Lactate Flashcards
Plasma lactate is a late but quantitative indicator of tissue hypoperfusion and can be used as a prognostic indicator and a treatment guide.
Lactate is an intermediary metabolite of glucose oxidation that serves as
Lactate production is an adaptive and protective response to cellular energy deficiency that allows
a carbohydrate energy substrate reservoir
continued energy production when cellular energy requirements exceed the capacity of cellular aerobic respiration
Lactate and lactic acid are not synonymous
Lactic acid, CH3CH(OH)COOH
lactate ion is conjugate base to lactic acid C3CH(OH)COOH
As the pKa of lactic acid is 3.8, at physiologic pH, lactic acid is essentially fully dissociated into lactate anions and protons
Increased plasma lactate concentration is termed hyperlactatemia, which may or may not be associated with a net acidemia depending
Lactate and lactic acid are not synonymous
is a strong acid that at physiologic pH is almost completely dissociated to the lactate anion CH3CH(OH)COO- and H+
cause of the increased lactate, concurrent acid/base disturbances, and buffer reserves
Glycolysis is the cytosolic process by which
1 mole of glucose is oxidized to
Pyruvate enters the mitochondria and is converted into
under normal aerobic conditions only a small quantity of pyruvate is converted into lactate
catalyzed by
Lactate may then be either transported out of the cell or used within the same cell. Ultimately lactate is either converted back into
2 moles of pyruvate
2ATP
2NADH
undergoes decarboxylation to produce acetyl‐CoA
acetyl CoA
proceeds through tricarboxylic acid (TCA) cycle
NADH and FADH2 - supply proton
electron transport chain
oxidative phosphorylation
produce 36 moles of ATP
lactate dehydrogenase (LDH)
pyruvate in local or distant tissues
oxidized to produce energy or converted back into glucose by gluconeogenesis
Glycolysis consumes NAD+ and produces
If there is a cellular oxygen deficiency, the TCA cycle and oxidative phosphorylation are slowed so NAD+ falls and
To allow glycolysis to continue, pyruvate converted into lactate and NADH looses H
Although glycolysis produces only 2 moles of ATP, it is very
NADH and pyruvate
pyruvate and NADH build up, thereby hindering ongoing glycolysis
conversion of pyruvate to lactate
fast and so can temporarily satisfy energy demands
Contrary to popular belief, the metabolic acidosis associated with lactate production is due to
Glycolysis produces the lactate ion rather than lactic acid. When the ATP made by glycolysis is utilized, H+ is released into the cytosol. This proton would usually enter the mitochondrion and be used to maintain the proton gradient required for the electron transport chain and oxidative phosphorylation. When oxygen supplies are insufficient this cannot happen and H+ ions accumulate and are then transported out of the cell. Hence, the acidosis from increased lactate production mostly is due to
Nevertheless, stoichiometrically, in acute anaerobic states, 1 mmol/L of lactate is associated with an equimolar production of H+ ions and a concomitant reduction of the standardized base excess of 1 mmol/
There are clinical states in which increased lactate production occurs while H+ consumption by the mitochondria in maintained. The result will be
ATP use, not lactate production
reduced H+ consumption, not increased lactate production per se
hyperlactatemia without concurrent acidosis
Lactate is produced in the cytosol and then either
predominant lactate-consuming organs
hepatic metabolism accounts for
renal cortex metabolizes
keeping with its role as a carbohydrate energy substrate (essentially half a glucose molecule), lactate is not excreted in the urine until its plasma concentration is high. It is reabsorbed by the proximal convoluted tubule
renal threshold
converted back to pyruvate to proceed through local aerobic cellular metabolism or exported out of the cell and transported to distant tissues in the bloodstream
liver and renal cortex
50% to 70% of lactate consumption, and the liver is capable of metabolizing markedly increased lactate loads
25% to 30% of circulating lactate
6 to 10 mmol/L
Tissue lactate production, distribution, metabolism, consumption, and excretion are different in disease states
dogs with hypovolemia what produces majority of lactate
During hyperlactatemia, some tissues, such as ____ increase their lactate uptake
liver continues to extract lactate until hepatic blood flow is less than
once in plasma lactate equilibrates with
whole blood lactate refers to the sum of
almost all analyzers measure lactate from plasma even though whole blood is aspirated by the machine
splanchnic circulation, skin, subcutaneous tissue, and skeletal muscle
skeletal muscle, cardiac muscle, and brain tissue, increase their lactate uptake
less than 30% of normal
it can actually become a net lactate producer with poor perfusion, severe hypoxia, or hepatic failure
intracellular space of erythrocytes
intraerythrocytic and plasma lactate
“Lactic acidosis”
hyperlactatemia with a concurrent metabolic acidosis
1961 Huckabee divided hyperlactatemia into
type I vs II:
type A vs B
Type II hyperlactatemia (lactic acidosis) was further classified into two categories: type A and type B
type I increased lactate without metabolic acidosis
type II w metabolic acidosis
Type A tissue oxygen deficiency
Type B occurs in the absence of clinical evidence of decreased oxygen delivery
may exist concurrently
type B usually results in a mild to moderate increase in lactate (3 to 6 mmol/L. Conversely, severe hyperlactatemia (>6 mmol/L) usually is due to global hypoperfusion. type A
Type A Hyperlactatemia
Increased Oxygen Demand (5)
Decreased Oxygen Delivery (5)
Exercise Trembling/shivering Muscle tremors Seizure activity Struggling
hypoperfusion
Severe anemia
Severe hypoxemia
Carbon monoxide poisoning
Type B Hyperlactatemia
B1:
B2:
B3:
B1: Associated with Underlying Disease Sepsis/SIRS* Neoplasia Diabetes mellitus Severe liver disease Thiamine deficiency Pheochromocytoma
B2: Associated with Drugs or Toxins Acetaminophen Activated charcoal β2 Agonists Bicarbonate Catecholamines Corticosteroids* Cyanide Ethanol Ethylene glycol Propofol Propylene glycol Glucose Halothane Insulin Lactulose Methanol Morphine Nitroprusside Salicylates Strychnine Terbutaline Theophylline TPN Xylitol
B3: Inborn Errors in Metabolism Mitochondrial myopathies Enzymatic deficiencies MELAS(mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) d-lactic acidosis
Exercise-related hyperlactatemia ranges from
resolves:
4.5 mmol/L- 30 mmol/L in racing Greyhound
T1/2 30 to 60 min
hypoperfusion grading
cats
mild 3 to 4 mmol/
moderate with 4 to 6 mmol/L
severe >6 mmol/L
Anecdotal clinical experience suggest that cats demonstrate an exponential increase with a lesser increase in mild and moderate hypoperfusion, then a rapid rise when it is severe.
Why is lactate a late indicator:
lactate production does not occur until oxygen extraction has been maximized
just as we recognize that falling blood pressure is a late indicator of hypovolemia
.:. corollary being that subclinical hypoperfusion may exist with a normal blood lactate concentration.
Hyperlactatemia in normotensive, normovolemic patients caused by decreased oxygen content and oxygen delivery as a result of anemic or hypoxic hypoxia is ____
hyperlactatemia does not develop until the packed cell volume (PCV) drops below ___
hypoxemia must also be severe ____before pure hypoxemia-related hyperlactatemia develops
.:. hypoxia should only rarely be considered as a sole diagnosis for increased lactate.
rare
15%
Dogs and cats with chronic, euvolemic anemia may remain eulactatemic with a PCV of 10% or less
PaO2 25 to 40 mm Hg
local hypoperfusion
organ torsion such as lung lobes, liver lobes, or spleens do not release much lactate and the systemic lactate concentration actually reflects the global perfusion status.
little washout
which isomer predominates
L‐lactate and D‐lactate
L‐lactate accounts for >99% of total body lactate
is lactate strong ion per Stewart approach
yes acidifying effect in a manner similar to chloride as per Stewart’s physicochemical approach
every 1 mmol/L (9 mg/dL) increase in lactate, SBE will decrease by ___
1 unit
For example, in one study investigating dogs with gastric dilatation and volvulus, 74% (23/31) of dogs with plasma lactate > (1999 study)
whereas in another, only 33% (8/24) of dogs with plasma lactate ≥ 6 mmol/L (54.0 mg/dL) had gastric necrosis (2011)
6.0 mmol/L (54.0 mg/dL) had gastric necrosis
Carbon monoxide binds to hemoglobin with a greater affinity than oxygen - carboxyhemoglobin
shifts the oxyhemoglobin curve
left
Warburg’s effect
lymphoma and hemangiosarcoma may exhibit hyperlactatemia despite apparently normal perfusion
malignant cells are known to exhibit atypical carbohydrate metabolism by preferentially utilizing glycolytic pathways for energy production despite oxygen availability (Warburg’s effect)
lactate may alter the tumor micro environment in a manner that inhibits destruction of neoplastic cells
MoA DM and > lactate
DKA 2 mech:
Cats DKA which type of lactate
upregulated glycolysis
impaired glycogenesis
reduced pyruvate dehydrogenase (PDH) activity
reduced oxidative metabolism
dehyd./decreased tissue perfusion
impaired lactate
higher D‐lactate concentrations not L-lactate
Liver is >lactate common?
no but severe hepatic dysfunction or failure, the liver can become a net lactate producer
severe liver disease is rarely associated with hyperlactatemia unless they are acutely challenged by a lactate load or are experiencing concurrent hypoperfusion
