Lactate Flashcards
What is the difference between lactate and lactic acid?
Lactic acid is a strong acid»_space; at physiologic pH»_space; dissociates into lactate and H+
How much ATP is produced during glycolysis versus TAC cycle versus oxidative phosphorilation/electron transport chain
glycolysis»_space; pyruvate NET: 2 ATP
Krebs Cycle NET: 2 ATP
Oxidative Phosphorylation NET: 32 ATP
Total 36
What enzyme catalyzes the conversion of pyruvate to lactate?
Lactate dehydrogenase
What causes the acidosis in lactic acidosis?
Anaerobic environment:
- ATP only produced from glycolysis
- ATP used via ATPase»_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
According to the semiquantitative acid base approach, the increase of 1 mmol/L of lactate reduces the standardized base excess by xxxxx mmol/L
1 mmol/L
What organs produce the majority of lactate in health?
brain
muscles
adipose tissue
what are the predominant lactate consuming organs?
liver 30-60%
kidneys 20-30%
How is lactate excreted in the kidneys?
typically not excreted. filtered but reabsorbed by the proximal tubules (like glucose)
but above renal threshold (6-10 mmol/L) some enters urine
What is type A versus type B hyperlactatemia?
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
If you have a patient with hyperlactatemia from excessive muscle activity, how fast should the lactate resolve if there are no other underlying issues?
20-60 minutes
In experimental acute euvolemic anemia, at what PCV does hyperlactatemia develops?
When does it develop in chronic anemia?
below 15%
at 10% or lower
How severe/low does hypoxemia need to be to cause hyperlactatemia (in mm Hg)?
PaO2 of 25-40 mm Hg
What are B1, B2, and B3 hyperlactatemia?
B1: underlying disease associated
B2: drug or toxin associated
B3: Hereditary metabolic defects
List examples for B1 hyperlactatemia
- Sepsis
- Thiamine deficiency
- Diabetes mellitus
- Neoplasia
- Liver disease
- Pheochromoytoma
- Hyperthyroidism
- Alkalosis
List implicated causes for hyperlactatemia from sepsis
- 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
Why does neoplasia lead to hyperlactatemia
- hypoperfusion
- malignant cells preferentially using glycolysis for energy production even in aerobic environment
List 4 examples of drugs or toxins causing hyperlactatemia
- Epinephrine»_space; upregulates glycogenolysis and hence glycolysis + increases NaKATPase activity
- EG/ethylene glycol/ethanol»_space; increaes NADH/NAD+ ration»_space; drives lactate dehydrogenase towards lactate production
- prednisone»_space; both antiinflammatory and immunosuppressive doses
- Propylene glycol»_space; metabolized to L-lactate and D-lactate (in some activated charcoal formulations)
What are the 2 stereoisomeric forms of lactate?
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
How does neonatal lactate cc differ?
higher lactate in the first 2-3 months of life
How could thiamine supplementation help with hyperlactatemia?
cofactor for pyruvate dehydrogenase
Is lactic acid produced in vivo?
No, only is conjugate base lactate is produced via lactate dehydrogenae
When DO2 drops and Krebs cycle/oxidative phosphorylation are not possible, how does lactate production help keep glycolysis up for ATP production?
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
under resting healthy conditions, how much of produced pyruvate is converted to lactate?
only 10%
How does an increase in lactate affect the strong ion difference?
decreases SD
according to the law of electroneutrality decreasing SD will increase H+»_space; acidosis
What are the 2 subcategories of Type A hyperlactatemia?
Relative - e.g., exercise, seizures
Absolute - decreased DO2
What is “occult” shock?
Tissue hypoperfusion despite normal standard hemodynamic variables
What are the underlying mechanisms of elevated lactate in diabetes mellitus?
- reduced pyruvate dehydrogenase
- reduced oxidative metabolism
- upregulated glycolysis
- impaired glycogenesis
also: D-lactate elevated
What is thiamine cofactor for?
- pyruvate dehydrogenase
- TCA cycle
- alpha-ketoglutarate dehydrogenase
- pentose phosphate pathway
- ketoacid dehydrogenase
How does tylenol cause hyperlactatemia
Type B2
* impairs mitochondrial respiration
* hepatic dysfunction
How does cyanide toxicity cause hyperlactatemia?
What medication can cause this iatrogenically?
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
How can lactulose administration cause hyperlactatemia?
broken down to lactate and acetate in the colon
What pathway do mammalian cells use to produce D-lactate?
glyoxalase
What does an increased lactate cc with an increased peripheral venous oxygen concentration indicate?
mitochondrial dysfunction, impaired oxygen utilization - e.g., sepsis
microcirculatory shunting
How is most lactate measured?
amperometry
lactate sensitive electrode coated with lactate oxidase»_space; converts lactate to Hydrogen peroxide and pyruvate
> > machine measures the hydrogen peroxide
How do POC lactatemeters compare to benchtop analyzers?
tend to underestimate lactate
larger dissagreement at higher lactate
List diseases for dogs and cats in which elevated lactate has been shown to predict an increased risk of mortality
Dogs
* GDV
* hypotension in the ICU
* IMHA
* caval syndrome
* Babesiosis
* SIRS
* severe soft tissue infections
Cats:
* septic peritonitis
* HCM
Can you use peritoneal fluid lactate cc to asess for septic peritonitis in cats?
No, does not appear useful according to previous studies
How do most blood gas machines measures SvO2?
measure PvO2 and calculate SvO2 with an inbuild algorithm according to the predicted oxygen hemoglovin dissociation curve
Explain temperature gradient monitoring
- 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
