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Mechanisms of Disease:Mechanisms of Disease:Disorders of CirculationDisorders of Circulation
Sharon M. Dial, DVM, PhD
Arizona Veterinary Diagnostic Laboratory
Disorders of CirculationDisorders of Circulation
Disturbances of blood flow
Hemostasis and Thrombosis
Obstacles of Blood Flow
Disturbances of Fluid Exchange
Ischemia and Shock
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)
Disturbances of Fluid Disturbances 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.
Disturbances of Fluid Disturbances 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
From: Mechanisms of Disease, ed D.O. Slauson, B.J. Cooper, 2nd Ed.
Fluid CompartmentsFluid Compartments
Extracellular Fluid
Intracellular Fluid
Intravascular FluidPlasma
RBC mass
Albumin 4.5%Globulin 2.5%Fibrinogen 0.3%
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
Disturbances of Fluid Disturbances of Fluid ExchangeExchange
Lymphatics– Vessel structure
Thin wall Valves
– Maintain negative pressure
Disturbances of Fluid Disturbances 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
Disturbances of Fluid Disturbances 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
Disturbances of fluid Disturbances of fluid exchangeexchange
Generalized edema – often associated with transudation of fluid into body cavities.– Hydropericardium– Hydrothorax– Hydroperitoneum
Generalized subcutaneous edema - Anasarca
From: Robbins Pathologic Basis of Disease, ed. Cotran, Kumar, Collins.
Ascites Ascites
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.
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
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
Acute local active hyperemiaAcute local active hyperemia
http://www.vetmed.ufl.edu/path/pbteach/wlc/vem5161/circ/circ2.htm
Oral MucosaBovine
MalignantCatarrhal
Fever
Acute local passive hyperemiaAcute local passive hyperemia
http://www.vetmed.ufl.edu/path/pbteach/wlc/vem5161/circ/circ2.htm
Lung TorsionNote dark red/black
Lung lobe
Chronic local passive Chronic local passive hyperemiahyperemia
http://www.bayinsider.com
Deep venous thrombosis
Consequences of chronic Consequences of chronic congestioncongestion
Lung – interstitial fibrosis and alveolar hemorrhage
Liver – central lobular necrosis and fibrosisSpleen – hyperplasia and thrombosis
– Can be associated with hematoma.
www-medlib.med.utah.edu/WebPath/LUNGHTML
Hemosiderin-laden macrophages“heart failure cells”
cv
http://www.vh.org/Providers/Textbooks/LiverPatholog
http://www.vh.org/Providers/Textbooks/LiverPatholog
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
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
Hemorrhage by diapedesisHemorrhage by diapedesishttp://medlib.med.utah.edu/WebPath
Acute Gastritis
Hemorrhage by rhexisHemorrhage by rhexis
Ruptured PulmonaryArtery
HemorrhageHemorrhage
Causes– Trauma
Ruptured spleen or splenic hematoma
– Infectious disease Vasculitis Disseminated intravascular coagulation
– Coagulopathies– Platelet abnormalities
The Vocabulary of The Vocabulary of HemorrhageHemorrhage
Hemopericardium Hemothorax Hemoperitoneum Hemarthrosis
Hemoptysis Epistaxis Petechia Ecchymoses Purpura
HemopericardiumHemopericardium
http://medlib.med.utah.edu
Hemorrhage into pericardiumwith cardiac tamponade
Ruptured aortic aneurysm
HemothoraxHemothoraxhttp://medlib.med.utah.edu
Warfarin Toxicity
HemoperitoneumHemoperitoneum
HemarthrosisHemarthrosishttp://www.mednet.gr/pim/ht2.htm
Acute hemarthrosis dueTo hemophilia
EpistaxisEpistaxis
http://web.vet.cornell.edu/public/popmed/clinpath
HemorrhageHemorrhage
Resolution of hemorrhage– Resorption – by phagocytosis– organization
http://dermatology.cdlib.org
9-year-old NM Labrador 9-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)
9-year-old NM Labrador 9-year-old NM Labrador RetrieverRetriever
“Bear” Normal comparison
9-year-old NM Labrador 9-year-old NM Labrador RetrieverRetriever
“Bear” Normal comparison
9-year-old NM Labrador 9-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)
10-year-old Miniature Poodle10-year-old Miniature Poodle
Presented for “weight gain”
Increased drinking and urination (polydipsia/polyuria)
10-year-old Miniature Poodle10-year-old Miniature Poodle
Fluid Analysis:– Clear/ colorless fluid– Total Protein - < 1.0 g/dl– Cell count - < 100 /ul
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).
10-year-old Miniature Poodle10-year-old Miniature Poodle