Pathology Chapter 4

Pathology – Chapter 4
 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
 Fluid collections in the different body cavities
 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
• 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
• 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
• 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
 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
 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
 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
 Congestion
 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
 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
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
• Nutmeg liver
 Morphology
Microscopic examination
 Centrilobular
 Hemosiderin-laden macrophages
 Degeneration of hepatocytes
 Extravasation of blood into the extravascular
 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
 Ecchymoses
Larger (>1 to 2 cm) subcutaneous hematomas
 Red cells in these lesions are degraded and
phagocytized by macrophages
 Hemoglobin
(red-blue color)
• Enzymatically converted into bilirubin (blue-green
Hemosiderin (gold-brown color), accounting for the
characteristic color changes in a bruise
 Large accumulation of blood in a body cavity
 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
 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
 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
 Anticoagulant effects
Heparin-like molecules
 Act
 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
 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
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
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
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
Initiate an intracellular protein phosphorylation
 Leads
to degranulation
 Various agonists can bind platelet surface
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
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
 Stabilizes the platelet plug via two
Thrombin binds to a protease-activated receptor
on the platelet membrane
 Platelet
• 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
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
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
 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
 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
 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
 Releasing plasminogen activator inhibitor
Blocks fibrinolysis by inhibiting t-PA binding to
 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
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
 Over ulcerated plaques in atherosclerotic arteries
 Sites of traumatic or inflammatory vascular injury
 Endothelium
Does not need to be denuded or physically
disrupted to contribute to the development of
 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, including
hypertension, turbulent blood flow, bacterial
endotoxins, radiation injury, metabolic
abnormalities such as homocystinemia or
hypercholesterolemia, and 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
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 through flowinduced changes in endothelial cell gene expression
Disrupt laminar flow and bring platelets into
contact with the endothelium
 Prevent washout and dilution of activated clotting
factors by fresh flowing blood and the inflow of
clotting factor inhibitors
 AKA thrombophilia
 Less frequent contributor to thrombotic
 Any alteration of the coagulation pathways
that predisposes to thrombosis
Divided into primary (genetic)
 Secondary (acquired) disorders
 Of the inherited causes of hypercoagulability
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
May be due to thioester linkages formed between
homocysteine metabolites and a variety of
proteins, including fibrinogen
 Rare inherited causes of primary
Deficiencies of anticoagulants
 Antithrombin
III, protein C, or protein S
 Present with venous thrombosis and recurrent
thromboembolism beginning in adolescence or early
 Acquired thrombophilic states
Heparin-induced thrombocytopenia (HIT)
 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)
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
 Fetal loss
 Autoantibodies induce a hypercoagulable
Cause endothelial injury by activating platelets
and complement directly
 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
 Lack evidence of other autoimmune disorders
 Association with certain drugs or infections
 Can develop anywhere in the cardiovascular
 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
Arterial thrombi tend to grow retrograde from the
point of attachment
 Venous thrombi extend in the direction of blood
 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
• Endomyocardial injury (myocarditis or catheter
 Arterial thrombi
Frequently occlusive
 Most common sites
 Coronary, cerebral,
and femoral arteries
Consist of a friable meshwork of platelets, fibrin,
red cells, and degenerating leukocytes
 Usually 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,
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
where red cells have settled by gravity and a
yellow "chicken fat" upper portion
 Usually not attached to the underlying wall
 Red thrombi
 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
 Survival of the initial thrombosis
 Ensuing days to weeks thrombi undergo some
combination of the following four events:
• Thrombi accumulate additional platelets and fibrin
• Thrombi dislodge and travel to other sites in the vasculature
• Result of fibrinolysis, which can lead to the rapid 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 and
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
 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
Fibrinolytic mechanisms are activated
 Initially thrombotic disorder
Evolve into a bleeding catastrophe
 Embolus
 Detached intravascular solid, liquid, or gaseous
mass that is carried by the blood to a site distant
from its point of origin
 Thromboembolism
 Rare forms of emboli include fat droplets,
nitrogen bubbles, atherosclerotic debris
(cholesterol emboli), tumor fragments, bone
marrow, or even 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
 Size of occluded vessel
 Pathophysiologic response
 Clinical significance
 Number of emboli
 Status of the cardiovascular
 Release of vasoactive factors
 Pathophysiologic consequences
Respiratory compromise
 Hemodynamic compromise
 Adequate cardiovascular function
Bronchial artery compensation
 Hemorrhage without
 Infarction
Inadequate circulation
 Rare in young
 Clinical course
Cardiopulmonary resuscitation
 Electromechanical
• Electrocardiogram has a rhythm
• No pulses are palpated
Survival (post-sizable pulmonary embolus)
 Mimics
myocardial infarction
Spiral CT
Other diagnostic methods
perfusion scanning
Pulmonary angiography
Duplex ultrasonography
• Deep vein thrombosis
 Prevention
 Major clinical problem
 Prophylactic therapy
 Early
 Stockings
 Anticoagulation
 Filter
 Treatment
 Thrombolysis
 Anticoagulation
 Gross examination
 75%
of all infarcts affect the lower lobes
 Greater than 50%--multiple lesions
 Wedge shaped
 Hemorrhagic
Fibrinous pleural exudate
 Scar
 Embolus
 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
 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 that obstruct
vascular flow (and cause distal ischemic injury)
 More than 100 cc of air are required to have a
clinical effect in the pulmonary circulation
 Decompression sickness
 Sudden
decreases in atmospheric pressure
 Scuba and deep sea divers, underwater construction
workers, and individuals in unpressurized aircraft in
rapid ascent are all at risk
 The bends
Rapid formation of gas bubbles within skeletal
muscles and supporting tissues in and about joints
 The chokes
Gas bubbles in the vasculature cause edema,
hemorrhage, and focal atelectasis or emphysema,
leading to a form of respiratory distress
 Caisson disease
Chronic form of decompression sickness is called
(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; the
more common sites are the 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
 Final common pathway for several potentially
lethal clinical events
Including severe hemorrhage, extensive trauma or
burns, large myocardial infarction, massive
pulmonary embolism, and microbial sepsis
 Shock is characterized by systemic hypotension
due either to reduced cardiac output or to
reduced effective circulating blood volume
 The consequences are 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; and cool, clammy,
cyanotic skin
 Septic shock
Skin may initially be warm and flushed because of
peripheral vasodilation
 Rapidly, however, the cardiac, cerebral, and
pulmonary changes secondary to shock
worsen the problem
 Electrolyte disturbances and metabolic