Mo's circulatory pathology

• how are blood vessels structured (their layers) what is the difference between veins and arteries?


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• what are some of the functions of endothelial cells?

  Endothelium is a continuous sheet of cells lining the entire vascular tree that regulates many aspects of blood and blood vessel function:

  •permeability barrier

  •anti-coagulant, anti-thrombotic, and fibrinolytic regulators

  •prothrombotic molecules

  •extracellular matrix

  •blood flow and vascular reactivity

  •inflammation and immunity

  •cell growth

  •Oxidation of LDL
• what is the function of smooth muscle cells

  •SMCs participate in both normal vascular repair and pathologic processes such as atherosclerosis.

  •When stimulated by various factors, SMCs can:

  Proliferate, Upregulate ECM collagen, elastin, and proteoglycan production

  •Secrete growth factors and cytokines

  •vasoconstriction or vasodilation
• what are the two key histological features of HTN?

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• intimal thickening is a classic response to vascular injury -> outline this process.

  •Vascular injury -> EC loss or dysfunction -> SMC growth, ECM synthesis, and thickening of the vascular wall.

  •Healing of injured vessels involves the migration of SMCs or SMC precursor cells into the intima.

  •These cells then proliferate and synthesize ECM in much the same way that fibroblasts fill in a wound elsewhere in the body, forming a neointima that typically is covered by an intact EC layer.

  •Neointimal response occurs with any form of vascular damage.

  
• which three factors make up virchow's triad and increase the risk of an embolism (application to PE and DVT)?

  • endothelial injury
  • hypercoagulability
  • abnormal blood flow
• how does endothelial injury contibute to clots?

  •Promotes Platelet adhesion and aggregation

  •Cause production of pro-coagulant factors

  •In heart and arterial circulation

  Over ulcerated plaques in Atherosclerosis

  Endocardial injury in MI- mural thrombus

  Traumatic or inflammatory vascular injury -  vasculitis
• how does abnormal flow contribute to the formation of clots?

  •Prevents blood diluting activated clotting  factors

  •Stasis (venous thrombosis)–allows platelets to encounter endothelium (due to loss of laminar blood flow) and slows the washout of activated clotting factors

  •Turbulence (arterial, near valves/cardiac thrombosis)–Physical trauma to endothelial cells or dysfunction–Countercurrents and local pockets of stasis
• hypercoagulability can be divided into primary and secondary, give examples of both:

  Primary - Leiden factor V mutation, Congenital deficiency of  antithrombin III, protein C & S,

  Secondary: increased concentration of fibrinogen and prothrombin

  •Immobilization, MI, neoplasia, tissue damage  (surgery, fracture, burns), cancer, prosthetic  cardiac valves

  •Heparin induced thrombocytopaenia syndrome

  •Antiphospholid antibody syndrome
• compare arterial and venous thrombi


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• infarction - what are common causes of arterial occlusion?


  • embolism
  • thrombus
  • vasospasm or compression of a vessel
• infarction - what are common causes of venous occlusion?

  • strangulated bowel hernia
  • testicular torsion
  • ovarian torsion
  • bowel volvulus
• In most tissues the histological characteristic of infarction is ischemic ................. necrosis (except in the brain it is ........................ necrosis)


  In most tissues the histological characteristic of infarction is ischemic coagulative necrosis (except in the brain it is liquefactive necrosis)
• red and white are two types of infarct, where do red infarcts occur?

  1.Venous blockage

  2.Loose tissues (lungs)

  3.Dual circulation (small intestine)

  4.Congested organs

  5.Re-established blood flow in an infarcted tissue
• red (haemorrhagic) and white (anaemic) are two types of infarct, where do white infarcts occur?

  1.Arterial occlusions

  2.Solid organs

  3.End arterial circulation organs:

  •heart, spleen and kidney

  4.Dense tissues
• what do white infarcts look like?

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• what do red infarcts looks like?

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• pulmonary red infarct


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• what are the three factors that affect infarct development?

  1. presence of a collateral supply
  2. rate of occlusion
  3. tissue vulnerability to hypoxia
• how does the anatomy of vascular supply affect the likelihood of infarct

  The presence or absence of an alternative blood supply is the most important factor in determining whether occlusion of an individual vessel causes damage.

  Dual supply of lung by pulmonary and bronchial arteries means obstruction of pulmonary arterioles does not cause lung infarction unless bronchial circulation also is compromised. Similarly, the liver, which receives blood from the hepatic artery and the portal vein, and the hand and forearm.

  kidney and spleen both have end-arterial circulations -> infarct
• how does the rate of occlusion affect the development of infarcts?

  Slowly developing occlusions are less likely to cause infarction because they allow time for the development of collateral blood supplies.
• what is mean by the 'tissue vulnerability to infarct'?

  •Neurons undergo irreversible damage when deprived of their blood supply for only 3 to 4 minutes.

  •Myocardial cells die after only 20 to 30 minutes of ischemia.
• what is the difference between a dry and wet infarct?

  •Dry gangrene: tissue dies and mummified, and healing occurs over it (sterile process)

  •Wet gangrene: bacterial infections in a gangrene leading on to sepsis, can be blistering, wet and smell bad
• what causes gangrene?


  Whole areas of limb or a region of the gut have their arterial supply cut off and large areas of tissue die in bulk
• what are the three pathological patterns of arterosclerosis?

  1. arteriolosclerosis
  2. atherosclerosis
  3. Mönckeberg medial calcific sclerosis

  
• histology of a atherosclerosis - label L, C, F

  •fibrous cap (F)

  •central necrotic (largely lipid) core (C)

  •The lumen (L) is moderately narrowed by this eccentric lesion, which leaves part of the vessel wall unaffected (arrow)

  Collagen (blue) is stained with Masson trichrome

  
• histology of artherosclerosis - what is shown in the internal and external elastic membrane and the media of the artery?

  internal and external elastic membranes are attenuated

  media is thinned

  
• what can be seen in the fibrous cap and core

  scattered inflammatory cells,

  calcification (arrowheads)

  neovascularization (small arrows)

  
• what are the 4 outcomes of plaque formation?

  1.Rupture, ulceration, or erosion -> thrombus formation.

  2.Haemorrhage into a plaque -> intra-plaque haemorrhage (resulting haematoma may cause rapid plaque expansion/rupture)

  3.Atheroembolism -> microemboli composed of plaque contents

  4.Aneurysm formation Atherosclerosis-induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue, causes structural weakening that can lead to aneurysmal dilation and rupture
• what is the difference between a vulnerable and a stable plaque

  stable because there is a thick fibrous plaque to prevent rupture of the plque

  
• what are the two most important risk factors for aneurysms?

  • hypertension
  • artherosclerosis

  
• dissections are classified by the debakey system which, what does each stage indicate? which is the most serious with the greatest mortality risk?

  •Type A dissections (proximal) involve the ascending aorta

  extensive dissection (DeBakey type I)

  isolation (DeBakey type II).

  •Type B dissections (distal, or DeBakey type III) arise after the branching of the great vessels.

  •Type A dissections typically have the most serious complications and the greatest associated mortality.