Pathophysiology of vascular tone. Arterial hypertension.
• Prof. Olha V. Denefil
• Increased blood pressure is found in 15-30 % of the adult population in the world. There are significant differences in this indicator over the world: from 6 % - in Africa to 30-35 % - in the Scandinavian countries, in the USA is 23-31 %, in Ukraine – nearly 40 %.
• Arterial hypertension is a major risk factor of many pathological conditions and diseases of the cardiovascular system:
• atherosclerosis• left ventricular hypertrophy and
heart insufficiency,• ischemic heart disease
(myocardial infarction)• cerebrovascular disease
(ischemic and hemorrhagic brain stroke)
• renal insufficiency
„RULE of HALF”
About 50% of people do not know about an increase
of their blood pressure!!!
Of those who know50% of untreated!!!
Thus, only about 25 % of patients taking medications to
lower blood pressure
Effective antihypertensive therapy have only 12-13 % of
patients
REGULATORY SYSTEM,THAT PROVIDE
STABILITY OF BLOOD PRESSURE
Haemodynamic systems Systems of control
Stable Arterial Pressure
Regulation of arterial pressure (АP)
Systems of AP control
SYSTEMof BRIEFACTION
SYSTEMof LONG TERM
ACTION
Baroreceptors andchemoreceptors of
aortic arch and sinocarotid zones
renin -angiotensin II -
arterioles
angiotensin IIaldosterone
Regulative systems of AP
Regulative systems of AP
Regulative systems of AP
Classification
Arterial hypotension
Arterial hypertension
Acute(collapse)
Chronic
(hypotonic disease, symptomatically)
Secondary (symptomatically)
AP above 139/89 mm Hg
Primary(essential)
AP less than 100/60 mm Hg
Classification
Primary AH (essential, hypertonic disease)
80 % of all increase of AP
Secondary AH (that is happened in 5 - 10 % cases).
It’s a symptom of some disease course
Etiology of AH
Reason is unknown (AH is polyetiological disease).AH arises on the ground of genetically peculiarities of
metabolism. That is possible to have genetically defect of the systems, which
control relaxation of the smooth muscle cells of the arterioles.It is possible to:
1. Hereditary defect of Ca-ATPase (myocyte relaxation of arterioles involves the movement of Ca in the sarcoplasmic
reticulum against the concentration gradient)2. Genetically caused sodium retention in the body
3. The variability of the gene that controls the synthesis of receptors for angiotensin 2
4. Genetically caused by increased activity of ACE5. Lack of endothelial nitric oxide synthesis
Etiology of primary AH Etiology of primary AH
Theories of primary hypertensionTheories of primary hypertension• 1. Recognized the leading role of the nervous system
• Essence: disorders of the nervous regulation of vascular tone
• against failure mechanisms of hormonal regulation of arteriolar tone carried over earlier kidney disease, age-related changes in blood vessels, endocrine disorders during menopause
• 1. Recognized the leading role of the nervous system
• Essence: disorders of the nervous regulation of vascular tone
• against failure mechanisms of hormonal regulation of arteriolar tone carried over earlier kidney disease, age-related changes in blood vessels, endocrine disorders during menopause
• 2. Recognized the leading role of the kidneys
• Essence: imbalance pressor and depressor functions
• Increased vascular tone occurs on the background of exhaustion
depressor of kidneys
• 2. Recognized the leading role of the kidneys
• Essence: imbalance pressor and depressor functions
• Increased vascular tone occurs on the background of exhaustion
depressor of kidneys
Contributing factorsFamily history
Age-related changes in blood pressureHigh salt intake
Stress
Hyperinsulinemia:
causes high activity sympathetic link of ANS and its effect on cardiac output, peripheral vascular resistance and renal sodium retention;
stimulates sodium and calcium transport across the cell membrane of vascular smooth muscle, thereby sensitizing blood vessels to vasopressor stimuli
Obesity (hyperinsulinemia)Excess alcohol consumption
(mechanism in unclear)
Race
(for example: AH isn’t only more prevalent in African Americans than whites, it is also more severe).
Possible explanation: due to evolutionary adaptation to the severe environment (western Africa and Western hemisphere) in condition of salt and water deprivation survival is possible due to retention of sodium and water in organism. That leads to conserve sodium.
There is little information about other racial groups
1. Increased blood volume1. Increased blood volume
Pathogenesis
Causes
NaCl (use of more than 5 g per day) - mountain population of Japan, the
Ukrainian Carpathian and Crimean often suffer from hypertension disease
due to the use of water that contains a lot
of NaCl
NaCl (use of more than 5 g per day) - mountain population of Japan, the
Ukrainian Carpathian and Crimean often suffer from hypertension disease
due to the use of water that contains a lot
of NaCl
Reduced of Na+ excretion by the kidneys(kidney disease)
Reduced of Na+ excretion by the kidneys(kidney disease)
Genetically caused decrease Na excretion by the kidneys
Genetically caused decrease Na excretion by the kidneys
1. Renal (resulted from kidney pathology)
Etiologysecondary АHEtiologysecondary АH
GlomerulonephritisGlomerulonephritis
Kidney damage at collagenosis
Kidney damage at collagenosis
Kidney amiloidosisKidney amiloidosis
Glomerulosclerosis because diabetes mellitus
Glomerulosclerosis because diabetes mellitus
Nephropathy of the pregnant
Nephropathy of the pregnant
Hereditary defect of renal vessels
Hereditary defect of renal vessels
Renal vessels atherosclerosis, embolism or thrombosis
Renal vessels atherosclerosis, embolism or thrombosis
Kidney tumorKidney tumor
Uri stone diseaseUri stone disease
3. Angiogene(is caused by vessels pathology)
2. Renoprive (arises after kidney remove)
Etiologysecondary АHEtiologysecondary АH
Aorta damageAorta damage Arteries carotids damage
Arteries carotids damage
4. Endocrinopathy (develops in the result of endocrine glands pathology)
Etiologysecondary АHEtiologysecondary АH
Cushing's disease (Adrenocorticotropin over production by
the pituitary gland anterior part)
Cushing's disease (Adrenocorticotropin over production by
the pituitary gland anterior part)
Acromegaly (Somatotropin over production by
the pituitary gland anterior part)
Acromegaly (Somatotropin over production by
the pituitary gland anterior part)
Hyperaldosteronism (aldosteron over excretion by suprarenal
glands)
Hyperaldosteronism (aldosteron over excretion by suprarenal
glands)
Menopause(age-depended decrease of female
gonads activity – estrogens excretion decrease)
Possible mechanism – deficit of NO synthesis by endotheliocytes
Menopause(age-depended decrease of female
gonads activity – estrogens excretion decrease)
Possible mechanism – deficit of NO synthesis by endotheliocytes
5. Neurogene (is accompanying to nerves system pathology)
Etiologysecondary АHEtiologysecondary АH
Brain hemorrhageBrain hemorrhage
EncephalitisEncephalitis
Brain tumorBrain tumor
Brain traumaBrain trauma
Brain ischemiaBrain ischemia
7. Drug-induced
6. Cardiac
Etiologysecondary АHEtiologysecondary АH
Heart failureHeart failureHeart defectHeart defect
Drugs, which cause vessels spasm (influent on kidney), hormonal contraceptives
Drugs, which cause vessels spasm (influent on kidney), hormonal contraceptives
Emotional excitement (SNS activation)
Emotional excitement (SNS activation)
Increase of circulative blood volume (CBV)Increase of circulative blood volume (CBV)
Cardiac output (CО) increaseCardiac output (CО) increase
Kidney functions violationKidney functions violation
Peripheral vessels resistance increasePeripheral vessels resistance increase
Pathogenesis
Increase of circulative blood volume (CBV)Increase of circulative blood volume (CBV)
Pathogenesis
Reasons
NaCl (intake more 5 g/day) NaCl (intake more 5 g/day)
Decrease Na excretion by kidney
(kidney diseases)Decrease Na excretion by kidney
(kidney diseases)
1. CBV increase1. CBV increase
Na+ retention in bloodNa+ retention in blood
Blood osmotic pressure increase
Blood osmotic pressure increase
HypervolemiaHypervolemia
Cardiac output increaseCardiac output increase
AP elevationAP elevation
Na accumulation in vessels smooth muscle wall and increase of its
osmotic pressure
Na accumulation in vessels smooth muscle wall and increase of its
osmotic pressure
Vessels wall edemaVessels wall edema
Vessels narrowingVessels narrowing
Peripheral vessels resistance increasePeripheral vessels
resistance increase
Vessels smooth muscle sensitivity to
vasoconstrictive influences increase
(noradrenalin, adrenalin, endotheline, angiotensin)
Vessels smooth muscle sensitivity to
vasoconstrictive influences increase
(noradrenalin, adrenalin, endotheline, angiotensin)
Formula: АP = CO · PRFormula: АP = CO · PR
Pathogenesis
Vessels spasm
Vessels spasm
2. Cardiac output increase (CO)2. Cardiac output increase (CO)
Reasons
Circulative blood volume increase (CBV)
Circulative blood volume increase (CBV)
physical (overload) stress
physical (overload) stress
Emotional stress Emotional stress
HyperthyreosisHyperthyreosis
Pathogenesis
2. Cardiac output increase2. Cardiac output increase
SAS activationSAS activation
Adrenalin excretionAdrenalin excretion
Increase of cardiac contractility force
Increase of cardiac contractility force
Increase of cardiac output
Increase of cardiac output
Increase of heart beats Increase of heart beats
AP elevationAP elevation
Pathogenesis
Formula: АP = CO · PRFormula: АP = CO · PR
3. SAS activation3. SAS activation
Interaction adrenalin and alpha-adrenoreceptors
Interaction adrenalin and alpha-adrenoreceptors
Arterioles smooth muscles spasm
Arterioles smooth muscles spasm
Suprarenal glands activationSuprarenal glands activation
Venues and veins smooth muscles
spasm
Venues and veins smooth muscles
spasm
Increase of circulative blood in big blood
circle
Increase of circulative blood in big blood
circle adrenoreceptors of
heartadrenoreceptors of
heart
АdrenalinАdrenalinNoradrenalinNoradrenalin
Increase of CBVIncrease of CBV
CO increaseCO increase
Arterioles vasoconstriction
Arterioles vasoconstriction
alpha-adrenoreceptors of vessels
alpha-adrenoreceptors of vessels
CO increaseCO increase
AP increaseAP increase
SAS activationSAS activation
Arterioles vasoconstriction
Arterioles vasoconstriction
PR increasePR increase
Pathogenesis
Formula: АP = CO · PRFormula: АP = CO · PR
Production of catecholamineProduction of catecholamine
4. Kidney functions violation4. Kidney functions violation
Long time spasm of kidney’s arteries
Long time spasm of kidney’s arteries
AP increaseAP increase
AP decrease in renal capillaries
AP decrease in renal capillaries
Activation of JGAActivation of JGA
Renin excretionRenin excretion
Angiotensin 2 synthesis
Angiotensin 2 synthesis
Angiotensin 2 effects
• Smooth muscles contraction in the vessels
• Stimulation of the vasoactive center in brain
• Noradrenalin excretion increase• Adrenalin excretion increase from
suprarenal glands• Aldosteron excretion increase from
suprarenal glands (Na retention due to kidney)
• Activation of Na and water reabsorption in the kidney without aldosterone
Angiotensin 2 effects
• Smooth muscles contraction in the vessels
• Stimulation of the vasoactive center in brain
• Noradrenalin excretion increase• Adrenalin excretion increase from
suprarenal glands• Aldosteron excretion increase from
suprarenal glands (Na retention due to kidney)
• Activation of Na and water reabsorption in the kidney without aldosterone
Pathogenesis
Formsof hypertensive
disease
Decrease concentration
of rennin in blood (25-30%)
Increase concentration
of rennin in blood (10-20 %)
Norm concentration of rennin in blood
(55-60 %)
Depressive function of kidney – synthesis of the substances for AP reduce
Depressive function of kidney – synthesis of the substances for AP reduce
PG Е 2PG Е 2
Phospholipids Renin Inhibitor
Phospholipids Renin Inhibitor
AngiotensinaseAngiotensinase
Phosphatydilcholin alkali ethers
Phosphatydilcholin alkali ethers
! ! !
Exhaustion of kidney depressive function
leads to arterial hypertension stabilization
dilates renal arteries, reduces renin synthesis and reduces Na
reabsorbing in kidney
dilates renal arteries, reduces renin synthesis and reduces Na
reabsorbing in kidney
1st period
functional violations
(heart hypertrophy)
2d periodPathological changes in arteries and arterioles (dystrophy):- Arterioles sclerosis
- Arteriole’s wall infiltration by plasma (leads to dystrophy)
- Arterioles necrosis (hypertonic crisis arises in clinic)
- Vein’s wall thickening
Arterial hypertension after-effects
3d period
Secondary changes in organs and systems
Kidney
(nephrosclerosis and chronic kidney insufficiency)
Kidney
(nephrosclerosis and chronic kidney insufficiency)
CNS
– brain hypoxia
– neurons destruction
– apoplexy (because vessels destruction and rupture leads to brain hemorrhages and brain destruction)
CNS
– brain hypoxia
– neurons destruction
– apoplexy (because vessels destruction and rupture leads to brain hemorrhages and brain destruction)
Heart
Decompensate heart failureHeart
Decompensate heart failure
Organs of vision- retinopathy (retina’s vessels injury)- hemorrhages and separation (exfoliation) of
retina, that leads to blindness
Organs of vision- retinopathy (retina’s vessels injury)- hemorrhages and separation (exfoliation) of
retina, that leads to blindness
Endocrine system
Glands atrophy and sclerosisEndocrine system
Glands atrophy and sclerosis
Arterial hypertension after-effects
Pathogenetic principles of treatment
1. Decrease of consumption and increased excretion of fluid and Na+ - decrease of CBV and vascular sensitivity to pressor effects
• 2. Decrease of emotional and physical stress - decrease CNS activity (including sympathoadrenal activity)
• 3. Block of adrenoreceptors - reduce the effects of catecholamine in the heart, i.e. CO
• 4. Block of adrenoreceptors - reduce the effects of catecholamines in the arterioles, i.e. reducing vasomotor arteriolar tone
• 5. Block of ACE - reduce the formation of angiotensin 2 - decrease basal arteriolar tone
• 6. Decrease the effects of angiotensin 2 - blocking receptors for angiotensin 2 - decrease basal arteriolar tone
• 7. Decrease admission of Ca in myocytes of arterioles - decrease basal arteriolar tone
• 8. Increase of depressor kidney function - decrease basal arteriolar tone
• 9. Increase of vasodilator function of blood vessels involving nitric oxide - reducing basal arteriolar tone
1. Decrease of consumption and increased excretion of fluid and Na+ - decrease of CBV and vascular sensitivity to pressor effects
• 2. Decrease of emotional and physical stress - decrease CNS activity (including sympathoadrenal activity)
• 3. Block of adrenoreceptors - reduce the effects of catecholamine in the heart, i.e. CO
• 4. Block of adrenoreceptors - reduce the effects of catecholamines in the arterioles, i.e. reducing vasomotor arteriolar tone
• 5. Block of ACE - reduce the formation of angiotensin 2 - decrease basal arteriolar tone
• 6. Decrease the effects of angiotensin 2 - blocking receptors for angiotensin 2 - decrease basal arteriolar tone
• 7. Decrease admission of Ca in myocytes of arterioles - decrease basal arteriolar tone
• 8. Increase of depressor kidney function - decrease basal arteriolar tone
• 9. Increase of vasodilator function of blood vessels involving nitric oxide - reducing basal arteriolar tone
• Plasma lipoproteins are produced and secreted by the liver parenchymal cells and epithelial cells of the small intestine.
General structure of lipoprotein.There is a lipid drop inside (nucleus),
which contains triglycerides (TG) and cholesterol esters (ACh).
Membrane covers the nucleus and consists of protein (apoprotein, or apo-), phospholipids (PhL) and non-ester cholesterol (NACh).
The outer membrane of lipoprotein is hydrophilic and inner core is hydrophobic.
Lipoproteins are soluble in water, it is a transport form of lipids in the blood.
• In plasma of healthy people is
• 4-8 g/l - total lipids
• 0.8-1.5 g/l - VLD
• 3,2-4,5 g/l - LDL• 2,7-4,3 g / l -
HDL• 3,9-6,5 mmol/l -
general chylomicrons
Kinds of the lipoproteins
Indexes Chylomicron VLDL, pre--LP
LDL, -LP HDL, -LP
Diameter, nm 500-1000 25-75 19-24 6-12
Chemical structure (%):
Cholesterol 0,5- 3 15-17 35-48 20-37
% Cholesterol esters
46 57 66-70 78
Phospholipids 3-9 13-20 11-30 24-40
Triglycerides 80-95 50-70 5-10 3-5
Protein 1-2 5-12 14-25 45-55
Apoproteins A, B, C, E B, C B, C, E A, C, D, E
The value of cholesterol
• 1. Necessary for maintaining of cell shape
• 2. Together with PL and proteins provides selective permeability of cells to different substances
• 3. Source of sex and steroid hormones
• 4. Source of bile acids
• 5. Necessary for growth of the organism and cell division
Balance of cholesterol
• One day in the human body• 450 mg of cholesterol oxidized to bile acids• 450 mg of cholesterol excreted with faeces• 100 mg of cholesterol excreted with dermal fat
• 300 mg of cholesterol derived from food• 700 mg of cholesterol is synthesized from acetyl-CoA in
the cells of various organs, the highest in the liver and small intestine
• In adult is about 140 grams of cholesterol (93% is in the cells, 7% is transported in the form of LP mainly LDL in plasma).
Аpо-В-receptorАpо-Е-receptor(receptor connects the LDL, depends on Cholesterol needs of the cell)
Role of LP in Cholesterol transport inside the cell. That is due to receptor-mediated mechanism.
It was discovered by American scientists M.Brown and J.Goldstein in 1973-1975
(Nobel Prize in 1985)
Skin fibroblast
Smooth muscles
cell of artery
Lymphocyte
Macrophage
Receptor-mediated endocytosis
Regulation of cholesterol contents• Except the receptor-mediated cholesterol
admission into the cell to regulate the content exists by removing cholesterol from the cell membrane surface. This is done by HDL.
• In blood this cholesterol undergoes etherification
under influence of lecithin-cholesterol-acetyltransferase, is transported to the liver, where partially oxidized to bile acids.
• Normally, these two processes are balanced.
• 10% of the population have congenital molecular abnormalities in cholesterol metabolism or LP:
• 1) increased synthesis of cholesterol, atherogenic LP in the liver and small intestine
• 2) the prevalence of violations outlet of atherogenic LP in the bloodstream by help of HDL
Violation of regulating processes of cholesterol metabolism
Inherited defects in exchange of LP (cause early atherosclerosis and coronary artery disease)
• 1) Tangier disease - (also known as "Familial alpha-lipoprotein deficiency") or Hypoalphalipoproteinemia is a rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein (HDL), often referred to as "good cholesterol," in the bloodstream.
• 2) familial hypercholesterolemia - genetically caused by the absence or deficiency of receptors on the surface of parenchymatous and connective tissue-type cells
Receptor-mediated and nonreceptor (unregulated) endocytosis (basis of atherosclerosis
development)
Atherosclerosis is the variable combination of changes in arteries intimae, which consists of focal accumulation of lipids, complicated carbohydrates, blood substances, fibrous tissue and calcium, and associated with changes in media (WHO definition)
First experimental model of atherosclerosis was created on rabbits in 1913. Every day
within 3-4 months A.Anichkov added 10 g of Cholesterol in rabbits ration.
“Atherosclerosis is impossible without cholesterol”.
А.N.Аnichkov
Ways of LDL transport in the arterial wall
• 1. Nonspecific unregulated endocytosis
• 2. Through the intercellular channels of endothelial monolayer (action of adrenaline, noradrenaline, serotonin, angiotensin II, histamine)
• 3. Through the damaged endothelial monolayer (nicotine, autoimmune complexes, high blood pressure, turbulent blood flow, push of pulse wave, the tension shift)
Cholesterol metabolism violation
1. Hypercholesterolemia
2. Dislipoproteinemia
а) LDL concentration
b) Kch = (LDL+VLDL)/HDL (high coefficient correlates to higher probability of atherosclerosis)
Endothelium damage 1. Action of Hemodynamic
factorsа) arterial pressure stroke
volume blood push endotheliocytes
displacement and damage
b) Turbulent moving of blood(arch of aorta, bifurcation of
arteries, branching of arteries, winding section - in these places often formed
plaques)
2. Damage by immune complexes
ЕТHIOLOGY
Peculiarities Are produced- in blood- extra cellular space- in arterial wall
Modified LDL
Properties1. They do not interact with
аpоВ- and аpоЕ-receptors 2. They interact with “scavenger
– receptors ”. Entrance of LDL inside the cell results from the gradient concentration (uncontrolled еndocytosis)
3. Supply cholesterol in cells and stimulate put-off of cholesterol in artery walls
Peroxides modified LDL
LDL+Glucose
LDL+protein
LDL+Ig
LDL+glycosaminoglycan
Their accumulation promotes the forming of foam cells
There are persons who have normal concentration of LDL, but suffer from atherosclerosis!
Reducing of HDL concentration is important
Anti atherosclerosis role of HDL
1. Very easy penetration inside the intimae (due to apоprotein-А) and take out cholesterol
2. Reduce coming up of LDL inside endotheliocytes3. Retention of LDL damage by free radicals
4. Increase prostacyclin synthesis and and decrease thrombocytes aggregation
5. Decrease proliferation of the smooth muscle cells, which is induced by LDL
6. Decrease synthesis of glycosaminoglycans by smooth muscle cells
In the occurrence of atherosclerosis there are 4 defining mechanisms:
• 1. Hereditary factors (lipid metabolism associated with mutation of genes, which encoding receptor of cells to low-density lipoprotein: decreasing the quantity of receptors for LDL on the surface of hepatocytes or they are absent; hereditary hyperlipoproteinemy; deficiency of lipoprotein lipase, enzymes of β-oxidation of fatty acids; defects of NO-synthase genes, polymorphisms of genes encoding of angiotensinogen, angiotensin receptors, angiotensin-converting enzyme, and endothelin receptors to them, growth factor of platelets and fibroblasts).
• 2. Lipid metabolism disorders (increase level of total cholesterol above 5.2 mmol/l; serum cholesterol LDL above 4 mmol/l; decrease serum level of high density lipoprotein cholesterol below 0.9 mmol/l).
• 3. Changes in the vascular wall of arteries.• 4. Violation receptors of cells (E.I. Chazov, 1998).
Theories of atherosclerosis• 1. Hypothesis response
to injury
• 2. Monoclonal hypothesis
• 3. Lysosomal theory
Morphological stages of atherosclerosis1) lipid spots 2) fibrous plaques 3) complications: ulceration, calcification,
thrombosis
1 STAGE –
“FOAM CELLS” PATHOGENESIS
Macrophages have main role:
1. They have “scavenger”-
receptors so Cholesterol
comes in macrophage only
due to concentration
gradient
2. They can accumulate a lot
of Cholesterol inside the cell (process is
controlled by HDL)
3. Modified LDL stimulate
macrophages activity
1 STAGE –
“FOAM CELLS”
Migration of macrophage in intimae
Capture of LDL
Decrease of LDL
concentration in intimae
Many macrophages change into “foam cells”
Role of endotheliocytesThere is no deposit of LDL inside the endotheliocytes!!!!!!!!!а) Due to Аpо-В,Е-receptors entrants of LDL is controlledб) Using of scavenger receptors stimulates retroendocytosis
But!!!1. At hypercholesterolemia absorption of LDL is activated.
That causes endotheliocytes proliferation and accumulation of LDL in intimae.
2. Endothelium injury is common uncontrolled penetration of LDL inside the vessel wall.
3. On endothelium surface is activated lipoprotein lipase, which controls dissociation of VLDL into LDL and HDL
1 STAGE –
“FOAM CELLS”
Role of the smooth muscle cellsDeposit of LDL in intimae causes excretion of
hemotaxis factors by endotheliocytes, macrophages and fibroblasts. These substances conduce smooth muscle cell (SMC) hemotaxis into intimae (contractile cells have ability to change in secretory).
What do they do ???1. They absorb of LDL (they have Аpо-В and Аpо-Е
receptors)2. They proliferate (due to thrombocyte growth factor.
Their DNA synthesis activates and mitosis occurs)3. They synthesize collagen, elastin,
glycosaminoglucans (connective tissue matrix of plaque)
1 STAGE – “FOAM CELLS”
2 stage – LIPID SPOTS
They are formed on different parts of
arterial system (in elastic and elastic-muscle type of vessels):
They have different square in different age:
in aorta – 10 % in 10 years,
30-50% in 25-30 years
in coronary arteries are
appear in 15 years
in cerebral arteries are
appear in 35-45 years
There is proved that this stage can be reversible due to prolonged uncholesterol diet
Formation mechanismFoam cells overload by
cholesterol causes their damage. At this time hydrolytic lisosomal enzymes release, which causes necrosis of surround tissue.
2 stage – LIPID SPOTS
Contents of LIPID SPOTS:
- Foam cells
- Моnocytes/macrophages
- Smooth muscle cells
- Lymphocytes
- Free cholesterol
- Connective tissue
Main characteristic – don’t violate blood flow
3 stage – FIBROUS PLAQUE
Cholesterol and lisosomal enzymes
irritates intimae (because they are the foreign bodies)
Excreation of proliferation factors by macrophages, еndotheliocytes, lymphocytes and thrombocytes
SMC migration in intimae and active proliferation collagen and elastin (capsule that isolates place accumulation of cholesterol and damage of blood vessels by lysosomal enzymes)
characteristic- Contents: ЕChol, NEChol,
leavings of elastin and collagen, foam cells, Chol crystals, necrotic mass
- Vessel narrowing- Stage unalterable
- Partial regression (dilipidation) - diet without Cholesterol (150-160mg/dl) during 1,5-2 years
3 stage – FIBROUS PLAQUE
1. THROMBOSIS (due to endothelium
damage)
2. Ulceration(necrotic
disintegration content plaques leads to thinning of its walls)
3. Calcinations(deposit of insoluble
calcium salts)
4 stage - COMPLICATIONS
4 stage - COMPLICATIONS
Risk factors of atherosclerosis development• 1. Irreversible (endogenous)• Age (men over 40, women over 50 years)• Gender (male, anti-sclerotic effect of estrogen, cholesterol in the case of nonatherosclerotic α-
lipoprotein)• Genetic predisposition (sudden death, myocardial infarction or brain stroke in parents: at
age before 50 in men and before 55 in women)
• 2. Inverse (managed)• Smoking• Hypertension• Obesity
• 3. Potential or partially reverse• Hyperlipidemia - Hypercholesterolemia and / or hypertriglyceridemia• Hyperglycemia and diabetes mellitus• Low levels of high density lipoprotein
• 4. Other possible factors• Low physical activity• Emotional stress and / or personality type• Intoxication, infection
Thank you for your attention!
Top Related