Lisa Stevens, D.O.
Part 1
 60% of lean body weight is water
Two thirds of the body's water is intracellular
 Remainder is in extracellular compartments
 About 5% of total body water is in blood plasma

 Movement of water and low molecular
weight solutes (salts)
Between the intravascular and interstitial spaces
 Controlled primarily by opposing effect of:

 Vascular
hydrostatic pressure
 Plasma colloid osmotic pressure
 Increased interstitial fluid
Increased capillary pressure
 Diminished colloid osmotic pressure

 Fluid accumulation

Movement of water into tissues (or body cavities)
exceeds drainage
 Abnormal increase in interstitial fluid within
tissues

Edema
 Fluid collections in the different body cavities
Hydrothorax
 Hydropericardium
 Hydroperitoneum (ascites)

 Anasarca
Severe and generalized edema
 Widespread subcutaneous tissue swelling

 Transudate

Edema caused by:
 Increased
hydrostatic pressure
 Reduced plasma protein
Typically a protein-poor fluid
 Heart failure, renal failure, hepatic failure, and
certain forms of malnutrition

 Inflammatory edema
Protein-rich exudate
 Result of increased vascular permeability

 Lymphedema
Impaired lymphatic drainage
 Typically localized
 Causes

 Chronic
inflammation with fibrosis
 Invasive malignant tumors
 Physical disruption
 Radiation damage
 Certain infectious agents

Parasitic filariasis
 Lymphatic
obstruction
• Extensive inguinal lymphatic and lymph node fibrosis
• Edema of the external genitalia and lower limbs
• Massive = elephantiasis
 Severe edema of the upper extremity

Complicate surgical removal and/or irradiation
 Breast
and associated axillary lymph nodes
• Breast cancer
 Morphology
Edema is easily recognized grossly
 Microscopic examination

 Clearing
and separation of the extracellular matrix
 Subtle cell swelling
 Most commonly seen:

Subcutaneous tissues, lungs, and brain
 Subcutaneous edema
Diffuse or more conspicuous in regions with high
hydrostatic pressures
 Distribution is influenced by gravity

 Dependent
edema
• Legs when standing, the sacrum when recumbent
 Subcutaneous edema

Pitting edema
Finger pressure over substantially edematous
subcutaneous tissue
 Displaces the interstitial fluid and leaves a depression

 Edema secondary to renal dysfunction
Affect all parts of the body
 Manifests in tissues with loose connective tissue
matrix (eyelids)

 Periorbital
edema
• Characteristic finding in severe renal disease
 Soft tissue edema
Important because it signals underlying cardiac or
renal disease
 Impairs wound healing or the clearance of infection

 Pulmonary edema
Lungs are often two to three times their normal
weight
 Sectioning yields frothy, blood-tinged fluid

 Mixture
of air, edema, and extravasated red cells
Common clinical problem
 Most frequently seen with left ventricular failure

 Pulmonary edema
Lungs are often two to three times their normal
weight
 Sectioning yields frothy, blood-tinged fluid

 Mixture
of air, edema, and extravasated red cells
Common clinical problem
 Most frequently seen with left ventricular failure

 Brain edema
Localized or generalized
 Depending on the nature and extent of the
pathologic process or injury
 Generalized edema

 Brain
is grossly swollen with narrowed sulci
 Distended gyri show evidence of compression
against the unyielding skull
 Brain edema
Life-threatening
 Severe edema

 Brain
substance can herniate (extrude)
• Foramen magnum
 Brain
stem vascular supply can be compressed
 Either condition can injure the medullary centers
• Cause death
 Stem from locally increased blood volumes
 Hyperemia
Active process
 Arteriolar dilation

 Sites
of inflammation
 Skeletal muscle during exercise
 Hyperemia
 Leads

to increased blood flow
Affected tissues turn red (erythema)
 Engorgement
of vessels with oxygenated blood
 Congestion
Passive process
 Reduced outflow of blood from a tissue
 Systemic

 Cardiac
failure
 Congestion

Local
 Isolated

venous obstruction
Dusky reddish-blue color (cyanosis)
 Red
cell stasis
 Accumulation of deoxygenated hemoglobin
 Long-standing chronic passive congestion

Lack of blood flow causes chronic hypoxia
 Results

in ischemic tissue injury and scarring
Capillary rupture
 Cause
small hemorrhagic foci
 Subsequent catabolism of extravasated red cells
• Leave residual telltale clusters of hemosiderin-laden
macrophages
 Morphology

Cut surfaces
 Discolored
due to the presence of high levels of
poorly oxygenated blood

Microscopic examination
 Acute
pulmonary congestion
• Engorged alveolar capillaries
• Alveolar septal edema
• Focal intra-alveolar hemorrhage
 Morphology

Microscopic examination
 Chronic
pulmonary congestion
• Septa are thickened and fibrotic
• Alveoli often contain numerous hemosiderin-laden
macrophages

Heart failure cells
 Morphology

Acute hepatic congestion
 Central
vein and sinusoids are distended
 Centrilobular hepatocytes can be frankly ischemic

Chronic passive hepatic congestion
 Centrilobular
regions are grossly red-brown
• Areas are accentuated against uncongested
parenchyma
• Nutmeg liver
 Morphology

Microscopic examination
 Centrilobular
hemorrhage
 Hemosiderin-laden macrophages
 Degeneration of hepatocytes
 Extravasation of blood into the extravascular
space
 Increased tendency to hemorrhage (usually
with insignificant injury)
Occurs in a variety of clinical disorders
 Collectively called hemorrhagic diatheses

 Distinct patterns of tissue hemorrhage

Hemorrhage may be external
 Contained
within a tissue
 Hematoma
 Petechiae
Minute 1- to 2-mm hemorrhages into skin,
mucous membranes, or serosal surfaces
 Most commonly associated:

 Locally
increased intravascular pressure
 Low platelet counts (thrombocytopenia)
 Defective platelet function (as in uremia)
 Purpura
Slightly larger (≥3 mm) hemorrhages
 Associated with many of the same disorders that
cause petechiae
 Secondary to trauma, vascular inflammation
(vasculitis), or increased vascular fragility
(amyloidosis)

 Ecchymoses
Larger (>1 to 2 cm) subcutaneous hematomas
(bruises)
 Red cells in these lesions are degraded and
phagocytized by macrophages

 Hemoglobin
(red-blue color)
• Enzymatically converted into bilirubin (blue-green
color)

Hemosiderin (gold-brown color), accounting for the
characteristic color changes in a bruise
 Large accumulation of blood in a body cavity
Hemothorax
 Hemopericardium
 Hemoperitoneum
 Hemarthrosis (in joints)

 Normal hemostasis
Consequence of tightly regulated processes
 Maintain blood in a fluid state in normal vessels
 Permit the rapid formation of a hemostatic clot at
the site of a vascular injury

 Thrombosis
Pathologic counterpart of hemostasis
 Involves blood clot (thrombus) formation

 Both hemostasis and thrombosis involve
three components:
Vascular wall (particularly the endothelium)
 Platelets
 Coagulation cascade

 Endothelial cells
Key players in the regulation of homeostasis
 Exhibit antiplatelet, anticoagulant, and fibrinolytic
properties
 After injury or activation

 Acquire

numerous procoagulant activities
Activated by infectious agents, hemodynamic
forces, plasma mediators, and cytokines
 Antiplatelet effects
Intact endothelium prevents platelets from
engaging the highly thrombogenic subendothelial
ECM
 Nonactivated platelets

 Do
not adhere to endothelial cells
• Even if platelets are activated, prostacyclin (PGI2) and
nitric oxide produced by the endothelial cells impede
platelet adhesion
 Antiplatelet effects

Endothelial cells
 Also
elaborate adenosine diphosphatase
• Degrades adenosine diphosphate (ADP)
• Further inhibits platelet aggregation
 Anticoagulant effects

Mediated by endothelial membrane-associated
heparin-like molecules
 Thrombomodulin
• Binds to thrombin
• Converts it from a procoagulant into an anticoagulant

Via its ability to activate protein C, which inhibits clotting
by inactivating factors Va and VIIIa
 Anticoagulant effects

Mediated by endothelial membrane-associated
heparin-like molecules
 Tissue
factor pathway inhibitor
• Cell surface protein
• Directly inhibits tissue factor-factor VIIa and factor Xa
activities
 Anticoagulant effects

Heparin-like molecules
 Act
indirectly
 Cofactors that enhance the inactivation of thrombin
and several other coagulation factors
• Through the use of plasma protein antithrombin III
 Fibrinolytic effects

Endothelial cells synthesize tissue-type
plasminogen activator (t-PA)
 Protease
that cleaves plasminogen to form plasmin
• Plasmin cleaves fibrin to degrade thrombi
 Platelet effects
Endothelial injury allows platelets to contact the
underlying extracellular matrix
 Subsequent adhesion occurs through interactions
with von Willebrand factor (vWF)

 Product of normal endothelial
cells and an essential
cofactor for platelet binding to matrix elements
 Procoagulant effects

Response to cytokines (TNF or IL-1) or bacterial
endotoxin
 Endothelial
cells synthesize tissue factor
• Major activator of the extrinsic clotting cascade
• Activated endothelial cells

Augment the catalytic function of activated coagulation
factors IXa and Xa
 Antifibrinolytic effects

Endothelial cells secrete inhibitors of plasminogen
activator (PAIs)
 Limit
fibrinolysis and tend to favor thrombosis
 Intact, nonactivated endothelial cells inhibit
platelet adhesion and blood clotting
 Endothelial injury or activation

Results in a procoagulant phenotype that
enhances thrombus formation
 Disc-shaped
 Anucleate cell fragments
 Shed from megakaryocytes in the bone
marrow into the blood stream
 Play a critical role in normal hemostasis
Forming the hemostatic plug that initially seals
vascular defects
 Providing a surface that recruits and concentrates
activated coagulation factors

 Function depends on several glycoprotein
receptors
Contractile cytoskeleton
 Two types of cytoplasmic granules

 α-Granules
• Adhesion molecule P-selectin on their membranes
• Contain fibrinogen, fibronectin, factors V and VIII,
platelet factor 4, platelet-derived growth factor
(PDGF), and transforming growth factor-β (TGF-β)
 Function depends on several glycoprotein
receptors

Two types of cytoplasmic granules
 Dense
(or δ) granules
• Contain ADP and ATP, ionized calcium, histamine,
serotonin, and epinephrine
 Following vascular injury…

Platelets encounter ECM constituents
 Collagen
and the adhesive glycoprotein vWF
 On contact with these proteins, platelets
undergo:
Adhesion and shape change
 Secretion (release reaction)
 Aggregation

 Mediated largely via interactions with vWF
Acts as a bridge between platelet surface
receptors (glycoprotein Ib) and exposed collagen
 vWF-GpIb associations

 Necessary
to overcome the high shear forces of
flowing blood
 Mediated largely via interactions with vWF
 Genetic
deficiencies of vWF or its receptor result in
bleeding disorders
• Von Willebrand Disease
• Bernard-Soulier syndrome
 Occurs soon after adhesion
 Various agonists can bind platelet surface
receptors

Initiate an intracellular protein phosphorylation
cascade
 Leads
to degranulation
 Various agonists can bind platelet surface
receptors

Release of the contents of dense-bodies
 Important
 Calcium
is required in the coagulation cascade
 ADP is a potent activator of platelet aggregation
• Causes additional ADP release

Amplifies aggregation process
 Platelet activation

Appearance of negatively charged phospholipids
(particularly phosphatidylserine) on their surfaces
 Bind
calcium and serve as critical nucleation sites for
the assembly of complexes containing the various
coagulation factors
 Follows adhesion and granule release
 Vasoconstrictor thromboxane A2
Important platelet-derived stimulus
 Amplifies platelet aggregation
 Formation of the primary hemostatic plug

 Initial wave of aggregation is reversible
 Concurrent activation of the coagulation
cascade
Generates thrombin
 Stabilizes the platelet plug via two mechanisms:

 Thrombin
binds to a protease-activated receptor on
the platelet membrane
• In concert with ADP and TxA2 causes further platelet
aggregation
 Stabilizes the platelet plug via two
mechanisms:

Thrombin binds to a protease-activated receptor
on the platelet membrane
 Platelet
contraction
• Event that is dependent on the platelet cytoskeleton
• Creates an irreversibly fused mass of platelets
• Constitutes the definitive secondary hemostatic plug

Thrombin converts fibrinogen to fibrin in the
vicinity of the platelet plug
• Cements the platelets in place
 Noncleaved fibrinogen

Important component of platelet aggregation
 Platelet activation by ADP
Triggers a conformational change in the platelet
GpIIb-IIIa receptors
 Induces binding to fibrinogen

 Large
protein that forms bridging interactions
between platelets that promote platelet
aggregation
Lisa Stevens, D.O.
Part 2
 Third arm of the hemostatic process
 Amplifying series of enzymatic conversions

Each step proteolytically cleaves an inactive
proenzyme into an activated enzyme
 Culminates
in thrombin formation
 Thrombin is the most important coagulation
factor

Can act at numerous stages in the process
 Conclusion of the proteolytic cascade

Thrombin converts the soluble plasma protein
fibrinogen into fibrin monomers that polymerize
into an insoluble gel
 Fibrin
gel encases platelets and other circulating
cells in the definitive secondary hemostatic plug

Fibrin polymers are covalently cross-linked and
stabilized by factor XIIIa (which itself is activated
by thrombin)
 Assess the function of the two arms of the
coagulation pathway

Two standard assays
 Prothrombin
time (PT)
 Partial thromboplastin time (PTT)
 The PT assay

Assesses the function of the proteins in the
extrinsic pathway
 Factors VII, X,
II, V, and fibrinogen
 Accomplished by adding tissue factor and
phospholipids to citrated plasma (sodium citrate
chelates calcium and prevents spontaneous clotting)
 Coagulation is initiated by the addition of
exogenous calcium and the time for a fibrin clot to
form is recorded
 Partial thromboplastin time (PTT)

Screens for the function of the proteins in the
intrinsic pathway
 Factors XII, XI, IX, VIII, X, V,
II, and fibrinogen
 Clotting is initiated through the addition of negative
charged particles (ground glass)
• Activates factor XII (Hageman factor), phospholipids,
and calcium, and the time to fibrin clot formation is
recorded
 Thrombin
Exerts a wide variety of proinflammatery effects
 Most effects of thrombin occur through its
activation of a family of protease activated
receptors (PARs)

 Belong
to the seven-transmembrane G proteincoupled receptor family
 PARs are expressed on endothelium, monocytes,
dendritic cells, T lymphocytes, and other cell types
 Coagulation cascade must be restricted to the
site of vascular injury

Prevent runaway clotting of the entire vascular tree
 Three categories of endogenous anticoagulants
 Antithrombins (antithrombin III)
Inhibit the activity of thrombin and other serine
proteases, including factors IXa, Xa, XIa, and XIIa
 Antithrombin III is activated by binding to heparin-like
molecules on endothelial cells

• Clinical usefulness of administering heparin to minimize
thrombosis
 Three categories of endogenous anticoagulants

Proteins C and S
 Vitamin
K-dependent proteins
 Act in a complex that proteolytically inactivates factors
Va and VIIIa

TFPI is a protein produced by endothelium
 Inactivates
tissue factor-factor VIIa complexes
 Fine-tune the coagulation/anticoagulation
balance
 Releasing plasminogen activator inhibitor
(PAI)
Blocks fibrinolysis by inhibiting t-PA binding to
fibrin
 Confers an overall procoagulant effect
 Production is increased by thrombin as well as
certain cytokines

 Three primary abnormalities that lead to
thrombus formation (called Virchow's triad):
Endothelial injury
 Stasis or turbulent blood flow
 Hypercoagulability of the blood

 Particularly important for thrombus
formation in the heart or the arterial
circulation

Normally high flow rates might otherwise impede
clotting by preventing platelet adhesion and
washing out activated coagulation factors
 Endothelial cell injury
Thrombus formation within cardiac chambers (i.e.
after endocardial injury due to myocardial
infarction)
 Over ulcerated plaques in atherosclerotic arteries
 Sites of traumatic or inflammatory vascular injury
(vasculitis)

 Endothelium

Does not need to be denuded or physically
disrupted to contribute to the development of
thrombosis
 Any perturbation in the dynamic balance of
the prothombotic and antithrombotic
activities of endothelium can influence local
clotting events
 Endothelial dysfunction

Induced by a wide variety of insults
 Hypertension
 Turbulent blood
flow
 Bacterial endotoxins
 Radiation injury
 Metabolic abnormalities
• Homocystinemia or hypercholesterolemia
 Toxins
absorbed from cigarette smoke
 Turbulence
Contributes to arterial and cardiac thrombosis by
causing endothelial injury or dysfunction
 Forming countercurrents and local pockets of
stasis

 Stasis
is a major contributor in the development of
venous thrombi
 Normal blood flow is laminar

Platelets (and other blood cellular elements)
 Flow
centrally in the vessel lumen
• Separated from endothelium by a slower moving layer
of plasma
 Stasis and turbulence therefore:

Promote endothelial activation
 Enhancing
pro-coagulant activity
Disrupt laminar flow
 Bring platelets into contact with the endothelium
 Prevent washout and dilution of activated clotting
factors

 Fresh
flowing blood
 Inflow of clotting factor inhibitors
 AKA thrombophilia
 Less frequent contributor to thrombotic
states
 Any alteration of the coagulation pathways
that predisposes to thrombosis
Divided into primary (genetic)
 Secondary (acquired) disorders

 Inherited causes

Most common
 Point
mutations in the factor V gene
 Prothrombin gene
 Elevated levels of homocysteine

Contribute to arterial and venous thrombosis
 Prothrombotic effects of homocysteine

Due to thioester linkages
 Between
proteins
homocysteine metabolites and a variety of
 Rare inherited causes of primary hypercoagulability

Deficiencies of anticoagulants
 Antithrombin
III, protein C, or protein S
 Clinical presentation
• Begins in adolescence or early adulthood
• Venous thrombosis
• Recurrent thromboembolism
 Acquired thrombophilic states

Heparin-induced thrombocytopenia (HIT)
syndrome
 Occurs following
the administration of
unfractionated heparin
• May induce the appearance of antibodies

Recognize complexes of heparin and platelet factor 4 on
the surface of platelets
 Heparin-induced thrombocytopenia (HIT)
syndrome

Occurs following the administration of
unfractionated heparin
• Complexes of heparin-like molecules and platelet
factor 4-like proteins on endothelial cells
• Binding of these antibodies to platelets

Results in their activation, aggregation, and consumption
 Prothrombotic
state, even in the face of heparin
administration and low platelet counts
 AKA lupus anticoagulant syndrome
 Clinical manifestations
Recurrent thromboses, repeated miscarriages,
cardiac valve vegetations, and thrombocytopenia
 Pulmonary embolism, pulmonary hypertension,
stroke, bowel infarction, or renovascular
hypertension
 Fetal loss

 Autoantibodies induce a hypercoagulable
state

Cause endothelial injury
 Directly
activates platelets and complement
 Primary and secondary forms

Secondary antiphospholipid syndrome
 Individuals
with a well-defined autoimmune disease
 Systemic lupus erythematosus
 Primary and secondary forms

Primary antiphospholipid syndrome
 Exhibit
only the manifestations of a hypercoagulable
state
 Lack evidence of other autoimmune disorders
 Association with certain drugs or infections
 Can develop anywhere in the cardiovascular
system
 Size and shape of thrombi
Depend on the site of origin and the cause
 Arterial or cardiac thrombi

 Begin

at sites of turbulence or endothelial injury
Venous thrombi
 Occur at
sites of stasis
 Focally attached to the underlying vascular
surface

Arterial thrombi
 Grow retrograde

from the point of attachment
Venous thrombi
 Extend
in the direction of blood flow
 Gross and microscopic laminations

Lines of Zahn
 Represent
pale platelet and fibrin deposits
alternating with darker red cell-rich layers
 Signify that a thrombus has formed in flowing blood
 Presence can therefore distinguish antemortem
thrombosis from the bland nonlaminated clots that
occur postmortem
 Thrombi occurring in heart chambers or in
the aortic lumen

Mural thrombi

Abnormal myocardial contraction
• Arrhythmias, dilated cardiomyopathy, or myocardial
infarction
• Endomyocardial injury (myocarditis or catheter
trauma)
 Arterial thrombi
Frequently occlusive
 Most common sites

 Coronary, cerebral,
and femoral arteries
Friable meshwork of platelets, fibrin, red cells, and
degenerating leukocytes
 Superimposed on a ruptured atherosclerotic
plaque

 Venous thrombosis (phlebothrombosis)
Invariably occlusive
 Thrombus forming a long cast of the lumen
 Thrombi form in the sluggish venous circulation
 Contain more enmeshed red cells

 Red, or stasis,

thrombi
Veins of the lower extremities are most commonly
involved (90% of cases)
 Postmortem clots
Mistaken for antemortem venous thrombi
 Gelatinous with a dark red dependent portion

 Red
cells have settled by gravity
 Yellow "chicken fat" upper portion

Usually not attached to the underlying wall
 Red thrombi
Firmer
 Focally attached
 Gross and/or microscopic lines of Zahn

 Vegetations
Thrombi on heart valves
 Blood-borne bacteria or fungi

 Adhere
to previously damaged valves (rheumatic
heart disease)
 Directly cause valve damage
 Infective endocarditis
 Vegetations

Sterile vegetations
 Nonbacterial

thrombotic endocarditis
Sterile, verrucous endocarditis
 Libman-Sacks
endocarditis
 Survival of the initial thrombosis
 Ensuing days to weeks thrombi undergo some
combination of the following four events:

Propagation
• Thrombi accumulate additional platelets and fibrin

Embolization
• Thrombi dislodge and travel to other sites in the vasculature

Dissolution
• Result of fibrinolysis


Leads to shrinkage and total disappearance of recent thrombi
Organization and recanalization
• Older thrombi become organized by the ingrowth of
endothelial cells, smooth muscle cells, and fibroblasts
 Deep venous thrombosis (DVT)
Larger leg veins-at or above the knee
 Thrombi more often embolize to the lungs

 Give
rise to pulmonary infarction
 Venous obstructions from DVTs can be
rapidly offset by collateral channels
DVTs are asymptomatic in approximately 50% of
affected individuals
 Recognized only in retrospect after embolization

 Obstetric complications to advanced
malignancy
 Sudden or insidious onset of widespread
fibrin thrombi in the microcirculation
 Not grossly visible
 Diffuse circulatory insufficiency, particularly
in the brain, lungs, heart, and kidneys
 Widespread microvascular thrombosis results
in platelet and coagulation protein
consumption

Fibrinolytic mechanisms are activated
 Initially thrombotic disorder

Evolve into a bleeding catastrophe
 Embolus
 Detached intravascular solid, liquid, or gaseous
mass
 Carried by the blood to a site distant from its point
of origin
 Thromboembolism
 Rare forms of emboli
 Fat
droplets, nitrogen bubbles, atherosclerotic
debris (cholesterol emboli), tumor fragments, bone
marrow, or foreign bodies

Unless otherwise specified, emboli should be
considered thrombotic in origin
 Occlusions—embolic
 95% from deep leg veins
 Indwelling central venous lines

Right atrial thrombi
 50,000 deaths/year in US
 Origin of emboli

Leg or pelvic veins
 Large emboli

Sudden death
 Lodging
• Major branches of pulmonary arteries
• Saddle emboli
 Acute
cor pulmonale
 Small emboli
Minimal symptoms
 Exception

 Inadequate
bronchial circulation
• Symptoms
 Causes of emboli
Immobilized individuals
 Hypercoagulable state (primary vs. secondary)
 Heart failure

 Extent of pulmonary artery
obstruction
 Size of occluded vessel
 Pathophysiologic response
 Clinical significance
 Number of emboli
 Status of the cardiovascular
system
 Release of vasoactive factors
 Pathophysiologic consequences
Respiratory compromise
 Hemodynamic compromise

 Adequate cardiovascular function

Bronchial artery compensation
 Hemorrhage without
infarction
 Infarction
Inadequate circulation
 Rare in young

 Clinical course

Cardiopulmonary resuscitation
 Electromechanical
dissociation
• Electrocardiogram has a rhythm
• No pulses are palpated

Survival (post-sizable pulmonary embolus)
 Mimics
myocardial infarction
Diagnosis
Spiral CT
Other diagnostic methods
Ventilation
perfusion scanning
Pulmonary angiography
Duplex ultrasonography
• Deep vein thrombosis
 Prevention
 Major clinical problem
 Prophylactic therapy
 Early
ambulation
 Stockings
 Anticoagulation
 Filter
 Treatment
 Thrombolysis
 Anticoagulation
 Gross examination

Parenchyma
 75%
of all infarcts affect the lower lobes
 Greater than 50%--multiple lesions
 Wedge shaped
 Hemorrhagic
Fibrinous pleural exudate
 Scar
 Embolus

http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=714&viewer=java&lay=&jpg=493
 Microscopic examination

Ischemic necrosis
 Alveolar

walls, bronchioles, and vessels
Infected embolus
 Intense
neutrophilic inflammatory reaction
 Septic infarct
 Microscopic fat globules-with or without
associated hematopoietic marrow elements
 Fractures of long bones (which have fatty
marrow)
 Soft tissue trauma and burns
 Common incidental findings after vigorous
cardiopulmonary resuscitation
 No clinical consequence
 Gas bubbles within the circulation
 Coalesce to form frothy masses
 Obstruct

vascular flow (causes distal ischemic injury)
More than 100 cc of air
 Required
to have a clinical effect in the pulmonary
circulation

Decompression sickness
 Sudden
 At
decreases in atmospheric pressure
risk:
• Scuba and deep sea divers, underwater construction
workers, and individuals in unpressurized aircraft in
rapid ascent
 The bends

Rapid formation of gas bubbles within skeletal
muscles and supporting tissues in and about joints
 The chokes

Gas bubbles in the vasculature
 Causes
edema, hemorrhage, and focal atelectasis or
emphysema, leading to a form of respiratory
distress
 Caisson disease
Chronic form of decompression sickness
 Named for the pressurized vessels used in the
bridge construction

 Workers in
these vessels suffered both acute and
chronic forms of decompression sickness

Persistence of gas emboli in the skeletal system
 Leads
to multiple foci of ischemic necrosis
 More common sites
• Femoral heads, tibia, and humeri
 Amniotic fluid embolism
Ominous complication of labor and the immediate
postpartum period
 Sudden severe dyspnea, cyanosis, and shock

 Followed
by neurologic impairment ranging from
headache to seizures and coma
 If the patient survives the initial crisis, pulmonary
edema typically develops, along with (in half the
patients) DIC, as a result of release of thrombogenic
substances from the amniotic fluid
 Underlying cause

Infusion of amniotic fluid or fetal tissue into the
maternal circulation via a tear in the placental
membranes or rupture of uterine veins
 Classic findings

Presence of squamous cells shed from fetal skin,
lanugo hair, fat from vernix caseosa, and mucin
derived from the fetal respiratory or
gastrointestinal tract in the maternal pulmonary
microvasculature
 Final common pathway for several potentially
lethal clinical events

Severe hemorrhage, extensive trauma or burns,
large myocardial infarction, massive pulmonary
embolism, and microbial sepsis
 Clinical findings

Systemic hypotension
 Due
to reduced cardiac output or to reduced
effective circulating blood volume
 Consequences

Impaired tissue perfusion and cellular hypoxia
 Three general categories
Cardiogenic shock
 Hypovolemic shock
 Septic shock

 Depend on the precipitating insult
 Hypovolemic and cardiogenic shock

Patient presents with hypotension
 Weak,
rapid pulse; tachypnea
 Cool, clammy, cyanotic skin
 Septic shock

Skin may initially be warm and flushed because of
peripheral vasodilation
 Cardiac, cerebral, and pulmonary changes
secondary to shock worsen the problem
 Electrolyte disturbances and metabolic
acidosis