Dietary proteins provide the body with amino acids for endogenous protein synthesis and are also a metabolic fuel for energy (1 g of protein provides 4 Kcal). Nine essential amino acids (histidine, isoleucine, leucine, lysine, methionine/cystine, henylalanine/tyrosine, theonine, tryptophan and valine) must be supplied by dietary intake as these cannot be synthesised in the body. The recommended average requirement of proteins for an adult is 0.6 g/kg of the desired weight per day. For a healthy person, 10-14% of caloric requirement should come from proteins.
The following metabolic changes take place in starvation: Glucose. Glucose stores of the body are sufficient for one day’s metabolic needs only. During fasting state, insulinindependent tissues such as the brain, blood cells and renal medulla continue to utilise glucose while insulin-dependent tissues like muscle stop taking up glucose. This results in release of glycogen stores of the liver to maintain normal blood glucose level. Subsequently, hepatic gluconeogenesis from other sources such as breakdown of proteins takes place. Protein stores and the triglycerides of adipose tissue have enough energy for about 3 months in an individual. Proteins breakdown to release amino acids which are used as fuel for hepatic gluconeogenesis so as to maintain glucose needs of the brain. This results in nitrogen imbalance due to excretion of nitrogen compounds as urea. 3. Fats. After about one week of starvation, protein breakdown is decreased while triglycerides of adipose tissue breakdown to form glycerol and fatty acids. The fatty acids are converted into ketone bodies in the liver which are used by most organs including brain in place of glucose. Starvation can then continue till all the body fat stores are exhausted following which death occurs.
The major characteristic of long-term starvation is a decreased dependence on gluconeogenesis and an increased use of ketone bodies (products of lipid and pyruvate metabolism) as a cellular energy source. During long-term starvation, depressed insulin levels and increased glucagon, cortisone, epinephrine, and growth hormones promote lipolysis in adipose tissue. Lipolysis liberates fatty acids, which supply energy to cardiac and skeletal muscle cells, and ketone bodies, which sustain brain tissue. Fatty acid, or ketone body, oxidation meets most of the energy needs of the cells. (Some glucose is still needed as fuel for brain tissue.) Once the supply of adipose tissue is depleted, proteolysis begins. The breakdown of muscle and visceral protein is the last process the body engages to supply energy for life. Death results from severe alterations in electrolyte balance and loss of renal, pulmonary, and cardiac function. Adequate ingestion of appropriate nutrients is the obvious treatment for starvation. In medically induced starvation the body is maintained in a ketotic state until the desired amount of adipose tissue has been lysed. Starvation imposed by chronic disease, long-term illness, or malabsorption is treated with enteral or parenteral nutrition. Perioperative management of nutrition is necessary to prevent unnecessary starvation.
In severe malnutrition, notably kwashiorkor, a combination of low plasma protein, a poorly understood increased vascular permeability and deficiencies in vitamins and other essential dietary components is responsible. Proteins have a huge array of vital functions within the human body. Inadequate dietary protein can lead to a number of diseases, particularly in children. The child in the picture above is suffering from kwashiorkor, a disease rare in developed countries but more common in those that experience famine. Its symptoms include oedema (fluid accumulation beneath the skin), decreased muscle mass, failure to grow and a large belly that sticks out. This condition is fatal if untreated.
Kwashiorkor is a condition characterized most notably by protruding bellies among other symptoms. Think of the starving children in Africa which big bellies, except with even bigger bellies. Those who suffer from it typically aren’t straight up starving like you might think. Instead they are able to get a substantial amount of calories from starches (like yams), and yet they are much worse off than those who survive on only a fraction of the food. The reason for this discrepancy is that individuals with Kwashiokor are unable to receive the necessary proteins essential for life. If you’re wondering well people with Marasmus can’t get any protein either since their eating even less you would be absolutely right in a certain sense. However one thing that the body keeps in supply for emergency situations is protein in the form of muscle mostly. When we starve our bodies know were starving and consequently know that we need certain things essential for life. Instead of trying to preserve our beautiful biceps and six packs, it eats away at it so we can use the breakdown products for processes essential for life.
The sneaky part about Kwashiorkor is that even though the body get almost no protein from yams or any other starch in this particular case, the body is tricked into being satisfied (if you know where I’m going with this now don’t ruin it for someone else). So as all these sugars from the yams are flooding into our body, more than even what we need at the moment, our body starts telling itself store the energy were saved! And so it stores and stores the sugar, usually as fat, and consequently forgets about those “insignificant proteins.” Because during our starvation our hunger is the main problem, not the other stuff. So what happens is that without essential amino acids, we can’t make proteins that are very useful for living. Things like immune function go down as well as the oncotic pressure in our blood vessels which basically means all our blood leaks out and we have swelling all over the place (Hence the big bellies). Ultimately, Kwashiorkor victims die much more quickly than Marasmus victims. The scary thing is that in a sense, those dying from Kwashiorkor are actually eating to their death.
Marasmus is what you get when you basically don’t eat anything. Occasionally you might have a meal, but overall you’re starving. Think of it as a state anorexics are in. They are emaciated and probably have a lot of health problems on top of the psychological issues, but they survive for quite some time. When you really don’t have much to eat though and are starving you eventually die prematurely.
Carbohydrates. Dietary carbohydrates, are the major source of dietary calories, especially for the brain, RBCs and muscles (1 g of carbohydrate provides 4 Kcal). At least 55% of total caloric requirement should be derived from carbohydrates.
Where does the sugar in our body go? It&apos;s well and good that sugar from fruit and grain gets into our bodies, but what happens to it thereafter? Let&apos;s look at a model of our &quot;Sugar Central&quot; or, more correctly, blood sugar. The barrel represents the storeroom of sugar in the body. Food provides input in good times (read &quot;after a meal&quot;). There are three major routes out of that storeroom:
Major index which describes metabolism of carbohydrates, is a sugar level in blood. In healthy peoples it is 4,4-6,6 mmol/l. This value is summary result of complicated interaction of many exogenous and endogenous influences. The first it reflects a balance between amount of glucose which entrance in blood and by amount of glucose which is utilized by cells. The second, glucose level in blood reflects an effect of simultaneous regulatory influence on carbohydrates metabolism of the nervous system and endocrine glands: front pituitary gland (somatotropic, thyreotropic, adrenocorticotropic hormones), adrenal cortex (adrenalin ,noradrenalin) layer, pancreas (insulin, glucagone, somatostatin), thyroid (thyroxin, triiodthyronine). Among enumerated hormones only insulin lowers glucose concentration in blood the rest of hormones increase it. Counter-insulin hormones ACTH, growth hormone, cortisol, thyroid hormone, glucagon, adrenaline 1.Stimulate absorption of carbohydrates (cortisol, thyroid hormone) 2. Increase glycogenolysis in liver and muscles, inhibit glycogenesis (adrenaline, cortisol, thyroid) 3. Inhibit hexokinase activity and therefore its utilization (cortisol, growth hormone) 4. Stimulate gluconeogenesis (cortisol, thyroid, glucagon) 5. Activate insulinase (growth hormone, thyroid)
http://ajpendo.physiology.org/content/298/4/E807 Neither MIP-GFP nor Glucagon-Cre-YFP islets show a difference in the direction of islet blood flow during hyperglycemia and hypoglycemia. However, total islet blood flow intensity increased in the hyperglycemic state (Fig. 3A). After a bolus injection of fluorescent dextran, the amount of fluorescence measured in the islet vasculature was greater during hyperglycemia than during hypoglycemia (Fig. 3, A and 3B). To assess whether this change in flow intensity could be attributed to the duration of insulin administration, the order of the hypoglycemic and hyperglycemic clamp experiments was varied (i.e., in some studies we performed the hyperglycemic clamp before the hypoglycemic clamp and in others we clamped hypoglycemia before hyperglycemia). Islet blood flow intensity was decreased during hypoglycemia regardless of whether hypoglycemia or hyperglycemia was clamped first (Fig. 3, C and D), indicating that blood flow intensity changes were likely due to changes in blood glucose rather than to the order of hyperglycemia/hypoglycemia or duration of insulin administration.
Hyperglycemia is connected, foremost with lowering of glucose utilization by muscular and fatty tissues. Lowering of glucose utilization has membranogenic nature. In case of insulinopenia and in case of insulin-resistance interaction of insulin and receptor is damaged. Therefore protein-transporters of glucose are not included in membranes of cells-targets. This limits glucose penetration in cells. It is use on power needs (in myocytes) diminishes. Lypogenesis is slowed-glucose deposit in fats form (in lypocytes). Glycogenesis slows- synthesis of glycogene (in hepatocytes and myocytes). On other hand, attached to diabetes a supplementary amount of glucose is secreted in blood. In liver and muscles of diabetics glycogenolysis is a very active. Definite endowment in hyperglycemia belongs to gluconeogenesis. Here with glucose will is derivated in liver from amino acids (mainly from alanine).
ORAL GLUCOSE TOLERANCE TEST. Oral GTT is performed principally for patients with borderline fasting plasma glucose value (i.e. between 100-140 mg/dl). The patient who is scheduled for oral GTT is instructed to eat a high carbohydrate diet for at least 3 days prior to the test and come after an overnight fast on the day of the test (for at least 8 hours). A fasting blood sugar sample is first draw. Then 75 gm of glucose dissolved in 300 ml of water is given. Blood and urine specimen are collected at half-hourly intervals for at least 2 hours. Blood or plasma glucose content is measured and urine is tested for glucosuria to determine the approximate renal threshold for glucose. Venous whole blood concentrations are 15% lower than plasma glucose values.
Pathogenesis of insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus has genetic base. Inclination to diabetes of this type is conditioned by some genes of major histocompatibility complex (MHC). The system of HLA genes is situated on small extent of short shoulder of 6 chromosome. Here are identified several locuses – A, B, C and area D which includes three locuses – DP, DQ and DR. High probability of insulin-depending diabetes mellitus is to area D and nominally with locuses DR. Genes DR3 and DR4 are diabetogenic. The very high risk of illness is created in those person who have both gene – DR3 and DR4. Inclination to insulin-depending diabetes is associated also with locus DQ (genes DQ2 and DQ8). Diabetes arises only in part of person with diabetogenic genes. For example, alleles DR3 and DR4 occur in 50-60 % healthy person of european race, and illness develops only in 0,25 %. Inheritance of insulin-depending diabetes is conditioned, presumably, by not one gene, but by group of kindred genes. Where in essence of genetic defect in peoples with genes DR3, DR4, DQ2, DQ8? Exact answer on these questions while is not found. Think, that the enumerated genes in lone or in combinations form a low resistibility of β-cells of pancreas to external actions. β-Cells of such persons lightly collapse and very difficult restore. High readiness to destruction combines in them by limited capacity for regeneration. The system of HLA genes are inherited from generation to generation, therefore inclination of β-cells to destruction also is inherited from generation to generation. However general amount of β-cells is attached to birth identically in patients and healthy. Typical affection of Langergans islets attached to insulin-depending diabetes is infiltration of them by lymphocytes and selective destruction of β-cells. Clinical illness picture develops when 80-95% of β-cells are already destroyed. In such patients mass of pancreas is less, than in healthy people. Amount and volume of Langergans islets also is less. Thus insulin-depending diabetes is result of equilibrium violation between destruction of β-cells and their regeneration. Both process – increase of destruction and limitation of regeneration – are genetically conditioned. Depending upon affection mechanism of β-cells there are two forms of insulin-dependent diabetes mellitus – autoimmune and virus-inductive.
Diabetogenic action has diet is result of diet, which contains a surplus of high-calorie products. They are fats and purified simple carbohydrates. Such action is result of diet, which contains a small amount of complex carbohydrates (food fibres). Inhibiting influence of obesity on insulin receptors very clearly displays in conditions of low physical activity. Regular physical exercises on the contrary raise receptor affinity to insulin and raise tolerance to glucose.
Pathophysiology of carbohydrates and proteins metabolism
1. Regulation of protein metabolism.
5. Regulation of glucose metabolism.
6. Diabetus mellitus.
7. Types of diabetus mellitus.
8. Complications of diabetus
• Disorders related to mmaallnnuuttrriittiioonn, 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.
• MMaallnnuuttrriittiioonn 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.
• DD ii aabbeetteess mmeelllliittuuss 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
a. Self-induced starvation leading to PEM
b. Distorted body image
22.. CClliinniiccaall ffiinnddiinnggss::
a. Secondary amenorrhea
1) Decreased gonadotropin-releasing hormone
• Caused by excessive loss of body fat and weight
2) Decreased serum gonadotropins produces
1) Caused by hypoestrinism
• Estrogen normally enhances osteoblastic activity and
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
• Bingeing with self-induced
22.. CClliinniiccaall ffiinnddiinnggss::
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.
Gout is a syndrome caused by an
inflammatory response to uric acid
production or excretion resulting in high
levels of uric acid in the blood
(hyperuricemia ) and in other body
fluids, including synovial fluid.
MMaanniiffeesstteedd bbyy tthhee ffoolllloowwiinngg ffeeaattuurreess,,
ooccccuurrrriinngg ssiinnggllyy oorr iinn ccoommbbiinnaattiioonn::
1. Increased serum uric acid concentration (hhyyppeerruurriiccaaeemmiiaa).
2. Recurrent attacks of characteristic type of acute arthritis in which ccrryyssttaallss ooff
mmoonnoossooddiiuumm uurraattee mmoonnoohhyyddrraattee may be demonstrable in the leucocytes present
in the synovial fluid.
3. Aggregated deposits of monosodium urate monohydrate (ttoopphhii) in and
around the joints of the extremities.
4. Renal disease involving interstitial tissue and blood vessels.
5. Uric acid nneepphhrroolliitthhiiaassiiss.
6. Other factors include age (rare before 30 years), genetic predisposition (XX--lliinnkkeedd
aalltteerraattiioonn ooff eennzzyymmee hhyyppooxxaanntthhiinnee--gguuaanniinnee pphhoosspphhoorriibboossyyllttrraannssffeerraassee
[[HHGGPPRRTT]]), excessive alcohol consumption,
obesity, certain drugs (especially tthhiiaazziiddeess),
and lead toxicity.
When the uric acid reaches a certain
concentration in fluids, it crystallizes,
forming insoluble precipitates that
are deposited in connective tissues
throughout the body.
Crystallization in synovial fluid
causes acute, painful inflammation
of the joint, a condition known as
With time, crystal deposition in
subcutaneous tissues causes the
formation of small, white nodules,
or tophi, that are visible through
the skin. Crystal aggregates deposited
in the kidneys can form urate renal
stones and lead to renal failure.
In classic gouty arthritis, monosodium urate
crystals form and cause joint inflammation.
Pseudogout is caused by the formation
of calcium pyrophosphate dihydrate (CPPD)
crystals. The effect of either crystal is the same—
the onset of a cytokinemediated acute
Carbohydrates must be broken down into monosaccharides, or single
sugars, before they can be absorbed from the small intestine.
The average daily intake of carbohydrate in the American diet is
approximately 350 to 400 g. SSttaarrcchh makes up approximately 50% of this
total, sucrose (i.e., table sugar) approximately 30%, lactose (i.e., milk
sugar) approximately 6%, and maltose approximately 1.5%.
Digestion of starch begins in the mouth with the action of amylase.
Pancreatic secretions also contain an amylase. Amylase breaks down
starch into several disaccharides, including maltose, isomaltose, and α-
dextrins. The brush border enzymes convert the disaccharides into
monosaccharides that can be absorbed.
DDiieettaarryy CCaarrbboohhyyddrraatteess EEnnzzyymmee MMoonnoossaacccchhaarriiddeess PPrroodduucceedd
Lactose Lactase Glucose and galactose
Sucrose Sucrase Fructose and glucose
Starch Amylase Maltose, maltotriase, and α-dextrins
Maltose and maltotriose Maltase Glucose and glucose
α-Dextrins α-Dextrimase Glucose and glucose
• 1. TToo tthhee lliivveerr. Here excess sugar
from meals is stored to cover sugar
shortages between meals and to
make fat from excess sugar.
• Transport of sugar goes both to and
from the liver. The liver fills the
"Sugar Central" between meals.
• 2. TToo tthhee bbrraaiinn. The brain is
completely dependent upon sugar
combustion for its supply of energy,
in any case under normal
conditions. It uses really huge
amounts of sugar.
• 33.. TToo mmuusscclleess aanndd ffaatt ttiissssuuee.. At
least 40% of the body is comprised of
skeletal muscles. These can use both
fats and sugar to supply energy.
•The rate of sugar uptake and burning
follows physical activity; more work;
more sugar burned.
• MMuusscclleess do take up and store
glucose to cover future activity but
they cannot release sugar back to the
blood stream or "Sugar Central".
•FFaatt ttiissssuuee stores surplus sugar as
fat. About half of this comes from the
liver, the rest is made by fat itself.
PPrriimmaarryy DDMM –– ((pprriimmaarryy -- nnoo ootthheerr ddiisseeaassee))
TTyyppee II –– IIDDDDMM // JJuuvveenniillee –– 1100%%..
(absolute insulin deficiency)
Subtype 1A (immune-mediated) DM characterised by autoimmune destruction
of β-cells which usually leads to insulin deficiency.
Subtype 1B (idiopathic) DM characterised by insulin deficiency with tendency
to develop ketosis but these patients are negative for autoimmune markers.
TTyyppee IIII –– NNIIDDDDMM //AAdduulltt oonnsseett –– 8800%%..
(insulin resistance with an insulin secretory deficit)
MMOODDYY ((Maturity-onset diabetes of the young)) –– 55%% mmaattuurriittyy
oonnsseett -- GGeenneettiicc
(other specific types)
SSeeccoonnddaarryy DDMM –– ((sseeccoonnddaarryy ttoo ootthheerr ddiiss..))
PPaannccrreeaattiittiiss,, ttuummoorrss,, hheemmoocchhrroommaattoossiiss..
IInnffeeccttiioouuss –– ccoonnggeenniittaall rruubbeellllaa,, CCMMVV..
DDrruuggss –– CCoorrttiiccoosstteerrooiiddss..
The criteria for the diagnosis of diabetes include
symptoms, elevated fasting plasma glucose
(FPG) concentration, and/or abnormal oral
glucose tolerance test (OGTT).
Two conditions associated with a high risk for
diabetes, impaired fasting glucose (IFG) and
impaired glucose tolerance (IGT), are considered
Age < 25 Years
Family History: No
Insulin levels: very low
50% in twins
Adult >25 Years
Insulin Independent *
Months to years
Normal or high *
Normal / Exhaustion
60-80% in twins
Carbohydrate metabolism in normal conditions and
1. Increase in permeability of myocyte and adipocyte membranes
for glucose (Glut-4)
2. Increase glycolysis, pentose-IIMMPPAAIIRRMMEENNTT
in activity of glucokinase, glycogen-sythetase, aerobic
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
• 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
• Pathogenic viruses
action is not specific. It
consists in development
of inflammatory process
in Langergans islets.
Lymphoid infiltration of
damaged islets develops
at first after then
• 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
• There is one more possibility. Membrane β-cells is lightly
damaged by much chemical substances even in insignificant
• 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.
GGeenneettiicc ffaaccttoorrss determine
hereditary liability to disease.
Specific genetic marker (special
diabetogenic gene) is not found.
It is known only, that inclination
to insulin-independent diabetes
is not coupled with major
complex of histocompatibility.
FFuunnccttiioonn ooff ββ--cceellllss of patient
diabetes is violated. Amount of
them is diminished. Attached to
loading by glucose they do not
multiply insulin secretion in
Diabetologist connects these
violations with amyloidosis of
Pathogenesis of Type II DM
ßß cceellll ddeeffeecctt
LLiiffee ssttyyllee ??
TTyyppee IIII NNIIDDDDMM
• 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
• Hyperinsulinemia diminishes
amount of receptors and their
affinity to insulin.
Hypoinsulinemia on the
contrary multiplies amount of
receptors and their affinity to
• Chronic resistance ooff iinnssuulliinn
rreecceeppttoorrss 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
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
Mitochondrial DNA is inherited maternally
and encodes several genes in the oxidative
phosphorylation pathway, ribosomal RNAs, and 22
transfer RNAs (tRNAs). In rare cases, (<1%),
diabetes is associated with point mutations in a
mitochondrial tRNA gene, tRNALeu(UUR).
Mitochondrial diabetes is caused by a primary
defect in β-cell function. Recall that ATP is
required for insulin secretion in β cells, and
impairment of mitochondrial ATP synthesis results
in decreased insulin secretion.
IMPAIRMENT OF LIPID METABOLISM IN DIABETES MELLITUS
Decreased glucose utilization
Mobilization of fats to depoes
Metabolic acidosis Increased ketogenesis and
Loss of Na+
Increased RBF (hyperperfusion)
Renal vasodilation Protein glycation
Increased protein excretion
• Loss of negative charge
• Thickening of basement membrane
• Mesangial expansion
RBF - Renal blood flow Decreased GFR and renal failure
GFR - Glomerular filtration rate
• Glucose is osmotic active
• Increasing of it’s concentration in
primary urine raises osmotic
• Water is exuded from organism
together with glucose (osmotic
• Patient excretes 3-4 L of urine per
day, sometimes till 10 L.
PATHOGENESIS OF HYPERGLYCEMIC CCOOMMAA
Decreased glucose utilization
Increased glucose production
Hyperosmolarity and dehydration
C O M A DEATH SHOCK
Complication of diabetes mellitus
The very frequent
• Microangiopathy develop in shallow vessels
– arterials, venues, capillaries. Two process
form their pathogenic base – thickining of
basal membrane and reproduction
• Direct cause of microangiopathy is
hyperglycemia and synthesis of glycoproteids
in basal membrane.
• There are two main clinical forms
microangiopathy: diabetic retinopathy
A composite photograph showing a pretreatment fundus photograph (A), and a
photograph demonstrating radiation retinopathy at 24 months (B). A fluorescein
angiogram demonstrates intraretinal microangiopathy next to the tumour (C), and
regression to chorioretinal scar after laser photocoagulation (D).
• Neuropathy manifest
by violation of nerves
Essence of these
• This is hereditary
illness. In it’s base lies
an blockade of
• There are two the main
forms of galactosemia
on base of:
Deficit of glucose-1-phosphat
• This enzyme converts galactose-1-phosphate in glucose-1-phosphate.
Attached to it’s insufficiency galactose-1-phosphate and sugar alcohol
of galactose (galactit) accumulates in tissues lens of the eye, liver,
brain, kidneys. Mammal and cow milk contains lactose.
• Therefore the illness symptoms appear with first days of child life.
• Diarrhea, vomiting, dehydrotation occur.
• Liver increases (splenomegalia). Hepatocytes lose ability to conjugate
bilirubine. Children become yellowish.
• Affection of kidneys displays in proteinuria, aminoaciduria and
• For galactosemia cataract is very typical. Their beginnings related to
accumulation of osmotic active galactite in vitreous bodies of eyes.
Galactite absorb in water, and water breaks tissues.
• Dangerous consequences arise in the brain. This foremost is delay of
• Mortal end is possible.
• Cure method is diet without galactose.
• Simple 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 α–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.
Here upon starts intensive glycogenolysis. Supplementary amount of
glucose is secreted in blood.
• In other situation after consuming of carbohydrates in blood
accumulates surplus of glucose. β-cells of pancreas multiply insulin
synthesis. Insulin raises activity of glycogensyntase. Active
glucogenesis starts too. Surplus of glucose reserves in appearance of
glucogen in liver and muscles.
• There are illnesses in base of which is accumulation of glycogen in
organs. They are called ggllyyccooggeennoosseess. All of them are hereditary
enzymopathy. There are seven main types of glycogenoses.
Glycogenosis type I – Girke’s disease.
• Girke’s disease cause deficit of
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 deposed in
liver and kidneys.
Glycogen Storage Disorders:
• Type 1= Von Gierke’s:
– Shortly after birth: Severe lifethreatening Hypoglycemia
– Lactic acidosis –due to isolated glycolysis of G6Po
– Hyper-uricemia, hhyyppeerr lliippiiddeemmiiaa
– Increased association with epistaxis
– **AAddvveerrssee rreessppoonnssee ttoo GGlluuccaaggoonn wwiitthh wwoorrsseenniinngg LLaaccttiicc aacciiddoossiiss
• Management requires IV glucose, and then as output,
close NG corn-starch or glucose solution administration
to achieve close to nl glucose homeostasis.
• Frequent snacks and meals. Continuous nighttime
glucose infusions up to the age of 2.
Type ІІ glycogenosis – Pompe’s disease.
• Illness is related to
deficit of lysosomal
enzyme – sour
maltase, or α-1,4-
• This enzyme slits
glycogene to glucose
in digestive vacuoles.
Attached to it’s deficit
accumulates at first in
then in cytosole of
Type 2- Pompe’s disease:
• Normal Glucose
• Do to an accumulation of
glycogen in lysosomes.
• **Ancient city of Pompeii was destroyed
by Mt. Vesuvius- 79 AD**
• Manifested by massive
• Fatal If results in CHF.
• Limited therapies in Neonatal
– Attempts at enzyme replacement
Glycogen in the Liver (left stained
to show glycogen, right normal)
Glycogen in Muscle Cells
Type ІІІ glycogenosis –
This illness is named
limited ecstrinosis. In
it’s base lies a deficit of
glycogen pauses in
sites of branching.
accumulates in liver
and muscles. Cure is
diet with big proteins
Type ІV glycogenosis –
• It is called by deficit of amilo-
• 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
• 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
• Illness arises as result of insufficiency of
hepatic phosphorilase complex.
• Glycogen accumulates in liver.
• Typical sign is hepatomegalia.
1. ROBBINS BASIC PATHOLOGY / [edited by] Vinay Kumar, Abul K. Abbas, Jon
C. Aster. – 9th ed. – 2013.
2. Kathryn L. McCance . Pathophysiology: the biologic basis for disease in adults
and children / [edited by] Kathryn L. McCance, Sue E. Huether; section editors,
Valentina L. Brashers, Neal S. Rote - 6th ed. – 2010.
3. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.
Banasic // Elsevier Inc. – 2010.
4. General and clinical pathophysiology. Edited by prof. A.V. Kubyskin. Simferopol.
5. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth,
Glenn Matfin.– New York, Milwaukee. – 2009.
6. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott
Williams & Wilkins), Trade paperback (2003) / Carol Mattson Porth, Kathryn J.
Gaspard. Chapter 32
7. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.
Stuttgart. New York. – 2000.
8. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine
Publishing. – 2010.