Lecture # 4

General medicine Faculty

Pathology of blood circulation.

(Edema, hyperemia, ischemia, hemorrhage,

thrombosis, embolism).

Prepared by:

Associate Professor,

Ph.D. R. Deev

M.Mavlikeev. MD Kazan, 2018

• Edema

• Anasarca

• Hydrotorax

• Hydropericardium

• Ascites

(hydroperitoneum)

The pathology of the circulation (hemodynamic disorders) includes:

Edema Violations of the

blood volume

• Arterial hyperemia

• Venous plethora

(acute / chronic)

• Anemia (Ischemia)

(acute / chronic)

Violation of the

permeability of

the vascular wall

Disturbance of

blood flow

• Bleeding

• Hemorrhage

• Plasmorrhagia

• Stasis

• Thrombosis

• Embolism

1. Edema - accumulation of tissue fluid in serous cavities, or stroma of organs.

Mechanisms of formation

1 - Increased hydrostatic pressure in capillaries; 2 - Low osmotic pressure of plasma; 3 - Sodium and water retention; 4 - Lymphatic obstruction; 5 - Increased permeability of the vascular wall.

In the thoracic duct and eventually

into the left subclavian vein

Hydrostatic pressure

in capillaries

Increased interstitial

fluid pressure

Colloid-osmotic

plasma pressure

Terminal arteriole Postcapillary venule Capillary

Classification

Depending on the pathological condition,

which is accompanied by edema, edema

may be:

• traumatic

• allergic

• inflammatory

• toxic

• congestive

• lymphatic

• oncotic (including cahetical)

• dysmetabolic

Edema

General edema

Edema

Osmotic plasma

pressure

Albumin

Blood volume

Retention of

,

Activation of the renin-angiotensin-

aldehsterone system

Hydrostatic

pressure in

capillaries

Renal blood flow

Kidney

failure

Clinical significance of edema Ascites due to liver cirrhosis

Clinical significance of edema Pulmonary edema

Hydrotorax

CAUSES

A) cardiac (AH, decreased contractility of the heart, etc.)

B) non-cardial (hypervolemia, hypoproteinemia, shock,

gas poisoning, etc.)

Clinical significance of edema Cerebral edema

Clinical significance of edema Elephantiasis

Bancroft's filaria

Dehydration (Exicosis)

total

intracellular

intravascular

interstitial

General Local

Food

Drink

ml

excrement

urine

breathing/ skin

Due to insufficient

water intake

Due to excess

water loss

Classification by

mechanism

loss o

f m

ore

th

an

22%

is f

ata

l

Violations of the blood volume Arterial plethora – hyperemia –

is increased blood filling of the tissue due to increased arterial blood flow. It can be general - with an increase in the volume of circulating blood and local arising from local effects of various factors.

1. angioneurotic (neuroparalytic)

2. collateral

3. postischemic

6. vacant 5. inflammatory

4. hyperemia caused by

arteriolovenous fistula

Causes of general arterial plethora

• Increased plasma volume (intensive infusion therapy)

• Erythrocytosis

- Primary (erythremia)

- Secondary (hypoxic conditions: lung

diseases, high altitude, etc.)

Violations of the blood volume Venous plethora –

is increased blood filling of an organ or tissue due to the reduction (difficulty) of the outflow of blood; the blood flow is not changed or reduced.

Stagnation of venous blood leads to widening of veins and

capillaries, slowing of blood flow in them, to the development of

, which is the main pathogenetic factor determining

changes in organs with venous plethora.

acute chronic

local general

Violations of the blood volume General acute venous plethora

General acute venous plethora is occurs with acute heart failure. CAUSES: myocardial infarction, acute myocarditis, cardiac tamponade (and other causes leading to a acute weakening of the contractility of the heart) Due to hypoxia and increased hydrostatic pressure, capillary permeability rises acute, plasma steepness and edema, stasis in capillaries and multiple diapedemic hemorrhages develops in the stroma of the organs; in the parenchyma - dystrophic and necrotic changes.

Left ventricle Right ventricle

General acute venous plethora

• Lungs: • Edema, • Hemorrhage.

• Acute pulmonary edema is one of the main causes of death of patients with acute cardiovascular insufficiency.

• Kidney: • Dystrophy, • Necrosis of the tubular epithelium.

• Liver: • Centrolobular hemorrhages, • Necrosis.

2. Violations of the blood volume General chronic venous plethora (congestion)

A general chronic venous plethora occurs with chronic cardiovascular failure (coronary heart disease, chronic myocarditis, cardiomyopathy, heart disease).

Prolonged tissue hypoxia leads not only to plasmorrhage, edema, stasis and hemorrhages, dystrophy and necrosis, but also to atrophy and sclerosis (proliferation of connective tissue): stagnant consolidation (induration) of organs and tissues develops.

skin serous

cavities spleen kidneys lungs liver

- Anasarca -Hydrotorax

-Hydropericardium

-Ascites

- Cyanotic

induration

- Cyanotic

induration - Brown

induration - Nutmeg

liver

2. Violations of the blood volume General chronic venous plethora (congestion)

spleen kidneys

2. Violations of the blood volume General chronic venous plethora (congestion)

lungs

2. Violations of the blood volume General chronic venous plethora (congestion)

Nutmeg liver

Local venous plethora

• Occurs when the outflow of venous blood from the body or part of the body in connection with closure of the lumen of the vein (thrombus or embolus) or squeezing it from the outside (swelling, expanding tissue).

• In the organs, the same changes occur as with a common plethora.

• Muscat liver and nutmeg cirrhosis may occur with thrombophlebitis of the hepatic veins (Badd-Chiari syndrome).

2. Violations of the blood volume Ischemia (local anemia) –

is decrease in the blood filling of the tissue, organ, part of the body as a result of insufficient blood flow. Tissue changes that occur with anemia are due to the duration of the hypoxia that occurs.

• With acute anemia, dystrophic and necrotic changes usually occur. • With chronic anemia, there are atrophy of parenchymal elements and sclerosis of the stroma.

spastic obturating compression due to

repartition

3. Bleeding and hemorrhage

Bleeding is the process of the discharge of blood from the lumen of

a blood vessel or cavities of the heart into the environment or into

the body cavity, as well as interstitial.

Hemorrhage (hematoma) is a kind of internal bleeding with a

accumulation of blood in tissues.

A special type of hemorrhage - apoplexy - is a rapidly developing

massive hemorrhage.

OUTER INTERNAL

PRIMARY SECONDARY

Classification of hematomas * * also distinguish uniform hemorrhagic impregnation of the tissue

petechiae

• 1-2 mm

• CAUSES:

AH (1), impaired

number and

function of

platelets (2)

purpura

• 3 mm - 1 cm

• CAUSES:

trauma, vasculitis

ecchymosis

• more than 1 cm

• CAUSES:

injury

hematoma in

cavities • hemothorax

• hemopericardium

• hemoperitoneum

• hemarthrosis

• hemocephalia

Mechanisms of bleeding

• per rhexin

• due to rupture

• CAUSES:

• trauma

• inflammation

• necrosis

• aneurysm

• developmental

vascular

malformations

• sclerosis

• hyalinosis

• per diabrosin

• due to corroding

• CAUSES:

• cancer

• necrosis

• inflammation

• ectopic pregnancy

• per diapedesis

• due to impregnation

• CAUSES:

• hypoxia

• intoxication

• hemorrhagic diathesis

1 2 3

Bleeding due to rupture – per rhexin

Bleeding due to corroding – per diabrosin

Bleeding due to impregnation – per diapedesis

Outcome of hematoma

• The formation of a "rusty" cyst (accumulation of hemosiderin)

• Encapsulation or fibrosis of the hematoma

• Suppuration with infection

Plasmorrhagia

• Plasmorrhagia - the exit of plasma from the bloodstream due to increased vascular permeability.

• It occurs as a result of neuro-vascular disorders (spasm), tissue hypoxia, immunopathological reactions

• Diseases with plasmorrhagia: hypertensive disease, atherosclerosis, decompensated cardiac defects, infectious, infectious-allergic and autoimmune diseases

• Outcome – fibrinoid necrosis and hyalinosis

• Plasmorrhagia is important pathophysiological factor in burn disease

Blood stasis

• Stasis of blood - a sharp slowing and stopping the flow of blood in the vessels of the microcirculation

• Causes of stasis: • Infection,

• Intoxication,

• Venous plethora,

• Shock

• Of great importance is the sludge-phenomenon, for which characteristic is the adherence of red blood cells to each other, leukocytes and platelets and a build-up of viscosity plasma, which leads to difficulty in blood perfusion through the vessels of the microcirculatory bed.

Blood Stasis

• Stasis in the capillaries of the brain: • Capillaries and venules are sharply expanded,

• Overfilled by columns of erythrocytes in the form of coins

• Swelling of the brain substance.

• Prolonged stasis in the brain leads to development focal necrosis; clinically it manifests with brain coma.

4. Thrombosis

A thrombosis is an intravital coagulation of blood in vessels or cavities of the heart with the formation of fibrin.

Blood coagulation occurs in 4 stages:

1. thromboplastinogen + activators

active thromboplastin.

2. prothrombin + Ca2 + +

thromboplastin thrombin.

3. fibrinogen + thrombin fibrin

monomer.

4. fibrin monomer + fibrin-stimulating

factor fibrin polymer.

Internal pathway Outer pathway

Tissue destruction

Tissue factor

(thromboplastin)

Tissue factor

kallikrein

prekallikrein

high-

molecular

weight

kininogen,

collagen

Thrombin

(IIa)

Thrombin (IIa)

Thrombin (IIa)

prothrombin thrombin

fibrinogen fibrin fibrin polymer

Common pathway

Active factor

Non-active factor

Phospholipid surface

endothelium

endothelium

basal membrane

basal

membrane

smooth muscle of an arteriola Primary hemostasis

Secondary hemostasis

collagen

collagen

release of endothelin

causes vasoconstriction reflex

vasoconstriction

Destruction site

fibrin

Tissue factor Tissue factor

Expression of

the phospholipid

complex

Thrombin activation

Fibrin polymerization

B

C D

Thrombosis and angiotembotic events

von Willebrand

factor

Platelet adhesion

platelet shape

change ADP,

TxA2

granule

release

platelet

mobilization

Adhesion and

formation of a

hemostatic plug

Release of

- t-PA (fibrinolysis)

- Thrombomodulin

(coagulation

cascade blocking)

Captured neutrophils Captured

erythrocytes

Polymerized

fibrin

Thrombosis factors: • General:

• Changes in the vascular wall

• Slowing and disturbing blood flow

• Local: • Misbalance between coagulation and anticoagulation systems of blood

• Violation of rheological properties of blood (increased viscosity).

4. Thrombosis Classification of thrombi by morphological features (by

color, composition)

RED

Erythrocytes +

fibrin + platelets

In the veins

WHITE

Platelets + fibrin

In large arteries

COMPOSITE

Layered

Veins, aortic

aneurysm,

chambers of the

heart

HYALINE

Destroyed

erythrocytes,

plasma proteins

Microcirculatory

bed

• In relation to the lumen of the vessel:

1. Parietal - lying at the wall of the vessel, thus there is a free part of

the lumen.

2. Obturating or occluding the lumen of the vessel.

3. Axial, freely lying in the lumen of the vessel or cavity of the heart.

• According to the shape:

1. Elongated thrombi.

2. Spherical thrombi in the cavities of the heart or in the saccular

aneurysm.

3. Small blood clots resembling beads, the so-called "warts". They

are often found on valve flaps.

4. Thrombosis Classification of thrombi

Thrombosis: structure of composite thrombus

1. head (has the

structure of a

white clot),

attached to the

vascular wall;

2. body (actually

mixed thrombus);

3. tail (has the

structure of a red

blood clot). 3

3

1

Thrombus vs post-mortem blood clot

Thrombus Criteria Postmortem clot

Dark-red Color White-red

Dry Consistency Elastic

Rough, dim Surface Smooth, glance

Attached with head In relation to vascular wall Free lying

Thrombus vs post-mortem blood clot

Zahn lines in trombus on cut

Outcomes of thrombosis

FAVORABLE:

• Aseptic autolysis (dissolution of a blood clot)

• Organization of a thrombus, that is, the

replacement of a thrombus with a connective

tissue that grows from the side of the intima;

The process can be accompanied by

recanalization and vascularization.

• Calcification (in the veins, there are stones -

phlebolites)

ADVERSE:

• Septic autolysis with the

development of septicopyemia

• Disengage the thrombus with the

development of thromboembolic

events

• Progression

Clinical significance: thrombosis - > ischemia - > infarction and gangrenes thrombosis - > thromboembolism - > infarction and gangrenes

Embolism

• Embolism - circulation in the blood (or lymph) not occurring under normal conditions particle with blockage of vessels

• Such particles are called embolus (emboli)

Embolism classification

• Depending on the direction of embolus movement: • Orthograde embolism – with blood flow, • Retrograde embolism - against blood flow, • Paradoxical embolism - embolus from the veins of a large circle, bypassing the lungs,

enters the arteries of a large circle (through defects in the septa of the heart).

• Depending on the nature of the emboli: • Thromboembolism (venous and arterial), • Fat embolism, • Air embolism, • Gas embolism, • Tissue (cellular) embolism (+Amniotic fluid embolism) • Microbial embolism, • Embolism with foreign bodies

Venous embolism: pulmonary embolism (PE)

• Source: thrombi of the veins of the lower limbs, veins of the pelvic floor, arising with venous stasis, as well as thrombi of the right heart chambers

• In the genesis of death in PE, closure of the lumen of the vessel with the development of acute right ventricular failure, as well as pulmonary-coronary reflex (Kitaev’s reflex): spasm of the bronchi, branches of the pulmonary artery and coronary arteries

• Outcomes: • Heart arrest and death

• Hemorrhagic lung infarction

2-4 cases per

1000

hospitalizations

(USA)

95% - source

of thrombus -

veins of lower

extremities

(above the

knee joint)

Arterial embolism

• Source: thrombi formed in left heart chambers (with endocarditis, heart defects, myocardial infarction, arrhythmia, etc.) and in the aorta (or large arteries) atherosclerosis

• Outcomes: • Ischemic infarctions and gangrenes in organs

Thromboembolic syndrome = systemic thrombosis • Includes:

• Thrombosis

• Multiple arterial thromboembolism

• Infartion of gangrene (brain – 10%, lower limbs – 75%, other – 10%)

• Causes • Cardiovascular diseases,

• Oncological diseases,

• Infectious (sepsis) diseases,

• Postoperative period.

Fat embolism

• Develops when drops of fat enter the bloodstream: • In case of traumatic bone marrow injury (fractures of long tubular bones), • Crushing subcutaneous fat, • After intravenous administration of oil solutions.

• Fat drops obturate capillaries of the lungs and through arteriovenous anastomoses enter a large circle blood circulation, obturate the capillaries of the kidneys, brain and other organ

• Fat droplets can be revealed by sudan III staining in interalveolar septae capillaries

• Outcomes: acute pulmonary insufficiency, brain capillaries obturation with multiple brain hemorrhages

Fat embolism

Air embolism

• Develops air enters the bloodstream: • After the wounds of the veins of the neck (negative pressure) • After childbirth and abortion, • through the sclerotized lung, • with occasional intravenous injection air together with the drug substance.

• Air bubbles in the blood cause embolism of capillaries of a lung; when air bubbles reach a large circle blood circulation embolism of capillaries the brain can develop .

• Air embolism can be detected on the autopsy by release of air from the right heart after puncturing it underwater and a foamy blood in the cavities of the heart.

Air embolism test

Gas embolism

• Typical for caisson disease=decompression sickness: develops with rapid decompression (transfer from increased pressure to normal atmospheric pressure or from normal to decreased).

• Released nitrogen bubbles (located at high blood pressure in the dissolved state) cause blockage of the brain and spinal cord, liver, kidneys and other body’s parts capillaries , which is accompanied by the appearance in them small foci of ischemia and necrosis.

Tissue embolism

• May occur when tissue is destroyed due to trauma or pathological process leading to the inflow of pieces of tissue (cells) into the blood.

• Embolism of amniotic fluid in woman in labor may be accompanied by the development of DIC syndrome and lead to death.

• Embolism of malignant tumor cells lies in the tumor metastasis: in organs numerous tumor nodes round in shape are revealed, often with a dip in the center (necrosis).

Tissue embolism (cancer cells)

Microbial embolism

• Bacteria, fungi, protozoa circulate in the blood and obturate the capillaries lumen.

• Often, bacterial emboli are formed in purulent melting of thrombus - thrombobacterial embolism.

• At the site of occlusion of the vessel with bacterial emboli formed metastatic abscesses.

• An example of bacterial embolism may embolic purulent nephritis (often found in septicopyemia):

• The kidney is enlarged in size, • Cortex and medulla show multiple small yellowish foci (purulent

inflammation).

Foreign bodies embolism

• Catheters, bullets, as well as crystals of cholesterol from ulcerating atherosclerotic plaques

Shock

• Shock - circulatory collapse, accompanied by hypoperfusion of tissues and decrease in their oxygenation.

Shock morphology • Kidney:

• Necrotizing nephrosis (acute renal failure)

• Lungs: • Adult Respiratory Distress Syndrome (ARDS). • Foci of atelectasis, • Serous hemorrhagic edema with accumulation of fibrin in lumen of the alveoli (hyaline

membranes), • Stasis and thrombi in microcirculatory bed.

• Liver: • Centrolobular necrosis.

• Brain: • Foci of necrosis, • Minor hemorrhages.

• Gastrointestinal tract: • Hemorrhages.

Disseminated intravascular blood coagulation syndrome (DIC) • The syndrome of disseminated intravascular coagulation of blood

(coagulopathy of consumption, thrombohemorrhagic syndrome) - a condition, characterized by the formation of multiple blood clots in the vessels of the microvasculature due to the activation of coagulation factors and developing deficit with subsequent activation of fibrinolysis and development of numerous hemorrhages.

Stages of DIC

• Stage I - hypercoagulation and thrombus formation: • It is characterized by intravascular aggregation of blood cells, disseminated blood

coagulation with the formation of multiple blood clots in microvessels of various organs and tissues.

• As a rule, it is short-term, duration up to 8 -10 min. • Clinically manifests as a shock.

• Stage II - increasing coagulopathy of consumption: • Characterized by a significant decreased amountof platelets and fibrinogen, spent on

the formation of thrombi. • There is a transition from hyper- to hypocoagulation, manifesting by hemorrhagic

syndrome. • Removal of active coagulation factors from the blood stream is due to phagocytosis,

so the presence of fibrin in cytoplasm of macrophages and neutrophils is confirmation of this stage.

Stages of DIC

• Stage III - pronounced hypocoagulation and activation fibinolysis: • There is a lysis of previously formed microthrombi and often the degradation

of circulating clot factors

• Developing hyperplasminemia leads to the appearance of readily soluble and fibrin-containing complexes, fibrin degradation products, and fibrin-monomer looses its ability to polymerize.

• It usually develops 2 to 8 hours after the onset of DIC.

• Complete blood incoagulability, severe bleeding and hemorrhage, microangiopathic hemolytic anemia are noted.

Stages of DIC

• Stage IV - Restorative (residual manifestations): • Dystrophic, necrotic and hemorrhagic lesions of organs and tissues.

• In most cases, there is a reverse development of tissue changes.

• In severe cases of DIC syndrome, lethality is 50% due to acute polyorganic insufficiency.

• In newborns, especially premature born, mortality is 75 - 90% (due to imperfect fibrinolytic system, insufficient synthesis of liver clotting factors, etc.)

Morphology of DIC • Morphology and morphogenesis of DIC syndrome are due to a number of

factors, among which an important role play: • The main disease,

• DIC triggering mechanisms,

• Time,

• Treatment measures

• Regardless of the combination of these factors, the main morphological manifestations of DIC syndrome are:

• Microthrombi,

• Necrosis,

• Hemorrhages.

Morphology of DIC • Multiple microthrombi in the vessels of microcirculatory bed:

• Fibrin clots: • Detected most often and in the largest quantity.

• Consist of fibrin with single red blood cells.

• Hyaline thrombi,

• White (leukocytic) thrombi,

• Red (erythrocyte) blood clots.

Morphology of DIC • Lungs:

• Serous-hemorrhagic edema,

• Fibrin and hyaline thrombi,

• Sludge and agglutination of erythrocytes,

• Multiple hemorrhages,

• Small hemorrhagic infarctions (in some cases),

• Hyaline membranes (consisting of fibrin).

• Pancreas: • Edema,

• Hemorrhages,

• Microthrombi,

• In severe cases, pancreatic necrosis.

Morphology of DIC • Kidney:

• Dystrophy of the proximal and distal convoluted tubules epithelium,

• In severe cases, necrotic nephrosis (necrosis tubular epithelium, tubulorhexis, symmetrical focal and total corticonecrosis),

• Multiple hemorrhages, incl. subcapsular,

• Multiple microtrombi.

• Liver: • Dystrophic and necrotic changes in hepatocytes (up to centrolobular necrosis),

• Fibrin thrombi in the central veins,

• filaments of fibrin lying freely in sinusoids.

“Shock kidney”

“Shock liver”

Morphology of DIC • Adrenal glands:

• Dystrophy with loss of lipids and necrosis of cells in cortex and medulla,

• Multiple microthrombi,

• Extensive hemorrhage (Waterhouse –Friderixen syndrome).

• Skin: • Multiple petechial hemorrhages,

• Rarely - extensive hemorrhages (ecchymosis),

• Small necrotic foci (in some cases).

• Gastrointestinal tract: • Multiple small hemorrhages,

• Erosions and acute ulcers.

Morphology of DIC • Spleen

• Small-scale hemorrhages in parenchyma and capsule

• Hyaline and fibrin thrombi in small arteries and veins

• Fibrin fibers in sinusoids

• Myocardium and brain (rarely affected) • Single microtrombi

• Dystrophic changes

• Edema