PPT lecture 1 outline

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