1. General Pathology Circulation Disorders - II Manifestations & Causes of Local Circulatory Disturbances Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

2. Manifestations of Local Circulatory Disturbances  local hyperemia  local anemia LOCAL ISCHEMIA

3. Manifestations of Local Circulatory Disturbances  local hyperemia – active arterial (fluxe) capillary (peristatic) – passive venous (stasis)

4. Manifestations of Local Circulatory Disturbances  local anemia – slow development – vascular atrophy – fast development – dystrophy, necrosis

5. Ischemia – stratification of changes  complete necrosis - central part  myomalacia  hyperemia  interstitial leucocyte infiltration – vital reaction  dystrophic steatosis (& glycogenosis)  healthy

6. Causes of Local Circulatory Disturbances  local anemia stenosis to occlusion of artery  lumen embolism  wall atherosclerosis, thrombosis ( spasmus, depositions, inflammations, tumours)  combination of previous  neighbourhood compression

7. Causes of Local Circulatory Disturbances  local hyperemia active  function  inflammatory vasodilation passive (outflow blocade)  lumen  wall  neighbourhood

8. Thrombosis Def.: intravital intravascular blood clotting Range: parietal obturative

9. Haemostasis 1.Endothelium damage – vWF secretion 2.Thrombocytes adhesion & aggregation  Thrombocytes secretion  serotonin, PDGF, thromboxan A 2 vasoconstriction  fibronectin, vWF, fibrinogen aggregation 3.Plasma factors - proteins synthesized in hct, (vit. K dependence) cascade activation

10. Coagulum x Thrombus postmortem  autolysis protein activation  thrombin liberation  no platelet thrombus  fibrinogen - fibrin  non adherent  elastic intravital  platelet based  adherent to the vessel wall  friable /crumbly

11. Types of Thrombi v red stagnation v white fluxe v mixed v hyaline

12. Thrombosis - causes  blood stagnation  endothelium damage  blood composition changes

13. Thrombosis - causes  blood stagnation – heart failure – vein insufficiency – local factors (compression) laminar flow disturbance

14. Thrombosis - causes  endothelium damage – atherosclerosis – inflammation – injury – hemodynamic stress – high cholesterol levels

15. Thrombosis - causes  blood composition changes – increased platelet number (over 400 000/mm 3) – thromboplastin liberation (e.g. following pancreas and lung surgery) –endotoxin - DIC – amniotic fluid embolism – contraceptives……

16. Hypercoagulation inborn mutations with increased levels of thrombocytes or lack of anticoag. proteins acquired  pregnancy  contraceptives  disseminated neoplasms  atrial flutter  arteficial valves  surgery…….

17. Thrombus development v no v lysis v organisation (decoloration, recanalization, hyalinization, dystrophic calcification - phlebolith) v lysis + organisation v embolism v puriform softening v infection

18. Natural Anticoagulant Systems 1.Antithrombins – e.g.antithrombin III inhibits fcts IXa,Xa,XIa,XIIa 2.Proteins C, S (vit K dependent) – inh. fcts Va, VIIIa 3.Plasminogene – plasmin system fibrin breakdown

19. Embolism Def.: transport of a compact particle in circulation with stopping in the place of anatomic narrowing

20. Emboli – Types v thrombotic v fat v air v amniotic fluid v cellular (neoplastic, bacterial trophoblastic) v foreign body

21. Embolism – Fate THROMBOTIC  no  organisation  lysis, resorption  progression v fat v air v amniotic fluid life threatening

22. Embolism – Fate CELLULAR v lysis trophoblastic v progression neoplastic METASTASES bacterial metastatic sepsis

23. Caisson Disease (Decompression thickness – gas microembolism) v divers v underwater construction workers v unpressurized aircraft in high altitudes life threatening

24. Factors Influencing Vessel Occlusion Result  anatomy  time  tissue/organ sensitivity to hypoxy  functional status  general circulation status  MEDICAL INTERVENTION

25. Haemorrhagia Def.: blood extravasation (and the presence of blood in the tissue)

26. Hemorrhage – Classification Localisation: – external – internal Source: – arterial – capillary – venous

27. Hemorrhage - pathogenesis Haemorrhagia – per rhexin (trauma – tear of the vessel wall) –per diabrosin (arosion – ulcus, neoplasm) –per diapedesin (increased vessel permeability- leakage)

28. Haemostasis 1.Endothelium damage – vWF secretion 2.Thrombocytes adhesion & aggregation  Th secretion  serotonin, PDGF, thromboxan A 2 vasoconstriction  fibronectin, vWF, fibrinogen aggregation 3.Plasma factors - proteins synthesized in hct, (vit. K dependence) cascade activation

29. Hemorrhagic Statuses Thrombocytopaties thrombocytopenia, thrombasthenia Coagulopaties hemofilia, hypoprothrombinemia, afibrinogenemia, Vasculopaties scurvy, m. Osler, m. Schönlein – Henoch