Hemodynamic disorders, thrombosis, atherosclerosis

1 - Organized thrombus

2 - Pulmonary bone marrow embolism

3 - Pulmonary haemorrhagic infarct

4 - Fresh ischaemic infarct

5 - Coronary atherosclerosis

1. Thrombus

Blood clot (latin: cruor, coagulum sanguinis ): a mass of coagulated blood.

A. extravascularly during life

B. within the cardiovascular system after death (post mortem blood clot)

Thrombus (latin: ante mortem blood clot): a mass of clotted blood formed within cardiovscular system during life.

Thrombosis designates the phenomenon of intravital coagulation of blood.

Thrombus and thrombosis appear only in pathological conditions and create a risk of severe consequences.

It is very important to distinguish a post mortem clot from a thrombus particularly during autopsy.

1. Thrombus

Virchow’s TriadInterrupted blood flow (stasis)

Endothelial injury

Hypercoagulability

• Interrupted blood flow– Venous stasis

• Long surgical operations• Immobilization

– Turbulent flow

• Endothelial injury– Trauma to endothelial cells

• Hypertension• Burn• Irradiation

– Infections– Foreign material

• Hypercoagulability– Factor V (Leiden) mutations– Antithrombin III deficiency

– Trauma or burn– Malignant neoplasms– Cigarette smoking– Obesity– Hormonal contraception

1. Thrombus

Blood clot (latin: cruor, coagulum sanguinis)Macroscopically , intravascular post mortem clot: a homogenous,

gelatinous, elastic, moist coagulum with a smooth, glistening

surface. It produces a mould of the vessel and lacks attachment to its wall.

It can be red or yellow.

Thrombus (ante mortem blood clot)Macroscopically , thrombus presents as a dry, matt, friable mass, closely

adhering to the vessel wall, and ranging in color from gray to red.

Microscopically both (blood clot and thrombus) are similar –They consist of fibrin framework with confined erythrocytes, leukocytes,

platelets

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Fate of thrombus

Thrombus may undergo numerous changes. There are 4 main changes of the thrombus:

1. Propagation. The thrombus may accumulate more platelets and fibrin (propagate), eventually leading to vessel obstruction.

2. Embolization. Thrombi may dislodge and travel to other sites in the vasculature.3. Dissolution. Thrombi may be removed by fibrinolytic activity.4. Organization and recanalization .

The term „organization” means the replacement of thrombus by connective

tissue. Thrombus becomes penetrated by macrophages, fibroblasts, smooth myocytes and capillaries. It is gradually dissolved, phagocytized by macrophages and replaced

by proliferating connective tissue . The vascular lumen becomes narrowed or occluded. The dilatation of capillaries which are present in the organized thrombus restores to a limited degree the blood flow („recanalization” )

1 - Organized thrombus

MICROSCOPICALLY. Histological appearance of organized thrombus

depends on its age. In general, lumen of the vessels is obstructed by fibrous

connective tissue or, earlier, by highly cellular granulation tissue. Dilated

capillaries are present. Haemosiderin visible in the slides derives from break-

down of erythrocytes phagocytized by macrophages.

Low-power view of a thrombosed artery. A, H&E-stained section. B, Stain for elastic tissue. The original lumen is delineated by the internal elastic lamina (arrows) and is totally filled with organized thrombus, now punctuated by a number of small recanalized channels.

Consequences of thrombosis

Thrombosis may result in:

1. Ischemia by occlusion or narrowing of arterial lumen

2. Passive congestion due to the impairment of venous blood outflow without an efficient venous collateral circulation

3. Thromboembolism after the detachment of an entire thrombus or its fragments

EMBOLISMEmbolism consists in occlusion of a vessel by an embolus (=stopper) disloged by blood from broader segment of the circulatory system.

The material of the embolus may be solid, fluid, semifluid or gas.Thromboembolism is the most frequent representative of solid embolismIt may derive from: heart, arteries, veins (particularly those of the lower limbs and pelvis).

Although the rate of fatal pulmonary emboli (as assessed at autopsy) has declined pulmonary embolism still causes about 200 000 deaths per year in the United States. In more than 95% of instances, venous emboli originate from deep leg vein thrombi above the level of the knee.

Depending on the size of the embolus, it may occlude the main pulmonary artery, impact across the bifurcation (saddle embolus ), or pass out into the smaller, branching arterioles.

Frequently, there are multiple emboli

Large embolus derived from a lower extremity deep venous thrombosis and now impacted in a pulmonary artery branch.

2 - Pulmonary bone marrow embolism

Pulmonary bone marrow embolism is the most frequent fat embolism.

Microscopic fat globules may be found in the circulation:

fractures of long bones (which have fatty marrow)

soft tissue trauma and burns .

Although traumatic fat embolism occurs in some 90% of individuals with severe skeletal injuries, less than 10% of such patients have any clinical findings.

Fat embolism syndrome is characterized by pulmonary insufficiency, neurologic symptoms, anemia, and thrombocytopenia.

Symptoms typically begin 1 to 3 days after injury, with sudden onset of tachypnea, dyspnea, and tachycardia.

2 - Pulmonary bone marrow embolismMACROSCOPICALLY : lungs are dark red and oedematous

MICROSCOPICAL EXAMINATION reveals alveolar capillaries distended by globules of fat which present as empty spaces since lipid is removed by fat-solving reagents used in routine processing of the specimen. Identification of fat emboli requires special techniques of preparation i.e. Sudan stain. Additionally, lung tissue exhibits hyperaemia and sometimes oedema

Bone marrow embolus in the pulmonary circulation. The cleared vacuoles represent marrow fat that is now impacted in a distal vessel

Infarct (infarction) means a necrotic focus which results from insufficient inflow of arterial blood to a given territory in situation of ineffective collateral circulation or from a sudden stop in the outflow of venous blood, simultanously with inadequate arterial supply.

Infarcts are grossly subdivided into ischaemic (white) and haemorrhagic (red) ones.

Ischaemic infarct occurs in organs with anatomically or functionally terminal arteries such as heart, spleen, kidney.

It is most commonly caused by arterial occlusion arising from thrombosis or embolism.

Macroscopically it has a shape of cone with its base at the periphery of organ and apex pointing towards occluded artery

Sharply demarcated white infarct in the kidney.

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4 - Fresh ischaemic infarct (Infarctus anaemicus rec ens)

Histological examination reveals characteristic signs of ischaemic coagulative necrosis .

Necrotic tissue is entirely blurred with lost cytological details, and indistinguishable individual cells, although architectural features are preserved for some nuclei. It is composed of homogenous shadows of cells lacking their nuclei.

In places, however, there are remnants of nuclei representing various phases of damage (under high magnification), such as:

• pyknosis - nuclei are shrunken and more intensively stained with hematoxylin,

• karyorhexis - nuclei undergo fragmentation• karyolysis – nuclei progressively lose ability to stain with hematoxilin and

eventually disappear

Necrotic area is surrounded by a rim of neutrophils which in turn is encircled by a zone of hyperaemia.

Both hyperaemia and cellular exudate reflect the inflammatory reaction to the presence of necrotic tissue

This is the microscopic appearance of a fresh renal infarct . At the far right is normal kidney, then to the left of that hypraemic kidney that is dying, then to the left of that pale pink infarcted kidney in which both tubules and glomeruli are dead

3 - Pulmonary haemorrhagic infarct (Infarctus haemorrhagicus pulmonis )

The term „haemorrhagic infarct of lung ” designates local necrosis of lung tissue (interalveolar septa) accompanied by massive haemorrhage within pulmonary parenchyma. The lesion results from embolic (very rarely thrombotic) occlusion of a peripheral branch of pulmonary artery but its appearence is determined by efficiency of left ventricle.

Lung tissue is supported by double arterial supply- pulmonary circulation and the bronchial one.

In case of normal cardiovascular condition (efficient left ventricle), pulmonary embolism does not lead to infarction because bronchial circulation preserves viability of lung tissue; however lead to extravasations into alveolar spaces. The resulting lesion, identical grossly with haemorrhagic infarct of lung referred to as post-embolic focus. In favorable cases it entirely disappears with restoration of pulmonary parenchyma to its normal state.

On the contrary, in case of passive congestion of lungs in the course of left-ventricular failure , bronchial circulation fails to sustain the pulmonary parenchyma and infarction ensue.

3 - Pulmonary haemorrhagic infarct

MA: the lesion is cone-shaped with its base at the pleural surface, dark red, firm

MI: histological examination reveals stuffing alveolar spaces with blood; necrotic alveolar walls, full of blood, are poorly visible within masses of accumulated erythrocytes

Atherosclerosis

Atherosclerosis afflicts the intima of arteries of the systemic circulation.

It is characterized by intimal lesions called atheromas , or atheromatousplaques , which protrude into and obstruct vascular lumens.

Atherosclerotic plaques develop primarily in elastic arteries (e.g., aorta, carotid arteries) and large and medium-sized muscular arteries (e.g., coronary arteries).

Myocardial infarction, cerebral infarction (stroke), aortic aneurysms, and peripheral vascular disease are the major consequences of atherosclerosis.

AtherosclerosisMorphology

The key processes in atherosclerosis are intimal thickening and lipid accumulation .

Fatty streaks are the earliest lesions of atherosclerosis. They are composed of lipid-filled foam cells. They are not significantly raised and thus do not cause any disturbance in blood flow. Fatty streaks begin as multiple yellow, flat spots less than 1 mm in diameter.

Aorta with fatty streaks (arrows)

Photomicrograph of fatty streak demonstrating intimal, macrophage-derived foam cells (arrow).

Atherosclerosis

Morphology

-An atheroma or atheromatous (atherosclerotic) plaque is an essential lesion. Initially, as a yellow streak, it constitutes the accumulation of lipoproteins with cholesterol, phagocytized by myocytes and macrophages (yellow plaque ). Then is covered by a firm, white fibrous cap (white plaque )

- Atheromatous plaques vary in size from approximately 0.3 to 1-2 cm in diameter Atherosclerotic lesions usually involve only a partial circumference of the arterial wall (focal lesions). Focal and sparsely distributed at first, atherosclerosis lesions become increasingly numerous and diffuse as the disease progresses.

Gross view of atherosclerosis in the aorta - mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow.

Atherosclerotic plaques have three principal compon ents: 1. cells , including SMCs, macrophages, and other leukocytes; 2. ECM, including collagen, elastic fibers, and proteogly cans; and 3. intracellular and extracellular lipids

These components form:- superficial fibrous cap (composed of SMCs and relatively dense ECM; beneath and to the

side of the cap is a cellular area consisting of macrophages, SMCs, and T lymphocytes.- necrotic core , containing a disorganized mass of lipid (primarily cholesterol and cholesterol

esters), cholesterol clefts, debris from dead cells, foam cells, fibrin, variably organized thrombus, and other plasma proteins. Foam cells are large, lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages)

Finally, particularly around the periphery of the lesions, there is usually evidence of neovascularization (proliferating small blood vessels).

Schematic depiction of the major components of well-developed intimal atheromatous plaque.

36 - Coronary atherosclerosisHistologic features of atheromatous plaque in the coronary artery

A, Overall architecture demonstrating fibrous cap (F) and a central necrotic (largely lipid) core (C). The lumen (L) has been moderately narrowed. Note that a segment of the wall is plaque free (arrow).In this section, collagen has been stained blue (Masson's trichrome stain).

C, Higher-magnification photomicrograph at the junction of the fibrous cap and core, showing scattered inflammatory cells, calcification (broad arrow), and neovascularization (small arrows).

Here is an occlusive coronary atherosclerosis. The coronary at the left is narrowed by 60 to 70%. The coronary at the right is even worse with evidence for previous thrombosis with organization of the thrombus and recanalization such that there are three small lumens remaining, one of which contains additional recent thrombus.