Name : Malath Adel Hamad Othman

ID :211010
Department : Department of Biochemistry

BIOCHEMICAL CAUSES OF LACTIC ACIDOSIS

The development of acidosis during intense exercise has traditionally
been explained by the increased production of carboxylic acid,
causing the discharge of a proton and also the formation of the acid salt
sodium lactate. On the premise of this explanation, if the speed of lactate
production is high enough, the cellular proton buffering capacity may
be exceeded, leading to a decrease in cellular pH. These biochemical
events are termed lactic acidosis. The lactic acidosis of exercise has been
a classic explanation of the biochemistry of acidosis for quite 80 years.
This belief has led to the interpretation that lactate production causes
acidosis and, in turn, that increased lactate production is one in every
of the several causes of muscle fatigue during intense exercise. This
review presents clear evidence that there's no biochemical support for
lactate production causing acidosis. Lactate production retards, not
causes, acidosis. Similarly, there's a wealth of research evidence to
indicate that acidosis is caused by reactions aside from lactate production
Every time ATP is weakened to ADP and P(i), a proton is released. When
the ATP demand of shortening is met by mitochondrial
respiration, there's no proton accumulation within the cell, as protons
are employed by the mitochondria for biological process and to keep
up the proton gradient within the intermembranous space. it's only if the
exercise intensity increases beyond steady state that there's a
requirement for greater reliance on ATP regeneration from glycolysis and
also the phosphagen system. The ATP that's supplied from these
nonmitochondrial sources and is eventually accustomed fuel muscular
contraction increases proton release and causes the acidosis of intense
exercise. Lactate production increases under these cellular conditions to
stop pyruvate accumulation and provide the NAD(+) needed for phase 2
of glycolysis. Thus increased lactate production coincides with cellular
acidosis and remains a decent indirect marker for cell metabolic
conditions that induce acidosis. If muscle failed to produce lactate,
acidosis and muscle fatigue would occur more quickly and exercise
performance would be severely impaired.
.
An understanding of the pathophysiology of lactic acidosis is crucial in
facilitating the optimal care of critically ill patients. The relevant
biochemistry of lactic acidosis is reviewed, and also the more
controversial aspects referring to the genesis of the acidosis are
highlighted. the present system of classification of lactic acidosis divides
etiologies on the premise of the presence or absence of clinical signs of
tissue hypoperfusion. Several sorts of lactic acidosis during which clinical
evidence of tissue hypoperfusion is lacking demonstrate hemodynamic
evidence of occult hypoperfusion. The diagnostic and therapeutic
implications of this observation are discussed. Current diagnostic criteria
for lactic acidosis include a pH but 7.35 and blood lactate concentration
greater than 5 to six mM/L. a very important issue relates to the
implications of lactate values that are greater than normal but below this
diagnostic range. the utilization of the oxygen flux test is
also valuable within the diagnosis of occult tissue hypoperfusion in
patients with low-grade elevations in lactate levels. this therapy for lactic
acidosis involves addressing the first cause and supportive
management. the utilization of bicarbonate within the therapy for lactic
acidosis is controversial thanks to potential adverse effects on cardiac
function. The specifics of this controversy are outlined, and newer
therapeutic alternatives are reviewed. the employment of blood lactate
concentration as a prognostic index could also be more useful in patients
with shock than without shock
L-lactic acidosis (L-LA) is that the commonest explanation
for acidosis within the critical care setting, which has been related to an
oversized increase in mortality. the aim of this text is to
produce clinicians with an outline of the biochemical and metabolic
background required to know the various pathophysiological
mechanisms that will result in the event of L-LA. We propose a
classification supported whether the pathophysiology of L-LA is due
predominantly to increased production or decreased removal of L-lactic
acid. during this article, we offer an summary of the biochemical and
metabolic aspects of glucose oxidation, the assembly and removal of L-
lactic acid, and a discussion of the pathophysiology of the assorted causes
of L-LA.
References :

https://emedicine.medscape.com/article/167027-
overview

https://pubmed.ncbi.nlm.nih.gov/15308499/