Lactate Flashcards

1
Q

What is the difference between lactate and lactic acid?

A

Lactic acid is a strong acid&raquo_space; at physiologic pH&raquo_space; dissociates into lactate and H+

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2
Q

How much ATP is produced during glycolysis versus TAC cycle versus oxidative phosphorilation/electron transport chain

A

glycolysis&raquo_space; pyruvate NET: 2 ATP
Krebs Cycle NET: 2 ATP
Oxidative Phosphorylation NET: 32 ATP

Total 36

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3
Q

What enzyme catalyzes the conversion of pyruvate to lactate?

A

Lactate dehydrogenase

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4
Q

What causes the acidosis in lactic acidosis?

A

Anaerobic environment:

  • ATP only produced from glycolysis
  • ATP used via ATPase&raquo_space; produces H+ ions
  • H+ ion would usually enter the mitochondria and be used for electron transport chain and oxidative phosphorylation
  • H+ accumulates and is transported out of the cell
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5
Q

According to the semiquantitative acid base approach, the increase of 1 mmol/L of lactate reduces the standardized base excess by xxxxx mmol/L

A

1 mmol/L

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6
Q

What organs produce the majority of lactate in health?

A

brain
muscles
adipose tissue

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7
Q

what are the predominant lactate consuming organs?

A

liver 30-60%
kidneys 20-30%

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8
Q

How is lactate excreted in the kidneys?

A

typically not excreted. filtered but reabsorbed by the proximal tubules (like glucose)

but above renal threshold (6-10 mmol/L) some enters urine

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9
Q

What is type A versus type B hyperlactatemia?

A

type A: tissue oxygen deficiency
type B: absence of clinical evidence of oxygen deficiency

technically type 2A and 2B
original classifition divided type 1 and 2 by presence (2) or absence (1) of acidemia

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10
Q

If you have a patient with hyperlactatemia from excessive muscle activity, how fast should the lactate resolve if there are no other underlying issues?

A

20-60 minutes

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11
Q

In experimental acute euvolemic anemia, at what PCV does hyperlactatemia develops?

When does it develop in chronic anemia?

A

below 15%

at 10% or lower

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12
Q

How severe/low does hypoxemia need to be to cause hyperlactatemia (in mm Hg)?

A

PaO2 of 25-40 mm Hg

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13
Q

What are B1, B2, and B3 hyperlactatemia?

A

B1: underlying disease associated
B2: drug or toxin associated
B3: Hereditary metabolic defects

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14
Q

List examples for B1 hyperlactatemia

A
  • Sepsis
  • Thiamine deficiency
  • Diabetes mellitus
  • Neoplasia
  • Liver disease
  • Pheochromoytoma
  • Hyperthyroidism
  • Alkalosis
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15
Q

List implicated causes for hyperlactatemia from sepsis

A
  • catecholamines stimulating NaKATPase pumps
  • mitochondrial dysfunction
  • increased hepatic lactate production and decreased hepatic lactate clearance
  • impaired tissue oxygen extraction
  • capillary shunting and other microcirculatory dysfunction
  • pyruvate dehydrogenase inhibition
  • adrenergic stimulation causing increased aerobic glycolysis
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16
Q

Why does neoplasia lead to hyperlactatemia

A
  • hypoperfusion
  • malignant cells preferentially using glycolysis for energy production even in aerobic environment
17
Q

List 4 examples of drugs or toxins causing hyperlactatemia

A
  • Epinephrine&raquo_space; upregulates glycogenolysis and hence glycolysis + increases NaKATPase activity
  • EG/ethylene glycol/ethanol&raquo_space; increaes NADH/NAD+ ration&raquo_space; drives lactate dehydrogenase towards lactate production
  • prednisone&raquo_space; both antiinflammatory and immunosuppressive doses
  • Propylene glycol&raquo_space; metabolized to L-lactate and D-lactate (in some activated charcoal formulations)
18
Q

What are the 2 stereoisomeric forms of lactate?

A

L-lactate (levorotatory)
* predominant form produced in mammalian cells
D-lactate (dextrorotatory)
* < 1% of lactate in health
* produced mostly by bacteria
* high D-lactate most commonly indicates GI dysbiosis

19
Q

How does neonatal lactate cc differ?

A

higher lactate in the first 2-3 months of life

20
Q

How could thiamine supplementation help with hyperlactatemia?

A

cofactor for pyruvate dehydrogenase

21
Q

Is lactic acid produced in vivo?

A

No, only is conjugate base lactate is produced via lactate dehydrogenae

22
Q

When DO2 drops and Krebs cycle/oxidative phosphorylation are not possible, how does lactate production help keep glycolysis up for ATP production?

A

glycolysis requires NAD+ - becomes depleted in low O2 environment

LDH oxidizes NADH to NAD+ and also uses and H+ ion

> > helps replenish NAD+ for glycolysis

23
Q

under resting healthy conditions, how much of produced pyruvate is converted to lactate?

A

only 10%

24
Q

How does an increase in lactate affect the strong ion difference?

A

decreases SD

according to the law of electroneutrality decreasing SD will increase H+&raquo_space; acidosis

25
Q

What are the 2 subcategories of Type A hyperlactatemia?

A

Relative - e.g., exercise, seizures
Absolute - decreased DO2

26
Q

What is “occult” shock?

A

Tissue hypoperfusion despite normal standard hemodynamic variables

27
Q

What are the underlying mechanisms of elevated lactate in diabetes mellitus?

A
  • reduced pyruvate dehydrogenase
  • reduced oxidative metabolism
  • upregulated glycolysis
  • impaired glycogenesis

also: D-lactate elevated

28
Q

What is thiamine cofactor for?

A
  • pyruvate dehydrogenase
  • TCA cycle
  • alpha-ketoglutarate dehydrogenase
  • pentose phosphate pathway
  • ketoacid dehydrogenase
29
Q

How does tylenol cause hyperlactatemia

A

Type B2
* impairs mitochondrial respiration
* hepatic dysfunction

30
Q

How does cyanide toxicity cause hyperlactatemia?

What medication can cause this iatrogenically?

A

inhibits aerobic metabolism by noncompetitively inhibiting ferric iron in cytochrom c oxidase = final step in the electron transport chain

Na-nitroprusside –> metabolized to NO and cyanide

31
Q

How can lactulose administration cause hyperlactatemia?

A

broken down to lactate and acetate in the colon

32
Q

What pathway do mammalian cells use to produce D-lactate?

A

glyoxalase

33
Q

What does an increased lactate cc with an increased peripheral venous oxygen concentration indicate?

A

mitochondrial dysfunction, impaired oxygen utilization - e.g., sepsis
microcirculatory shunting

34
Q

How is most lactate measured?

A

amperometry

lactate sensitive electrode coated with lactate oxidase&raquo_space; converts lactate to Hydrogen peroxide and pyruvate

> > machine measures the hydrogen peroxide

35
Q

How do POC lactatemeters compare to benchtop analyzers?

A

tend to underestimate lactate

larger dissagreement at higher lactate

36
Q

List diseases for dogs and cats in which elevated lactate has been shown to predict an increased risk of mortality

A

Dogs
* GDV
* hypotension in the ICU
* IMHA
* caval syndrome
* Babesiosis
* SIRS
* severe soft tissue infections

Cats:
* septic peritonitis
* HCM

37
Q

Can you use peritoneal fluid lactate cc to asess for septic peritonitis in cats?

A

No, does not appear useful according to previous studies

38
Q

How do most blood gas machines measures SvO2?

A

measure PvO2 and calculate SvO2 with an inbuild algorithm according to the predicted oxygen hemoglovin dissociation curve

39
Q

Explain temperature gradient monitoring

A
  • get central temp (e.g., rectal)
  • compare to peripheral limb temp

difference should be < 7.5 C for dogs and < 6.5 C for cats