Transcript DISORDER OF CARBOHYDRATE METABOLISM

DISORDER OF
CARBOHYDRATE
METABOLISM
Ph.D., MD, Assistant Professor
Hanna Saturska
molecular formula C12H22O11
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Major
index
which
describes
metabolism
carbohydrates, is a sugar level in blood.
In healthy people it is
4,4-6,6 mmol/l.
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Sucrose is the organic compound commonly
known as table sugar and sometimes
called saccharose.
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The molecule is a disaccharide composed of
the monosaccharides glucose and fructose
of
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glucose level in blood
3,3-5,5 mmol/l.
GlucoseC6H12O6, also known
as D-glucose, dextrose, or grape
sugar) is a
simple monosaccharide
Open-chain form
Cyclic forms
This value is summary result of complicated
interaction of many exogenous and
endogenous influences.
 1. The first it reflects a balance between
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amount of glucose
which entrance in blood
amount of glucose
which is utilized by cells
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2. The second,
glucose level in
blood
reflects
an
effect
of
simultaneous regulatory influence on
carbohydrates metabolism of the
nervous system and endocrine
glands:
pituitary gland adrenal cortex
(somatotropic
(adrenalin,
thyreotropic
noradrenalin)
adrenocorticotropic
layer
hormones)
pancreas
thyroid
(insulin,
(thyroxin,
glucagone,
triiodthyronine)
somatostatin)
Among enumerated hormones only
insulin lowers glucose concentration in
blood the rest of hormones increase it .
 The glucose concentration in blood
describes carbohydrates metabolism
both of healthy man and sick.
 Illnesses base of which is disorder of
carbohydrates metabolism can flow with
rise of glucose concentration in blood
and with lowering of it.
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Rise of glucose concentration is named
hyperglicemia lowering hypoglicemia.
For example, hyperglicemia is very typical
for diabetes mellitus, hypoglycemia – for
glycogenosis.
hyperglicemia
hypoglicemia
diabetes mellitus
glycogenosis
Diabetes mellitus
Diabetes mellitus, often simply referred to
as diabetes—is a group of metabolic
diseases in which a person has high
blood sugar,
 either because the body does not produce
enough insulin,
 or because cells do not respond to the
insulin that is produced.
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This high blood sugar produces the
classical symptoms:
polyuria (frequent urination),
polydipsia (increased thirst)
polyphagia (increased hunger).
There are three main types of
diabetes:
 Type 1 diabetes: results from the
body's failure to produce insulin,
and presently requires the person
to inject insulin.
 (Also referred to as insulindependent diabetes mellitus,
 IDDM for short, and juvenile
 Type
2 diabetes: results from
insulin resistance, a condition in
which cells fail to use insulin
properly, sometimes combined
with an absolute insulin
deficiency. (Formerly referred to
as non-insulin-dependent
diabetes mellitus, NIDDM for short,
and adult-onset diabetes.)
 Gestational
diabetes: is when
pregnant women, who have never
had diabetes before, have a high
blood glucose level during
pregnancy. It may precede
development
of type 2 DM.
 Other
forms of diabetes mellitus
include
 congenital diabetes, which is
due to genetic defects of insulin
secretion,
 cystic fibrosis-related diabetes,
steroid diabetes induced by high
doses of glucocorticoids,
 several forms of monogenic
 As
of 2000 at least 171
million people worldwide
suffer from diabetes, or
2.8% of the population.
 Type 2 diabetes is by far the
most common, affecting 90
to 95% of the diabetes
population
Feature
Onset
Age at onset
Type 2 diabetes
Gradual
Mostly in adults
Body habitus
Type 1 diabetes
Sudden
Any age
(mostly young)
Thin or normal
Ketoacidosis
Common
Rare
Autoantibodies Usually present
Endogenous
Low or absent
insulin
Concordance
in identical
twins
Prevalence
Often obese
50%
Absent
Normal,
decreased
or increased
90%
Less prevalent
More prevalent-
Type 1
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Type 1 diabetes mellitus is
characterized by loss of the insulinproducing beta cells of the islets of
Langerhans in the pancreas leading to
insulin deficiency.
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In 1869, while
looking down the
microscope, the
Berlin physician
Paul Langerhans
discovered small
“islets” of cells
scattered
throughout the
pancreas. These
cells are
responsible for
the production of
insulin.
Somatostatin
 Digestive enzymes
glukagon
insulin
include trypsin,
chymotrypsin,
pancreatic lipase,
and pancreatic
amylase, and are
produced and
secreted by acinar
cells of the
exocrine pancreas.
Type 2
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Type 2 diabetes mellitus is characterized
by insulin resistance which may be
combined with relatively reduced insulin
secretion. The defective responsiveness
of body tissues to insulin is believed to
involve the insulin receptor. However,
the specific defects are not known.
Diabetes mellitus due to a known defect
are classified separately. Type 2
diabetes is the most common type.
In the early stage of type 2 diabetes, the
predominant abnormality is reduced
insulin sensitivity. At this stage
hyperglycemia can be reversed by a
variety of measures and medications
that improve insulin sensitivity or reduce
glucose production by the liver.
Gestational diabetes
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Gestational diabetes mellitus (GDM)
resembles type 2 diabetes in several
respects, involving a combination of
relatively inadequate insulin
secretion and responsiveness. It
occurs in about 2%–5% of all
pregnancies and may improve or
disappear after delivery. Gestational
diabetes is fully treatable but
requires careful medical supervision
throughout the pregnancy. About
20%–50% of affected women
develop type 2 diabetes later in life.
When a woman has high blood sugar
only while she is pregnant, it is a special
type called Gestational Diabetes. Usually
the blood sugar is kept in the normal
range by insulin made by the body. Most
of the time, pregnant women make more
insulin
to
lower
the
blood
sugar.
However, some women
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cannot do this, and these
are the women who
 develop gestational
diabetes. This usually
occurs in the second half
of pregnancy.
Symptoms:
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Increased thirst
Increased urination
Weight loss in spite of increased appetite
Fatigue
Nausea and vomiting
Frequent infections including those of the
bladder, vagina, and skin
Blurred vision
Note: Usually there are no symptoms.
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People (usually with type 1 diabetes) may
also present with diabetic ketoacidosis, a
state of metabolic dysregulation
characterized by the smell of acetone; a
rapid, deep breathing known as Kussmaul
breathing; nausea; vomiting and
abdominal pain; and an altered states of
consciousness.
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A rarer but equally severe possibility is
hyperosmolar nonketotic state, which is more
common in type 2 diabetes and is mainly the
result of dehydration. Often, the patient has
been drinking extreme amounts of sugarcontaining drinks, leading to a vicious circle in
regard to the water loss.
A number of skin rashes can occur in diabetes
that are collectively known as diabetic
dermadromes.
Causes
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Type 1 diabetes is also partly inherited and then
triggered by certain infections, with some
evidence pointing at Coxsackie B4 virus. There
is a genetic element in individual susceptibility to
some of these triggers which has been traced to
particular HLA genotypes (i.e., the genetic "self"
identifiers relied upon by the immune system).
However, even in those who have inherited the
susceptibility, type 1 diabetes mellitus seems to
require an environmental trigger.
Causes
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The cause of diabetes depends on the
type. Type 2 diabetes is due primarily to
lifestyle factors and genetics.
Diagnosis
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Diabetes mellitus is characterized by recurrent or
persistent hyperglycemia, and is diagnosed by
demonstrating any one of the following
Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL).
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours
after a 75 g oral glucose load as in a glucose tolerance
test.
Symptoms of hyperglycemia and casual plasma glucose
≥ 11.1 mmol/L (200 mg/dL).
Glycated hemoglobin (Hb A1C) ≥ 6.5%
Glycosylated hemoglobin and Glucose tolerance test
Complications
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Diabetes doubles the risk of vascular problems, including
cardiovascular disease.
Glycated hemoglobin is better than fasting glucose for
determining risks of cardiovascular disease and death
from any cause
The complications of diabetes mellitus are far less
common and less severe in people who have wellcontrolled blood sugar levels.
Wider health problems accelerate the deleterious effects
of diabetes. These include smoking, elevated cholesterol
levels, obesity, high blood pressure, and lack of regular
exercise.
Complications of diabetes
mellitus
Acute
Complications of diabetes
mellitus
Diabetic ketoacidosis
 Hyperglycemia hyperosmolar state
 Hypoglycemia
 Diabetic coma
 Respiratory infections
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Chronic
Complications of diabetes
mellitus
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Angiopathy Chronic
elevation of blood
glucose level leads
to damage of blood
vessels
The endothelial
cells lining the
blood vessels take
in more glucose
than normal, since
they do not depend
on insulin.
Fundus photo showing scatter laser
surgery for diabetic retinopathy
Galactosemia
This is hereditary illness. In it’s base lies an
blockade of galactose metabolism. In organism
intermediate metabolits accumulate. There are two
the main forms of galactosemia on base of
transferase insufficiency and on base of
galactokinase insufficiency.
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transferase insufficiency
galactokinase insufficiency
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 Simple
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Glycogenoses
carbohydrates
deposit
in
organism as polysaccharides. In muscles
and liver accumulates glycogen. It consist
of 4 % of liver weight and 2 % of muscles
weight. Muscles glycogen is used as of
ready
fuel
source
for
immediate
guaranteeing by energy. Liver without
interruption provides cerebrum and
erythrocytes with glucose .
Synthesis and splitting of glycogen are
exactly
adjusted
and
coordinated
processes. Attached to immediate need in
glucose –cells of pancreas secret
glucagone. It activates adenylatcyclase of
hepatic cells. Adenilatcyclase stimulates
derivation of cAMP. Under action of cAMP
takes place activation of proteinkinase and
this
enzyme
raises
activity
glycogenphosphorilase and oppresses
activity of glucogensynthase.
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Glycogenosis type I – Girke’s
disease. Girke’s disease cause
deficit of glucose-6-phosphatase.
This enzyme provides 90 % of
glucose which disengages in liver
from glycogen.
It play central role in normal glucose
homeostasis.
Glucose
which
disengages attached to disintegration
of glycogen or is derivated in process
of gluconeogenesis obligatory goes
over stage of glucose-6-phosphate.
Enzyme
glucose-6-phosphatase
tears away a phosphate group from
glucose. There free glucose is
formed it goes out in blood.
Attached to Girke’s disease stage of
tearing phosphate group is blocked.
There
are
no
free
glucose
hypoglycemia occur.
Hypoglycemia arises. Attached to
Girke’s disease glycogen is deponed
in liver and kidneys.
Girke’s disease
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Type ІІ glycogenosis – Pompe’s disease.
Illness is related to deficit of lysosomal
enzyme – sour maltase, or -1,4glucosidase. This enzyme slits glycogene to
glucose in digestive vacuoles. Attached to
it’s deficit glycogen accumulates at first in
lysosomes and then
in cytosole of
hepatocytes and myocytes.
Type ІІІ glycogenosis – Cori’s disease,
Forbs’ disease. This illness is named
limitdecstrinosis. In it’s base lies a deficit of
amylo-1,6-glucosidase.
Degradation
of
glycogen pauses in sites of branching.
Glycogen accumulates in liver and muscles.
Cure is diet with big proteins maintenance.
Type ІV glycogenosis – Anderson’s
disease. It is called by deficit of amilo1,4,1,6-transglucosidase
(branching
enzyme). As result of this There is derivated
anomalous glycogen with very long
branches and rare points of branching. It is
not
exposed
to
degradation
and
accumulates in liver, heart, kidneys, spleen,
lymphatic nods, skeletal muscles.
Glycogen storage disease II (Micro)
The myofibers are engorged with glycogen. On cross sections the myofibrils are pushed to the periphery.
Despite the thick walls, this is not hypertrophy. These patients present with congestive failure.
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Type V glycogenosis – McArdel’s
disease. It’s cause is deficit of
phosphorilase of myocytes. Typical
pain displays
in muscles after
physical loading. Glycogene does
not slit only in muscles. Here it
accumulates. In liver mobilization of
glycogen comes normal.
Type VІ glycogenosis – Hers’
disease. Illness arises as result of
insufficiency
of
hepatic
phosphorilase complex. Glycogen
accumulates in liver. Typical sign is
hepatomegalia.
Type VІІ glycogenosis. Illness
essence is in oppression of muscle
phosphofrutkinase. Symptoms are
similar to McArdles disease.