1. Edema
• accumulation of abnormal amounts of
fluid in tissue/body cavities
• inflammatory edema
– due to increased vascular permeability
– exudate, rich in protein, specific gravity > 1.02
• non-inflammatory edema
– due to hemodynamic forces across capillary wall
– transudate, low in protein, specific gravity <1.012
6. Fluid movement across capillaries:
• Starling's Law
– Pc = Capillary Hydrostatic Pressure (outward)
– Pif = Interstitial Hydrostatic Pressure (inward)
– OSMpl = Plasma Protein Osmotic Pressure
(inward)
– OSMif = Insterstitial Protein Osmotic Pressure
(outward)
– Net Pressure = (Pc - Pif) - (OSMpl - OSMif)
7. Edema Pathogenesis
• increase in intravascular hydrostatic
pressure
• decrease in intravascular osmotic
pressure
• impairment in lymph flow
• renal retention of salt and water
11. Edema: Clinical Importance
• Minor
– local
– mild reflection of renal or heart disease
• Major
– pulmonary
– brain
• may cause physical shear (herniation) of brain
(fatal)
13. Hemorrhage
• hematoma: blood trapped in tissue
• ecchymosis: large hematoma (bruise)
• natural history:
– hemoglobin converted to bilirubin via biliverdin
– red to brown with some green
• volume, rate, site important in
determining clinical significance
18. Coagulation System
• Extrinsic (tissue factor stimulated) vs.
Intrinsic
• Each step: enzyme-substrate-cofactor
• Assembled on phospholipid surface, held
together by calcium
– allows localization
• Anticoagulant mechanisms
– antithrombins; proteins C and S;plasminogen-
plasmin
26. Primary (Genetic)
Common (>1% of the Population)
•Factor V mutation (G1691A mutation; factor V Leiden)
•Prothrombin mutation (G20210A variant)
•5,10-Methylene tetrahydrofolate reductase (homozygous C677T mutation)
•Increased levels of factor VIII, IX, or XI or fibrinogen
Rare
•Antithrombin III deficiency
•Protein C deficiency
•Protein S deficiency
Very Rare
•Fibrinolysis defects
•Homozygous homocystinuria (deficiency of cystathione β-synthetase)
Secondary (Acquired)
High Risk for Thrombosis
•Prolonged bed rest or immobilization
•Myocardial infarction
•Atrial fibrillation
•Tissue injury (surgery, fracture, burn)
•Cancer
•Prosthetic cardiac valves
•Disseminated intravascular coagulation
•Heparin-induced thrombocytopenia
•Antiphospholipid antibody syndrome
Lower Risk for Thrombosis
•Cardiomyopathy
•Nephrotic syndrome
•Hyperestrogenic states (pregnancy and postpartum)
•Oral contraceptive use
•Sickle cell anemia
•Smoking
27. Thrombosis Pathogenesis
• Major factors:
– Injury to endothelium
• e.g. at atherosclerotic plaques, damaged valves
– Alterations in normal blood flow
• turbulence (arterial/cardiac thrombi)
• stasis (sluggish flow, venous thrombi)
– mechanisms: disruption of laminar flow, less dilution of
factors
– Alterations in blood
• hypercoaguability (predisposition to clot)
28. Fate of Thrombi
• propagation
– increase in size
• embolization
– dislodge, travel and block distant vessel
• dissolution
– fibrinolysis
• organization and recanalization
– inflammation, fibrosis and repair
34. Arterial Thrombosis
• cardiac
predispositions
– infarction, atherosclerosis,
aneurysms
• associated with
damage to
endothelium
• may embolize to
downstream organs,
e.g. kidney, spleen
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
35. Pulmonary Embolism
• occlusion of large/medium sized artery by
thrombus
• usually from deep leg vein thrombi
• majority clinically silent (small)
• can manifest as chest pain, shortness of
breath, sudden death (if massive)
• can cause infarction (10%)
36. Shock: Symptoms & Signs
• Cold, clammy, cyanotic skin
• Hyperventilation
• Tachycardia with weak pulse
• Cloudy consciousness to coma
• Oliguric
• Low blood pressure
37. Shock: definition & types
• Systemic hypoperfusion due to reduction either
in cardiac output or effective circulating blood
volume
• ‘ineffective delivery of oxygen to tissues’
• Types:
– Cardiogenic
– Hypovolemic
– Septic
– Anaphylactic
– Neurogenic
38. Types of
shock
Type of
Shock
Clinical Examples
Principal Pathogenic
Mechanisms
Cardiogenic
Myocardial infarction
Failure of myocardial pump
resulting from intrinsic
myocardial damage,
extrinsic pressure, or
obstruction to outflow
Ventricular rupture
Arrhythmia
Cardiac tamponade
Pulmonary embolism
Hypovolemic
Hemorrhage
Inadequate blood or plasma
volume
Fluid loss (e.g., vomiting,
diarrhea, burns, trauma)
Septic
Overwhelming microbial
infections
Peripheral vasodilation and
pooling of blood; endothelial
activation/injury; leukocyte-
induced damage;
disseminated intravascular
coagulation; activation of
cytokine cascades
Endotoxic shock
Gram-positive septicemia
Fungal sepsis
Superantigens (e.g., toxic
shock syndrome)
39. Causes of Shock: I
• Decreased intravascular volume
– Acute hemorrhage
– Fluid loss
– Vasodilatation
• Cardiac dysfunction (‘cardiogenic’)
– Acute myocardial infarction
– Myocarditis
– Arrhythmias
– Mechanical compression or obstruction
42. Time sequence of critical
mediators of septic shock
LPS
TNF
IL-1
IL-6/IL-8
TIME
43. Shock: Symptoms & Signs
• Cold, clammy, cyanotic skin
• Hyperventilation
• Tachycardia with weak pulse
• Cloudy consciousness to coma
• Oliguric
• Low blood pressure
44. Shock: Compensatory
mechanisms
• Increased oncotic pressure draws
extracellular fluid into capillaries
• Sympathetic nervous system stimulate
arterial vasoconstriction
– leads to many of the signs and symptoms of shock
• Compensatory mechanisms have limited
capacity
