Pathophysiology Lecture 7: Cardiovascular System (Part 2) PDF

Pathophysiology ‫خالد‬.‫د‬ Lecture 7 Cardiovascular system (part 2) Morphologically atherosclerosis passes in 2 stages: 2- Atheromatous 1- Fatty streaks Plaques: ...

Pathophysiology ‫خالد‬.‫د‬ Lecture 7 Cardiovascular system (part 2) Morphologically atherosclerosis passes in 2 stages: 2- Atheromatous 1- Fatty streaks Plaques:  1- Fatty streaks: characterized by intimal thickening and lipid accumulation These streaks are composed of lipid-laden macrophages (foam cells). Gross: multiple yellow, fat spots (fatty dots) less than 1mm in diameter that coalesce into large streaks of 1cm or more. The lesions are not raised or slightly raised and do not cause significant flow disturbance. 2- Atheromatous Plaques: Also called fibro-fatty plaque (atheroma): are white to yellow raised lesions; they range from 0.3 to 1.5 cm in diameter but can coalesce to form larger masses. When a thrombus is superimposed on ulcerated plaques, a red-brown color imparts.  These plaques consist of two parts: Core: soft, yellow, consists of Cap: firm, white, cholesterol & fibrous cap. cholesterol esters.  Atherosclerotic plaques have four principal components: (1) cells including variable numbers of SMCs, macrophages, and T lymphocytes (2) ECM including collagen, elastic fibers, and proteoglycans (3) intracellular and extracellular lipids (4) calcifications in later stage plaques.  Acute Plaque Change Plaque erosion or rupture typically triggers thrombosis, leading to partial or complete vascular obstruction and often tissue infarction Atherosclerotic plaques are susceptible to several clinically important changes: 1. Rupture, ulceration, or erosion of the surface of atheromatous plaques exposes the bloodstream to highly thrombogenic substances and leads to thrombosis. 2. Organization of thrombus: If the patient survives thrombosis formation, the thrombus may organize and become incorporated into the growing plaque. 3. Hemorrhage into a plaque. Rupture of the overlying fibrous cap or of the thin-walled vessels in the areas of neovascularization can cause intraplaque hemorrhage 4. Atheroembolism. Plaque rupture can discharge atherosclerotic debris into the blood stream, producing microemboli. 5. Aneurysm formation. Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes weakness and potential rupture. Intra-plaque hemorrhage  Aneurysms Aneurysms are congenital or acquired dilations of blood vessels or the heart. True” aneurysms involve all three layers of the artery (intima, media, and adventitia) or the attenuated wall of the heart. False aneurysm (pseudoaneurysm) results when a wall defect leads to the formation of an extravascular hematoma that communicates with the intravascular space (“pulsating hematoma”).  Vasculitis Is a general term for vessel wall inflammation. The clinical manifestations largely depend on the specific affected blood vessels. Vasculitis mostly affects small vessels (arterioles, capillaries, and venules). However large vessels (e.g., large or medium-sized muscular arteries), can be affected The most common pathogenic mechanisms of vasculitis Immune-mediated inflammation Direct vascular invasion by infectious pathogens.  Infections also can indirectly precipitate immune-mediated vasculitis By generating Triggering cross- immune complexes reactivity.  Other causes of vasculitis Physical and chemical injury, including that due to radiation, mechanical trauma, and toxins.  It is critical to distinguish between Infectious and immunologic mechanisms because immunosuppressive therapy is appropriate for immune-mediated vasculitis But could Exacerbate infectious vasculitis  Noninfectious Vasculitis The main immunologic mechanisms underlying noninfectious vasculitis are Immune complex deposition Antineutrophil cytoplasmic antibodies Anti-endothelial cell antibodies Autoreactive T cells 1-immune Complex–Associated Vasculitis. This form of vasculitis is seen in immunologic disorders such as systemic lupus erythematosus that are associated with autoantibody production. Immune complex deposition is implicated in the following vasculitides: ❑ Drug hypersensitivity vasculitis. ❑ Vasculitis secondary to infections.  Drug hypersensitivity vasculitis. In some cases, drugs (e.g., penicillin) act as haptens by binding to host proteins; Other agents are themselves foreign proteins (e.g., streptokinase). The clinical manifestations can be mild and self-limiting, or severe and even fatal; skin lesions are common. It is always important to consider drug hypersensitivity as a cause of vasculitis since discontinuation of the offending agent usually leads to resolution.  Vasculitis secondary to infections. Antibodies to microbial constituents can form immune complexes that circulate and deposit in vascular lesions. In up to 30% of patients with polyarteritis nodosa, the vasculitis is attributable to immune complexes composed of hepatitis B surface antigen (HBsAg) and anti-HBsAgs antibody.  2- Anti-Neutrophil Cytoplasmic Antibodies. Many patients with vasculitis have circulating antibodies that react with neutrophil cytoplasmic antigens, so-called anti-neutrophil cytoplasmic antibodies (ANCAs). Anti-neutrophil cytoplasmic antibodies are very useful diagnostic markers The two most important ANCAs are Antiproteinase-3 (PR3-ANCA), Anti-myeloperoxidase (MPO-ANCA),  Infectious Vasculitis Localized arteritis may be caused by the direct invasion of arteries by infectious agents, usually bacteria or fungi. Vascular infections can weaken arterial walls and result in aneurysms or can induce thrombosis and infarction.  Disorders of blood vessel hyperreactivity Myocardial Raynaud Vessel Phenomenon Vasospasm  Raynaud Phenomenon Raynaud phenomenon results from exaggerated vasoconstriction of arteries and arterioles in the extremities, particularly the fingers and toes, but also sometimes the nose, earlobes, or lips. The restricted blood flow induces paroxysmal pallor or cyanosis. Produce red-white-and-blue” color changes. Raynaud phenomenon can be A primary Secondary to other disorders. Primary Raynaud phenomenon (previously called Raynaud disease) Is caused by exaggerated central and local vasomotor responses to cold or emotion. It affects 3%-5% of the general population and mostly occurs in young women. The course usually is benign, but in chronic cases, atrophy of the skin, subcutaneous tissues, and muscles may occur. Secondary Raynaud phenomenon refers to vascular insufficiency due to other arterial diseases including systemic lupus erythematosus, scleroderma, or even atherosclerosis  Myocardial Vessel Vasospasm Excessive constriction of myocardial arteries or arterioles may cause ischemia and persistent vasospasm can even lead to tissue infarction. It is aggravated by endogenous mediators (epinephrine) or exogenous (cocaine or phenylephrine). In some susceptible persons, extreme psychological stress with the concomitant release of catecholamines can lead to pathologic vasospasm.  When vasospasm of cardiac arterial or arteriolar beds (so-called cardiac Raynaud) is of sufficient duration (20 to 30 minutes), a myocardial infarction occurs. The outcome can be 1. Sudden cardiac death (probably caused by a fatal arrhythmia). 2. An ischemic dilated cardiomyopathy—so-called Takotsubo cardiomyopathy (also called “broken heart syndrome,” because of the association with emotional duress).