Hemodynamic Disorders

1. Hemodynamic Disorders Ye Liu（刘 晔） Dept. Pathology, SMC

2. Containing • Heart, artery, Vein • General circulation Pulmonary circulation Functions • Deliver oxygen and nutrients • Carry away metabolic wastes A Healthy circulatory system ♠ Normal blood volumn ♠Homeostasis

3. Normal homeostasis vessel wall integrity intravascular pressure osmolarity normal hemostasis Edema Hyperemia & congestion Thrombosis & Embolism Infarction Hemorrhage Shock Three Major Causes of morbidity and mortality ♦ Myocardial infarction ♦ Pulmonary embolism ♦ Cerebral vascular accident

4. EDEMA (水肿) • Increased fluid in the interstitial tissue spaces • General & local • Pathogenesis • Vascular hydrostatic pressure • Plasma colloid osmotic pressure • Lymphatic drainage

5. EDEMA • Increased hydrostatic pressure ( cardiac edema, etc.) • Reduced plasma osmotic pressure (nephrotic, hepatic, malnutrient edema, etc. ) • Lymphatic obstruction (filariasis infection — elephantiasis，breast surgery, etc ) • Sodium and water retention (ARF, etc) elephantiasis Minimal Change Disease Pitting edema

6. EDEMA • Morphology LM: Clearing and separation of the extracellular matrix elements Cell swelling Subcutaneous edema Pulmonary edema Edema of the brain

7. EDEMA • Hydrothorax • hydropericardium • hydroperitoneum (ascites) • anasarca • Clinical correlation from annoying to fatal indicate subtle disease benefit or harmful

8. Arterial hyperemia (hyperemia，充血) An augmented blood flow inducing arteriolar and capillary dilation Venous hyperemia (congestion，淤血) Accumulation of Blood in Small Veins and capillaries result from drainage difficulty of veins HYPEREMIA & CONGESTION A local increased volume of blood in a particular tissue

9. HYPEREMIA & CONGESTION Hyperemia: Active process; Red, raised tempreture, increased volume ; Enhanced function; Congestion: passive process; general of local; Reddish blue color (cyanosis), low temperature, increased volume, edema; Decreased function

10. HYPEREMIA • Types Physiological:Shy, exercise, taking Meal Pathological:Inflammatory, post-decompressed • Significance －Benefits Plenty supply of O2, functional enhancement, nutrition substance － Hazards Headache , hemorrhage, stroke

11. CONGESTION Causes: Systemic: general or pulmonary Cardiac dysfunction (right or left) Local: local venous compression or obstruction External Compression --- Tumor, Bandage Occlusion of lumen --- Thrombosis, Embolism Thickening of venous wall Paralysis of neurogenic modulation --- Burn, frostbite

12. CONGESTION Chronic congestion Raised venous pressure Anoxia Metabolite accumulation Enlarged interendothelial gap Base membrane degeneration ParenchymalInterstitial fibrosis Atrophy Reticular fiber collapsed Increase permeability Degeneration Collagen increased Necrosis Fibroblast proliferation Microscopic scarring Edema Hemorrhage Congestive sclerosis

13. CONGESTION Morphology • Grossly hemorrhagic and wet • Microscopically rich of red blood cells in small vessels

14. CONGESTION Lung: Acute pulmonary congestion Gross: Plump swollen lung with shining pleura, edematous fluid flowing out while cutting the lung LM: Alveolar capillaries highly dilated (rosary- like appearance) and engorged with blood Alveolar cavity filled with eosinophilic edema fluid Manifestation Pink colored foamy sputum

15. CONGESTION Lung: Chronic pulmonary congestion Gross: Hard, with brown spots scattered —— Brown induration LM: Septa thickened and fibrosis Alveolar spaces containing ‘heart failure cells’— hemosiderin-laden macrophages Manifestation Rusty sputum, dyspnea, etc.

16. CONGESTION Liver: Acute hepatic congestion LM: — Dilation of central vein and sinusoids with blood — Atrophy, degeneration and necrosis of central hepatocytes

17. CONGESTION Liver: Chronic hepatic congestion Nutmeg liver Gross: red-brown zones accentuated against the yellow surrounding zones LM: centrilobular necrosis and congestion, and perilobular fatty change; fibrosis Long-standing, severe hepatic congestion: hepatic fibrosis (cardiac cirrhosis)

18. Hemorrhage （出血） Causes • Rupture of blood vessels Trauma Peptic ulcer, aneurism, atherosclerosis • Diapedesis Enlarged interendothelial gap (basement membrane injury). The intergrity of the vessels remains intact Injury to vascular wall: sever infection, anoxia, toxins Change in number and quality of platelets uremia, leukemia, idiopathic Disturbance of coagulation mechanism congenital disease, DIC , deficiency of Vit. K

19. Petechiae Purpuras Ecchymoses Hematoma Hemothorax Hemopericardium Hemoperitoneum hemoarthrosis The clinical significance depends on the volume, the rate of loss and the site. Hemorrhagic shock Stroke hemorrhage

20. Hemostasis & thrombosis Normal hemostasis • Maintain blood in a fluid, clot-free state • Localized hemostatic plug <>Thrombosis （血栓形成） Blood clot (thrombus，血栓) formation in cardiovascular system of a living body

21. Hemostasis Three components Vascular wall Platelets Coagulation cascade Events in hemostasis vasoconstriction primary hemostasis secondary hemostasis antithrombotic counter-regulation

22. Hemostasis & thrombosis • Endothelium • Antithrombotic • Antiplatelet • Anticoagulant • fibrinolytic • Prothrombotic

23. Hemostasis & thrombosis • Platelet • Adhesion • Secretion • Aggregation • Coagulation casecade

24. thrombosis Pathogenesis • Endothelial injury • Turbulence of blood flow • Hypercoagulability

25. thrombosis Morphology • Arterial thrombi • Originate from injury sites • Venous thrombi (phlebothrombi) • Originate from the sites of stasis both extends to the heart pale platelet and fibrin layers Lines of Zahn dark erythrocyte-rich layers

26. thrombosis Lines of Zahn

27. thrombosis LM: Platelets Trabeculae + Neutrophil fibrin + red cells

28. thrombosis Types Mural thrombus Occlusive thrombus Globular thrombus Vegetation Pale thrombus Mixed thrombus Red thrombus Hyaline thrombus Bacterial thrombus Tumor thrombus

29. thrombosis Mural thrombus Vegetation Hyaline thrombus

30. thrombosis Differentiation between thrombus from postmortem clot

31. thrombosis Fate • Propagation and obstruction • Dissolution • Embolization • Organization and recanalization • Calcification

32. thrombosis Clinical correlations • Venous thrombosis (phlebothrombosis) • Varicosities, embolism (sometimes fatal), • DVT, trauma, surgery, post partum • Cancer associated thrombosis • Cardiac and arterial thrombosis • Mural thrombus • cardiac infarction, rheumatic heart disease • Embolize peripherally, brain, kidney, spleen, etc

33. thrombosis DIC (Disseminated intravascular coagulation)  Usually happens in many severe disorders severe bacterial or viral infection, allergic disease, anoxia, trauma, shock, malignancy ,etc.  Coagulation System is Activated Microthrombi are Formed in Capillaries of Many Organs Platelets + Fibrin ( lung ,brain ,kidney,liver,GI tract,adrenal gland,etc.) Consumption of coagulation substance and activation of fibrinolytic system hemorrhage diathesis, mutiorgan dysfunction consumption coagulopathy / defibrination syndrome 消耗性凝血病/ 去纤维蛋白综合征

34. Embolism （栓塞） Occlusion of cardiovascular system by some insoluble mass. The mass is termed “Embolus （栓子）”. Solid, liquid, gaseous mass • Thromboembolism 99% • Fat, air, amniotic fluid, tumor fragments, bits of bone marrow, etc

35. Embolism Route of emboli • Arterial emboli —— systemic embolism • Venous emboli —— pulmonary embolism • Portal vein emboli —— hepatic embolism • Paradoxical emboli Emboli from veins of the general circulation pass through an atrial or ventricular septal defect, entering arteries of the general circulation. • Retrograde emboli

36. Embolism Incidence: 20-25/100,000 hospitalized patients Source: >95% from DVT above the knee Pulmonary Thromboembolism

37. Embolism Results: (depends on the size, number and the clinical setting) Few Emboli with Small Size : asymptomatic → infarction (pain and dyspnea) Numerous Small Emboli : decrease the volume of pulmonary circulation sharply, pulmonary hypertension and right ventricular failure Medium Sized Emboli: hemorrhage, infarction Large Emboli: sudden death, saddle embolus

38. Embolism • Source: 80% from intracardiac mural thrombi; aortic aneurysms, ulcerated AS plaques, vegetations • Target sites: lower extremities, brain, intestines, kidney, spleen • Consequences: infarction Systemic Thromboembolism

39. Embolism Fat Embolism • Source: Fractures of long bones Soft tissue trauma • Results: ф > 20μm, pulmonary embolism ф < 20μm, cerebral embolism or other organ embolism Special staining (Sudan III )

40. Embolism Fat Embolism • Pathogenesis obstruction & toxic effect of free fatty acid • Symptoms Tachypnea, dyspnea, tachycardia; irritability, restlessness, delirium or coma; anemia and thrombocytopenia

41. Embolism Gas Embolism • Source: Exogenic: transfusion, operation or trauma in the neck or chest, artificial pneumothorax, pneumoperitoneum Endogenic: caisson disease or decompression sickness • Results: Small amount of gas may be absorbed Occupies the heart ventricle, interrupted the blood flow cause death Gas embolism in multiple organs (brain, pulmonary)

42. Embolism Amniotic Fluid Embolism Low Incidence (1/10,0000~80, 000) with high mortality rate (70%~80%) Amniotic fluid may enter vascular system through Sinusoids which placenta attached Torn cervical vessels Emboli consists squamous epithelial cells, lanugo hair, fat, fetal feces, mucin and TXA2 Cause of death multiple embolism; reflex vasoconstriction, pulmonary embolism; allergic shock ; DIC

43. INFARCTION （梗死形成） The formation of a localizad area of ischemic necrosis within a tissue or organ due to impaired arterial supply or the venous drainage The necrosis area is called “infarct”. An extremely important cause of clinical illness: myocardiac infarction cerebral infarction

44. INFARCTION Causes • Occlusion of arterial supply or venous drainage Thrombosis, embolism, athermanous plaques, external compression • Functional spasm of arteriole Types • White infarcts (anemic infarcts) • Red infarcts (hemorrhagic infarcts) • Septic infarcts

45. INFARCTION White infarction • Arterial occlusion • Solid, compact organs • Few collateral circulation • (spleen, kidney, heart, brain, etc.) • Morphology • Gross • Dull pale, dry, wedge-shaped necrotic lesion • A hemorrhagic zone surrounding

46. INFARCTION LM Ischemic coagulative necrosis Hemorrhagic zone : inflammatory and granulation tissue. Most undergo organization and scarring in the end.

47. INFARCTION Spleen infarction

48. INFARCTION Cardiac infarction

49. INFARCTION Brain infarction (liquefied necrosis)

50. INFARCTION Red infarction ♦ Arterial occlusion ♦ Venous occlusion ♦ Loose tissue ♦ Dual circulations: lung , small intestine • Previously congested Re-established blood flow to a site of previous arterial occlusion and necrosis