Blood Vessels: Pathology of the Intravascular Highway 12/12/12 Henry Sánchez, MD, MS

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1 Biography: Blood Vessels: Pathology of the Intravascular Highway 12/12/12 Henry Sánchez, MD, MS Henry Sánchez received his undergraduate degree in Biological Sciences with Honors at Stanford University. He received Medical and Master of Science (Experimental Pathology) degrees from the Keck School of Medicine (University of Southern California), trained at the Los Angeles County/USC Medical Center in Preliminary Internal Medicine and Anatomic Pathology, and finished his training in Anatomic Pathology at the University of California San Francisco. During his training, he has received numerous research fellowships in the areas of chemical carcinogenesis and AIDS associated lymphomas. He is currently holding a fulltime faculty position in the UCSF Department of Pathology as a Professor of Clinical Pathology and holds dual appointments in the schools of medicine and dentistry at UCSF. His pathology specialty is clinical autopsy pathology and current research area is prion diseases. He teaches, directs and develops curriculum for health allied professional students including dental, medical, pharmacy and physical therapy students at UCSF. Over the years, he has received numerous outstanding teaching awards in the schools of medicine, dentistry and pharmacy. He is a founding member of the UCSF Haile T. Debas Academy of Medical Educators since 2001 and has held The Endowed Chair in Pathology Medical Student Education. He is a strong student advocate and mentor to students. His university service includes membership on committees within the different schools, UCSF campus and UC Office of the President. Dr. Henry Sánchez is strongly committed to public service as an elected governing board member of the San Bruno Park School District and participating in numerous outreach programs at the elementary, middle school, high school and college levels. Bibliography: Sanchez, H. and Ursell, P. Use of autopsy cases for integrating and applying the first two years of medical education. Acad. Med. May;76(5):530 1, Seligman, V., Bolton, P.B., Sánchez, H.C. and Fye, K. Propylthiouracil induced microscopic polyangiitis. Journal of Clinical Rheumatology, 7(3): , Shiboski, C.H., Regezi, J.A., Sanchez, H.C. and Silverman, S. Oral Lesions as the First Clinical Sign of Microscopic Polyangiitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 94(6):707 11, Yeh, B.M., Coakley, F.V., Gotway, M.B., Sanchez, H.C., Wilson, M., and Reddy G.P. Prevalence and Importance of Azygos Arch Valves on Intravenous Contrast Enhanced CT. Radiology Jan; 230(1): Epub 2003 Nov 26. Safar, J.G., Gerschwind, M.D., Deering, C., Didorenko, S., Sattavat, M, Sanchez, H., Serban, H., Vey, M., Baron, H., Giles, K., Miller, B., DeArmond, S.J. and Prusiner, S.B. Diagnosis of Human Prion Disease. Proc Natl Acad Sci USA. Mar 1;102(9):3501 6, Kerlikowske, K., Molinaro A., Gauthier, M., Berman H., Waldman, F., Bennington, J., Sanchez, H., Jimenez, C., Stewart, K., Ljung, B.M., and Tlsty, T. Biomarker Expression and Risk of Subsequent Tumors After Initial Ductal Carcinoma In Situ Diagnosis. Journal of the National Cancer Institute. May 5; 102(9):585 7, May 5, DeArmond, S.J., Tousseyn, T., Gheyara, A., Sanchez, H., Ahn, M., Sattavat, M., Bajsarowicz, K., Gambettii, P., Prusiner, S. B. Increased Incidence of Alzhemier s Disease Neuropathological Changes in Patients with Prion Diseases. Journal of Neuropathology and Experimental; 102(9): Epub 2010 Apr 28. Erratum in: J Natl Cancer Inst. Jul 7;102(13):993, Tartaglia, M.C., Thai, J.N., See, T., Juo, A., Harbaugh, R., Raudabaugh, B., Cali, I., Satavat, M., Sanchez, H., DeArmond, S.J., Geschwind, M.D. Pathologic Evidence that the T188R Mutation in PRNP is Associated with Prion Disease. J. Neuropathology Experimental Neurology. Dec;69(12):1220 7, Schmucker, D.L. and Sanchez, H. Liver Regeneration and Aging: A Current Perspective. Current Gerontology and Geriatrics Research (Special Issue), 2011;2011: Epub 2011 Sep 8.

2 Blood Vessels: Pathology of the Intravascular Highway Dr. Henry Sánchez, M.D. 12/12/12 Objectives! Define pathology and describe the role of the pathologist! Describe the cellular and tissue responses to increase stress, demand, or injury! Describe common conditions involving hemodynamic derangements including edema, congestion, thrombosis, and embolism! Define and describe atherosclerosis of the elastic and muscular arteries Fiction: CSI Toe Tags Fact: Actual Autopsy Introduction to Pathology! Definition: study of disease ( suffering )! Pathology is the convergence of basic science and clinical medicine! Study of structural and functional changes in cells, tissues and organs that underlie disease! Fundamental knowledge that is relevant to all other medical disciplines The Roles of the Pathologist! The study of disease! Morphologic description of disease! Experimental studies! Molecular analyses (studying expression of genes and molecules in diseased tissue)! The diagnosis of disease! The clinical discipline of Pathology! Anatomic (surgical pathologist, cytopathologist and autopsy pathologist) and clinical pathology (laboratory medicine) 1

3 Overview of Pathology! Etiology or cause! Pathogenesis! Morphologic changes! Functional derangements and clinical significance Adapt or Die! Important Variables of the Cardiovascular System Cardiovascular System: Blood Vessels! Pressure (blood pressure)! Volume (intravascular volume)! Contractility (heart muscle and vascular muscle)! Compliance (amount of stiffness) Edema Atherosclerosis Edema Congestion Thrombus Embolus! Injury to endothelial cells/blood vessel wall! Increase hydrostatic pressure! Increase interstitial sodium! Decrease colloid osmotic pressure (albumin)! Lymphatic obstruction 2

4 ! Local Edema! Acute inflammation, urticaria, venous thrombosis, left-sided heart failure! Systemic (Anasarca)! Heart - congestive heart failure! Liver - cirrhosis! Kidney - nephrotic syndrome! Iatrogenic - fluid resuscitation Anasarca (Generalized Edema) Pitting Edema Congestion! Definition: Dilated blood vessel! Passive congestion (e.g., mechanical effect - congestive heart failure, venous thrombosis)! Active congestion (hyperemia) - acute inflammation, hypersensitivity reaction type I Congestion 3

5 Normal Liver Nutmeg Chronic Passive Congestion Normal Liver Nutmeg liver Passive Congestion! Definition: sequence of events leading to the cessation of bleeding by the formation of a stable fibrin-platelet hemostatic plug! Vascular Wall! Platelets! Coagulation cascade 4

6 Intravascular Coagulation! Platelets! Circulating platelets = 150k to 400k per mm3! Derived from megakaryocytes in the bone marrow! Thrombocytopenia = decreased number of platelets! Decreased production! Increased destruction! Coagulation! Intravascular transformation of fluid blood into a gel matrix entrapping cellular constituents (red blood cells and white blood cells)! Coagulation! Intrinsic system! All substrates necessary for clotting are present within the circulating blood! Activated by contact with a foreign surface - usually collagen, Ag-Ab complexes, glass, etc.! Contact-sensitive protein is Hageman factor (factor XII)! Coagulation! Extrinsic system! After tissue injury, phospholipid protein complex (tissue thromboplastin) is released into the circulating blood! Activating the extrinsic pathway (inactive factor VII to active factor VII) 5

7 Fibrin-Platelet Thrombus 6

8 Thromboembolism Laminar Flow of Blood! Three Predisposing Factors Leading to Abnormal Thrombosis! Injury to vascular endothelium - atherosclerosis! Changes in laminar flow of blood - increased viscosity (polycythemia), stasis of blood (deep leg veins), and turbulence (aneurysms)! Hypercoagulability - increased level of platelets or clotting factors, decreased fibrinolytic activity Thrombus Thrombus ( Lines of Zahn ) Abdominal Aortic Aneurysm with Thrombus 7

9 Thromboembolism Evolution of a Thrombus! Evolution of a Thrombus! Enlarge and cause obstruction with the formation of Lines of Zahn (early)! Give rise to an embolus! Be removed by fibrinolytic action (small thrombi) or! Become organized leading to recanalization (large thrombi) Thromboembolism Blood Clot! Thrombus vs Blood Clot! Thrombus only occurs within the intravascular space while a blood clot can occur in either intravascular (postmortem), or extravascular compartments! Blood clot does not have Lines of Zahn! Blood clot contains minimal number of platelets Thromboembolism! Pulmonary Embolus! Origin - deep leg veins, prostatic venous plexus! Outcome! Resolution in 70 to 80%! Infarction in 10 to 15%! Chronic pulmonary hypertension in 5%! Death in 10% Pulmonary Saddle Embolus 8

10 Pulmonary Saddle Embolus Adventitia Normal Aorta Media Intima Media Intima Degenerative Diseases of Arteries! Arteriosclerosis! Arteriolosclerosis (hypertension, diabetes, and aging)! Atherosclerosis! Monckeberg medial sclerosis Atherosclerosis! Age and Sex! Primary Risk Factors! Diabetes mellitus! Hyperlipidemia! Hypertension! Smoking! Obesity Atherosclerosis! Secondary Risk Factors! Lack of exercise! Aggression/Stress (competitiveness)! Elevated levels of homocystiene! Bacteremia from oral flora! Increasing age! Diet 9

11 Atherosclerotic Disease Progression Overview of Atherosclerosis Pathogenesis of Atherosclerosis Fatty Streaks Aorta Fatty Streak with Intimal Lipid Deposition Intima Media 10

12 Advanced Atherosclerotic Plaque The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Severe Atherosclerotic Disease Aorta Advanced Atherosclerotic Plaque Advanced Atherosclerotic Plaque (Elastin Stain) Advanced Atherosclerotic Plaque Atherosclerosis: Consequences of Stenosis H&E Stain Elastin Stain 11

13 Atherosclerosis: Thrombosis Atherosclerotic Aortic Aneurysm Atherosclerosis! Clinical Significance! Cerebrovascular accidents (stroke) leading to infarction! Ischemic heart disease! Aortic aneurysms with or without rupture! Renal failure! Cholesterol embolization! Peripheral vascular disease - lower extremities Atherosclerotic Basal Artery Aneurysm Atherosclertic Coronary Artery Disease 12

14 Atherosclerotic Peripheral Artery Disease Summary Edema Atherosclerosis Congestion Thrombus Embolus 13