DISORDERS OF

CARBOHYDRATES
METABOLISM
Asst.Prof . Dr. Qasim Jawad AL-Daami
 Blood Glucose
Sources:
1. Exogenous: diet.
2. Endogenous:

a. Glycogenolysis.
b. Gluconeogenesis.
Glucose is essential to the brain since
the brain:
1. Can't synthesize glucose.
2. Can't store glucose.
3. Can't utilize substrate other than glucose
and ketones.
 Carbohydrates and the liver
Liver maintains plasma glucose
concentration within a narrow range by
taking up -  of the absorbed glucose,
oxidizing some of it and storing the rest as
glycogen or converting it into fat.
In the postabsorptivestate, the liver
provides much needed glucose to the
central nervous system and other glucose-
utilizing tissues by breaking down glycogen
(glycogenolysis) and/or by new formation of
glucose from non-glucose precursors
(gluconeogenesis).
Disturbances of any one of these processes
can result in either hyperglycaemiaor
 Hormonal control:
1. Insulin: produced by β-cells of Islets
of Langerhans and released in response
to increased blood glucose. It is an
anabolic hormone, its actions are:
a.↑ uptake of glucose into tissues and
glycolysis.
b. Promote glycogenesis) and lipogenesis.
c. Inhibits gluconeogenesis &
glycogenolysis.
d. ↑ protein synthesis & ↓ protein
breakdown.
2. Glucagon: secreted by α-cells of the
pancreas in response to a need for
increased blood glucose. Its actions are:
a. Stimulate glycogenolysis and
gluconeogenesis.
b. Inhibits glycolysis.
c. Depresses glycogen synthesis.
3. Adrenaline: a catecholamine secreted
by adrenal medulla; its actions are:
a. Stimulates glycogenolysis, lipolysis &
decrease glucose utilization.
b. Stimulate glucagon secretion & inhibits
insulin secretion by the pancreas.
4. Growth hormone: a polypeptide
secreted by the anterior pituitary:
a. Stimulates gluconeogenesis and
lipolysis.
b. Antagonizes insulin stimulated glucose
uptake.
5. Cortisol: is secreted by the adrenal
cortex:
a. Stimulates gluconeogenesis.
b. Increase breakdown of protein & fat.
6. Thyroxine: a thyroid hormone, increases
glycogenolysis and gluconeogenesis and
inhibits absorption of dietary glucose
through the intestine.
 DIABETES MELLITUS
1. Type 1 diabetes is characterized by lack of
insulin production and secretion by the beta
cells.
One cause of the hyperglycemia of type 1
diabetes mellitus is an autoimmune
destruction of the beta cells of the pancreas.
Autoantibodies are present in the circulation of
many individuals with type 1 diabetes. There
appears to be a genetic susceptibility to
development of autoantibodies. However, the
development of disease is complex; triggering
factors, such as rubella, mumps, and other
viral infection, and chemical contact may be
necessary for progression of disease.
2. Type 2 diabetes is a disorder of both
insulin resistance and relative deficiency of
insulin.
Insulin resistance syndrome, also known as
metabolic syndrome and syndrome X
Individuals with metabolic syndrome may
show abdominal obesity and high blood
pressure and at increased risk for
cardiovascular disease.
The etiology of type 2 diabetes is complex
and multifaceted. There is evidence to
show that there is an association of obesity
with the development of type 2 diabetes.
Other factors, such as family history of type
2 diabetes and lack of physical activity,
have also been associated with the
disorder.
3. Gestational diabetes is similar in
etiology to type 2 diabetes.
Pregnancy is associated with increased
tissue cell resistance to insulin. Most
pregnant women will compensate with
increased secretion of insulin; those
individuals who are unable to compensate
may develop gestational diabetes.
The hyperglycemia of gestational diabetes
diminishes after delivery; however, the
individual who has developed gestational
diabetes is at higher risk for the
development of type 2 diabetes
thereafter.
4. other specific causes of diabetes
(previously called secondary diabetes).
This form of hyperglycemia may be
the secondary result of non–insulin-
related events (ex.Cushing’s
syndrome; cystic fibrosis; and specific
drugs, such as protease inhibitors
(e.g. Ritonavir) and glucocorticoids.
Other causes of this form of diabetes
are the result of genetic defects that
affect pancreatic beta cells or the
action of insulin.
Approximately 10% of diabetics are of the
type 1 variety. The type 1 disease state
usually occurs as acute
illness(glucocoricoid)?, while type 2
diabetes progresses slowly over time. Type
1 glucose blood levels are usually more
severe than type 2. Type 1 diabetics are
more likely to develop ketoacidosis than
are type 2 diabetics.

Type 1 diabetics are younger (<18 years

old when diagnosed) and thinner; type 2
diabetics are usually older (>40 years old
when diagnosed) and more likely to be
obese. However, these characteristics of
presentation are not uniform to all type 1
and type 2 diabetics.
5. Impaired Glucose Tolerance (IGT) and
Impaired Fasting Glucose (IFG)
(IGT) and (IFG) represent metabolic states
lying between diabetes and
normoglycemia. People with IFG have
increased fasting blood glucose levels but
usually have normal levels following food
consumption.
Those with IGT are normoglycemic most of
the time but can become hyperglycemic after
large glucose loads. IGT and IFG are not
considered to be clinical entities; rather, they
are risk factors for future diabetes. The
pathophysiology of IFG and IGT is related
primarily to increased insulin resistance
whereas endogenous insulin secretion is
normal in most patients.
 THE DIAGNOSIS OF DIABETES
MELLITUS

The normal fasting blood sugar is

usually between 65-110 mg/dl. After a
meal it would rarely exceed 145 mg/dl.
Normally there is no glucose in urine
(renal threshold above is about 175
mg/dl).
Dipsticking urine for the presence of
glucose is therefore often used as a
screening test for diabetes mellitus.
The diagnosis of diabetes mellitus is
made by finding a fasting blood glucose
of over 126 mg/dl or a random glucose
of >180 mg/dl. If a patient presents with
symptoms of diabetes and is found to
have a single very high glucose
measurement eg >270 mg/dl then this
can be diagnostic.
If there is any doubt about the diagnosis
then a further test can be performed.
This test is called the oral glucose
tolerance test and it measures how the
body responds to a glucose load. The
patient is asked to fast overnight and
then attends for the test.
 THE COMPLICATIONS OF
DIABETES:
The complications of diabetes can be
classified as:
1. ACUTE PROBLEMS:
Diabetic ketoacidosis.
Hypoglycaemia.
2. THE CHRONIC COMPLICATIONS OF
DIABETES:
Microvascular complications.
Macrovascular complications.
 1. THE ACUTE COMPLICATIONS OF DIABETES.
i. Diabetic ketoacidosis.
Ketoacidosis develops predominantly in persons
with type 1 diabetes.
Lack of insulin does not allow glucose to enter
insulin-dependent tissues. Glycolysis and
lipogenesis are inhibited, and glycogenolysis,
lipolysis, ketogenesis, and gluconeogenesis are
stimulated. Increased endogenous glucose
production, together with impaired glucose
transport, lead to fasting hyperglycemia.
Simultaneously, unopposed lipolysis produces an
excess of acetyl-CoA. Ketogenesis is stimulated.
Overproduction of acetoacetic and b-
hydroxybutyric acids decreases the pH of blood,
and causes metabolic acidosis. In a type 1
diabetic patient, ketoacidosis can develop quickly,
even after missing a single insulin dose. In type 2
diabetes, ketoacidosis is relatively rare but may
be precipitated by a major stress, such as MI?
Because glucose is osmotically active, its
increased renal excretion causes water loss
(osmotic diuresis). Poorly controlled diabetic
patients complain of polydypsia and polyuria
leads to dehydration.
Insulin increases potassium uptake by
cells. Since uncontrolled diabetes is
accompanied by an osmotic diuresis, the
released potassium is excreted through the
kidney. Most diabetic patients admitted to
hospital with ketoacidosis are potassium-
depleted but often have normal or raised
levels of plasma potassium.
Exogenous insulin can lead to Hypokalemia.
Thus, except for patients with very high
potassium levels, potassium supplementation
needs to be considered in the treatment of
diabetic ketoacidosis.
i. Hypoglycaemia.
Hypoglycemia is the most common acute
complication of diabetes. It develops when
the balance between insulin dose,
carbohydrate supply, and physical activity
becomes disrupted.
Thus, hypoglycemia may occur as a result of
taking too much insulin or missing a meal.
Exercise increases tissue glucose uptake
independently of insulin; therefore diabetic
patients must decrease their insulin dose
before strenuous exercise to prevent
hypoglycemia.
Severe hypoglycemia, however, is a medical
emergency that requires immediate
treatment with either intravenous glucose
or glucagon.
2. THE CHRONIC COMPLICATIONS OF
DIABETES.
These are the complications that occur
because of the chronic exposure of the
body’s tissues to hyperglycaemia,
hypoinsulinaemia or their associated
metabolic disturbances.
1. MICROVASCULAR (Microangiopathic)
disease.
1. DIABETIC RETINOPATHY.
After 20 years of diabetic life virtually all
patients will have evidence of background
retinopathy, but by contrast proliferative
changes only ever develop in approximately
30% of people with diabetes.
Diabetes may threaten sight by one of
A. Macular oedema:
Increased vascular permeability is a
feature of microvascular disease that lead
to structural disruption of the
photoreceptors and ultimately to visual
disturbance.
A. Retinal ischaemia:

Retinal ischaemia can impact on vision in

one of two ways
i. The retina’s response to ischaemia is to
generate angiogenic factors, which
stimulate new vessel formation with the
intention of reperfusing the ischaemic
areas.
ii. Retinal ischaemia at the central macula
leads to loss of central vision; ischaemic
diabetic maculopathy.
2. DIABETIC NEUROPATHY.
Causative factors in diabetic
neuropathy are thought to include
hyperglycaemia and vascular damage.
The cause is not fully understood but
glycosylation of proteins, a
structural change which has profound
functional consequences, has been
implicated (enz or recepter)?.
3. DIABETIC NEPHROPATHY.
Diabetic nephropathy is the commonest
cause of premature death in type 1
diabetes. Diabetic nephropathy is a
specific microvascular disease affecting
the renal glomerulus. Nephropathy is
almost always associated with retinopathy.
In diabetes, glomerulus becomes
seriously disrupted with two consequences;
it starts with proteinuria, and it fails to
excrete waste products efficiently.
Patients with diabetes who are in renal
failure, tend to progress rapidly to
proliferative retinopathy, and once this is
established it is often very resistant to
treatment.
Once end stage renal failure has
intervened patients have to be
maintained on renal dialysis
treatment; often requiring hospital
treatment every 2 or 3 days, to clear
the bodies waste products. Renal
transplant surgery can be very
successful in selected patients, but
typically premature death is 10
times higher in diabetic than non-
diabetic patients receiving renal
transplant therapy.
4. SKIN AND THE DIABETIC FOOT.
Capillary closure within the skin means that
injuries often heal very slowly if at all and
this has profound implications for the care of
foot ulcers.
Peripheral neuropathy means patients are
often unaware of skin trauma making foot
ulceration more common. Their loss of
pain sensation may be compounded by
poor eye sight, if the patients can’t see the
ulcers it goes unnoticed and untreated.
As people with diabetes have an increased
propensity to bacterial infection, any
untreated skin wound can rapidly get
infected
2. MACROVASCULAR DISEASE.
ATHEROSCLEROSIS.
Atherosclerosis is the deposition of plaques
of a mixture of lipid, and fibrovascular tissue
(atheroma) on the inside of the vessel wall of
the large blood vessels. Once established
these plaques usually slowly increase in size
with two important clinical consequences:
1. Chronic ischaemia.

2. Acute vessel ischaemia (Myocardial

infarction).
Atheromatous plaques may rupture. Plaque
rupture activates the bodies intrinsic clotting
system, which forms a blood clot over the
rupture site. This clot may completely block
the affected vessel leading to acute
ischaemia and cell death of all the tissues
supplied by that vessel.
ARTERIOSCLEROSIS.
Arteriosclerosis is a histological term
meaning the loss of elastic tissue from
the walls of the medium and large
arteries (arterio-), which consequently
become rigid (-sclerosis) and become
less able to absorb the pressure wave,
which is pumped into the circulation
with every heartbeat, the pressure
within the system therefore rises and
the blood pressure goes up.
High blood pressure accelerates the
process of atherosclerosis, and is also
associated with an increased mortality
from strokes and heart attacks.
3. OTHER METABOLIC DISTURBANCES
ASSOCIATED WITH DIABETES.
The most important of these is
hyperlipidaemia or
hypercholesterolaemia. It is now therefore
routine for doctors to check the cholesterol
level in all patients with diabetes.
4. INCREASED SUSCEPTIBILITY TO INFECTION.
For reasons not totally understood people with
diabetes have an increased susceptibility to
bacterial infection. This is an important factor
in the development of diabetic foot ulceration
and explains why people with diabetes have a
much higher risk of limb amputation compared
to the normal population.
THE TREATMENT OF DIABETES.
The treatment of patients with
type 1 diabetes
The treatment of type 1 diabetes is
relatively straight forward; insulin.
Each individual’s daily insulin
requirements are different and will
depend upon such diverse factors as
their age, sex, build and physical
activity, but an average daily
requirement is about 1 unit of insulin
per Kg weight per day.
The treatment of patients with type 2
diabetes.
In treating type 2 diabetes, you start with one type
of tablet, if that fails to control the blood sugar
adequately add the other type of tablet. If the blood
sugar is still not controlled one has to resort to
insulin.
1. Tablets (Oral hypoglycaemics)
There are two principle types of oral
hypoglycaemics; the suphonylureas and
metformin. The sulphonylureas; of which
gliclazide, glibenclamide, and tolbutamide work by
stimulating the pancreas to produce more insulin
than it otherwise would at a particular blood sugar
level. This has the effect of driving the blood sugar
level down to normal limits.
Note that these tablets have no effect in type 1
diabetes?
Metformin, the other type of oral
hypoglycaemic acts by making the
insulin the body has produced more
effective. It achieves this by assisting
insulin drive glucose into the peripheral
cells, which thereby reduces the blood
glucose level.
2. Insulin.
Some type 2 diabetics cannot achieve an
acceptable blood sugar level by tablets
alone and therefore require insulin
therapy instead.
Hypoglycemia
Hypoglycemia is characterized by blood
glucose levels that are less than normal.
Symptoms of hypoglycemia usually occur
when blood glucose has fallen below 50
mg/dL. Two types of hypoglycemia occur,
reactive (postprandial, or after meals) and
fasting (postabsorptive).
Hypoglycemia that is caused by a stimulus
such as excessive insulin administration,
ethanol ingestion, or over-regulation of
diabetes is termed reactive hypoglycemia.
Reactive hypoglycemia is not usually related
to any underlying disease; fasting
hypoglycemia often is.
Fasting hypoglycemia may occur as a
response to insulin-producing tumors of
the pancreas (insulinomas) or other
tissues, hepatic dysfunction, glucocorticoid
deficiency, sepsis, or low glycogen stores.
Fasting hypoglycemia may be diagnosed
with differentiation of the etiology by a 72-
hour fast that is conducted in a hospital.
Most patients with true fasting
hypoglycemia show low glucose blood
levels within 12 hours after the fast
begins. Insulin and C-peptide levels help
differentiate among the causes of the
hypoglycemia.
 Causes
Drugs
Insulin- most common cause, Timing,
dose, type
clearance of insulin (eg, renal failure);
altered counter regulation
Sulfonylureas
High dose salicylates, b –blockers,
quinine,quinolones
 Renal failure
Second gluconeogenic organ
decreased clearance of renally excreted drugs or their
metabolites
(eg, insulin, chlorpropamide, metabolite of glyburide)
Hepatic Failure
Decreased glycogenolysis
Decresed gluconeogenesis
Large functional reserve,( 20% func required to prevent
hypoglycemia)
Genetic defects in glyco metabolic pathways
Finally, compromised drug metabolism (tolbutamide,
glyburide,
glipizide )
Endocrinopathies
Adrenal (glucocorticoid) insufficiency
Growth hormone deficiency
Glucagon deficiency
Pituitary disease ( decreased
combined corticotropin and GH
deficiecy)
 Poisoning
(ethanol, propanolol, salicylates)
Ethanol inhibits gluconeogenesis
Ethanol-induced hypoglycemia
occurs 12-72 hrs after ingestion
 Neoplasm
Non–islet-cell tumors
Mesenchymal tumors,
hepatocellular carcinoma,
adrenocortical tumors,
carcinoid tumors,
leukemia, and lymphomas
Most of these tumors secrete IGF –II
molecule
Some also secrete Glucagon- like
peptide(GLP-1) and Somatostatin
 Insulinoma
Pancreatic β-cell tumors that secrete
Insulin
Small,solitary, benign ( < 10% malignant)
Inability of insulinoma cells to suppress
insulin secretion during lowlevels of
circulating glucose, leading to severe
hypoglycemia
Diagnosis and Tumor Localization
Very high Insulin levels
spiral CT, arteriography, ultrasonography
 Islet Hyperplasia
Also called nesidioblastosis or diffuse
islet hyperplasia or the syndrome of
noninsulinoma pancreatogenous
hyperinsulinism
Represent hyperplastic processes and
budding of islet cells from ducts
(nesidioblastosis).
infants have an identifiable genetic
mutations in sulfonylurea receptor 1
(SUR1) ,potassium channel, glucokinase.
 Autoimmune causes
Anti-insulin receptor antibody
Ø Rarely, hypoglycemia is caused by
autoantibodies that bind the insulin
receptor and mimic the biologic action of
insulin
Ø Most patients have elevated ESR.

Anti-insulin antibody
Ø autoantibodies against insulin bind free
circulating plasma insulin when its
concentration is high and release insulin when
the concentration of free plasma insulin
drops.
Ø Release of insulin at inappropriate times
can cause hypoglycemia.
 Symptoms
Adrenergic Symptoms
Ø usually seen early with a rapid decline
in blood glucose and include:
tachycardia, tachypnea, vomiting, and
diaphoresis
Neuroglycopenic
Ø usually associated with slower or
prolonged hypoglycemia, include:
poor feeding, altered mental status,
lethargy, and seizures
 Reactive hypoglycemia is controversial
Ø low postprandial plasma glucose levels alone
are not
sufficient
Ø 10% to 30% of normal individuals
undergoing oral GTT have plasma glucose <50
mg/dl, with no symptoms
Ø Only patients with severe (eg, loss of
consciousness,
traumatic injury or accident) attributed to
postprandial
hypoglycemia require further workup
 Pathophysiology of Hypoglycemia
Responses to Hypoglycemia is our ability to
suppress insulin in response to hypoglycemia
Ø In Diabetics, it does not occur as Insulin is
supplied exogenously
Ø Main defense is increased release of
counterregulatory hormones, as
Glucagon, Epinephrine, Cortisol, and Growth
hormone
Ø Glucagon stimulates both glycogenolysis
and gluconeogenesis
Ø Epinephrine acts via ß-adrenergic receptors
and stimulates glycogenoalysis and
gluconeogenesis ,also acts on alpha-2-
receptors to inhibit insulin secretion
Ø Cortisol and Growth hormone contribute
only after prolonged hypoglycemia by
limiting peripheral uitilization of glucose.
Glucagon and epinephrine secretion rises
when plasma glucose concentrations fall
below 65 to 70 mg/dL (3.6 to 3.9
mmol/L)
Growth hormone secretion increases
when plasma
glucose concentrations fall below 60
to 65 mg/dL (3.3 to 3.6 mmol/L)
Cortisol secretion increases when plasma
glucose
concentrations fall below 60 mg/dL
(3.3 mmol/L
GALACTOSEMIA
Neonatal galactosemia is an inborn error of
metabolism for galactose due to deficiency of
one of three possible enzymes. The most
common defect is that of galactose- 1-
phosphate uridyl transferase, causing an
accumulation of galactose. Some aspects of
glucose metabolism are affected, such as a
decrease in glycogenolysis, as conversion to
glucose is inhibited by galactose accumulation.
Initial symptoms of galactosemia are diarrhea
and vomiting after the ingestion of milk.
Continued accumulation of galactose results in
more serious conditions such as mental
retardation, cataracts, and possibly liver
disease.
Prevention of permanent damage to the
developing brain, eyes, and liver involves
removal of sources of galactose from the diet,
especially milk products.
Lactose in food (such as dairy products) is
broken down by the enzyme lactase into glucose
& galactose. In individuals with galactosemia, the
enzymes needed for further metabolism of
galactose are severely diminished or missing
entirely, leading to toxic levels of galactose
1-phosphate in various tissues as in the case of
classic galactosemia, resulting in hepatomegaly (an
enlarged liver), cirrhosis, renalfailure, cataracts, vomiting, seizure,
hypoglycemia, lethargy, brain damage, and ovarian failure.
Without treatment, mortality in infants with
galactosemia is about 75%.
Galactosemia is inherited in an autosomal recessive
manner, meaning a child must inherit one
defective gene from each parent to show the
disease. Heterozygotes are carriers, because
they inherit one normal gene & one defective
gene.Carriers show no symptoms of
galactosemia.
Diagnosis
Infants are routinely screened for galactosemia in the United
States, and the diagnosis is made while the person is still an
infant. Infants affected by galactosemia typically present
with symptoms of lethargy, vomiting, diarrhea, failure to
thrive, and jaundice. None of these symptoms are specific to
galactosemia, often leading to diagnostic delays.. If the
family of the baby has a history of galactosemia, doctors
can test prior to birth by taking a sample of fluid from
around the fetus (amniocentesis) or from the placenta (chorionic
villus sampling or( CVS).
A galactosemia test is a blood test (from the heel of the infant) or
urine test that checks for three enzymes that are needed to
change galactose sugar that is found in milk and milk
products into glucose, a sugar that the human body uses for
energy. A person with galactosemia doesn't have one of
these enzymes. This causes high levels of galactose in the
blood or urine.
Galactosemia is normally first detected through newborn
screening,. Affected children can have serious, irreversible
effects or even die within days from birth. It is important
that newborns be screened for metabolic disorders without
delay. Galactosemia can even be detected through
ingestion of galactose-containing formula or breast milk.
Detection of the disorder through newborn
screening (NBS) does not depend on protein or
lactose ingestion, and, therefore, it should be
identified on the first specimen unless the
infant has been transfused. A specimen should
be taken prior to transfusion. The enzyme is
prone to damage if analysis of the sample is
delayed or exposed to high temperatures. The
routine NBS is accurate for detection of
galactosemia. Two screening tests are used to
screen infants affected with galactosemia—the
Beutler's test and the Hill test.The Beutler's
test screens for galactosemia by detecting the
level of enzyme of the infant. Therefore, the
ingestion of formula or breast milk does not
affect the outcome of this part of the NBS, and
the NBS is accurate for detecting galactosemia
prior to any ingestion of galactose.
Treatment
The only treatment for classic galactosemia is eliminating
lactose and galactose from the diet. Even with an early
diagnosis and a restricted diet, however, some individuals
with galactosemia experience long-term complications such
as speech difficulties, learning disabilities, neurological impairment
(e.g. tremors, etc.), and ovarian failure.

Galactosemia is sometimes confused with lactose intolerance, but

galactosemia is a more serious condition. Lactose intolerant
individuals have an acquired or inherited shortage of the
enzyme lactase, and experience abdominal pains after
ingesting dairy products, but no long-term effects. In
contrast, a galactosemic individual who consumes galactose
can cause permanent damage to their bodies.
Long term complication of galactosemia includes:
Speech deficits.
Ataxia
Dysmetria
Diminished bone density
Premature ovarian failure
Cataract
 OTHER CARBOHYDRATE
METABOLIC DISORDERS
Glycogen Storage Disorders
• Glycogen storage disease type I (von Gierke’s
disease) is due to glucose-6-phosphatase deficiency
causing ineffective glycogenolysis, hypoglycemia
during fasting states, growth retardation, ketosis,
lactic acidosis, and pronounced hepatomegaly due to
accumulation of glycogen in liver.
• Determining insulin and glucagon levels as well as
measuring glucose response after administration of
epinephrine (the epinephrine tolerance test) may be
helpful in obtaining a diagnosis.
• Types II, V, and VII are due to other enzyme defects
and tend to cause milder symptoms and accumulation
of glycogen primarily in skeletal muscle.
• Types III and VI, like type I, are also liver forms of
glycogen storage disease but are rarer in occurrence.
• Type IV is a severe liver form of glycogen storage
disease with cardiac and skeletal muscle disease.
Fructosuria
Fructosuria can be due to enzyme
defects in fructokinase, fructose-1-
phosphate aldolase, or fructose-1,6-
diphosphatase. These are rare
autosomal recessive inherited
diseases, with only fructokinase
deficiency causing a harmless
presence of fructosuria.
Lactate
Lactic acid is a by-product of glucose
metabolism in the Embden-Myerhof
pathway resulting directly from the
conversion of pyruvate and NADH in the
presence of lactate dehydrogenase (LD).

Equilibrium favors the right side of the
reaction at a pH of approximately 7.5 and
the left side at a pH of approximately 9.0 to
9.6. Lactate formation is most prevalent in
erythrocytes, the brain, liver, kidneys, and
skeletal muscle in association with
decreased uptake of pyruvate by the citric
acid cycle.
Blood levels accumulate when the liver is
saturated with lactate during strenuous
exercise, decreased tissue oxygenation,
toxin accumulation, or diseases.
Tissue oxygenation problems are
associated with hypovolemia, shock, and
heart failure, particularly of the left
ventricle.
Diseases such as diabetes mellitus, liver
disease, and malignancies or
accumulation of toxins from methanol,
ethanol, or salicylate metabolism can
result in impaired oxygen use by
mitochondria and increased production
of lactate.