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Pathophysiology of Carbs and Proteins Metabolism
Pathophysiology of Carbs and Proteins Metabolism
2. Starvation.
3. Kwashiorkor.
4. Marasmus.
5. Regulation of glucose metabolism.
6. Diabetus mellitus.
7. Types of diabetus mellitus.
8. Complications of diabetus
mellitus.
• Disorders related to malnutrition, while potentially preventable, produce
moderate to severe disabilities.
• Nearly 800 million people in the world do not have enough to eat, most
of them living in developing countries. In these regions, inadequate
amounts of food (causing conditions such as child malnutrition and
retarded growth) and inadequate diversity of food (causing micronutrient
deficiencies) continue to be priority health problems.
• Malnutrition increases the risk of disease and early death and affects all
age groups, but it is especially common among poor people and those with
inadequate access to health education, clean water, and sanitation.
• Diabetes mellitus is a disease resulting from
absolute or relative insulin insufficiency and
accompanying by disturbance of metabolism
mainly, carbohydrate one.
• The main manifestation of diabetes mellitus
is hyperglycemia, sometimes reaching 25
mmol/l, glucosuria with glucose in urine up to
555-666 mmol/l (100-200 g/day), polyuria (to
10-12 L of urine per day), polyphagia and polydipsia.
Proteins from the diet must be broken into amino acids to be absorbed.
Protein digestion begins in the stomach with the action of pepsin.
Pepsinogen, the enzyme precursor of pepsin, is secreted by the chief cells in
response to a meal and acid pH.
Acid in the stomach is required for the conversion of pepsinogen to pepsin.
Pepsin is inactivated when it enters the intestine by the alkaline pH.
Proteins are broken down further by pancreatic enzymes, such as trypsin,
chymotrypsin, carboxypeptidase, and elastase.
As with pepsin, the pancreatic enzymes are secreted as precursor
molecules. Trypsinogen, which lacks enzymatic activity, is activated by an
enzyme located on the brush border cells of the duodenal enterocytes.
Activated trypsin activates additional trypsinogen molecules and other
pancreatic precursor proteolytic enzymes.
The amino acids are liberated intramurally or on the surface of the villi by
brush border enzymes that degrade proteins into peptides that are one, two,
or three amino acids long. Similar to glucose, many amino acids are
transported across the mucosal membrane in a sodium-linked process that
uses the Na+/K+- ATPase pump as an energy source.
Starvation is a state of overall
deprivation of nutrients. Its causes may
be the following:
I) deliberate fasting—religious or political;
II) famine conditions in a country or
community;
III) secondary undernutrition such as due
to chronic wasting diseases (infections,
inflammatory conditions, liver disease),
cancer etc.
Cancer results in malignant cachexia as
a result of which cytokines are
elaborated e.g. tumour necrosis factor-α,
elastases, proteases etc.
A starved individual has lax, dry skin,
wasted muscles and atrophy of internal
organs.
Anorexia nervosa
1. Pathogenesis Isabelle Caro
a. Self-induced starvation leading to PEM
b. Distorted body image
2. Clinical findings:
a. Secondary amenorrhea
1) Decreased gonadotropin-releasing hormone
• Caused by excessive loss of body fat and weight
2) Decreased serum gonadotropins produces
hypoestrinism.
b. Osteoporosis
1) Caused by hypoestrinism
French model
and actress • Estrogen normally enhances osteoblastic activity and
Isabelle Caro inhibits osteoclastic activity,
2) Lack of estrogen leads to decreased osteoblastic
activity and increased osteoclastic activity.
c. Increased lanugo (fine, downy hair)
d. Increased hormones associated with stress (e.g.,
cortisol, growth hormone)
e. Most common cause of death is ventricular
arrhythmia
Ex-model Frail
Jeremy
Gillitzer has
suffered from
anorexia for
25 years.
He now
weighes only
41.275 kg
Bulimia nervosa
1. Pathogenesis
• Bingeing with self-induced
vomiting
2. Clinical findings:
a. Complications of vomiting
1) Acid injury to tooth enamel
2) Hypokalemia and metabolic alkalosis
b. Ventricular arrhythmia is the
must common cause of death.
PROTEIN-ENERGY MALNUTRITION
The inadequate consumption of protein and energy as a
result of primary dietary deficiency or conditioned deficiency
may cause loss of body mass and adipose tissue, resulting
in protein energy or protein calorie malnutrition (PEM
or PCM).
The primary deficiency is more frequent due to
socioeconomic factors limiting the quantity and quality of
dietary intake, particularly prevalent in the developing
countries of Africa, Asia and South America. The impact
of deficiency is marked in infants and children.
The spectrum of clinical syndromes produced as a result of PEM
includes the following:
1. Kwashiorkor which is related to protein deficiency though calorie
intake may be sufficient.
3.85 6.05
Hypoglycemia NORM Hyperglycemia
GLUCOSE
Blood Glucose & Hormones
Hormone Action
Insulin Glucose
Glucortocoids Glucose
Glucagon Glucose
Growth Hormone Glucose
Epinephrine Glucose
Counter-insulin hormones
ACTH, growth hormone, cortisol, thyroid hormone,
glucagon, adrenaline
Exogenous
Functional
Endogenous
Exogenous
hypoglycemia
• Insulin injection
Impaired absorption
Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo
Lara R. Nyman , Eric Ford , Alvin C. Powers , David W. Piston / American Journal of
Physiology - Endocrinology and MetabolismPublished 1 April 2010Vol. 298no. E807-
E814DOI: 10.1152/ajpendo.00715.2009
Functional Hypoglycemia
1. Alimentary (after gastrectomy, demping syndrome)
2. Spontaneous reactive (cause is not known diarrhea,
tachycardy, tremor, headache, weakness)
3. Alcohol (consumption in hungry state)
4. Endocrine insufficiency (decrease in counter-insulin
hormone )
5. Hepatic failure
6. Malnutrition
7. Heavy physical load (without carbohydrate uptake)
8. Transient functional hypoglycemia of children
• Neonatal (10%)
• Maternal diabetes
• Erythroblastosis
• Ketogenic
Manifestations of hyperglycemia
Glucosuria
Polyuria
Polydypsia
Hypohydration of the organism
Arterial hypotension
Manifestations of hypoglycemia
Starvation
Tremor
Excessive sweating
Tachycardia
Headache, dizziness
Impaired vision
Anxiety, fear
Impaired cognition
• Diabetes mellitus is not a single disease but a
group of clinically heterogeneous disorders that
have glucose intolerance in common. It
encompasses many causally unrelated diseases and
includes many different etiologies of disturbed
glucose tolerance.
IMPAIRMENT
glycolysis, pentose-phosphate shunt and Krebs cycle enzymes
3. Increased rate of glycogen synthesis in liver
4. Increase in synthesis of lipids from glucose
5. Inhibition of gluconeogenesis
HYPERGLYCEMIA
Forms of insulin-dependent
diabetes mellitus
Autoimmune – DR3
Virus-induced – DR4
Maturity-onset diabetes of the young
Insulin insufficiency
Fatty acids
Blood glucose level
Ketone bodies
Metabolic polyuria
acidosis Ketonuria
dehydration Poly-
Kussmaul's CNS depression thirst dipsia
respiration
SHOCK
Hypovolemia
Autoimmune insulin-dependent
diabetes arises in persons with genome
DR3. It is associated with other
autoimmune endocrinopathies, for
example, with illnesses of thyroid gland
(autoimmune thyroiditis, diffuse toxic
goiter), adrenal gland (Addison’s
disease).
This diabetes type develops in any age
more frequent in women.
Autoimmune is diabetes described by
presence in blood of patient
autoantibodies against of Langergans
islets.
• Virus-induced insulin-dependent diabetes mellitus binded
with genome DR4 and different from autoimmune on
mechanisms of development. In this case there are no
autoantibodies against islets of pancreas. Its certainly can
appear in blood but rapidly (pending of year) disappear. They
do not perform essential role in pathogenesis of illness.
• Development of this
diabetes type frequently
precede from viral
infectious epidemic
parotitis, german
measles, measles,
viral hepatitis.
• Pathogenic viruses
action is not specific. It
consists in development
of inflammatory process
in Langergans islets.
Insulitis arises. Lymphoid
infiltration of damaged
islets develops at first
after then destruction.
• Sometimes the specific (immune) destruction mechanisms of β-
cells are linked. The viruses pervert antigen membranes
properties of affected β-cells and are followed with attack of
autoimmune mechanisms.
• There is one more possibility. Membrane β-cells is lightly
damaged by much chemical substances even in insignificant
concentrations.
• Such substances are called
β-cytotoxic. They are, for
example, alloxane and
streptosocine. They create
a favourable background for
immediate viruses action on
membrane of β-cells.
• Virus-induced diabetes
arises early before 30 years
of life. It is identically
widespread and among
males, both among women.
Insulin-independent diabetes mellitus
This diabetes type principle differs from the first.
Patients, as a rule don’t need to exogenic insulin.
Metabolic disorders attached to this diabetes are
minimal. Diet therapy and per oral glucose
decreasing medicines are sufficiently for their
compensation.
Only in stress (trauma action, sharp infection)
conditions patient use insulin.
Illness can course for years without hyperglycemia.
Sometimes it is disclosed in age more 40 years.
There are three factors group, which play a decisive
role in forming of this diabetes type. Here are:
Abnor. Secretion
Insulin Resistance
Relative
IDDM Insulin Def.
ß cell
exhaustion
Type II NIDDM
Insulin-resistance
• Insulin-resistance arises or on genetic base or as result of influence
of external factors (risk factors). Biological insulin action is mediated
over receptors. They are localized on cells-targets membranes
(myocytes, lypocytes). Interaction of insulin and receptor is followed
with changes of physical state of cells-targets membrane.
• As result of this transport system is activated, which carries glucose
over cellular membrane.
• Transmembrane moving of
glucose is provided by proteins-
transmitters.
• Amount of glucose carried in cell
depends on closeness of insulin
receptors on membrane and on
receptor affinity to insulin. These
parameters depend on insulin level in
blood.
• Hyperinsulinemia diminishes
amount of receptors and their
affinity to insulin.
Hypoinsulinemia on the contrary
multiplies amount of receptors
and their affinity to insulin.
• Chronic resistance of insulin
receptors causes a chronic
hyperfunction of β-cells and surplus
production of insulin. This in turn
raises receptor resistance. Thus arises
a vicious circle. Protracted loading of
β-cells conduces to exhaustion of their
functions.
About 4% pregnant women develop
DM due to metabolic changes during
pregnancy. Although they revert back to
normal glycaemia after delivery, these
women are prone to develop DM later in
their life.
Insulin deficiency
Decreased lipogenesis
Hyperlipidemia
Keto-acidotic coma
IMPAIRMENT OF PROTEIN METABOLISM IN DIABETES MELLITUS
Insulin deficiency
Increase in proteolysis
1. Activation of gluconeogenesis
Insulin deficiency
Hyperglycemia
Glucosuria
Osmotic diuresis
DIC syndrome
• Manifested by massive
Cardiomegaly, Hepatomegaly,
Macroglossia.
• Fatal If results in CHF.
• Limited therapies in Neonatal
Variant.
– Attempts at enzyme replacement
ongoing.
Type ІІІ glycogenosis –
Cori’s disease,
Forbs’ disease
This illness is named Glycogen in Muscle Cells
limited ecstrinosis. In
it’s base lies a deficit of Glycogen in the Liver (left stained
amylo-1,6-glucosidase. to show glycogen, right normal)
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 amilo-
1,4,1,6-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.
• 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.
• 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.
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