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PPT lecture 1 outline

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  • 1. Mechanisms of Disease:Mechanisms of Disease: Disorders of CirculationDisorders of Circulation Sharon M. Dial, DVM, PhD Arizona Veterinary Diagnostic Laboratory
  • 2. Disorders of CirculationDisorders of Circulation Disturbances of blood flow Hemostasis and Thrombosis Obstacles of Blood Flow Disturbances of Fluid Exchange Ischemia and Shock
  • 3. Fluid HomeostasisFluid Homeostasis Depends on three major physical factors – An intact and functional circulatory system – An intact and functional lymphatic system – Normal concentration of serum proteins (specifically albumin)
  • 4. Disturbances of FluidDisturbances of Fluid ExchangeExchange Starling’s law The amount of fluid filtered out into the interstitium at the arterial side of the microcirculation is “approximately” equal to that reabsorbed at the venous end.
  • 5. Disturbances of FluidDisturbances of Fluid ExchangeExchange Normal fluid exchange – Starlings law:  Intravascular hydrostatic pressure (blood pressure)  Oncotic pressure of plasma proteins  Oncotic pressure of extravascular proteins  Interstitial hydrostatic pressure
  • 6. From: Mechanisms of Disease, ed D.O. Slauson, B.J. Cooper, 2nd Ed.
  • 7. Fluid CompartmentsFluid Compartments Extracellular Fluid Intracellular Fluid Intravascular Fluid Plasma RBC mass Albumin 4.5% Globulin 2.5% Fibrinogen 0.3%
  • 8. Arteriolar Venous Intravascular Hydrostatic Pressure 30 mm Hg 17 mm Hg Interstitial Hydrostatic Pressure 8 mm Hg 8 mm Hg Intravascular Oncotic Pressure 25 mm Hg 25 mm Hg Interstitial Oncotic Pressure 10 mm Hg 10 mm Hg From: Robbins Pathologic Basis of Disease, ed. Cotran, Kumar, Collins. 7 mmHg out 6 mmHg in
  • 9. Disturbances of FluidDisturbances of Fluid ExchangeExchange Lymphatics – Vessel structure  Thin wall  Valves – Maintain negative pressure
  • 10. Disturbances of FluidDisturbances of Fluid ExchangeExchange  Edema – Accumulation of Excess interstitial fluid  Mechanisms of edema – Increased vascular permeability – Increased intravascular hydrostatic pressure – Decreased intravascular osmotic pressure – Decreased lymphatic drainage
  • 11. Disturbances of FluidDisturbances of Fluid ExchangeExchange – Edema  Regional – – venous or lymphatic obstruction, – localized inflammation (increased vascular permeability) • Vasoactive mediators – histamine, bradykinin, leukotrienes • Mediators that alter endothelial cell structure – IL-1, TNF, gIF  Generalized – – Cardiogenic – Nephrogenic – Hepatic – Hypoproteinemic
  • 12. Disturbances of fluidDisturbances of fluid exchangeexchange Generalized edema – often associated with transudation of fluid into body cavities. – Hydropericardium – Hydrothorax – Hydroperitoneum Generalized subcutaneous edema - Anasarca
  • 13. From: Robbins Pathologic Basis of Disease, ed. Cotran, Kumar, Collins.
  • 14. AscitesAscites  Cardiac disease – Low cellularity – High protein  Associated with increased portal pressure (portal hypertension)  Primary hypoproteinemia – Low cellularity – Low protein  Associated with decreased plasma oncotic pressure.
  • 15. Disturbances of Blood FlowDisturbances of Blood Flow Alterations in Circulation – Hyperemia  Active – Physiologic (exercise, blushing, increased mental activity) – Pathologic (diabetes, inflammation)  Passive – hepatic congestion in right heart failure  Classification – Duration – acute versus chronic – Extent – localized versus generalized – Mechanism – active versus passive
  • 16. Disturbances of Blood FlowDisturbances of Blood Flow Examples – Acute local active hyperemia  Hyperemia of inflammation – Acute local passive hyperemia  Hyperemia (congestion) of torsion – Chronic local passive hyperemia  Venous occlusion or valvular incompetence – Chronic generalized passive hyperemia  Systemic hyperemia (congestion) of cardiac disease
  • 17. Acute local active hyperemiaAcute local active hyperemia http://www.vetmed.ufl.edu/path/pbteach/wlc/vem5161/circ/circ2.htm Oral Mucosa Bovine Malignant Catarrhal Fever
  • 18. Acute local passive hyperemiaAcute local passive hyperemia http://www.vetmed.ufl.edu/path/pbteach/wlc/vem5161/circ/circ2.htm Lung Torsion Note dark red/black Lung lobe
  • 19. Chronic local passiveChronic local passive hyperemiahyperemia http://www.bayinsider.com Deep venous thrombosis
  • 20. Consequences of chronicConsequences of chronic congestioncongestion Lung – interstitial fibrosis and alveolar hemorrhage Liver – central lobular necrosis and fibrosis Spleen – hyperplasia and thrombosis – Can be associated with hematoma.
  • 21. www-medlib.med.utah.edu/WebPath/LUNGHTML Hemosiderin-laden macrophages “heart failure cells”
  • 22. cv http://www.vh.org/Providers/Textbooks/LiverPatholog
  • 23. http://www.vh.org/Providers/Textbooks/LiverPatholog
  • 24. HemorrhageHemorrhage Loss of blood elements externally, into body cavities or into interstitium – Hemorrhage by rhexis  Rupture of blood vessel with frank bleeding – Hemorrhage by diapedesis  Loss of red blood cells through intact vessels and across membranes – Hematoma – blood clot in interstitial tissues
  • 25. HemorrhageHemorrhage  Effects of hemorrhage – Depend on site  Subcutaneous vs subdural – Rate  Slow gastrointestinal blood loss by diapedesis (chronic gastritis)  Rapid blood loss by ruptured vessel – Total blood volume lost  Hemorrhagic shock – loss of 20-40% of total blood volume
  • 26. Hemorrhage by diapedesisHemorrhage by diapedesis http://medlib.med.utah.edu/WebPath Acute Gastritis
  • 27. Hemorrhage by rhexisHemorrhage by rhexis Ruptured Pulmonary Artery
  • 28. HemorrhageHemorrhage Causes – Trauma  Ruptured spleen or splenic hematoma – Infectious disease  Vasculitis  Disseminated intravascular coagulation – Coagulopathies – Platelet abnormalities
  • 29. The Vocabulary ofThe Vocabulary of HemorrhageHemorrhage  Hemopericardium  Hemothorax  Hemoperitoneum  Hemarthrosis  Hemoptysis  Epistaxis  Petechia  Ecchymoses  Purpura
  • 30. HemopericardiumHemopericardium http://medlib.med.utah.edu Hemorrhage into pericardium with cardiac tamponade Ruptured aortic aneurysm
  • 31. HemothoraxHemothorax http://medlib.med.utah.edu Warfarin Toxicity
  • 32. HemoperitoneumHemoperitoneum
  • 33. HemarthrosisHemarthrosis http://www.mednet.gr/pim/ht2.htm Acute hemarthrosis due To hemophilia
  • 34. EpistaxisEpistaxis http://web.vet.cornell.edu/public/popmed/clinpath
  • 35. HemorrhageHemorrhage Resolution of hemorrhage – Resorption – by phagocytosis – organization http://dermatology.cdlib.org
  • 36. 9-year-old NM Labrador9-year-old NM Labrador RetrieverRetriever Presented for lethargy and a distended abdomen. Physical exam – Increased heart rate (tachycardia) – Muffled heart sounds – Increased respiratory rate (tachypnea) – Distended abdomen (fluid filled)
  • 37. 9-year-old NM Labrador9-year-old NM Labrador RetrieverRetriever “Bear” Normal comparison
  • 38. 9-year-old NM Labrador9-year-old NM Labrador RetrieverRetriever “Bear” Normal comparison
  • 39. 9-year-old NM Labrador9-year-old NM Labrador RetrieverRetriever Fluid analysis – Pericardial fluid – hemorrhagic effusion – Peritoneal fluid – Modified transudate  High protein (4.0 g/dl)  Low cells (< 500/ul)
  • 40. 10-year-old Miniature Poodle10-year-old Miniature Poodle  Presented for “weight gain”  Increased drinking and urination (polydipsia/polyuria)
  • 41. 10-year-old Miniature Poodle10-year-old Miniature Poodle Fluid Analysis: – Clear/ colorless fluid – Total Protein - < 1.0 g/dl – Cell count - < 100 /ul
  • 42. 10-year-old Miniature Poodle10-year-old Miniature Poodle Hematology and Clinical chemistry values were all within normal limits except: – Hypoalbuminemia-1.5 g/dl (2.7-4.0) Urinalysis – Large amount of protein in urine (proteinuria).
  • 43. 10-year-old Miniature Poodle10-year-old Miniature Poodle