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Acid-Base, NHBR Series > Acid-Base > Flashcards

Acid-Base Flashcards

1
Q

What is the effect of acute metabolic acidosis on basolateral NBC1?

A

Acute metabolic acidosis results in recruitment of Na/HCO3 co-transporters into the basolateral membrane of the PCT. Met alk has the opposite effect.

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2
Q

What is the effect of respiratory acidosis on NBC1 protein synthesis?

A

It causes an increase in NCB1 protein synthesis.

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3
Q

where does H+ secretion predominantly occur?

A

The late distal tubule, connecting segment, and cortical and medullary collecting tubules at approx 1mEq/kg/d, reflecting dietary intake

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4
Q

How does the ENaC facilitate kaliuresis?

A

Sodium enters the principal cells via the apical amiloride-sensitive epithelial sodium channel (ENaC)
; The reabsorbed Na+ is subsequently reabsorbed on the basolateral side in exchange for intracellular K+ uptake via 3Na+-2K+-ATPase. The increase in intracellular K+ gives rise to a favorable chemical gradient for K+ secretion. The apical uptake of Na+ also creates a relative electronegative lumen that favors the secretion of positively charged K+ via the renal outer medullary potassium channel (ROMK in principal cells) and H+ via H+-ATPase and, to a lesser extent, H+-K+-ATPase (α-intercalated cells).

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5
Q

What are the conditions for optimal H+ and K+ secretion?

A
  1. sufficient Na+ delivery to the distal nephron,
  2. intact ENaC,
  3. presence of aldosterone, and
  4. good urine flow. Aldosterone increases the number of open ENac and ROMK channels and upregulates luminal H+-ATPase and basolateral 3Na+-2K+-ATPase, hence upregulating both H+ and K+ secretion.
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6
Q

The efficiency of H+ urinary secretion is dependent on the presence of what buffer system (for the most part)?

A

he efficiency of H+ urinary excretion depends on the presence of ammonia

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7
Q

Can you explain ammoniagenesis in the PCT?

A

The substrate for ammoniagenesis is glutamine.
• Glutamine is taken up into proximal tubular cells via the sodium-dependent amino acid transporters (SNAT3),
where NH4 + is formed in a multistep process:
• Rate-limiting enzymes for ammoniagenesis: phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK)
• NH3 is either transported as NH4 + into the lumen via NHE or freely diffused into lumen as NH3 . Angiotensin II
upregulates NHE , thereby increasing NH4 + secretion.
• Luminal NH3 and NH4 + are reabsorbed at thick ascending limb loop of Henle into interstitium, where they are subsequently secreted into cortical collecting tubules with H+ . NH4+ may be reabsorbed at the loop of Henle by
replacing K on the Na -K -2Cl -cotransporter. Secretion of NH3 at the connecting segments and collecting
tubules is facilitated by the nonerythroid glycoproteins RhBg and RhCg.
• In metabolic acidosis, there is:
1. Mobilization of glutamine from skeletal muscle and intestinal cells
2. Increased SNAT3 expression
3. Increased expression of the rate-limiting enzymes in ammoniagenesis

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8
Q

Can you express ammoniagenesis in a chemical equation?

A

Glutamine -> glutamate -> alpha ketoglutarate -> Glucose + Co2 + 2HCO3-. The rate limiting enzymes are PDG and PEPCK. Each reaction generates 1 NH3 molecule.

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9
Q

What is the formula for AG?

A

[Na+] - [Cl-] - [HCO3-] ~ 12 (approx)

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10
Q

What type of acid base disturbance does toluene cause?

A

NAGMA

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11
Q

What other drugs commonly cause a NAGMA?

A

Acetazolamide, topiramate, amphotericin B, trimethoprim, pentamidine, CaCl2, cholestyramine, K-sparing diuretics.

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12
Q

High AG but no met acidosis, causes?

A
  1. Severe metabolic alkalosis (pH >7.5), 2. cellular phosphate/anion leaks in nonketotic hyperglycaemia.
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13
Q

Causes for low AG but no acid-base disorder?

A

Hypoalbuminaemia; hyperproteinaemia; primary hyperparathyroidism (with hyperCa2+ and hypoPO43-).

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14
Q

What are the common causes of chloride sensitive metabolic alkalosis?

A
  • vomiting
  • nasogastric suction,
  • gastrocystoplasty for
    bladder augmentation
  • diuretics
  • villous adenoma
  • congenital chloride diarrhea
  • posthypercapnia
  • low dietary chloride intake.
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15
Q

What is the underlying mechanism for chloride sensitive metabolic alkalosis?

A
  • Reduced chloride delivery to the cortical collecting tubule because reduced renal perfusion means lower levels of chloride in the filtrate.
  • Whatever chloride enters the filtrate is avidly reabsorbed in the proximal tubule.
  • Pendrin, a chloride/bicarbonate exchanger on the intercalated cells is therefore inhibited.
  • The net effect is bicarbonate retention.
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16
Q

What is the underlying mechanism for chloride resistant metabolic alkalosis?

A

This is due to hypersecretion of acid (H+) due to increased mineralocorticoid activity. The high loss of acid
leads to metabolic alkalosis.
• This form of metabolic alkalosis is not due to the lack of chloride. Urine chloride is expected to reflect dietary
chloride intake, which is typically >20 mEq/L.

17
Q

What are the common causes for chloride resistant metabolic alkalosis?

A

Common causes of chloride-resistant metabolic alkalosis: (1) mineralocorticoid excess, (2) severe hypokalemia,
(3) exogenous alkali (crack cocaine with alkali load), (4) citrate from transfusion products, (5) transplacental transfer from mother with metabolic alkalosis, (6) excessive calcium carbonate ingestion, (7) Pendred syndrome [syndrome with mutation in pendrin where patients may present with goiter, sensorineural deafness, and metabolic alkalosis]. The latter is typically not clinically significant unless challenged with diuretics or alkali load.

18
Q

What drugs are commonly associated with respiratory alkalosis?

A

Theophylline and salicylate

19
Q

What is the phenotype of oxoproleine related met acidosis?

A

High acetaminophen use in malnourished chronically ill patients is associated with high AG metabolic acidosis due to excess production of oxoproline, a.k.a. pyroglutamic acid (OXO/PA), due to the lack of negative feedback from glutathione. Other notable associated labs include increased serum osmolality gap due to accumulation of OXO/PAand absence or low levels of lactate and ketones that could normally explain increased AG. Consider acetylcysteine therapy to replete glutathione

20
Q

How does lorazepam cause met acidosis?

A
  • Lorazepam contains propylene glycol

- Propylene glycol is metabolised to L-lactate

21
Q

What is the phenotype of “D” lactic acidosis?

A

D-Lactic acid produced by gut bacterial overgrowth in short bowel syndrome. This is not the same as what
humans produce, which is L-lactate. D-Lactate is filtered quickly and not reabsorbed well because human kidneys only recognize and reabsorb only the L-form of lactate. This can lead to a low or normal AG in those with D- lactate and good kidney function. Patients with D-lactate can present with altered mental status and cerebellar dysfunction, mimicking a “drunk.”

22
Q

What is the metabolic presentation of toluene toxicity?

A
  • dRTA
23
Q

What effect does toluene have on the urine osmolal gap?

A

The presence of hippurate in the urine also increases urine osmolality. Thus, when the urine osmolality is
measured, it will be much higher than what is normally expected in the urine. urine osmolality gap will be increased. The increased osmolal gap accounts for hippurate + associated NH4+ . Normal urine osmolality gap is <150 mEq/L. With toluene intoxication, urine osmolality gap will be >150 mEq/L.

24
Q

Serum ketones are found in what conditions, apart from DKA?

A

Starvation and isopropyl (rubbing) alcohol intoxication

25
Q

What is the clinical presentation of pRTA?

A
  • Serum [HCO –] (S ) is typically greater than 15 mEq/L.
  • Urine pH varies with serum [HCO –] (i.e., urine pH > 5.5) if receiving alkalinization therapy, but appropriately low (i.e., pH < 5.5) in the presence of metabolic acidosis.
  • Hypokalemia
26
Q

What are the aetiologies for pRTA?

A
  • Fanconi syndrome
  • SLC4A4 mutation (basolateral sodium bicarbonate transporter)
  • Drugs: ifosfamide, tenofovir, acetazolamide
27
Q

How do you diagnose pRTA?

A

Fractional excretion of HCO3 (FeHCO ) > 15% and urine pH typically >7.5 following HCO3 load (0.5 to 1.0
mEq/kg body weight/hour to increase serum [HCO3] > 20 mEq/L)

28
Q

What is the clinical presentation for dRTA?

A

Metabolic acidosis may be severe (i.e., serum [HCO –] may be <15 mEq/L).
• Growth impairment
• Polyuria
• Hypercalciuria, nephrocalcinosis, nephrolithiasis—due to increased bone resorption and reduced urinary citrate
secretion from chronic metabolic acidosis, high urine pH facilitating calcium phosphate precipitation
• High urine pH (e.g., >5.5), but pH could be lower if ammoniagenesis is suboptimal (e.g., seen in dRTA with
concurrent hyperkalemia as hyperkalemia inhibits ammoniagenesis). NH3 is needed to buffer/facilitate H+
secretion: NH3 + H → NH4+ . The lack of NH3 leaves more free H+ , which lowers urine pH.

29
Q

What are the aetiologies for dRTA with hypo or normokalaemia?

A
  • Autoimmune disease, think specifically of Sjogrens.
  • Hereditary causes: Genetic mutations in the basolateral HCO3- Cl- exchanger (SCL4a1 gene), apical hydrogen ATPase (ATP6V0A4 and ATP6V1B1 genes) are the major mutations associated.
  • Toluene intoxication
  • Ifosfamide
  • Amphotericin B
30
Q

What are the causes for hyperkalaemic (T4) dRTA?

A
  • Aldosterone deficiency or resistance (type 4 RTA associated with diabetes), tubulointerstitial nephropathy, nephrocalcinosis, obstruction, lupus nephritis
  • Medications: spironolactone, eplerenone, amiloride, triamterene, trimethoprim, calcineurin inhibitors, NSAIDS, ACEI, ARB, heparin
  • Factors affecting transmembrane voltage (e.g., obstructive uropathy, K-sparing diuretics)
  • Pseudohypoaldosteronism types 1 and 2 (see Hyperkalemia)
31
Q

How do you manage dRTA?

A

Measurement of [urine PCO2-blood PCO2] following bicarbonate load • If [urine PCO2-blood PCO2] > 30 mm Hg → normal
• If [urine PCO2-blood PCO2] < 10 mm Hg → dRTA
• NH4Cl (100 mg/kg lean body weight) oral load over 1 hour, or furosemide (40 mg) and fludrocortisone (1 mg)
orally with ad lib fluid:
• If there is increased urine NH4 + secretion and titratable acid within 2 to 3 hours → normal
• Otherwise → dRTA
• Management of dRTA:
• Treatment of underlying disease
• Bicarbonate supplement 1 to 2 mEq/kg lean body weight/day
• If hyperkalemic, hypoaldosterone: consider fludrocortisone ± furosemide, dietary K+ restriction

32
Q

What are the luminal transporters on the (1) Principal cell, (2) a-IC cell, and (3) b-IF cell?

A

Principal cell:

  1. ENaC
  2. ROMK

a-IC:

  1. H-ATPase
  2. H/K ATPase

b-IC:
1. Pendrin, Cl/HCO3 exchanger

33
Q

What is the principle difference in function between the alpha and beta intercalated cells?

A
  • Alpha cell reabsorbs HCO3

- Beta cell reabsorbs H+

34
Q

What are the causes of Type B L-lactic acidosis?

A
  • Any cause for enhanced glycolysis, glycogenolysis, or lipolysis
  • Inherited mitochondrial diseases
  • Acquired mitochondrial dysfunction

…. HAART (didanosine, stavudine)…. Mangosteen…. Metformin…. Propofol …. Linezolid …. Cyanide ….

  • Impaired pyruvate dehydrogenase activity (thiamine deficiency!!)
35
Q

What can be given to a patient with methanol poisoning to reduce formate toxicity?

A
  • IV folinic acid
36
Q

How do you test for dRTA?

A
  • Ammonia Chloride load
  • Combined loop diuretic and fludrocortisone

Individuals with dRTA cannot lower their urinary pH in response to increased H+ secretion

37
Q

How do you correct metabolic acidosis?

A
  • HCO3 deficit = 0.5 x LBW x [24 - HCO3-]

If severe….
- HCO3 deficit = [0.4 + 2.6/[HCO3]] x LBW x [24 - serum HCO]

Acid-Base, NHBR Series (4 decks)

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