| What are some vascular pathologies? | When blood passes through capillaries plasma proteins are retained in vascular system and there is a little movement of water and electrolytes in tissues, this balance may be disturbed by pathological conditions (altered endothelial function, increased hydrostatic pressure, or decrease in plasma protein content), all these promote edema (fluid accumulation in tissues from sharp movement of water extravascular.
Edema may be minimal to severe, in lower limb discomfort, in lung life threat, trauma compromises structural integrity, hemostasis in blood prevents excessive bleeding after vessel damage.
Inadequate hemostasis can lead to hemorrhage can lead to hypotension, shock and death.
Impaired clotting can lead to ischemia (MI, PE, stroke) |
| What are elemental lesions? | Flow can be disrupted by heart, venous or arterial damage, obstruction can lead to congestion, edema and rarely infarction, arterial obstruction can lead to angina/heart attack. |
| What is hyperemia and congestion? | Congested tissues get cyanosis, comes up from buildup of deoxygenated Hb in affected area, long term chronic congestion, inadequate perfusion and hypoxia lead to parenchymal cell death and tissue fibrosis.
In these conditions we may get high intravascular pressures, can cause edema or rupture capillaries producing focal hemorrhage. |
| What are macro and microscopic aspects of hyperemia? | Cutting surface of hyperemic tissue is moist and oozes bloo.
In lung (microscopic: blood engorged alveolar capillaries and varying degree of alveolar septa and intra-alveolar hemorrhage, in chronic pulmonary congestion septa thickens and become fibrous, contains hemosiderin-laden macrophages (HF cells) from phagocytosed RBC)
In liver (acute congestion we see distention of central vein and sinosiods and maybe centrilobular hepatocyte necrosis, periportal hepatocytes less hypoxia due to oxygenation by hepatic arterioles, only develop fatty alteration. Chronic passive liver congestion we see central reddish brown depressed (cell loss) hepatic lobules, sometimes fatty tanned liver (nutmeg liver) Microscopy shows necrosis of centrilobular hepatocytes, hemorhage and macrophages loaded w/hemisiderin) |
| What are types of congestion? | Passive (due to circulatory mechanism (stasis), like venous stasis/ hepatic stasis)
Active (during inflammation, increased arterial blood supply by vasodilation of arterioles of microcirculation, local redness and warmth, we see increased weight of organs, observed by reflex nervous mechanism by adaptation during increased functional stress or initial phase of inflammation)
Regardless of type it is associated with edema. |
| What is passive congestion? | 2 types
Loco-regional (venous): any obstruction of blood flow through a vein, by blockage, stenosis, compression, valvular insufficiency (vein occlusion by thrombus of leg/ varicose vein due to valvular insufficiency/ anoxia of endothelium due to increased venous pressure leading to edema (transudate), collagen sclerosis of venous walls, damage of adjacent tissue (varicose ulcers)
Passive Cardiac congestion: obstruction preventing venous return to heart, due to heart failure, birth defects, valvular diseases, myopathies, leads to increase in venous blood pressure in large/small circulation causing venous dilation and decreased blood flow, tissues suffer from hypoxia produce edema, and organs get cyanosis and increased weight |
| What is edema? | Edema is buildup of interstitial fluid in tissues, and can accumulate in body cavities form effusions, anasarca is generalized edema marked by swelling of subcutaneous tissues and accumulation of fluid in body cavities.
types/causes (hemodynamic [congestion due to venous stasis, elevated capillary pressure, post-radiation lymphatic stenosis], inflammatory [infectious, toxic])
Note that hemodynamic transudate edema is low in plasma proteins. |
| What are hemodynamic pathophysiological mechanisms? | Hydrostatic and oncotic pressures guide movement of fluids, elevated osmotic pressure in venous circulation regulates increased hydrostatic pressure in arteries, forms small nte flow of fluid to interstitial space drained by lymphatic vessels, increased hydrostatic pressure or decreased osmotic increase water movement to interstitium, increases fabric pressure until reaches equilibrium again, excess edema fluid will be retained by lymph vessels.
We may get increased hydrostatic pressure (obstruction of vein cause localized edema/global HF cause generalized edema), hydro-sodium retention (edema by increasing hydrostatic pressure and reducing osmotic pressure of plasma by excessive sodium retention seen in diseases compromising kidney function)
Decrease osmotic pressure (reduced albumin, nephrotic syndrome (most imp cause of albumin loss), cirrhosis (albumin not secreted) cause secondary hyperaldo.)
Obstacle in lymphatic drainage (localized obstruction by inflammatory/neoplastic [filariasis lower extremities/genitalia, infiltrates in breast, lymphedema due to radiation. |
| What are the macro and microscopic aspects of edema? | Macro (soft and pale, after incision may get pinkish liquid discharge, predominates in sloping areas (ankle), fabric sometimes retains fingerprint if pressed (bucket), can affect cavities (serous [PE/Ascites], joints [hydroarthrosis]).
Microscopic (pale, weakly eosinophilic, serosity, separating normal building blocks from each other, mostly seen in subcutaneous tissue, lungs, brain. Pulmonary edema see increase in weight, forthy fluid, tinged with blood, mix of air, fluid, RBC. Cerebral edema localized or general, acc to disease) |
| What are consequences of edema? | Depend on site and intensity, compression interfering w/organ function (impair ventricular function in tamponade), inflammatory rxn (prolonged edema), death (glottis edema, lung edema, cerebral edema) |
| What is hemorrhage? | Outflow of blood out of vessels, by rupture or coagulation, arterial hemorrhage bright red, jerky flow. Venous hemorrhage dark red, continuous flow. Capillary hemorrhage, layers, long-term congested tissues. |
| What are etiologies of hemorrhage? | Rupture of vessels/heart (external trauma), rupture of wall weakened by previous pathology (aneurysm, ischemic necrosis, extrinsic disease like tumor or gastric ulcer), erythro-diapedesis altered capillary walls, damage to endothelium by bacterial toxin, coagulopathies, shock, localized inflammation. |
| How is evolution of localized hemorrhage? | Sparse tissue hemorrhage (resorption and healing, inflammatory reaction, local degradation of Hb, macrophages load w/hemosiderin)
Abundant hemorrhage (tissue necrosis, inflammation lead to fibrosis and scar, sometimes calcified)
Hematoma (encased, fibrous shell around degraded blood, rarely secondary infection w/suppuration may occur)
Serous cavity (fibrin deposits make fibrous tissue, thicken serous tissue and give adhesions/symphyses. |
| What are petechia/purpura and echymosis? | Petechia (tiny hemorrhage of skin, mucus membrane or serous surfaces 1-2 mm diameter (thrombocytopenia, defective platelets, impaired vessel wall function/vit C deficiency)
Purpura (hemorrhage slight bleed, 3-4 mm (trauma, vasculitis, increased vascular fragility))
Echymosis (bruises larger subcutaneous hematoma, 1-2 cm, extravasation of RBC phagocytosed by macrophages, color red-blue to blue green to gold brown due to RBC enzymatic activity (Hb, bilirubin, hemosiderin) |
| What are types of hemorrhages? | External (hematemesis, melena, rectorrhagia, hemoptysis, epistaxis)
Intratissue (bruises, intertitial hemorrhage (purpura...))
Internal/collected serous cells (hemopericardium, hemothorax, arachnoid/meningeal sub-hemorrhage) |
| What are hemorrhage consequences? | Local but severe hemorrhage (intracranial even insignificant bleeding in SC tissue can lead to death in brain)
Generalized bleeding (hypovolemic shock if acute, iron deficiency anemia if chronic) |
| What is shock? | Condition in which decreased CO reduces blood perfusion causing cellular hypoxia.
Initially reversible, but if prolonged leads to irreversible tissue damage and fatal. Can complicate severe bleeding, trauma, burns, MI, PE, sepsis.
3 Categories, cardiogenic, hypovolemic and septic.
More rare shock due to loss of vascular tone due to anesthesia/spinal cord injury (neurogenic shock), anaphylactic shock systemic vasodilation and increased vascular permeability by IgE Hypersensitivity. |
| What are types of shock? | Cardiogenic shock (low CO due to HF, can be myocardial infarct, vetricular arrhythmia, compression (tamponade), or flow obstruction (PE))
Hypovolemic shock (low CO/volume to to loss of blood)
Septic shock (SIRS, microbial infection, massive outpouring of inflammatory mediators cause vasodilation and vascular leakage)
All these will lead to tissue hypoperfusion, cellular hypoxia, and metabolic alteration lead to organ dysfunction and organ failure and death (if persists) |
| How is morphology of tissues under effect of shock? | Effects of hypoxic lesions, most common affected brain, heart, kidney, adrenals, GI. We could see fibrin thrombus in any tissue, but more likely in renal glomeruli, we see lipid depletion in adrenal cortex due to increased steroid synthesis, sepsis or trauma in lungs can lead to diffuse alveolar damage causing shock lungs, affected tissues can recover completely if pt survives exception of neurons and cardiomyocytic loss. |
| What are shock lesions in different organs? | ➢ Kidney: massive cortical ischemia or disseminated epithelial necrosis (NTA)
➢ Myocardium: ischemia followed by localized or generalized necrosis.
➢ Lungs: especially severe in septic shock: DAD (diffuse alveolar damage)
➢ Liver: ischemic necrosis in the hepatocyte layer, in the centro-lobular regions, steatosis (sign of hypoxia).
➢ Gastrointestinal tract: mucous erosions or large hemorrhagic gastric and duodenal ulcerations
➢ Adrenals: Delipidation of superficial areas; Acute hemorrhage
➢ Brain: Ischemic encephalopathy, generalized or multifocal, followed by cerebral softening. Laminar necrosis of the hemispheric cortex
➢ Capillaries: disseminated intravascular coagulation
➢ During irreversible shock, necrosis lesions of the regions sensitive to anoxia are visible within a few days (kidney, myocardium, brain) |
| What is thrombosis? | in vivo clot, product of clot is called thrombus, formed thrombus excludes ones formed after death and a collection of blood clotted outside vessels (hematoma not thrombus)
May be occlusive (obliterating) or parietal (more likely to cause embolism)
Pathogenesis is by virshow triad (coagulability, endothelial integrity and change in blood flow) all interact to form thrombus. |
| What is parietal factor in thrombus? | main element, damage of vascular wall lead to endothelial interruption, allows contact of blood and subendothelial ECM, necessary factor for formation of thrombosis and sufficient on its own to form it, often isolated in arterial/intracardiac thrombosis.
Some conditions we have no true endothelial destruction but coagulant endothelial activation cause thromboresistance (bacterial toxins effect)
Causes (trauma [vascular compression/contusion], circulatory turbulence [valves/vascular junctions level], inflammation [arteritis, phlebitis, sepsis], atherosclerosis) |
| What is the hemodynamic factor in thrombosis? | In normal laminar blood flow, platelets (and other blood cells) are mostly found in the center of the vessel's lumen, separated from the endothelium by a slower-moving layer of plasma.
main causes (veins [varicose/prolonged immobilization], arteries [aneurysm/hypotension])
Deleterious effects (endothelial cell activation stimulate procoagulant activity, stasis gets platelets and leukocytes to come into contact w/endothelia, slows clearance of clotting factors and hinders influx of clotting factor inhibitors, endothelial hypoxia) |
| What is the blood factor in thrombosis? | The term hypercoagulability includes all alterations in the coagulation pathways that promote thrombosis.
Hypercoagulability is more inconsistently involved in the formation of thrombosis than the previous two factors.
risk factor, causes include (clotting disease, hyperviscous blood [polycythemia/hemoconcentration], OCP, high cholesterol |
| How is morphoolgy of thrombus? | Three parts: head (white thrombus made of platelet and fibrin adhering to the wall)
Body (mixed thrombus made of RBC/WBC/platelets and fibrin, heterogenous and striated appearance (Zahn's striae), mechanism of alternation is explained by tubrbulence following head obstacle, so we see red bands, white bands)
Tail (red thrombus, formed of coagulated blood w/a little fibrin, floating downstream of the vessel).
They are focally attached to endothelia and spread to heart, develop retrograde direction from point of attachment (Arterial thrombi) while venous extend in direction of blood flow.
spreading part of thrombus is poorly attached to endothelia and can become fragmented and migrated in blood as embolus. |
| What is the difference between red thrombus and post-morteum clot? | Post-mortum (gelatinous, dark red RBC sediment under gravity influence, yellow chicken fat part, not adhering to vein wall)
Red thrombus (more firm, anchor point, light grey ill-defined fibrous streaks on cross-section) |
| What are varieties of thrombus? | Depending on extension to lumen (occlusive/obliterating, or parietal (causing embolism))
Topographic (cardiac, arterial (atherosclerotic plaque), venous (phlebitis) or capillary (DIC)) |
| How are arterial thrombosis? | Triggered by alteration of arterial wall, obliterating, rich in platelets (process of formation activates platelets).
Main cause is atherosclerosis associated w/loss of endothelial integrity and abnormal blood flow, less common can be due to primary inflammatory damage (arteritis/angiitis) or deformation of wall (aneurysm)
Most common location (arteries affected by atherosclerosis, coronary>cerebral>femoral but also renal and mesenteric arteries. Occurs in arterial wall, whitish grey, friable places, main consequence is local ischemia and risk of embolism in upper circulation. |
| How are cardiac thrombosis? | MI can predispose mural cardiac thrombus by dyskinetic myocardial contraction and endocardial damage, rheumatic heart disease may cause arterial wall thrombus causing atrial dilation /fibrillation.
Cardiac and aortic walls are prone to embolization, brain, kidneys, spleen are more likely targets of embolization.
We could also have intracardiac thrombus, triggered by stasis in left atrium upstream of mitral stenosis (atrial stenosis in atrial fibrillation).
Often cause of parietal factor (mural thrombus on area of MI/ heart valves altered by bacterial infection (vegetations), prosthetic valves.) Main risk of progression is embolism.
Cardiac valve thrombus (may get sterile vegetations on uninfected valves in states of hypercoagulability (non-bacterial thrombotic endocarditis), less common sterile warty endocarditis (Libman -Sacks endo) in SLE) |
| How is venous thrombosis? | Main trigger (Stasis), slowing venous flow seen in disorders of prolonged recumbency, increased by disorders of tone of venous wall (varicose) slowing of CO (HF) or venous compression.
Can be associated w/damage to endothelium by toxins (inflammatory and infectious foci thrombus).
Main consequence is local stasis (edema and tissue trophic disorders) and risk of PE for deep vein thrombosis.
occlusive, travel a distant to heart forming long trial in lumen of vessel likely to give embolisms. more embedded in RBC since slow venous circulation (red thrombi), mostly veins of lower limb (90%) but can occur in upper extremities/periprostatic plexus/ovarian/periuterine veins.
Special circumstance (dural sinuses, portal vein, or hepatic vein) |
| How are capillary thrombosis? | Due to stasis and endothelial damage (anoxia, shock, toxin), multiple in case of DIC where we see multiple fibrin platelet thrombi in microcirculatory vascular bed, usually associated with consummate coagulopathy, leading to diffuse bleeding events. Etiologies (gram - sepsis, shock, amniotic embolism, trauma, toxins...)
Located in certain organs (lungs, renal glomeruli, brain, liver) |
| How is evolution of thrombosis? | 1- resolution w/restoration of vascular permeability (spontaneous or therapeutic fibrinolysis for small and recent thrombus)
2-Organization (most common, starts in 48 hours), fibrous in nature, thrombus covered and penetrated by endothelia, and cells from vascular wall to which it adheres, and gradually it is replaced by CT containing collagen, neocapillaries and macrophages. If obliterating thrombus new vessels lead to permeabilization of vascular lumen (mostly incomplete/rudimentary), if no permeabilization thrombus calcifies (Rare) and form varicose vein)
3-Local extension of thrombus (vessel occlusion)
4-Distant migration as embolism
5-Bacterial suppuration of thrombus (rare) |
| What are complications of thrombosis? | ➢The main complications are the local extension of the thrombus leading to sometimes vessel occlusion and embolisms (distant migration).
➢These complications result in heart attacks due to arterial thrombosis and infarctions due to venous thrombosis.
➢Bacterial suppuration of the thrombus is another complication, rarely observed |
| What are emboli? | detached solid, liquid or gaseous intravascular mass carried by blood from origin to remote site, most come from a thrombus (thromboembolism) rare fat droplets, air bubbles, nitrogen, atherosclerotic debris (cholesterol), tumor fragment, bone marrow, amniotic fluid...
cause partial or complete vascular occlusion, depending on site can stop anywhere in vascular tree, main consequence is ischemic necrosis (infarction) of downstream tissues, while embolization in pulmonary circulation results in hypoxia, hypotension and Righ HF. |
| What are types of emboli depending on composition? | Cruel (blood- 95%): fragment of thrombus in circulatory system, most are in veins of lower limbs/pelvis, cardiac arterial aneurysm, arterial near a bifucation (carotids)
Microbial, cellular (cancerous...), Fat (marrow/meds), Atheromateous (ulceration of a plaque), Gaseous (decompression sickness), Tumor. |
| What are different types of emboli depending on route? | Direct (w/direction of circulation, stops downstream when space cannot be passed, in veins of great circulation (stops at pulmonary artery branch, if large blocks trunk of pulmonary artery or right or left PA, smaller go intraparenchymal (right chamber) Left chamber stops in lower limb, kidney, spleen, brain, liver...)
Retrograde (small neoplastic emboli)
Paradoxical (right to left circulation through abnormal path (patent foramen ovale for example)) |
| What are different types of emboli depending on the seat? | Blood circulation system (small circulation (right/ PE) extensive circulation (systemic embolism cerebral, coronary, renal splenic lower limb, most embolus types)
Lymphatic circulatory system (carcinomatous embolus) |
| What are consequences of embolism? | Acc to location and size, Systemic embolism (ischemia, hypoxia, anoxia (acute/chronic/total/relative), if involve IMs cause intolerance to exertion, painful claudication or irreversible damage of ischemic gangrene, if involves viscera cause exterional intolerance, lead to angina/heart attack)
Embolism of small circulation (acute pulmonary heart (suddent pulmonary HTN lead to right heart failure w/anoxia /shock) and general manifestations (malaise to sudden death)) |
| What is pulmonary thromboembolism? | ➢ 99% are made up of all or part of a mobilized thromboembolism
➢ Consequences: Ischemic necrosis of distal tissues
➢ > 95% come from the deep veins of the IM
➢ Most (60-80%) silent, because the embolus is small
➢ Sudden death: by massive embolism in the trunk of the pulmonary artery (interruption of circulation leads to cardiac arrest).
➢ Acute right heart failure if a single pulmonary artery or large branch artery is occluded
➢ Chronic heart failure (called "chronic pulmonary heart") as a result of multiple small distal pulmonary embolisms that often go unnoticed (reduction of vascular bed leads to increased pulmonary resistance and pulmonary arterial hypertension) |
| What is systemic thromboembolism? | Those that migrate to mainstream, 80% intracardiac wall origin, remaining by aortic aneurysm, ulcerated plaques, fragmentation of vegetative valve. May be paradoxical embolisms
Can migrate to large number of locations (MI (75%), brain, intestines, kidneys, spleen, MS) consequence depends on collateral circulations, infarction in obilterated artery area. |
| What is ischemia? | Decrease in arterial blood supply in a limited area of body, causes hypoxia/anoxia.
causes include partial or total obliteration of arterial lumen (atherosclerosis, arteritis, thrombosis, embolism, compression, prolonged arterial spasm, arterial dissection)
Factors influencing impact (intesity, duration, sensitivity of tissues (neurons, myocardium epithelia very sensitive), possibility of substitue circulation like anastomse/collaterals, rapid installation (sudden no time for replacement, prolonged irreversible cell damage) |
| What are consequences of ischemia? | ➢Complete and extensive ischemia will be responsible for complete necrosis of the ischemic area: infarction, softening, gangrene.
➢Incomplete and transient ischemia will be accompanied by intense but transient pain occurring during the ischemic phase, and to which various semiological terms correspond: intermittent claudication of a lower limb/stress angina/intestinal angina
➢Incomplete and chronic ischemia will lead to the appearance of atrophy (with apoptosis of the most functional cells) with progressive replacement of the tissue by fibrosis (e.g. stenosis of the renal artery responsible for atrophy and fibrosis of the kidney). |
| What is an infarct? | Focus of ischemic necrosis due to abrupt interruption of arterial blood supply w/out collaterals, often brutal and total.
Size should exceed 1.5cm (brain) or 2cm (myocardium), most common in end-stage arterial vasculature organs.
Comes in morphological varieties (white/pale pure ischemia (solid organ bloodless w/arterial obstruction, coagulation necrosis, heart attack affects heart, kidneys, spleen, brain...) or red (hemorrhagic w/secondary blood infiltrates)) |
| How are red infarcts? | Occur due to venous occlusion (ovarian torsion eg), loose tissues where blood can pool (lungs), dual-circulation organs (or a lot of collaterals like lungs), previously congested tissues, flow restored after a heart attack. |
| What are the different phases of an infarct? | ➢ from 6 (and especially from 24) to 48 hours: the lesion gradually becomes visible.
✓ It corresponds to an arterial distribution area (pyramidal shape with a peripheral base), paler and softer than the rest of the organ,
✓ gradually becomes more distinctly white or yellowish and surrounded by a red congestive border;
➢ During the 1st and 2nd weeks:
✓ The limits of the infarction are becoming clearer and clearer, its surface is depressed compared to the healthy tissue.
✓ It is surrounded by soft, red tissue (inflammatory granulation tissue, then fleshy bud)
➢ From the 3rd week onwards, a whitish, fibrous scar gradually develops, with thinning and retraction of the injured area |
| How is the mechanism of an infarct? | Ischemia leads to anoxia lead to anaerobic glycolysis, no glycogen, oxidative phosphorylation stops, no ATP, K+ go out and Ca2+ become intracellular, phospholipase activity increase, membrane damage permits water entry to cells, then necrosis of epithelia by release of lysosomal enzymes, leading to cell death (apoptosis) |
| What are causes of a heart attack? | Organic arterial occlusion (most common), Thrombosis of an atherosclerotic plaque or arterial lesion, embolism, functional arterial occlusion (rare) due to spasm (coronary/cerebral/heroin), or low circulatory flow (renal/cerebral) |
| How is morphology of an infarct? | Early stage (6 hours) no visibile changes.
6-48 hrs: coagulation necrosis, cell contour preserved, acute inflammatory reactions surround it.
Remanider 1st week: necrotic territory undergoes progressive centripetal destruction by macrophages, replacement of necrotic tissue w/fleshy bud.
1-2 weeks (healing, fibrosis, conjunctival organization) |
| What are factors influencing tissue necrosis extent? | ➢ The duration of circulatory interruption
➢ Sensitivity of the tissue and cell to anoxia.The higher the oxidative metabolism, the more vulnerable they are; ́Nervous tissue is the most sensitive.
➢ The type of terminal circulatory system makes the tissue more vulnerable than the anastomotic system; The presence of innate or acquired anastomotic replacements of the circulatory system, or a dual-circulation device (lung) provide relative protection to the tissue. |
| What is an MI? | Important, main cause is arterial atherosclerosis, topography depends on location, depends on coronary artery affected, variable distribution on wall thickness (transmural - entire thickness, or subendocardial - innermost layer only)
Macroscopy (usually LV, red soft first, then yellow, then transluscent then white and hard)
Microscopy (necrosis w/in 48 hours acidophilic fibers (coagulation necrosis) or pale vacuolized fiber (liquefication), interstitial inflammatory cells, 10th day conjunctival organization (granuloma them cell poor fibrosis))
Complications (arrhythmias, HF, heart rupture, mural thrombus/embolus, cardiac aneurysm, angina, Dessler's syndrome, recurrence, sudden death |
| What are the topological forms of infarction? | ➢Softening: refers to a white cerebral infarction (which very quickly takes on a very soft consistency).
➢"Dry" gangrene: a localized infarction of one extremity (toe, limb, nose, ear) following the obliteration of a terminal artery.
➢Suppuration: due to superinfection or during a heart attack aftermigration of septic embolus |
| What are micro and macroscopic aspects of hemorrhagic infarct? | Macro (The infarction area is initially dark red, poorly bounded, firmer than the adjacent tissue. As with any infarction located in a solid organ, it is typically pyramidal in shape, with a peripheral base)
Micro (persist alveolar architecture, massive hemorrhage infiltrate, white heart attack course, scar pigmented w/histiocytes w/hemosiderin, at pulmo risk of secondary infection at intestine risk for peritonitis due to perforation (Surgery)) |
| What is an atherosclerosis? | ➢ Atherosclerosis affects the elastic arteries and the most important muscular arteries: larger ones (aorta, coronary trunks, renal arteries, extra-parenchymal cerebral arteries, etc.).
➢ In areas of turbulence, the following are particularly prevalent: bifurcations, bends, birth of collaterals (ostia) and artery segments "attached" to the skeleton (e.g. subdiaphragmatic aorta).
➢ According to the W.H.O. (1957), atheroma is a "variable association of reshuffling of the intima of large and medium caliber arteries, consisting of in a segmental accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue, and calcium deposits, all accompanied by changes in the media." |
| What are topological forms of atherosclerosis? | 1. On the aorta: the subdiaphragmatic abdominal segment is the most particularly affected at the level of the aortic junction. On the thoracic aorta, the ascending segment and the top of the arch are the most interesting.
2. On the cervico-cephalic arteries: the lesions affect the carotid and vertebral arteries, in their cervical and intracranial path.
3. At the level of the viscera: lesions develop on the first centimeters of the vessel (coronaries, renal arteries, mesenteric arteries, etc.)
4. At the level of the limbs: lesions mainly affect the limbs lower and may extend to the middle of the leg. Upper extremity involvement is rare.
5. At the level of the pulmonary arteries: atherosclerotic lesions only exist in the case of associated pulmonary arterial hypertension. |
| What are macroscopic classifications of atherosclerotic lesions? | The WHO offers four grades:
grade I: early stage consisting mainly of lipid streaks;
grade II: middle stage with uncomplicated atherosclerotic plaques;
grade III: ulcerated and necrotic plaques with hemorrhages;
grade IV: massively calcified and ulcerated plaques |
| What are microscopic classifications of atherosclerotic lesions? | ➢ Early lesions:
type I: presence of a few subendothelial foamy macrophages visible in OM
type II: lipid streak (visible macroscopically) corresponding to clusters of foamy histiocytes in the intima, more numerous than before.
➢ Intermediate lesions:
type III: accumulation of extracellular lipids in small quantities
➢ Advanced lesions:
type IV: appearance of a lipid center, with cholesterol crystals, without fibrosis
type V: classic fibro-lipid atherosclerotic plaque,
type VI: complicated atherosclerotic plaque (VIa: ulceration, VIb: hemorrhage, VIc: thrombosis) |
| What is an atherosclerotic plaque/ uncomplicated atheroma? | • Variable in size, yellowish
• It protrudes into the lumen of the artery.
• It is often calcified.
• Its section shows a lipid center, made up of foam cells and slits of cholesterol crystals, surrounded by a fibrous sheath.
• The fibrous sheath is made up of collagen fibers enclosing smooth muscle cells.
• T cells are also observed.
• The endothelium covering the plaque is intact. |
| How are early lesions of an atherosclerotisis? | ➢ The earliest, it is only microscopic: isolated foamy macrophages appear in the subendothelial layer of the intima.
➢ Lipid Streak:
▪ the first lesion seen on gross examination.
▪ Corresponds to the grouping of foamy macrophages into small clusters in the subendothelial layer of the intima.
▪ These elongated, yellowish, flat lesions run parallel to the blood flow.
▪ They are preferentially located on the thoracic aorta.
▪ These lesions can be observed before the age of one year and peak in extension and incidence in adolescence. They can either regress and disappear, or gradually progress to the other atherosclerotic lesions. They do not cause any clinical manifestations. |
| How are intermediate atherosclerotic lesions? | • Flat Gelatinous
• Macroscopy:
➢ Greyish, translucent plaque on the intima, 0.5 to 1 cm in diameter.
• Microscopy:
➢ subendothelial edema (rich in chondroitin and heparan sulfate, but lacking lipids).
➢ These lesions are due to an “exudate", i.e. the passage of plasma under the endothelium by increasing endothelial permeability.
➢ These lesions can regress, turn into fibrous plaque, or they can become lipid-laden and develop into atherosclerotic plaques. |
| How are advanced atherosclerotic lesions? | Atherosclerotic plaque
Macroscopy:
Lenticular lesion 0.5-3 cm in diameter, smooth, yellowish surface, becoming irregular and grayish
as size increases
Microscopy:
Center made up of "foamy" cells and necrosis rich in cholesterol crystals located in an extracellular position ("lipid slurry" = atheroma) Peripheral fibrosis gradually densifying by separating the central necrosis from the endothelium and dissociating the media in the deeper areas.
The atherosclerotic lesions that form will evolve over time and gradually spread: the plaques can converge and create a "paved aorta" appearance. During its evolution, the plaque can calcify, i.e. become impregnated with calcareous salts. The plaques can turn into "eggshells" that make the arterial wall rigid (visible on X-rays) |
| What are consequences of plaque and its complications? | Plaque ulceration (Partial destruction of coating, could be central or peripheral (if calcified), erosion to deep ulcer)
Hemorrhage and intraplaque hematoma (blood pressure breaches ulceration, or rutpure of intrapalque neovessels)
Plaque thrombosis (mural if large, obliterative if small, affect organs downstream, e.g thrombosis obliterans)
Arterial dissection (in media, blood enters ulcer)
Embolism (cruoric/platelet/atheroma, favored by ulceration)
Stenosis (medium sized arteries, progressive ischemia)
Aneurysm (can get mural thrombus) |
| What are anatomical clinical correlations of plaque? | ➢The clinical manifestations related to the presence of atherosclerotic plaque are very inconsistent and the correlations are imprecise, making it difficult to predict clinical manifestations based on the size and evolution of a plaque.
➢Schematically, uncomplicated stenotic plaques (> or = 70% in the coronary territory) are associated with symptomatology appearing on exertional stress (exertional angina, intermittent claudication).
➢Complicated plaques are responsible for paroxysmal symptomatology and clinical accidents: myocardial infarction, sudden death, resting angina, stroke for example.
➢But these manifestations are inconsistent and a complicated plaque can remain asymptomatic. |
| What are anatomical forms of atherosclerosis? | ➢Aortic atherosclerosis
Predominates in the subdiaphragmatic aorta (or abdominal aorta).
May be associated with aortic junction syndrome associated with circulatory failure of the lower limbs and progressive sexual impotence.
➢ Peripheral Atherosclerosis
That of the visceral arteries, the collaterals of the aorta and the arteries of the lower limbs. The consequences are directly related to the topography of the arterial involvement:
➢ coronaries: angina pectoris and myocardial infarction;
➢ carotid arteries and Willis polygon: stroke;
➢ renal arteries: secondary arterial hypertension;
➢ arteries of the limbs (especially lower limbs): intermittent claudication and dry gangrene
➢ Mesenteric arteries: intestinal angina syndrome. |
| What are risk factors of atherosclerosis? | ➢Atherosclerosis is common in developed countries, rarer in countries in Asia, Africa, or Latin America.
➢The risk is higher in men than in women during periods of estrogenic activity; A family predisposition exists, sometimes genetic
(hypercholesterolemia) but mostly linked to eating habits.
➢Hyperlipidemia, high blood pressure, smoking, and vascular lesions (senescence, diabetes) are the main risk factors. |
| How is histogenesis of atherosclerosis? | 1. Thrombogenic Theory
2. "Aggression" Theory
3. Theory of intimal myocyte multiplication
➢Atherosclerosis is a complex disease involving multiple exogenous and interfering with each other and resulting in a common lesion of lipidoprotidoglucidic and macrophage infiltration of the arterial wall, with sclerosis.
➢Atherosclerosis is considered to be a chronic inflammatory response of the wall to an initial endothelial attack, the progression of which would be maintained by interactions between plasma lipoproteins, monocyte-macrophages, T lymphocytes and the constituents of the arterial wall. In fact, cells inflammatory processes are present within the lesions, underscoring the role of the inflammation in lesional development. In addition, inflammatory phenomena are also implicated in the occurrence of complications |
| How is synthesis of atherosclerosis? | ➢Damage to the endothelium leads to increased patency and adhesion of platelets.
➢Lipoproteins enter the intima.
➢These lipoproteins undergo oxidative degradation.
➢Monocytes adhere to the intima, penetrate it, are activated, phagocytose the released lipids and transform into foamy macrophages.
➢Growth factors are produced. They lead to the migration of muscle cells from the media to the intima, their multiplication, the elaboration of an extracellular collagen matrix on which mineral salts (in particular calcium) are deposited.
➢Complications occur, especially as soon as the intima is ulcerated (thrombosis and embolisms) and the elastic laminae are destroyed (aneurysm). |
| What is Moenckeberg medicalosis? | ➢Affects the muscular arteries
➢It causes calcified fibrosis that begins in the LEI and then spreads to the entire media
➢Its risk factors are senescence and hypertension
➢Consequences: Null |
| What is arteriosclerosis? | ➢It is a diffuse intimal thickening without lipid deposits that ispart of age-related changes and arterial hypertension.
➢Its spread is more diffuse than that of atherosclerosis.
➢Arteriosclerosis should not be confused with atherosclerosis |
