¡GoConqr estrena diseño! Cuéntanos qué te parece.

Regístrate gratis

Fichas

ATHEROSCLEROSIS MFS

Dua Ga Inglés 89 fichas

Fichas del conjunto (89)

  1. 1ATHEROSCLEROSISMFS
  2. 2Other names?atheroma, atheromatous/ fibrofatty/ fibrolipid plaque.
  3. 3Definition?-lipid deposition and intimal thickening of large and medium sized arteries→ fatty streaks and atheromatous plaques→ protrude into and obstruct vascular lumina and may weaken the underlying media.
    -Intimal plaque that obstructs blood flow Consists ot a necrotic lipid core (mostly cholesterol) with a fibromuscular cap often undergoes dystrophic calcification
  4. 4What arteries does it normally affect?abdominal aorta, coronary artery,
    popliteal artery, and internal carotid artery are commonly alfected.
  5. 5what are the risk factors (Major and Minor)?“ATHEROMAS”
    -A: Arterial Hypertension
    -T: Tobacco Smoking
    -H: Hereditary, Familial Hypercholesterolemia
    -E: Endocrine (Diabetes Mellitus, hypothyroidism, Hyperestrinism, Oral contraceptive use).
    -R: Reduced physical activity; Sedentary lifestyle
    -O: Obesity
    -M: Male gender
    -A: Age( Increasing age)
    -S: Stress
  6. 6What are the risk factors (nonmodiliable)?-age (number and severity of lesions increase with age),
    -gender (increased risk males and postmenopausal females; estrogen
    is protective)
    -genetics (multifactorial, but family history is highly predictive of risk).
  7. 7What are the MAJOR (modiliable) risk factors ?• Hypertension
    • Smoking
    • DM
    • Hyperlipidemia
  8. 8What are the OTHER (modiliable) risk factors ?• Inflammation
    • C Reactive Protein
    • Lipoprotein(a)
    • Hyperhomocystenuria
    • Metabolic syndrome
    • Exercise/stressful lifestyle/Type A personality
    • hypercholesterolemia {LDI.
    increases risk; HDL decreases risk),
    • smoking
    • diabetes.
  9. 9WHY are the major risk factors for atherosclerosis are at the same time the major risk factors for ischemic heart ?one causes the other
  10. 10why does Hyperlipidemia cause atherosclerosis?hypercholesterolemia is a major risk factor. Elevated cholesterol levels can induce atherosclerosis in the absence of other risk factors.
  11. 11why does Hypertension cause atherosclerosis?cause mechanical injury to the vessel wall and is a major risk factor in the development of ischemic heart disease, and cerebro–vascular disease.
    Males aged 45 – 62 years, with a blood pressure >169/95mm Hg are at 5X the risk for IHD as compared to normal individuals.
  12. 12why does Cigarette smoking cause atherosclerosis?increased levels of LDL and carbon monoxide in the blood→ carboxy-hemoglobin→ hypoxia in the arterial wall→ hypoxic injury→ atherosclerosis.
  13. 13why does diabetes cause atherosclerosis?increases the aggregation of platelets, level of LDL, and reduces level of HDL→ glycosylation of collagen.
  14. 14What is the "Hypothesis of atherogenesis"?based on the ‘response to injury hypothesis’
  15. 15What ‘response to injury hypothesis' states?-Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium
    -Progression of the lesion is due to interaction between lipoprotein, macrophages, T-Lymphocytes and normal cellular constituents of the arterial wall.
  16. 16What is the pathogenesis\steps involved i therogenesis-atheriosclerosis\responf to ijury hypothesis? KNOW ORDER U MF1. Endothelial injury/dysfunction
    2. Accumulation of lipoproteins (LDL/ cholesterol esters in the vessel wall
    3. Platelet adhesion
    4. Monocyte adhesion to injured endothelium by adhesion proteins (foam cells)
    5. Recruitment of SMC from media
    6. Proliferation of SMC and ECM Which leads to fibrous cap
  17. 17STEP 1 (Endothelial injury)-triggerS for development of atherosclerosis.
    -injury→ endothelial dysfunction→ increased permeability, leucocyte adhesion & thrombus formation.
    -Lipid accumulates in the intimal space by transcytosis and is associated with abnormal endothelial cell function such as vasodilatory response
  18. 18What are some Important causes of endothelial injury· Cigarette smoking. (toxins circulating and injuring the endothelial)
    · Viruses and other infectious agents.
    · Irradiation.
    · Immune complex deposition.
    · hemodynamic stress(hypertension causing some degree of endothelial dysfunction, altering their permeability)
    · Hyperlipidemia (high fat diet\high levels of LDL and low HDL)
  19. 19STEP 2 Accumulation of lipoproteins (LDL/ cholesterol esters) in the vessel wall-mainly LDL because of its high cholesterol content
    -disruption of the permeability cuz LDL in the circulation starting to move into the subendothelial space'
    -Activated endothelial cells express adhesion molecules such as ICAM1 and VCAM1
  20. 20STEP 3 Recruiting inflammatory cells(MONOCYTES) and formation of FOAM CELLSLDL enters into the intima→ Oxidised LDL
    → affects the monocytes and T lemphocytes to enter intimia(enter from blood through adhesion molecules)→they accumulate, proliferate→macrophages, →engulf lipid(oxidized LDL)→lipid laden foam cells
  21. 21How does LDL inversely affect the endothelium?Oxidised LDL → endothelial cytotoxicit y→ damage to endothelium
  22. 22What is CRP and why do many patients suffer from high CRP (c reactive protein?-It is an acute phase reactant by the liver as a response to INFLAMMATION and IL-6
    -ELEVATED IN OBESE PEOPLE cuz it paves the road for atherosclerosis and endothelial injury
  23. 23STEP 4 Adhesion of platelets to the area of atherogenesis-Injury and Exposure of underlying thrombogenic material->elicit platelet aggregation
  24. 24what does platelets secrete?cytokines and growth factors {ADP, PDGF, thromboxane A, FBGF, TGF alpha…}
  25. 25STEP 5 Recruitment of SMC from media TO INTIMIA (SO FAR ALL MOVES TO INTIMIA)Due to factors released by: ACTIVATED PLATELETS + MACROPHAGES + VASCULAR SMOOTH MUSCLE CELLS {VSMCs)
  26. 26Why is step 5 important?Because it is the trigger to ATHEROSCLEROSIS
    while all steps before were normal response to injury (LDL part happens in dyslipidemia smartass -_-
    -some undifferentiated cells from the circulation are recruited and differentiate into fibroblasts and smooth muscle cells
  27. 27STEP Intimal Vascular smooth muscle cell proliferation-under influnce of factors mentioned bfore
    -Fat may accumulate→VSMCs become another type of foam cells.
    -SYNTHESIS OF ECM AND DEPOSITING COLLAGEN (matrix proteins LIKE collagen, elastic fibres, proteoglycans)
  28. 28Are the smooth muscle cells in media similar to smooth muscle cells recruited to intima?NO
    -recruited:
    1.the effect of the cytokines and growth factors→WILL KEEP PROLIFRATING
    (high proliferating capacity mf)
    2.more extracellular matrix and collagen→mass that protrudes INSIDE the lumen and pushing the endothelial cells
    3. internal core is made up of foam cells+fat accumulating outside the foam cells extracellularly
    4. SMCs →FIBROUS
    5.THEY CHANGED FROM CONTRACTILE TO REPAIR SMCs
  29. 29Why does fibrous cap form?due to SMCs proliferating on the outer edge of the plaque forming collagen and fibrous tissue
  30. 30What is the stage that might be present before the development of the plaque?-fatty streaks
    -NOT elevated into the lumen
    -usually occur at the “ostia” of the blood vessels
    -not pathological
    -people with risk factors? probably develop the atherosclerosis plaques
  31. 31what is the diffrence between repair VSMC in intimia and Contractile VSMC in media?1.Repair VSMC – intima:
    -Contractile proteins-
    -Growth factors ++
    -High matrix production
    -Production of MMPs ++
    2.Contractile VSMC – media
    -Contractile proteins ++
    -Low growth factor
    -Low matrix production
    -Low MMPs production
  32. 32what is the ostia of the blood vessel?where small BV branch from the bigger one
  33. 33*STEP 7 Thrombosistheromatous plaque enlarges by attaching fibrin and cells from the blood→ thrombus formed becomes a part of the plaque.
  34. 34*STEP 8 (FINAL)8. Complicated atheromatous plaque
  35. 35(very important) why does the cover of the plaque from the lumen side has to be covered by normal endothelial cells?to prevent superadded thrombus formation
  36. 36Why are The edges of the plaque are the most fragile places of the plaque?bcz it has newly formed blood vessels and tends to rupture easily by any acciden
  37. 37When does the fibrous cap become fragile and thin?-There is always a balance between matrix metalloprotinases and inhibitors of MMPs in the tissue, the MMP break down the tissue
    It becomes fragile when MMP breakdown of tissue dominates
  38. 38what happens when the fibrous cap become fragile and thin?atheroma would be liable to rupture
  39. 39How does the fibrous cap(70% matrix protiens) remain thickned and more stable?through inhibitors of MMP to stop this breakdown
  40. 40What are the componants of Atheromatous plaque?1) Cells: {foam cells, smooth muscle cells, macrophages}
    2) lipids: {fats intracellular in foam cells, or extracellular }
    3) matrix: {collagen}
    CHECK SLIDE 14 RAHAFS SLIDES
  41. 41What are the charectaristics of stable atherosclerotic plaque1- Thick Fibrous cap (VSMCs and matrix)
    2- Intimal VSMCs (repair phenotype)2 - 3 - 3-Small lipid core(<30%)\High cholesteryl esters\High tissue factor
    4 – Low inflammatory cell count
    5 - Endothelial cells
  42. 42What are the characteristics of a valurnable atherosclerotic plaque?1- Denuded endothelium
    2- thin, friable fibrous cap with a reduced collagen and VSMC content
    3-Increased circumferential wall stress on the fibrous cap
    4- Large lipid core(>70%-exceeds 40% of tot plaque volume)\High cholesteryl esters\High tissue factor
    5-Disorganised collagen
    6- Neo intimal hyperplasia
    7- Loose connective tissue
    8-high infiltration of macrophage and T-lymphocyte cells
  43. 43What are Determinants of Plaque Stability?• 1 – Size of atheromatous core
    • 2 – Thickness of fibrous cap
    • 3 –Balance of Inflammation and repair of fibrous cap
  44. 44vulnerable plaques are believed to account for only 10–20% of all coronary lesionsresponsible for as many as 80–90% of acute clinical events
  45. 45What are Characteristic features of atherosclerotic plaques that are vulnerable to rupture include:{ large lipid core, a high infiltration of inflammatory cells, a thin, friable fibrous cap in which the concentrations of collagen and VSMCs are reduced, and increased circumferential wall stress on the fibrous cap}
    High levels of macrophage infiltration, and slowed proliferation and enhanced early senescence of VSMCs contribute to this increased risk of plaque disruption
  46. 46What happens in Advanced atherosclerosis?-Intimal VSMCs become senescent
    -Activated macrophages induce intimal VSMC apoptosis and degrade the matrix in the fibrous cap
  47. 47What other substance can cause endothelial damage beside oxLDL?nicotine
  48. 48How does the VSMCs lessen\become fewer?1-Activated macrophages: structurally weaken fibrous cap+induce VSMC apoptosis+reduce the capacity for plaque repair.
    2-Early senescence and slowed proliferation of intimal VSMCs are further features of advanced atherosclerosis→plaque instability and rupture(instead of repair)
  49. 49How does fibrous plaque confers stability on the atherosclerotic lesion?providing a barrier that separates the lipid-rich, thrombogenic materials within the plaque’s
    core from the circulating blood,
  50. 50Towards plaque rupture-Intimal VSMCs become senescent\apoptotic\lower rate of prolifration than medial
    -Macrophages kill VSMCs and degrade the matrix
  51. 51Why does the cap weaken?infiltration of macrophage-derived foam cells result in local tensile strength reduction within the cap
  52. 52What happens as a result of the weakned cap?-physical disruption of the collagen network by the infiltration of inflammatory cells
    -show active participation of inflammatory cells in the destruction of both the constituent materials of the fibrous cap and of the VSMCs.
  53. 53what are other factors that favour rupture than repair cuz they inc apoptosis of intimal VSMCs?-Inflammatory cell infiltration reduces local tensile strength in the fibrous cap
    -Inflammatory cells are active participants in the destruction of both the extracellular matrix (from which the cap is constructed)and the VSMCs (produce and maintain the cap)
  54. 54What is the balancing stability equation between stable and unstable plaque?-Stable->REPAIR
    lipid lowering antioxidants
    Mechanical injury
    -unstable->INFLAMMATION
    Inc lipids-> oxidation
    Infection
    Genetic susceptibility
  55. 55Unstable coronary artery disease(UCAD)-Encompasses: UA+ Non-Q-wave MI(NQMI)
    -Symptoms almost invariably & from disruption\erosion of atherosclerotic plaque→circulating blood contacts the lesion (highly thrombogenic, lipid-rich core)
    -plaque disruption and subsequent thrombosis may be symptomatic, giving rise to ischaemia, it has been observed that these events frequently occur silently
  56. 56What does the resulting sequence of events lead to?adhesion and aggregation of platelets at the site of rupture→formation of a partially occlusive, platelet-rich, ‘white’ thrombus
  57. 57What does the underlying pathology of UCAD involve?-atherosclerotic plaque rupture, with the subsequent formation of a platelet-rich, ‘white’ thrombus
  58. 58Summarise events of UCAD1.Platelets aggregate rapidlyat site of ruptur\erosion
    2.Thrombus form and extend into lumen
    3.Platelet rich white thrombus
    Intraplaque-intra-luminal
    partially or totally occulsive
  59. 59Fu*ck this sh*itFk all this atherosclerosis BS
  60. 60FASTEN UR SEAT BELTSIT'S MORPHOLOGY TIME MF BITCHES
  61. 61What is the main process?accumulation of lipid and thickening of the intima.
  62. 62What are the charictaristics of early lesions (FATTY STREAKS)·formed in adolescence.\present in most teenagers
    ·Begins as multiple yellow flat spots
    < 1mm, which join together forming streaks about 1 cm long.
    ·Composed of lipid filled macrophages.
    ·They are NOT raised and hence {DO NOT cause disturbance of blood flow}.
  63. 63Fatty streaks progress into ATHEROMA \ ATHEROMATOUS PLAQUE which are?·Yellowish white raised lesion on the intimal surface, particularly around the opening (ostia) of major arteries
    ·Variable in size.
    ·Usually eccentric\involving only part of the circumference of the vessel wall.
  64. 64What does the plaque mainly consist of?soft yellow core of lipid (mostly cholesterol), covered by a firm, white fibrous cap –called the{fibro-lipid / atheromatous plaque.}
  65. 65What are the three principal components of an atherosclerotic plaque?1.Lipid - Intracellular and extracellular.
    2.Cells - smooth muscle cells, macrophages & other leucocytes.
    3.Extra cellular matrix (ECM) - collagen, elastic fibres & proteoglycans.
  66. 66Where are streaks most noticeable?at the ostia of the aorta because that is where PRESSURE is the greatest.
  67. 67Thrombi are often....symptomatic
  68. 68When is stenosis symptomatic?USE RULE OF THUMB
    stenosis is symptomatic if > 70%
  69. 69Mild vs. advanced atheromatous plaquesMild: abdominal aorta show numerous slightly elevated yellowish atheromatous plaques in the intima of the vessel wall
    Advanced: some of the atheromatous plaques have ruptured or become ulcerated with formation of a superadded thrombi that are brownish in color
  70. 70You would notice that...the yellow areas are a little bit higher than the normal surface .. They look yellow bcz of all the lipids
    So they’re yellow patches ranging from 0.3 to 3-4 cm .. They might fuse and form laaarge areas…..but still not much narrowing and WON'T cause symptoms
    the advanced ones have{superadded thrombus} – darker red-brownish deposits
    -yellow patches of fat covered by an intact endothelium IN SLIDE 31
  71. 71UNDER THE MICROSCOPE MUST CHECK SLIDE 32pink to red recent thrombosis in this narrowed coronary artery(*). The intima of the blood vessel is markedly thickened causing narrowing of the lumen. It contains necrotic material as well as numerus cholesterol clefts. The open, needle-like spaces in the atheromatous plaque are cholesterol clefts (thick arrow).
  72. 72What are the Complications of atheroma??1. Calcification.
    2. Focal rupture, ulceration, erosion of the plaque→ thrombus formation, and occasionally embolisation.
    3. %Hemorrhage into plaque → formation of a hematoma.
    4. Aneurysmal dilatation - or weakness of the wall, cuz of atrophy of underlying media & loss of elastic tissue.
  73. 73What are some advanced features\accidents?• RUPTURE
    • ULCERATION
    • EROSION
    • ATHEROEMBOLI
    • HEMORRHAGE
    • THROMBOSIS
    • ANEURYSM
  74. 74Where does rupture usually happen and what can it lead to?1. around the corners of the atherosclerotic plaque (weakest)
    2. lead to:
    -exposing the subendothelial thrombogenic material to the circulation→aggregation of platelets & activation of clotting cascade→ thrombus formation (may lead to acute coronary syndrome)
  75. 75What happens if there is rupture of a vessel?cause blood leaking & hemorrhaging→thrombus would even be bigger and lumen is more constricted
  76. 76Why cystic medial degeneration can happen?atherosclerotic plaque→pressuring the media underneath→reduce blood oxygen & nutrient supply to it→media and its muscles becomes weak→fibrous tissue and heal by fibrosis→ANEURYSM due to the pressure inside
  77. 77When do accidents happen?plaque must be a vulnerable one (thin fibrous cap and thick lipid core)
  78. 78What are common sites of atherosclerosis?Abdominal aorta
    Coronary artery
    Carotid artery
    Popliteal and iliac arterty
    {causing intermittent claudication due to ischemia }
  79. 79Where can you find atheromatous plaques?1. Infrarenal abdominal aorta
    2. Coronories
    3. Popliteal
    4. internal carotid
    5. Circle of Willis
  80. 80Check slide 21 rahaf's slidesAchilles tendon xanthoma. Note the slightly yellow nodular lesions at the distal end of the Achilles tendon.
    B, Xanthelasma. Yellow, raised lesions are noted on the lower left eyelid.
    C, Palmar xanthomas. Note the yellow macules on the palm that are accentuated in the creases.
    D, Eruptive xanthomas. Note the numerous small yellow papular lesions distributed over the buttocks.
  81. 81WHAT ARE THE CLINICAL CONSEQUENSES?1. Atherosclerotic stenosis (fixed narrowing of the vascular lumina):, chronic IHD, intermittent claudication)
    2. Acute plaque changes (thrombosis) : Acute MI, stroke, small bowel infarction
    3. Vessel weakness : formation of an aneurysm/rupture
    4. Hypertension (renal artery atherosclerosis→narrowing and less perfusion→renin-angiotensin mechanism )
  82. 82WHAT ARE THE CLINICAL CONSEQUENSES?> 50% of disease in Western countries.
    1. Stenosis of medium-sized vessels results in impaired blood flow and ischemia
    leading to
    i. Peripheral vascular disease (lower extremity arteries, e.g., popliteal)
    ii. Angina (coronary arteries)
    iii. Ischemic bowel disease (mesenteric arteries)
    2. Plaque rupture with thrombosis results in myocardial infarction (coronary
    arteries) and stroke (e.g., middle cerebral artery).
    3. Plaque rupture with embolization results in atherosclerotic emboli, characterized
    by cholesterol crystals within the embolus (Fig. 7.6).
    4. Weakening of vessel wall results in aneurysm (e.g., abdominal aorta).
  83. 83WHAT ARE THE CLINICAL CONSEQUENSES?1. In large vessels eg Aorta – aneurysmal dilatation and thrombo –embolism.
    2. Heart – Ischemic Heart Disease & Myocardial Infarction.
    3. Brain – chronic ischemia, infarction.
    4. Small intestine – ischemic bowel disease, infarction.
    5. 'Lower extremity – intermittent claudication, gangrene.
  84. 84WHAT ARE THE CLINICAL CONSEQUENSES?Peripher al arterialdisease:
    • Intermittent claudication
    • Rest Pain
    • Gangrene
    • Necrosis
    Angina:
    • Stable
    • Unstable
  85. 85WHAT ARE THE CLINICAL CONSEQUENSES?-Atherothrombosis→ extensive vascular disease affecting the coronary, cerebral and peripheral circulation.
    It is a progressive, generalized disorder with many clinical manifestations – either acute or chronic and often multiple in any single patient.
  86. 86WHAT ARE THE CLINICAL CONSEQUENSES?Stenosis in an atherosclerotic artery may give rise to angina, a transient ischemic attack (TIA) or intermittent claudication.
  87. 87WHAT ARE THE CLINICAL CONSEQUENSES?Atherothrombosis in the coronary arteries is the major cause of acute
    coronary syndrome (ACS), defined as unstable angina and non Q–wave myocardial infarction.
    Atherothrombosis of the cerebral arteries may also result in TIA or
    ischemic stroke.
  88. 88WHAT ARE THE CLINICAL CONSEQUENSES?In the peripheral arteries, thrombosis superimposed on atherosclerosis can contribute to the progression of peripheral arterial disease, producing intermittent claudication (leg pain on walking that is relieved by rest) as well as ischemic necrosis and, potentially, loss of the limb.
  89. 89CHECK SLIDE 42U ALMOST DONE MF

Información

Descripción
Fichas sobre ATHEROSCLEROSIS MFS, creado por Dua Ga el 26/09/2018.
Creado por
Dua Ga · sep 2018
Actualizado
27 sep 2018
Visitas
4
Valoración

Más sobre Cardiovascular Pathology

Escríbenos

¿Sobre qué es tu mensaje?

¿Qué te parece el nuevo diseño?

¿Te gusta?