Phathology-3(disorders Of Blood Circulation)

Chapter 3 Disorders of Vascular Flow

DURGE RAJ GHALAN

Department of Pathology, The First Affiliated Hospital of Sun Yat-sen Universty

Contents: 1 ． Hyperemia 2 ． Thrombosis 3. Embolism 4. Infarction

1 ． Hyperemia Hyperemia means an increased volume of blood in an affected tissue or organ. Capillary beds are extended （ dilatation and opening of capillaries & venules closed in non-hyperemia state ）

1.1 Arterial Hyperemia Arterial or active hyperemia is caused by increased arterial inflow of tissues or organs. Physiological: blushing for shyness, muscular exercise Pathological: at the beginning of the inflammation

Inflammation inducing factors ( Bacterial, chemical, mechanical......etc) sympathetic neurogenic reflex (axial reflex) & Vasoactive substances arteriolar dilatation The organ in hyperemia is swollen and redder than in normal state

1.2 Venous Hyperemia (Congestion) Venous or passive hyperemia or congestion results from block (obstruction) of venous drainage (outflow) Occur systemically: in cardiac failure Occur locally because the vein is blocked by the obstruction more common and important than arterial hyperemia

1. Causes: 1) Compression of veins • pregnant uterus — iliac vein hyperemia • expansile tumors or scar tissue — leg vein hyperemia • intussusception / volvulus / hernia / fibrous adhesion of intestine — mesenteric veins congestion • cirrhosis (disturbance of lobular circulation) — portal vein hyperemia — gastrointestinal and spleen congestion

2) Obstruction of venous lumen: venous thrombi 3) Heart failure The heart fails to expel the normal amount of blood, the blood accumulate in venous system left heart failure —pulmonary congestion right heart failure —systemic venous congestion

Arterial Hyperemia Arteriole inflow increase Content of oxygen increase

Normal state

Venous Hyperemia Venule outflow decrease Content of oxygen decrease

2. General features of venous hyperemia 1) Morphology Grossly (macroscopically) : swollen, heavier, blue-red color (increased of deoxygenated hemoglobin), cut surface: excessively bloody Body surface: cyanosis (nail, lip), lower temperature Microscopically: engorgement of capillaries & venules, minute hemorrhage;

Edema: in loose tissues or organs (hydrostatic pressure↑and permeability↑of capillaries & venules) 2) Chronic (long-standing) congestion may lead to degeneration or death of parenchymal cells (liver) and fibrosis and hemosiderin (product of degradation of hemoglobin) deposition.

3. Congestion of important organs 1) congestion of the lung Causes: left heart failure (mitral stenosis or heart infarct, etc) —pulmonary congestion Acute pulmonary congestion: congestion of alveolar capillaries, edema, minute hemorrhage heart failure cells (hemosiderin-laden macrophages) in alveolar space

Symptoms: Dyspnea: difficult or labored breathing Hypoxia: absent or decrease of oxygen Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood

Bloody or tinged rusty sputum: there are many red cells in the alveolar space

Chronic pulmonary congestion: ♣

congestion

♣

fibrosis

♣

hemosiderin deposition (brown induration)

♣

pulmonary hypertension (fibrous

thickening of pulmonary arterioles and arteries )

2) congestion of the Liver Causes: ♣

right heart failure —systemic congestion (pulmonary heart diseases and congenital pulmonary stenosis) , such as liver congestion

♣

left heart failure can lead to right heart failure (left heart failure→pulmonary congestion →pulmonary hypertension→right heart failure)

Morphology of Liver congestion 1) central region of lobules (red-blue): engorgement of central veins and blood sinusoids nearby (dilatation ) , minute hemorrhage (bleeding) , atrophy and necrosis of liver cells

1) peripheral region of lobules (yellowbrown) peripheral sinusoids slight congestion fatty degeneration of liver cells Nutmeg Liver

central region dilatation, bleeding, atrophy and necrosis of liver cells;  peripheral sinusoids slight congestion, fatty degeneration of liver cells 

liver sinusoids dilatation, blood cells aggregate

Kupper cells laden with hemosiderin in liver sinusoids

3) longstanding chronic congestion of the liver— cardiac cirrhosis fibrosis of center of liver lobules, extension of fibrous tissue into peripheral of lobules and connection with portal areas leads to reconstruction of normal lobular structure (cardiac cirrhosis)

2 ． Thrombosis Thrombosis is the process of formation of a solid mass from constituents of the blood within vessels or the heart in a living body ． The solid mass is termed a thrombus ．

The composition of a thrombus is similar to the blood clot, but different in proportion of various components ． Thrombus contains more platelets and fibrin than blood clot ． Thrombus forms in moving blood ．

2.1 Predisposing factors of thrombosis Vascular and cardiac endothelial injury

Thrombosis

Hypercoagulability Slowing and turbulence of blood flow of blood

Vascular and cardiac endothelial injury ♣

It is particularly improtant in thrombus

formation in the heart and arterial circulation, for example, within the cardiac chambers when there has endocardial injury (rheumatic or bacterial endocarditis, etc); over ulaerated of plaques in severely atherosclerotic arteries; or at the site of traumatic or imflammatory vascular injury.

♣

Exposure of subendothelial collagens will lead to the release of platelets activators, and consequently PL aggregation initiate thrombosis.

♣

There are coagulation and fibrinolytic systems in blood. The balance between these two systems is very finely regulated. Exposure of subendothelial collagens will also activate the coagulative system and make the soluble fibrinogen become insoluble fibrin.

Slowing and turbulence of blood flow ♣

Normal blood flow in vessels central stream: white, red cells laminar stream: platelets peripheral stream: plasma

Slowing and turbulence of blood flow · bring platelets into contact with endothelium · cause mild injury of endothelium, and collagen exposure, the collagen prevents dilution and clearance of blood clotting factors in location ♣

A. Veins Thrombi are most commonly located in veins Thrombi in Low extremities accounts for 90% B. Arteries and the heart Arteries: occur in aneurysm Heart: Mural thrombi in left atria occur in case of mitral stenosis in rheumatic heart disease Mural thrombi in left ventricle occur on the endocardium overlying an infarct

Hypercoagulability of blood Increase in amount and viscosity of platelets (postpartum, postoperation, post-trauma high lipid diet, cigarette smoking, atherosclerosis, and the release of procoagulant tumor product in disseminated cancers) ♣

Increase in amount and viscosity of platelets will be seen in DIC (Disseminated Intravascular Coagulation) ♣

2.2 The process of thrombosis & types of thrombi

　 (1)

The process of thrombosis

1) It initiates from adhesion of PL to exposed subendothelial collagens and subsequent PL aggregate. Then they develop in different ways, their composition, size and shape are dependent on their locations and speed of local blood flow.

Platelets adhere to the subendothelial collagens, and leads to degranulation, releasing serotonin, ADP,ATP

ADP is a powerful platelet aggregator, and will cause further accumulation of platelets

2) Activation of intrinsic and extrinsic blood coagulation cascade, soluble fibrinogen become insoluble Fibrin; While the fibrinolytic activity are prevented

3)

The head of thrombus is mainly composed of platelet

trabecula with less fibrin network between PL trabecula

4) red ,white cells are trapped and form a blood plug

5) Development of thrombus

(2) Types of thrombus Pale (white) thrombus Mixed thrombus Red thrombus Hyaline thrombus (microthrombus)

1) White thrombus : ♣

White thrombus is formed under high speed of

blood flow in arteries & heart (in heart chamber , on heart valves). ♣

White thrombus is mainly composed of platelet

trabecula with less fibrin network between PL trabecula, and red and white cells trapped.

Thrombi lined on the heart Mitral valve, be gray-white and small, granulo-like. Firmly adherent to the valve.

Thrombi lined on the heart Aortic valve

White thrombus composed by platelets trabecula with less fibrin network, they are pink with pale lines in HE stained slides.

2) Mixed thrombus : Mixed thrombus is formed under slowermoving blood in veins and arteries (aneurysm) and heart (left atria dilated with mitral stenosis).

Mixed thrombus in veins can be divided into 3 parts Head: initial PL aggregate Body: platelet trabecula (gray layers, called zahn lines ) and alternately separated blood clot layers Tail: The tail is at down stream of the thrombus body under very slow-moving blood or blood stasis, which is composed by blood coagulates, so it can also be named Red thrombus. The red thrombus almost or completely occlude the venous lumen.

left ventricle dilate filled with mixed thrombus

aneurysm

pl tr atel ab et ec ul a

blood clot

3) Red thrombus: red thrombus closely resembles to blood clot

Mixed thrombus, especially it’s tail part (red thrombus) is readily to shed off (dislodge) and be carried by blood flow to impact vessels in a distal organ (thromboembolism) Thrombi in systemic veins - Pulmonary embolism Thrombi in portal veins – Liver embolism Thrombi in heart & aorta - spleen , kidneys, brain embolism, etc

4) Hyaline thrombus (microthrombus) ♣

♣

occur in DIC ( Disseminated Intravascular Coagulation) microscopically , occur in microcirculation, mainly composed of fibrin

There are numerous microthrombi in the glomerular capillaries

There are microthrombi in the alveolar capillaries. They are pink, and uniformly stained

(3) The fate of thrombi ♣

softening, dissolving ( in newly formed thrombi)

and the vascular lumen is reestablished, it is the ideal end result; ♣

Organization: the thrombus is displaced by

granulation tissue and collagen.

♣

Recanalization: the new small vessels in the

granulation tissue proliferate and enlarge, and may establish new channels across the thrombus. (in large thrombi) Organization and Recanalization may slightly improve tissue perfusion over the long term. ♣

Calcification: Calcium salt deposite in the thrombus

♣

Dislodge

Vascular wall and collagen area

a part of the out-of –date granulation tissue thrombus

(4) The effects of thrombi to the body 　　 Occlusion of vessels Thromboembolism Distorted cardiac valves Hemorrhage (occur in DIC)

DIC (Disseminated Intravascular Coagulation) A kind of clinical syndrome caused by multiple factors

Formation of hyaline thrombi throughout the microcirculation. Consumption of platelets and coagulation factors, bleeding tendency

3. Embolism Embolism is the occlusion or obstruction of a vessel by an abnormal mass transported from a different site by the circulation. An embolus is a detached intravascular solid, liquid, gaseous, or tumor cell mass.

3.1 Possible moving pathways of an embolus depends on the sites of its origin A. The emboli originateing from systemic vein  entering right heart  pulmonary Emboli in right heart  arterial system  pulmonary embolism

B. The emboli from left heart or main artery  entering systemic arteries  lodging in a distal systemic artery  such as brain arteriole, heart arteriole, kidney arteriole, extremity arteriole, intestine arteriole, etc. especially in the extremity arteriole.

C. The emboli from mesenteric vein or portal vein  liver embolism (rarely occur) D. Crossed embolism: occur uncommonly. There is a defect in the wall between the right and the left heart lumen, the thrombus in right heart lumen go directly into the left heart lumen, and consequently cause the embolism in distant systemic organs.

There is a defect in the interatrial septum, so the embolus in right heart go directly into the left heart, and consequently

Crossed embolism formation

3.2 Types of Embolism (1) Thromboembolism Obstruction of a vessel by a disloged thrombi that has been transported from a distant site by the blood stream. 1) Pulmonary embolism The origin of emboli: ＞ 90% from deep leg vein

The sequel of pulmonary embolism: Large emboli (several centimeters long and of the same diameter as the femoral vein) may lodge in the outflow of the right heart ventricle or in the main pulmonary artery , and cause circulatory obstruction and sudden death. Lodgment in a large branch of pulmonary artery may also cause sudden death by severe vasoconstriction of the entire pulmonary arterial circulation.

Pulmonary embolism. The pulmonary artery has been opened to reveal a large thromboembolus within it.

In healthy individuals, the bronchial artery supplies blood and oxygen to the lung, and the function of pulmonary artery is mainly gas exchange.

Medium-size emboli: often lodge in a major branch of the pulmonary artery.

In a normal person, a moderate-sized pulmonary embolus creates an area of lung having no gas exchange function, but infarction of the lung does not occur. In a patient with severe pulmonay hyperemia, the pulmonary blood and oxygen supplies dependent on both bronchial artery and pulmonary artery. In these patients, obstruction of pulmonary artery by a moderate-sized embolus results in pulmonary infarction.

Small emboli may lodge in minor branchs of the pulmonary artery, and usually be clinical silent However, if numerous small emboli occur for a long period, the pulmonary microcirculation may be so severely compromised that pulmonary hypertension results.

Pulmonary thromboembolus occluding a small branch of the pulmonary artery in the lung

2) Systemic embolism The origin of emboli: Most emboli arise from intracardiac mural thrombi

(infective endocarditis with vegetations on

the valves, mural thrombosis occurred in myocardial infarction, etc. )

The remainder emboli may originate from ulcerated atherosclerotic plaques

The sequel: The clinical effects is govened by the size of the obstructed vessel, the availability of collateral arterial circulation, and the susceptibility of the tissue to ischemia. Necrosis is common when arteriolar embolization occur in the brain, kidneys , spleen and intestines, etc.

Arterial embolization of brain,

shows impacted thromboemboli at the orifice of cerebral middle artery

The brain tissue suplied by the obstructed vessel necrose for ischemia and hypoxia

Arteriolar embolization of kidney the kidney tissue supplieded by the obstructed arteriole necrose for ischemia and hypoxia

Arteriolar embolization of spleen by tumor embolus

Arteriolar embolization of intestine because of volvulus Intestin tissue necrose for ischemia and hypoxia

（ 2 ） Fat embolism The origin of emboli: Fat globules in the circulation after fractures of long bone, trauma of sofe tissue and a liver with fatty change.

• Fat globules at trauma sites can enter the circulation, and the catecholamines due to the stress of trauma mobilizes free fatty acids to form progressively enlarging fat globules. • Adhesion of platelets to fat globules further increases their size and causes thrombosis.

• The sequel: depends on the size and the number of fat globules • Circulating fat globules first enter the capillary network of the lung. >20μm in diameter: be arrested in the lung and occlusion of the branching arterioles of pulmonary artery formation (dyspnea and normal gas exchange)

< 20μm in diameter: pass through the pulmonary circulation and enter left heart, and consequently obstruct small systemic arteries. Typical clinical features of fat embolism include a hemorrhagic skin rash and brain involvement for embolism of cerebral microvasculature formation.

Pulmonary fat embolus: occluding a small branch of the pulmonary arteriole by a piece of Bone marrow

Fat bubbles in the lumen of vessels stained by Sudan III ， Showing brilliant red color

Fat emboli in the pulmonary arterioles stained by Sudan III

Fat emboli in the brain arterioles stained by Sudan III

Necrosis of the area occluded by the fat emboli in the brain

（ 3 ） Air embolism Gas bubbles within the circulation can obstruct cardio-vascular flow. Generally, in excess of 100ml of air is required to produce a clinical effect.

The origin of gas: Air may enter the circulation during obstetric procedures or as a result of chest wall injury. Occur in caisson workers and under-sea divers, occasionally occur in the injury of chest or making a mistake to inject air into vessel lumen.

The sequel: • The gas bubbles may form frothy masses with blood in right heart, and then act like physical obstructions to occlude major vessels. • Platelets adhere to air bubbles in the circulation and active coagulation cascade.

Decompression sickness: Occur in caisson workers and under-sea divers. When air is breathed at high underwater pressure, an increased volume of air (mainly nitrogen) become dissolved in the blood and tissues. If the diver then ascends too rapidly, the nitrogen come out of solution and form bubbles in the tissues and bloodstream that act as gas emboli.

（ 4 ） Amniotic fluid embolism The amniotic fluid and its component are infused into the maternal circulation via a tear in the placental membranes and rupture of the uterine veins. The onset is characterized by sudden severe dyspnea, cyanosis, DIC and shock, followed by seizures and coma.

• Amniotic fluid contains fetal squamous epithelium, fetal hair, fetal fat, mucin, etc. All of them may lodge in the pulmonary capillaries, and may cause disseminated intravascular coagulation.

Several pieces of fetal hair in the alveolar space

( 5 ） Tumor embolism Cancer cells often enter the circulation during metatasis of malignant tumors. And this type of embolus is tumor embolus.

•

Infarction Tissue necrosis resulting from extreme reduction or loss of blood supply (vascular occlusion) is referred to as infarction. The necrotic tissues are called infarct.

1. Causes: Thrombosis: the most common cause Embolism of arteries Compression and obstruction of vessels Arterial spasm

2. General morphology of infarcts (1) Shape: depend on vascular distribution of the organ Wedge or pyramid shaped infarct: kidney, lungs, and spleen irregular, map shaped infarct: heart, brain

The arterial system in kindey is branching pattern, like wedge or pyramid shape When the branch of the arterioles are obstructed, the tissue supplied by the arterioles necrose. The necrotic foci are also wedge or pyramid shaped

•

Color: depends on the amount of the blood in the infarct foci

•

Texture: depends on pathological changes in different organs Coagulative necrosis – solid organs (kidenys, spleen), lungs and intestine etc Liquefactive necrosis – brain(cerebral malacia)cyst formation

3. Types of infarcts 3.1 Anemic infarcts (White infarcts) Organ involved: solid organs with deficient collateral circulation of arteries (heart, kidneys, spleen, etc.) Grossly: wedge-like or triangular necrotic foci with

peripheral hemorrhagic zone

Anemic infarcts of spleen: wedge shaped infarct, the top of the wedge directe to the hilum of the spleen

Anemic infarcts of kidney: wedge shaped infarct, the top of the wedge directe to the hilum of the kidney

• The shape of cerebral and myocardial infarcts is irregular. It is determined by the distribution of the occluded artery, and limits of collateral arterial supply.

Anemic infarcts in heart: irregular, map shaped infarct

Anemic infarcts of brain: irregular, map shaped infarct And cyst formation

Microscopically: ischemic coagulative necrosis The outline of tissue structure remains Nuclear changes: pyknosis, karyorrhesix, or karyolysis Leucocytic reaction at peripheral margin

Anemic infarcts of kidney: wedge shaped foci

keeping the outline of tissue structure, hyperemia and leucocytic reaction at peripheral margin

Coagulative necrosis, the tissue contour is kept, but the cell died with the changes of the nucli.

Anemic infarcts of spleen

Anemic infarcts of heart muscle

Anemic infarcts of brain Irregular shaped foci Liquefactive necrosis - cerebral malacia - cyst formation

Cerebral liquefactive necrosis

3.2 Hemorrhagic infarcts (Red infarcts) occur in an organ: composed of loose tissue, such as the lungs with double circulation (lungs) and rich collateral circulation (small intestine) associated with congestion

PA

Capillary network

PV

hydrostatic pressure increased dramatically

BA

bronchia

The changes of the blood circulation when embolism of pulmonary arteries occur

BV

Pulmonary hemorrhagic infarcts

Conditions: serious pulmonary congestion before infarction the organs are composed of loose tisssue

Grossly: wedge-like or triangular necrotic foci, red

Microscopically: coagulative necrosis plus with large amount of hemorrhage

Lung wedge-like or triangular necrotic foci, red color

Cut surface featrue: necrosis plus with large amount of hemorrhage

Microscopical feature in the lowest amplified: necrosis plus with large amount of hemorrhage

necrosis plus with large amount of hemorrhage

Intestine hemorrhagic infarcts (causing by volvulus)

Intestine hemorrhagic infarcts (causing by embolism)

Intestinal necrosis plus with large amount of hemorrhage

Cerebral hemorrhagic infarcts: coagulative necrosis plus with large amount of hemorrage

Cerebellum hemorrhagic infarcts: coagulative necrosis plus with large amount of hemorrage

4. Influence to the body and the sequal of the infarction Influence ： decided by the organ or the size The sequel: Orgnization and eventually form a scar Calcification Cystic cavity formation