will bind to CH3COO—> CH3COOH

As we are adding H+, the amount of free H+ does not change because it is binding to the buffer and changes to our pH are small. However, as we keep adding H+, we reach buffering capacity and the pH will drop dramatically.

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24
Q

What is the major buffering system in mammals?

A

Carbonic acid (H2CO3), which is made from CO2 and H2O.

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25
Q

H2CO3 has a pKa at 6.1.

What does this mean?

A
  • It is the pKa where the buffer is 1/2 saturated.
  • Meaning that 1/2 of the buffer exists as [H2CO3] and 1/2 is [dissociated HCO3- and H+].
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26
Q

Describe the stability of carbonic acid (H2CO3).

A

CA is unstable and spontaneously depolarizes in either direction.

CO2+ H2O ⇔ H2CO3 ⇔ H+ + HCO3-

CO2 is made by aerobic metabolism and can be blown out by the lungs.

HCO3 is made by anaerobic metabolism and ingested acids. It is slowly made and regulated by the kidneys . Normally, we have 600,000/free H+.

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27
Q

What happens if we hypoventilate?

A

Increase CO2= increase H2CO3= Increase H+ and HCO3 (but a v small amount)= decrease pH

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28
Q

What happens if we hyperventilate?

A

Decrease CO2= decrease H2CO3= decrease H+ and HCO3 (but a v small amount)= increase pH

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29
Q

Once again, what is the pKa of a buffer mean?

For example:

Carbonic acid= 6.1

Phosphate= 6.8

A

The pKa is the pH at which the buffer, acting as a sponge, has sopped up half of the H+ it can hold. You will see small changes in pH in the buffer zone.

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30
Q

How is CO2 transported?

A
  1. 70% is transported as bicarb
  2. 23% is transported with Hb (HbCO2)
  3. 7% is dissolved
31
Q

[buffering of H+ ion by plasma proteins and Hb]

A
32
Q

Buffering extracellular H+ changes by exchanging for ____

A

K+

33
Q

What happens in cases of acidemia?

A

The pH of the ECF is buffered because the ICF takes in H+ and exchanges it for a K+ (which has higher concentration inside of the cell).

34
Q

What happens in cases of alkalemia?

A

The ECF is buffered because the ICF donates a H+ and takes in a K+ from the ECF.

35
Q

What is the Henderson-Hasselbalch equation?

A

allows us to predict the pH of a buffered solution, given its pK, the concentration of conjugate base, and the concentration of conjugate acid.

pH =6.1 + log[HCO3-]/[H2CO3]

pH= 6.1 + log[HCO3]/0.03 * PCO2

Usually Pco2=40; [HCO3-]= 24

36
Q

In order to maintain a normal arterial pH of 7.4, the [HCO3-]/[CO2] ratio must be ______

A

20:1

Therefore, through our kidney and lungs, our body will try to keep the 20:1 ratio.

37
Q

If the ratio of [HCO3-]/[CO2] is <20,

we can assume conditions are _____.

A

acidosis

(deficiency in HCO3-; excess of H+/CO2)

38
Q

If the ratio of [HCO3-]/[CO2] >20,

we can assume conditions are _____.

A

Alkalosis

(Excess HCO3-, deficiency of H+/CO2)

39
Q

CO2/HCO3 buffer system is an open system.

How?

A

Bicarb is controlled by the kidneys, slow with large capacity.

CO2 is controlled by the lungs, fast with limited capacity.

40
Q

Renal reabsorption of bicarb

A

99% of filtered bicarb is reabsorbed in the nephron.

85% is reabsorbed in the PT, with a small amount being absorbed in the thick ascending lumb and a small “fine tuning” occuring in the DT and collecting duct.

41
Q

Bicarb reabsorption in the PT

A
  • 85% of Bicarb is reabsorbed in the PT via Na/H+ ATPase
  • HCO3 in the lumen binds with H+ –> carbonic acid
  • Carbonic anhydrase allows it to dissociate–>CO2 and H20.
  • CO2 and H20 is uptaken passively into the cells of the proximal tubule where carbonic anhydrase reforms it into H+ and HCO3-.
  • The HCO3- is shuttled out of the cell through either a Na/3HCO3- symporter, or a HCO3-/Cl- chloride antiporter.
  • The H+ ion is shuttled back into the intratubular fluid via a Na/ H+ antiporter.

The bicarbonate sodium symporter is an example of how the concentration gradient being created of bicarbonate within the cell carries the sodium against its concentration gradient (into the ECF) without having to use the Na/K ATPase.

42
Q

What are the primary factors that increase H+ secretion?

A
  1. Decrease in plasma HCO3- concentration –> decrease in pH –> increase H+ secretion
  2. Increase in PCO2 –> decrease in pH –> increase H+ secretion.
43
Q

What are the secondary factors that cause H+ secretion? (5)

(Factors not directly involved in maintaing acid-base balance).

A
  1. Increase in filtered load of bicarb will secrete more H+ so that we can reabsorb the HCO3-.
  2. Decrease in ECF volume
  3. Increase in angiotensin II–> stimulates Na+/H+ exchange in the proximal tubule
  4. Increase in aldosterone–> stimulates H+ ATPase in the intercalated cells of the collecting duct
  5. Hypokalemia
44
Q

Phosphate buffering of secreted hydrogens

How does phosphate buffer secreted H+ ions (those in the urine)?

A

In intercalated A cells (active in acidic conditions), we want to remove H+ and reabsorb bicarb.

  1. CO2 from the blood –> intercalated A cells.
  2. CO2+ H20–[CA]–> H2CO3–> H+ and HCO3-.
  3. H+ ATPase on the apical membrane pushes H+ ions out of the cells.
  4. In order to keep excreted H+ ions, we need to buffer it in the urine. Thus, NaHPO4 will bind a H–> NaH2PO4–> secrete it in the urine.
  5. The NEW bicarb in the cells moves from the cell–> blood via HCO3-/Cl- exchanger.

—-Aldosterone will promote the reabsorption of HCO3- by increasing the activity of the H+ ATPase, which is located on the apical membrane and moves the H+ out—-

45
Q

Ammonia can buffer H+, which helps to do what?

A

Reclaim HCO3-

46
Q

Ammonia: buffers H+ and reclaim bicarb.

How does this work?

A

Glutamine has 2 ammonias. The kidney has a infinite amount of glutamine and can make as much as it needs to act as a buffer.

  1. Cells in the proximal tubule rely on glutamine for energy, producing ammonia as a byproduct
  2. NH3 and H+ from the Na+/H+ antiporter enters the lumen and combine, to create ammonium (NH4+)
  3. At the thick ascending LoH, NH4+ is transported by Na, K and 2Cl in place of K–> interstitium
  4. In the interstium, it enters an equillbrium between ammonium (NH4+) and ammonia (NH3)
  5. NH3 diffuses through cell of collecting duct and enters the lumen
  6. In the tubular fluid, NH3 buffers H+–> NH4+
  7. H+ is removed from the bicarb reabsorption loop and drags it into the urine. For every H+ removed, one HCO3- is freed

Thus, ammonia is used to reclaim bicarb.

47
Q

What do the alpha and beta intercalated cells do?

A

Alpha intercalated cells–> secrete H+ and reabsorbs HCO3-

Beta intercalated cells–> reabsorb H+ and secrete HCO3-

48
Q

Review how intercalated alpha and B cells work

A
49
Q

Alpha intercalated cells secretes H+ in a process called urinary acidification. What is special about bicarb in this process?

A
  • H+ is secreted into the tubular fluid and combines with HCO3- to form CO2 and H20, which is then reabsorbed in the cell.
  • H+ can also be buffered by NH3–> NH4+ and excreted, creating new bicarb, while bicarb is absorbed.
50
Q

Net acid excretion

A

NAE = (UNH4+ ✕ V) + (UTA ✕ V) - (UHCO3- ✕ V)

  • Net acid excretion is equal to the urinary concentration of ammonia times urine flow rate, plus the urinary concentration of titratable acids (primarily phosphate) times urinary flow rate, minus urinary concentration of bicarbonate times urinary flow rate.
  • It must be equal to production of non-volatile sources of H+ ions (anaerobic breakdown of glucose, oxidation of cystein and oxidation of phosphoproteins)
51
Q

What are titratable acids (TA)?

A

TA- Salts that are mainly phosphate, but can be other constituents of urine, such as creatine.

They make up ~1/3 of NAE

52
Q

Is Ammonium (NH4+) a TA?

A
  • No. It has a high pK, meaning that no H+ can be removed when titrating to a pH of 7.4.
  • It is responsible for about 2/3 of net acid excretion
53
Q

Fill in the chart

A
54
Q

In chronic respiratory problems, there is a problem with the lungs, allowing the kidneys to have time to take over.

Thus, you can see large differences in plasma HCO3-, with ______ effect on pH.

A

little

55
Q

In acute respiratory alkalosis and acidosis,

changes in plasma HCO3- –> ___ changes in pH.

A

Large

56
Q

What occurs with metabolic acidosis?

A

Causes of acidosis:

  • Decrease in (HCO3-)
  • Increase in acid (H+)

—pH decreases–

Two things will happen:

  1. Respiratory compensation (lungs)
    1. Hyperventilation–> decrease PCO2–> decrease CO2 and H20–> Decrease in H2CO3–> decrease in H+–> increase pH
  2. Renal correction (kidneys)- will do what they can to make more bicarb and secrete more H+
    1. Increased acid titration–>
      1. Increased buffering of H: [NH3+ H+–> NH4+] and [HPO4 + H+ —> H2PO4]
    2. Increases bicarb regeneration and increases acid excretion

—increase pH—

57
Q

What is the anion gap?

A

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

Anion gap is the value of unmeasured anions in the plasma.

It is normally 8-16 mEq/L.

58
Q

What are causes of metabolic acidosis included in the anion gap?

(cause a high anion gap)

A

MUDPILERS

  1. Methanol
  2. Uremia
  3. DKA/alcoholic KA
  4. Paraldehyde
  5. Isoniazid
  6. Lactic acidosis
  7. EtOH/Ethylene Glycol
  8. Rhabdo/renal failure
  9. Salicylates
59
Q

What are causes of metabolic acidosis not included in the anion gap?

(non-anion gap acidosis)

A

HARDUPS

1. Hyperalimentation

2. Acetazolamide

3. Renal tubular acidosis

4. Diarrhea

5. Utero-pelvic shunt

6. Post-hypocapnia

7. Spironolactone

60
Q

Describe Type 1 Renal Tubular Acidosis *

A
  • In type I renal tubular acidosis, the alpha intercalated cant secrete hydrogen.
  • –> decreases the ability of NH3 and HPO to buffer that hydrogen creating “new” bicarbonate.
  • Plasma K is usually low.
61
Q

Describe Type 2 Renal Tubular Acidosis*

A
  • Impaired HCO3 reabsorption in the proximal tubule.
  • K is usually low.
62
Q

Symptoms of metabolic acidosis

A
  • Mild acidosis is asymptomatic. However, when pH is <7.10 (or higher if it developed rapidly), it can cause nausea, vomiting and malaise.
  • Respiratory compensation: large, deep breaths without dyspnea
63
Q

Draw out metabolic alkalosis, compensation and correction

A

Causes of metabolic alkalosis

  1. Increase in HCO3-
  2. Decrease in H+

—Increase in pH—

Respiratory compensation

  • Hypoventilation–> increase in PCO2–> Increase in CO2 +H20–> increase in H2CO3–> increase in H+–> decrease pH

Renal Correction

  • Decrease reabsorption of HCO3- –> increases excretion of HCO3- –> decreases pH
  • Decrease acid titration–> decreases acid loss by down-regulating the binding of H+ to NH3 and HPO4-
    • (-) in binding of H+ to NH3–> decreases acid excretion–> decreases pH
    • (-) bind binding of H+ to HPO4- –> decreases in bicarb regeneration–> decreases pH

—decrease pH—

64
Q

Causes of metabolic alkalosis

A

CLEVER PD

  1. Contraction
  2. Licorice
  3. Endo: (Conn, Cushing, [Bartter])
  4. Vomiting (loss of H+, HCO3- remains in the blood, maintained by volume contraction, hypokalemia)
  5. Excess alkali
  6. Refeeding alkalosis
  7. Post-hypercapnia
  8. Diuretics (volume contraction increases HCO3- reabsorption d/t increase angiotensin II and aldosterone)
65
Q

Symptoms of metabolic alkalosis

A

Mild: signs and symptoms of underlying disorder

More severe: increase HCO3- in the blood–> HCO3- can begin to bind calcium –> hypocalcemia.

  • Hypocalcemia will cause neuromuscular excitability, delirium, tetany, and seizures.
  • Hypocalcemia can also cause arrhythmias, much the same as hypokalemia.
66
Q

Respiratory acidosis with compensation

A

Cause: decreased ventilation

  • Increased PCO2
  • Increased H2CO3
  • Increased H+

—Decreases pH—

Renal compensation (increases production of NH3 and HPO4- to make more bicarb)

  • Increased acid titration
    • [NH3- + H+–> NH4]–> increased acid excretion
    • [HPO4- +H+ –> HPO4-]–> increased bicarb regeneration

—Increase pH—

67
Q

Causes of respiratory acidosis (acute and chronic)

A

Acute: CANS

  1. CNS depression
  2. Airway obstruction
  3. Neuromuscular disorders
  4. Severe pneumonia, embolism, edema

Chronic

  1. COPD
  2. Anything chronic that leads to impaired ventilation

—they’re selling acidic air in CANS—

68
Q

causes of respiratoy acidosis slide

A
69
Q

Symptoms of respiratory acidosis

A

Acute (neurological issues)

  • HA, confusion, anxiety, drowsiness, stupor, tremors, convulsions, coma

If slowly developing, stable

  • may be well tolerated
70
Q

Respiratory alkalosis with compensation

A

Cause: increased ventilation

  • Decrease PCO2
  • Decrease H2CO3
  • Decrease H+

—Increase pH—

Renal Compensation

  • Decreased acid titration
    • Decrease buffering of H+ by NH3- –> decreased acid excretion
    • Decreased buffering of H+ by HPO4- –> decreased bicarb regneration

—decrease pH—

71
Q

What are the causes of respiratory alkalosis?

A

CHAMPS

  1. CNS disease
  2. Hypoxia* (high altitude)
  3. Anxiety
  4. Mechanical ventilators
  5. Progesterone
  6. Salicyclates and sepsis
72
Q

Symptoms of respiratory alkalosis

A
  1. Acute respiratory alkalosis–> light headed, confusion, crapms and syncome due to change in cerebral blood flow and pH
    1. Tachypnea or hypernea is often the only sign
    2. Severe- carpopedal aspasm due to decreases levels of hypocalcemia
  2. Chronic–> usually asymptomatic; no signs
73
Q
A

David's- Renal Exam 2 (12 decks)

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