Plan of the lecturePlan of the lecture• Disorders of peripheral blood flow Disorders of peripheral blood flow • MicrocirculationMicrocirculation

• Disorders of lymphocirculationDisorders of lymphocirculation• EdemaEdema• Definition of the concept of arterial hyperemia, etiology and Definition of the concept of arterial hyperemia, etiology and

pathogenesis, classification. Symptoms.pathogenesis, classification. Symptoms.• Etiology and pathogenesis of venous hyperemia (congestion), Etiology and pathogenesis of venous hyperemia (congestion),

etiology and pathogenesis, symptoms.etiology and pathogenesis, symptoms.• Definition of the concept of ischemia. Etiology, pathogenesis of Definition of the concept of ischemia. Etiology, pathogenesis of

ischemia, symptoms. ischemia, symptoms. • Concept of reperfusion syndrome, ischemic toxicosis. Concept of reperfusion syndrome, ischemic toxicosis. • Definition of stasis. Etiology. Pathogenesis. Definition of stasis. Etiology. Pathogenesis. Capillary (true) Capillary (true)

stasis. stasis. • Embolism. Embolism. Etiology. Pathogenesis.Etiology. Pathogenesis.• Thrombosis as a reason of peripheral circulation disorder. Thrombosis as a reason of peripheral circulation disorder.

Etiology and pathogenesis.Etiology and pathogenesis.

Actuality of the lectureActuality of the lecture Blood vessels function in the delivery of oxygen and nutrients

to the tissues and in the removal of waste products from the tissues. Unlike disorders of the respiratory system or central circulation that cause hypoxia and impair oxygenation of tissues throughout the body, the effects of blood vessel disease usually are limited to local tissues supplied by a particular vessel or group of vessels.

Disturbances in blood flow can result from pathologic changes in the vessel wall (i.e., atherosclerosis, vasculities), acute vessel obstruction caused by thrombus or embolus, vasospasm (i.e., Raynaud’s phenomenon), abnormal vessel dilation (i.e., arterial aneurysms or varicose veins), or compression of blood vessels by extravascular forces (i.e., tumors, edema, or firm surfaces such as those associated with pressure ulcers).

Disorders of peripheral Disorders of peripheral blood flow:blood flow:

systemic disorderssystemic disorders, which , which connecting with insufficiency of connecting with insufficiency of cardio-vascular system (disorders cardio-vascular system (disorders of general hemodynamic)of general hemodynamic)

disorders of local peripheral flowdisorders of local peripheral flow – it is disorders circulation of the – it is disorders circulation of the blood in organs and tissues. blood in organs and tissues.

• Local peripheral flow disorders distinguish on

two groups in dependence on vessels

size:

• 11 – disorders of microcirculationmicrocirculation – the diameter of vessels is less 100 micrometer,

• 22 – disorders of macrocirculationmacrocirculation – the diameter of vessels is more 100 micrometer.

Disorders of Disorders of microcirculationmicrocirculation

1) disorders of hemomicrocirculationhemomicrocirculation (in blood vessels)

2)2) lymphcirculation lymphcirculation (in lymphatic vessels).

Microcirculatory Microcirculatory bloodstream bloodstream consists of:consists of:

• arterioles, • precapillaries, • precapillary

sphincters, • capillaries, • postcapillaries, • venules, • small veins, • arteriovenular

anastomoses, • lymphatic vessels.

Reasons of disorders of Reasons of disorders of hemomicrocirculation:hemomicrocirculation:

1)1) intravascularintravascular disorders

2) disorders of structure and function of vascular wall (transmuraltransmural),

3) extravascular disorders.

Changes of viscosity and blood and lymph volume develop as a result of hemoconcentration and hemodilution.

Intravascular Intravascular disordersdisorders

accompanied by aggregation of accompanied by aggregation of erythrocytes, platelets and leukocytes. erythrocytes, platelets and leukocytes.

Aggregation of platelets.Aggregation of platelets.

Etiology.Etiology. Causes of aggregation of Causes of aggregation of plateletsplatelets::

concentration ADP (as result concentration ADP (as result destroying of cell),destroying of cell),

concentration catecholamines concentration catecholamines (stress, emotion),(stress, emotion),

accumulation in the blood free fatty accumulation in the blood free fatty acids,acids,

activation of cellular phospholipases,activation of cellular phospholipases, activation of FOL (free lipid oxidation),activation of FOL (free lipid oxidation), concentration FAP (factor of concentration FAP (factor of

activation platelets),activation platelets), acidosis, etc.acidosis, etc.

Pathogenesis.Pathogenesis. Any cause → lead to Any cause → lead to activationactivation of of membrane membrane phospholipase A2 phospholipase A2 → → hydrolysis of hydrolysis of phospholipids of platelets membranes and appendixes phospholipids of platelets membranes and appendixes are formed on membrane →are formed on membrane → contacting two cells by contacting two cells by these appendixes → aggregation of platelets.these appendixes → aggregation of platelets.

Aggregation of Aggregation of RBCRBC

Etiology.Etiology. amount of albumins in the blood,amount of albumins in the blood, amount of globulins,amount of globulins, concentration fibrinogens and fibrins in concentration fibrinogens and fibrins in

the blood,the blood, concentration of H+(hydrogen) ions → concentration of H+(hydrogen) ions →

acidosis,acidosis, concentration ADP (as result concentration ADP (as result

destroying of cell),destroying of cell), accumulation in the blood free fatty accumulation in the blood free fatty

acids,acids, activation of FOL, etc.activation of FOL, etc.

SludgeSludge Sludge is a phenomenon characterized by Sludge is a phenomenon characterized by adhesionadhesion, ,

aggregation aggregation andand agglutination agglutination of blood cells which causes of blood cells which causes blood to disintegrate into conglomerates of erythrocytes, blood to disintegrate into conglomerates of erythrocytes, leukocytes, thrombocytes and plasma and induces leukocytes, thrombocytes and plasma and induces microcirculation disturbances.microcirculation disturbances.

Pathogenesis.Pathogenesis. Any cause lead to change membrane charge Any cause lead to change membrane charge from negative to positive on erythrocytes, and on from negative to positive on erythrocytes, and on endothelium vice versa. It is caused to electrostatic endothelium vice versa. It is caused to electrostatic relationship of these cells and aggregation of them. relationship of these cells and aggregation of them.

May be formed May be formed sludgesludge of erythrocytes: of erythrocytes:• classicalclassical (more than 100 erythrocytes), (more than 100 erythrocytes), • dextrindextrin• amorphousamorphous (3-4 erythrocytes). (3-4 erythrocytes).

Aggregation of Aggregation of leukocytesleukocytes

Etiology.Etiology. Causes are similar to causes of aggregation Causes are similar to causes of aggregation

of erythrocytes and platelets, plus of erythrocytes and platelets, plus most strong most strong factorfactor – – microorganisms and theirs toxinsmicroorganisms and theirs toxins..Pathogenesis.Pathogenesis.

Any cause → activation of Any cause → activation of phospholipase phospholipase A2 A2 → hydrolysis of phospholipids of → hydrolysis of phospholipids of leukocytes → production leukocytes → production arachidonic acid arachidonic acid → → creation the creation the leukotrienes leukotrienes under the action of under the action of lipoxygenaselipoxygenase..

Conclusion:Conclusion: aggregation of blood cells causes aggregation of blood cells causes to narrowing of lumen of vessels or their to narrowing of lumen of vessels or their occlusion.occlusion.

Disorders of structure and function of Disorders of structure and function of vascular wall vascular wall (TransmuralTransmural)

related with edema and destroying components of vascular structure: endothelium cells, basement membrane, connective tissue.

It leads to narrowing of lumen of vessels or their occlusion, disorders of hematocellular barriers → damage of cells, trophic disturbances.

Transmural disturbances are Transmural disturbances are subdivided into two categories:subdivided into two categories:

Transmural disturbances are Transmural disturbances are subdivided into two categories:subdivided into two categories:

1) 1) permeabilitypermeability disturbances disturbances 2) 2) emigrationemigration disturbances. disturbances.

Increased permeabilityIncreased permeability of microvascular walls activates the of microvascular walls activates the mechanisms of fluid transfer: mechanisms of fluid transfer:

filtrationfiltration (fluid transport according to hydrostatic pressure (fluid transport according to hydrostatic pressure gradient); gradient);

diffusiondiffusion (fluid transport which does not involve any energy (fluid transport which does not involve any energy losses); losses);

osmosisosmosis directed fluid diffusion according to osmotic pressure directed fluid diffusion according to osmotic pressure gradient).gradient).

Decreased permeabilityDecreased permeability Causes: thickening and/or induration of the vascular walls, or Causes: thickening and/or induration of the vascular walls, or

disturbances of energy supply of intracellular processes.disturbances of energy supply of intracellular processes. Consequences.Consequences. Decreased efficiency of fluid transfer Decreased efficiency of fluid transfer

mechanisms: filtration, diffusion, transcytosis, osmosis.mechanisms: filtration, diffusion, transcytosis, osmosis.

Extravascular disturbances of Extravascular disturbances of microcirculationmicrocirculation Increased Increased or or decreased decreased

volume of intracellular volume of intracellular fluid fluid which results in its which results in its slower flow slower flow into into microcirculatory vesselsmicrocirculatory vessels

Extracellular disorders Extracellular disorders are caused by structural are caused by structural and functional changes of and functional changes of components of connective components of connective tissue surround the vessels.tissue surround the vessels.

The The main role main role of this of this disorders played disorders played tissue tissue basophilesbasophiles (mast cells) (mast cells) and their and their degranulation.degranulation. It It has some granules of has some granules of biological activity biological activity substances: substances: histamine, histamine, heparin and serotonin.heparin and serotonin.

Causes of degranulation: ADP, LT Causes of degranulation: ADP, LT B4, complex antigen-antibody, B4, complex antigen-antibody, products of activating complements, products of activating complements, mechanical trauma, etc.mechanical trauma, etc.

Effects of histamine:Effects of histamine:Effects of histamine:Effects of histamine:• 1) 1) increase a permeability of increase a permeability of

vascular wallvascular wall (edema and (edema and contraction of endothelium cell) → contraction of endothelium cell) → increase extravascular oncotic increase extravascular oncotic pressurepressure,,

• 2) 2) edemaedema,,• 3) 3) pain or itchpain or itch – caused by – caused by

irritation of nervous receptors irritation of nervous receptors by by histamine,histamine,

• 4) 4) dilatation or constrictiondilatation or constriction blood blood vessels – vessels – HH22 (histamine) or (histamine) or HH11--receptors accordingly receptors accordingly (correspondingly, conformably,(correspondingly, conformably, suitably).suitably).

SerotoninSerotonin has similar effects + it has similar effects + it lead to venules constriction, that lead to venules constriction, that increase the hydrostatic pressure increase the hydrostatic pressure (hydrostatic load) in capillaries.(hydrostatic load) in capillaries.

HeparineHeparine –anticoagulative action → –anticoagulative action → may be a cause of bleeding may be a cause of bleeding (haemorrhage).(haemorrhage).

Exposed collagen Exposed collagen of basic membrane of basic membrane of vascular wall is of vascular wall is initiator of adhesion initiator of adhesion and and aggregationaggregation of platelets. of platelets.

Disorders of Disorders of lymphcirculationlymphcirculation

It is a typical pathological process, what characterized by It is a typical pathological process, what characterized by accumulation of lymph in tissues and development of lymphatic accumulation of lymph in tissues and development of lymphatic edema (edema (elephantiasiselephantiasis).).

Pathogenesis.Pathogenesis. Mechanisms of disorders of lymphcirculation: Mechanisms of disorders of lymphcirculation: 1) mechanical 1) mechanical – related to compression of lymphatic vessels (by – related to compression of lymphatic vessels (by

tumors, scars, edema) and their obstruction (by tumors cells, tumors, scars, edema) and their obstruction (by tumors cells, bacteria's, foreign body).bacteria's, foreign body).

2)2) akineticakinetic (hypokinetic) caused with decrease constriction (hypokinetic) caused with decrease constriction property of lymphatic vessels. We have this on disorders of property of lymphatic vessels. We have this on disorders of diaphragms or disorders of suction action of thorax.diaphragms or disorders of suction action of thorax.

3) dynamical3) dynamical caused by excessive production of intercellular caused by excessive production of intercellular liquids (diseases of heart, kidneys).liquids (diseases of heart, kidneys).

4) resorptive4) resorptive mechanism – it is disorders of drainage function of mechanism – it is disorders of drainage function of lymphatic vessels, in the presence of normal amount of lymph. lymphatic vessels, in the presence of normal amount of lymph. It causes by increase of colloid-osmotic pressure of intercellular It causes by increase of colloid-osmotic pressure of intercellular liquids (inflammation, allergy).liquids (inflammation, allergy).

ElephantiasisElephantiasisImpaired lymphatic drainage and Impaired lymphatic drainage and consequent consequent lymphedemalymphedema is usually is usually localized; it can result from inflammatory localized; it can result from inflammatory or neoplastic obstruction. For example, or neoplastic obstruction. For example, the parasitic infection the parasitic infection filariasisfilariasis can can cause extensive inguinal lymphatic and cause extensive inguinal lymphatic and lymph node fibrosis. The resultant lymph node fibrosis. The resultant edema of the external genitalia and edema of the external genitalia and lower limbs can be so massive as to lower limbs can be so massive as to earn the appellation earn the appellation elephantiasiselephantiasis..

LymphedemaLymphedemaa. Protein-rich fluida. Protein-rich fluidb. Non-pitting edemab. Non-pitting edema

The term The term edemaedema signifies signifies increased increased fluid fluid in the in the interstitial tissue interstitial tissue spacesspaces;

fluid collections in different body fluid collections in different body cavities are variously designated cavities are variously designated ::

AnasarcaAnasarca is a severe and is a severe and generalized edema with profound generalized edema with profound subcutaneous tissue swelling. subcutaneous tissue swelling.

hydrothorahydrothoraxx

hydropericardihydropericardiumum

HydroperitoneuHydroperitoneumm

(ascites)(ascites)

Increased hydrostatic pressureIncreased hydrostatic pressure, caused by a , caused by a reduction in venous return (as in heart failure).reduction in venous return (as in heart failure).

Decreased colloid osmotic pressureDecreased colloid osmotic pressure, caused by , caused by reduced concentration of plasma albumin (due to reduced concentration of plasma albumin (due to

☼ ☼ decreased synthesisdecreased synthesis, as in liver disease, , as in liver disease,

☼ ☼ increased lossincreased loss, as in kidney disease)., as in kidney disease).Lymphatic obstructionLymphatic obstruction that that impairs interstitial fluid impairs interstitial fluid

clearance clearance (as in scarring, tumors, or certain infections).(as in scarring, tumors, or certain infections).Primary renal sodium retention Primary renal sodium retention (in renal failure).(in renal failure).Increased vascular permeability Increased vascular permeability (in inflammation) (in inflammation)

Pathophysiologic Categories of EdemaPathophysiologic Categories of Edema

Impaired venous Impaired venous returnreturn•Congestive heart Congestive heart failurefailure•Constrictive Constrictive pericarditispericarditis•Ascites (liver Ascites (liver cirrhosis) cirrhosis) •Venous obstruction Venous obstruction or compressionor compression   ☼ ThrombosisThrombosis ☼ External External pressure (e.g., mass)pressure (e.g., mass)      ☼   Lower extremity Lower extremity inactivity with inactivity with prolonged prolonged dependencydependencyArteriolar dilationArteriolar dilation•    HeatHeat•    Neurohumoral Neurohumoral dysregulationdysregulation

Increased Increased Hydrostatic Hydrostatic

PressurePressure

•Protein-losing Protein-losing glomerulopathies glomerulopathies (nephrotic syndrome)(nephrotic syndrome)•Liver cirrhosis Liver cirrhosis (ascites)(ascites)•MalnutritionMalnutrition•Protein-losing Protein-losing gastroenteropathygastroenteropathy

Reduced Reduced PlasmaPlasma Osmotic Pressure Osmotic Pressure (Hypoproteinemia)(Hypoproteinemia)

•InflammatoryInflammatory•NeoplasticNeoplastic•PostsurgicalPostsurgical•PostirradiationPostirradiation

Lymphatic Lymphatic ObstructionObstruction

Excessive salt intake Excessive salt intake with renal with renal insufficiencyinsufficiencyIncreased tubular Increased tubular reabsorption of sodiumreabsorption of sodium☼ ☼ Renal hypoperfusionRenal hypoperfusion☼ ☼ Increased renin-Increased renin-angiotensin-angiotensin-aldosterone secretionaldosterone secretion

Sodium RetentionSodium Retention

•Acute Acute inflammationinflammation•Chronic Chronic inflammationinflammation•AngiogenesisAngiogenesis

InflammationInflammation

Factors Factors affecting affecting

fluid balance fluid balance across across

capillary capillary wallswalls

• Capillary hydrostatic and osmotic forces are normally balanced so that there is no net loss or gain of fluid across the capillary bed. • However, increased hydrostatic pressure or diminished plasma osmotic pressure leads to a net accumulation of extravascular fluid extravascular fluid

(edema). (edema). • As the interstitial fluid pressure increases, tissue lymphatics remove much of the excess volume, eventually returning it to the circulation via the thoracic duct. • If the ability of the lymphatics to drain tissue is exceeded, persistent tissue edema results.

Non-pitting edema:Non-pitting edema: is often referred to as lymphedema which is a disturbance is often referred to as lymphedema which is a disturbance

of the lymphatic system;of the lymphatic system; can develop after systemic tissue such as after a can develop after systemic tissue such as after a

mastectomy;mastectomy; does not respond to diureticsdoes not respond to diuretics protein-rich fluid.protein-rich fluid. Pitting edema:Pitting edema: Is the classical, most common type observed in clinic;Is the classical, most common type observed in clinic; Generally responds to diuretic therapy;Generally responds to diuretic therapy; Common causes include nephrotic syndrome, congestive Common causes include nephrotic syndrome, congestive

heart failure (right side HF due to heart failure (right side HF due to hydrostatic pressure hydrostatic pressure)), , cirrhosis (due to cirrhosis (due to oncotic pressure), pregnancy, idiopathic oncotic pressure), pregnancy, idiopathic and nutritional edema. and nutritional edema.

GlycosaminoglycansGlycosaminoglycansa. a. in hyaluronic acid and chondroitin in hyaluronic acid and chondroitin sulfatesulfateb. Non-pitting edema called b. Non-pitting edema called myxedemamyxedema

Applying pressure to the swollen Applying pressure to the swollen area causes an indentation that area causes an indentation that presents for some timepresents for some time

Disorders of macrocirculation Disorders of macrocirculation 100 mcm

• There are 6 types:

1. Arterial hyperemia.

2. Venous hyperemia.

3. Ischemia.

4. Stasis.

5. Thrombosis.

6. Embolism.

Arterial (active) Arterial (active) hyperemiahyperemia

Arterial hyperemia – pathological or physiological states, which are characterized by local increasing of local increasing of blood inflow blood inflow from arterial vessels to microcirculation.

The causes of arterial hyperemias can The causes of arterial hyperemias can be of various etiology and nature be of various etiology and nature

► Origin resulting from Origin resulting from endogenousendogenous and and exogenousexogenous agents.agents.

► Exogenous agentsExogenous agents::

► Endogenous factorsEndogenous factors, resulting in arterial , resulting in arterial hyperemia form in the organisms:hyperemia form in the organisms:

1)1) salt salt and and concrementconcrement deposits in the tissues of deposits in the tissues of kidneys, liver, subcutaneous fat;kidneys, liver, subcutaneous fat;

2)2) formation of formation of BASBAS causing the reduction of the tone causing the reduction of the tone of smooth muscle of arterioles (vasodilatation), of smooth muscle of arterioles (vasodilatation), adenosine, prostaglandin, kinines; adenosine, prostaglandin, kinines;

3)3) accumulation of accumulation of organic acids organic acids (lactic, pyruvic, (lactic, pyruvic, ketoglutaric).ketoglutaric).

Infectious Infectious (microorganisms and/or their (microorganisms and/or their

endo- and exotoxins) endo- and exotoxins) Noninfectious factors Noninfectious factors

of various natureof various nature

• By etiological agent:By etiological agent:

1)

2)

3)

mechanical exposuremechanical exposure

very high tvery high t00

electric currentelectric current

Biological agentBiological agent

organic and inorganic acidsorganic and inorganic acids

alkalialkali

aldehydesaldehydes

alcoholalcohol

nitrogen oxidenitrogen oxide

acetylcholineacetylcholine

adenosineadenosine

physiologically physiologically active substances active substances

forming in the bodyforming in the body

Chemical agentChemical agent

Physical agentPhysical agent

Classification and Classification and mechanismsmechanisms

I. Physiological arterial hyperemia: Physiological arterial hyperemia:• 1) working1) working – organ hyperfunction (muscle, – organ hyperfunction (muscle,

intestine, etc)intestine, etc)• 2) emotional (psychogenic) 2) emotional (psychogenic) – its conditional – its conditional

reflex (shame, excitement, confusion)reflex (shame, excitement, confusion)• 3) reactive (substitute3) reactive (substitute) ) – – hyperemia after hyperemia after

short-term (transitory) ischemia.short-term (transitory) ischemia.II. Pathological arterial hyperemia: II. Pathological arterial hyperemia: • 1) neurogenic (neurogenous):1) neurogenic (neurogenous):- a) neurotonic a) neurotonic - b) neuroparalytic b) neuroparalytic • 2) metabolic.2) metabolic.

Are caused by stimulation of:Are caused by stimulation of:

β-adrenorecetors,

M-cholinoreceptors,

H2-histaminoreceptors,

activation of parasympathetic nervous system,

irritation of vascular-dilatators part of vascular center or inhibition of vascular-constrictor part of this center.

• It is characterized by predominance of the It is characterized by predominance of the parasympathetic nervous system effects (in parasympathetic nervous system effects (in comparison with the sympathetic one) on comparison with the sympathetic one) on arterial vascular walls.arterial vascular walls.

Neurotonic arterial Neurotonic arterial hyperemiahyperemia

Neurotonic arterial Neurotonic arterial hyperemiahyperemia

Neuroparalytic arterial hyperemia• Are caused by damage or

blockage of α-adrenoreceptors sympathetic

nervous system. • As usual tone of vessels is

supplied by the impulses from sympathetic nerves sympathetic nerves (1-3 impulses for a second) to smooth muscle cell of vascular wall.

• It is characterized by It is characterized by reduction or absence reduction or absence (paralysis) of the (paralysis) of the sympathetic sympathetic nervous systemnervous system effects on the effects on the walls of the arteries and walls of the arteries and arterioles.arterioles.

Examples:Examples:

- Pathological arterial hyperemia of the brain in - Pathological arterial hyperemia of the brain in hypertensive crisis.hypertensive crisis.

- According to the - According to the neuromyoparalytic mechanism:neuromyoparalytic mechanism: in the organs of the abdominal cavity after ascites, in the organs of the abdominal cavity after ascites, in the skin and muscles after a tight in the skin and muscles after a tight tourniquet is tourniquet is

removedremoved; ; at the site of chronic inflammation; at the site of chronic inflammation; at the site which was exposed to heat for some at the site which was exposed to heat for some

hours (sun heat, hot-water bottle; mustard plaster hours (sun heat, hot-water bottle; mustard plaster application); application);

in the area of sympathetic denervation.in the area of sympathetic denervation.

Appears under the action different chemical factors, which cause microparalysis of vessels independently from nervous influences.

1)1) inorganic substancesinorganic substances (increase a concentration of potassium, (increase a concentration of potassium, hydrogen, carbon dioxide, decrease the NO-factors) hydrogen, carbon dioxide, decrease the NO-factors)

2) metabolic substances (prostaglandins, kinines, histamine, ADP),

3) substances from necrotic places.

• Humoral mechanismHumoral mechanism. It is characterized by a locally increased content of vasodilators – biologically active substances having a vasodilatating effect (adenosine, NO, PgE, kinines) and by increased sensitivity of receptors of arterial vascular walls to vasodilators.

• Metabolic and oxygen supply disorders may cause hypertrophy and hyperplasia.

TheThe effects of arterial hyperemia areeffects of arterial hyperemia are:: the increase of blood flow speed, the increase of blood flow speed, the increase of functioning capillaries amount, the increase of functioning capillaries amount, the rise of blood pressure, strengthens of the the rise of blood pressure, strengthens of the tissues oxygenation. tissues oxygenation.

• Arterial hyperemiaArterial hyperemia promotes: promotes: the derivation of the oxygen radicals for the protection of the the derivation of the oxygen radicals for the protection of the

organism against the microorganisms, organism against the microorganisms, forming of humoral plasma factors of the organism protection forming of humoral plasma factors of the organism protection

(complement, properdine, fibronectine), (complement, properdine, fibronectine), causes the movement of leucocytes into the area of injury. causes the movement of leucocytes into the area of injury. Arterial hyperemiaArterial hyperemia causes the causes the redness and warmthredness and warmth of the of the

injurious area injurious area (higher metabolic intensity).(higher metabolic intensity).

Venous hyperemiaVenous hyperemiaVenous hyperemiaVenous hyperemiaVenous hyperemiaVenous hyperemia – local or systemic decreasing – local or systemic decreasing of blood outflow from microcirculation.of blood outflow from microcirculation.

Causes:Causes:intravascular factorsintravascular factors – thrombosis, embolism, foreign bodies – thrombosis, embolism, foreign bodies etc.etc.extravascular factorsextravascular factors – compression the vessels by tumors, – compression the vessels by tumors, scars, enlargement organs (uterus with fetus).scars, enlargement organs (uterus with fetus).congenitalcongenital (innate) and (innate) and acquiredacquired defects of structure of defects of structure of vascular wall of venues (connective and muscular tissues).vascular wall of venues (connective and muscular tissues).generalized disordersgeneralized disorders of blood flow connect with heart failure. of blood flow connect with heart failure.

Consequences:Consequences: dystrophic changes, atrophy, excessive growth dystrophic changes, atrophy, excessive growth of the connective tissue, cirrhosis, phlebosclerosis.of the connective tissue, cirrhosis, phlebosclerosis.

Features:Features:

under microscope:under microscope: increase of lumen capillaries, increase of lumen capillaries, postcapillaries, venules; postcapillaries, venules; blood flow speed decrease, blood flow speed decrease, diapedesis (diapiresis, diapedesis (diapiresis, migration).migration).

Physiological and Physiological and clinical sings:clinical sings: • edema, edema, • cyanosis, cyanosis, • enlargement and enlargement and decrease decrease temperature of the temperature of the organ, organ, • inhibition of inhibition of metabolic processes, metabolic processes, • decrease of tissue decrease of tissue turgor.turgor.

Pathogenetic effects of Pathogenetic effects of venous hyperemiavenous hyperemia

The major pathogenic factors are:The major pathogenic factors are: • HypoxiaHypoxia (of circulatory type at the initial stage of the (of circulatory type at the initial stage of the

process and of mixed type when the process is long-process and of mixed type when the process is long-term), term),

• Tissue edemaTissue edema (resulting from increased (resulting from increased hemodynamic pressure on the wall of venules and hemodynamic pressure on the wall of venules and veins).veins).

• Tissue hematomasTissue hematomas (resulting from overdistension (resulting from overdistension and rupture of postcapillary and venular walls) and and rupture of postcapillary and venular walls) and hemorhages hemorhages (external and internal).(external and internal).

• Consequences:Consequences: reduction of specific and non-specific reduction of specific and non-specific functions of organs and tissues, hypotrophy and functions of organs and tissues, hypotrophy and hypoplasia of structural elements in tissues and hypoplasia of structural elements in tissues and organs, necrosis of parenchymatous cells and organs, necrosis of parenchymatous cells and connective tissue development (sclerosis, cirrhosis) in connective tissue development (sclerosis, cirrhosis) in organs.organs.

IschemiaIschemia IschemiaIschemia – is an imbalance between the supply of tissues – is an imbalance between the supply of tissues

with arterial blood flow and their need in it.with arterial blood flow and their need in it. The need in blood The need in blood supply always exceeds actual amount of blood flowing through arteries.supply always exceeds actual amount of blood flowing through arteries.

EtiologyEtiology According to its nature:According to its nature:1) 1) Physical factorsPhysical factors are compression of arterial vessels (e.g. by tumors, scar are compression of arterial vessels (e.g. by tumors, scar

tissue, foreign bodies, tourniquets), narrowing or blocking of a lumen from tissue, foreign bodies, tourniquets), narrowing or blocking of a lumen from inside (e.g. by a thrombus, embolus, atherosclerotic plaque), exposure to inside (e.g. by a thrombus, embolus, atherosclerotic plaque), exposure to extremely cold temperatures.extremely cold temperatures.

2) 2) Chemical factorsChemical factors. Many chemical compounds can stimulate contractions . Many chemical compounds can stimulate contractions of smooth muscle of arterial vessels and cause constriction of their lumen. of smooth muscle of arterial vessels and cause constriction of their lumen.

Examples:Examples: nicotine, a number of medicines (mezatone, ephedrine, nicotine, a number of medicines (mezatone, ephedrine, adrenaline derivatives, alcohol dehydrogenase, angiotensin).adrenaline derivatives, alcohol dehydrogenase, angiotensin).

3) 3) Biological factorsBiological factors:: biologically active substances having vasoconstrictive biologically active substances having vasoconstrictive effects effects (e.g. catecholamines, angiotensin II, alcohol dehydrogenase, (e.g. catecholamines, angiotensin II, alcohol dehydrogenase, endothelin), endothelin), biologically active substances of microbic origin, their exo- biologically active substances of microbic origin, their exo- and endotoxins, metabolites having a vasoconstrictive effect.and endotoxins, metabolites having a vasoconstrictive effect.

According to its origin:According to its origin:1)1) endogenousendogenous2)2) exogenous (infectious and noninfectious).exogenous (infectious and noninfectious).

PathogenesisPathogenesis There are three There are three

mechanisms of development mechanisms of development ischemia:ischemia:

compressivecompressive – compression of – compression of arterial vessels by tumors, arterial vessels by tumors, scars, ligatures, etc.scars, ligatures, etc.

obturativeobturative – occlusion of – occlusion of lumen vessels by thrombus, lumen vessels by thrombus, embolus, etc. embolus, etc.

angiospasticangiospastic – spasm of – spasm of vessels after excitation α-vessels after excitation α-adrenoreceptors or Hadrenoreceptors or H11--receptors, under the influences receptors, under the influences of vasopressin (antidiuretic of vasopressin (antidiuretic hormone), TxAhormone), TxA22, endotelin‑1, , endotelin‑1, angiotensin II, Pg Hangiotensin II, Pg H22, F, F22α, Gα, G22, , Lt BLt B44, C, C44, D, D44, E, E44..

There are three stages in There are three stages in pathogenesis of ischemiapathogenesis of ischemia.. 1) disoders of energetic metabolism1) disoders of energetic metabolism, as result of , as result of

activation of anaerobic oxidation with produce lactic activation of anaerobic oxidation with produce lactic and pyruvic acids, disorders of Kreb's cycle and and pyruvic acids, disorders of Kreb's cycle and phosphorylative processes with phosphorylative processes with insufficiency of ATP, insufficiency of ATP, development of acidosis.development of acidosis.

2) disorders energetic depending processes on the 2) disorders energetic depending processes on the cell.cell. That displays by disorders specific function of cell That displays by disorders specific function of cell (traction, transport, secretory), disorders of electrolytic (traction, transport, secretory), disorders of electrolytic pumps, activation of membranes phospholipases → pumps, activation of membranes phospholipases → destruction of membrane and cell organels, decrease destruction of membrane and cell organels, decrease production of albumins. All this processes finished by production of albumins. All this processes finished by necrobiotic changes and necrobiotic changes and formed regions of necrosisformed regions of necrosis..

3) activation production some elements of connective 3) activation production some elements of connective tissue:tissue: collagen, glycoproteins, etc. Than collagen, glycoproteins, etc. Than activate activate sclerotic processessclerotic processes of necrosis hotbed. of necrosis hotbed.

ClubbingClubbing is caused by decreased oxygenation, which leads to fibrous tissue hyperplasia in the area between the nail and distal portion of each digit, associated with lymphocytic extravasation, increased vascularity, and edema.

Stasis – Stasis – decrease or stop blood flow in capillaries, small arteries and venues

Distinguish some types of stasis:• ischemic• venous• capillary (primary)

• Reasons of capillary stasisReasons of capillary stasis: 1) physical (high – more than 80ºC, and low less than -7ºC temperature), 2) chemical (poisons, turpentine, mustard oil), 3) biological (toxins of microorganisms).

• Pathogenesis.Pathogenesis. Capillary stasis is caused by aggregation of blood cells, edema of endothelium cells, blood flow decreased, clotting of blood as result of increase of permeability of vascular walls (under the action of histamine, serotonin, heparin)

• The final stage of stasis involves the process of aggregation and agglutination of the corpuscular elements of blood which results in blood thickening and its fluidity reduction. This process is activated by proaggregants, cations and high molecular weight proteins.

are caused by accordingly ischemia and are caused by accordingly ischemia and venous hyperemiavenous hyperemia

Manifestations of stasisManifestations of stasis• reduction of the inner diameter in ischemic stasis;• increase of the lumen of vessels of microcirculation in

congestive stasis;• increased number of aggregates of blood corpuscles in the

lumen of vessels and on their walls;• microhemorrhages (more often in congestive stasis).

The consequences of stasis.* When agents causing stasis are quickly withdrawn blood flow in the vessels of microcirculation is restored without entailing any noticeable changes in tissues.* Prolonged stasis results in dystrophyc changes in tissues (quite often to death of a tissue site or an organ).

Embolus and embolism

• Embolism – is a pathological processes, which characterized by traveling of free bodies (embolus) in the vessels. An embolus is a substance that circulates from one location in the body to another, through the bloodstream.

• By origin emboles: 1) exogenous (air, gas, foreign bodies, bacteria etc) 2) endogenous (thrombus, amniotic fluids, fat, tumor

cells etc.)• There are three main types of embolism:There are three main types of embolism: 1) embolism of lesser [pulmonarypulmonary] circulation,2) embolism of greater [systemicsystemic] circulation,3) embolism of portal veinportal vein.

Embolism of pulmonary circulationEmbolism of pulmonary circulation• Embols that originate in the venous circulation,

such as from deep vein thrombosis, travel to the right side of the heart to the pulmonary circulation and eventually causing pulmonary infarction and even death.

• This syndrome characterized by:1) generalized spasm of vessels pulmonary

circulation → acute hypertension into pulmonary circulation and develop acute insufficiency of right heart;

2) abrupt decrease of blood pressure in systemic circulation, as result of decreasing cardiac output and general peripheral resistance;

3) disorders of external respiration → develop of respiratory failure.

Embolism of systemic circulationEmbolism of systemic circulation• Reasons: often is a thrombus,

what is formed in the left side of heart (as result of coarctation of aorta, aortic aneurysm, fibrillation, operation on the heart and artificial valves), air or fat emboli.

• Consequences depend on thrombus location.

• Coronary artery → infarction of heart; • renal artery → infarction of

kidney; • arteries of lower extremities → gangrene, etc.

Embolism of portal veinEmbolism of portal vein

Characterized by development of portal hypertension, that displays by triad signtriad sign:

1)1) ascitesascites, (abdominal [peritoneal] dropsy),

2)2) capute medusaecapute medusae – varicose veins of front wall of abdomen, veins of gullet (esophagus), and rectal veins,

3)3) splenomegalysplenomegaly.

• Tumor embolismTumor embolism is the way in which malignant tumors spread from the site of origin to distant metastatic sites using the bloodstream.

• The malignant tumor infiltrates through the wall of blood vessels (usually a venule or vein) at the primary site to occupy the lumen, and clumps of tumor cells break off and are carried in the venous system until they reach a vessel too small to permit further passage, than impact there and often grow to produce a distant metastasis.

• Fat and bone marrow embolismFat and bone marrow embolism may occur following severe fracture trauma of bones, fragments of fat released from traumatized adipocytes is the fatty bone marrow may enter the blood circulation through thin-walled veins torn by the fracture trauma.

• They pass trough the venous system to the right side of the heart, and then via pulmonary arteries to the lung capillaries, where some are trapped.

Embolism Embolism

Tumor embolus in the main pulmonary artery

EmbolisEmbolismm

• Air embolismAir embolism is usually due to accidental is usually due to accidental pumping of air into the venous circulation pumping of air into the venous circulation during intravenous injection or transfusion. If during intravenous injection or transfusion. If large quantities of air mixed with blood enter large quantities of air mixed with blood enter the right atrium, a bloody froth is formed and the right atrium, a bloody froth is formed and the patient may suffer cardiac arrest. the patient may suffer cardiac arrest.

• In deep-sea divers, inhaled air may dissolve In deep-sea divers, inhaled air may dissolve into the plasma due to the increased into the plasma due to the increased pressure at great depths, only to reform into pressure at great depths, only to reform into bubles of gasbubles of gas (gas embolismgas embolism) within the within the circulation if the diver comes to the surface circulation if the diver comes to the surface too quickly. This decompression sickness too quickly. This decompression sickness and embolization of the bubbles of mainly and embolization of the bubbles of mainly nitrogen gas may occlude small vessels, nitrogen gas may occlude small vessels, leading to widespread anoxia of tissues, and leading to widespread anoxia of tissues, and even death.even death.

• Amniotic fluid embolismAmniotic fluid embolism may occur rarely may occur rarely during childbirth; some of the amnoiotic fluid during childbirth; some of the amnoiotic fluid (containing fetal cells from the skin surface) (containing fetal cells from the skin surface) may enter the maternal circulation through may enter the maternal circulation through the exposed and bleeding placental bed in the exposed and bleeding placental bed in the uterus. The material passes in the the uterus. The material passes in the venous circulation to the lung capillaries and venous circulation to the lung capillaries and may cause acute alveolar wall damage and may cause acute alveolar wall damage and disseminated intravascular coagulation.

Retrograde Retrograde embolism:embolism: embolism of a vein by an embolus carried in a direction direction opposite opposite to that of the normal blood current, after being diverted into a smaller vein.

SYN: venous embolism.

• ThrombosisThrombosis – is a life-time processes to produce of thrombus in the vessel's lumen. A thrombus is a blood clot, consisting of platelets, fibrin, and a red and white blood cells, that forms anywhere within the vascular system, such as the arteries, veins, heart chambers or heart valves.

Three conditions, known as Three conditions, known as Virchow's triad, promote Virchow's triad, promote thrombus formation:thrombus formation:1) Endothelial injury,2) Alterations in laminar blood flow (slugging blood flow : hanges in laminar flow, turbulence → arterial thrombosis, changes to stasis of flow → venous thrombosis)3) Increased coagulability or decreased activity of anticoagulative and fibrinolytic systems.

Types of Types of thrombusthrombus

• Parietal [mural thrombosis] and obstructiveParietal [mural thrombosis] and obstructive.• White, red and mixed [complex]White, red and mixed [complex]There are There are two phases two phases of blood clotting: of blood clotting: 1) cellular, 2) plasmatic.• Cellular phase consist of of platelets.

• Plasmatic phase consist of several successive [consecutive, cascade] reactions, results of which is creation of fibrin fibrin

aadhesiondhesion,, aaggregationggregation,, aagglutinationgglutination

ThrombusThrombus Blood Clot Blood Clot (Postmorten)(Postmorten)

ConsistencyConsistency Dry and FriableDry and Friable Moist and Jelly-likeMoist and Jelly-like

SurfaceSurface Granular and RoughGranular and Rough Smooth and glisteningSmooth and glistening

ColorColor White and BuffWhite and Buff Intense red or yellowIntense red or yellow

LocationLocation IntravascularIntravascularExtravascular or Extravascular or intravascular intravascular (postmorten)(postmorten)

EndotheliumEndothelium Damaged/injuredDamaged/injured UndamagedUndamaged

CompositionCompositionPlatelets (primarily)Platelets (primarily)FibrinFibrinRBCs and WBCsRBCs and WBCs

Lacks plateletsLacks plateletsFibrin (primarily)Fibrin (primarily)RBCs and WBCsRBCs and WBCs

Rapidity of blood Rapidity of blood flowflow

Formed in flowing Formed in flowing stream of bloodstream of blood

Formed in stagnant Formed in stagnant column of bloodcolumn of blood

Lines of ZahnLines of Zahn PresentPresent AbsentAbsent

ShapeShape Has shapeHas shape Lacks shapeLacks shape

Attached to the Attached to the vessel wallvessel wall yesyes nono

OrganizationOrganization May be partially May be partially organizedorganized No organizationNo organization

Consequences Consequences of thrombosisof thrombosis

- ischemia, ischemia, - necrosis, necrosis, - trophic disorders, trophic disorders, - recanalization, recanalization, - septic melting septic melting

[dissolution], [dissolution], - calcification etc.calcification etc.

Literature• Robbins and Cotran Pathologic Basis of Disease 9th

edition./ Kumar, Abbas, Fauto. – 2013. – Chapter 2. • General and clinical pathophysiology. Edited by prof. A.V.

Kubyskin. Simferopol. – 2011. • Essentials of Pathophysiology: Concepts of Altered Health

States (Lippincott Williams & Wilkins), Trade paperback (2003) / Carol Mattson Porth, Kathryn J. Gaspard. – Ch. 9.

• Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasic // Elsevier Inc. – 2010.

• Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin.– New York, Milwaukee. – 2009.

• Pathophysiology, N.K. Symeonova. Kyiv, AUS medicine Publishing. – 2010.

Manage your Time..!