Pathology – Chapter 4

60% of lean body weight is waterTwo thirds of the body's water is

intracellularRemainder is in extracellular

compartmentsAbout 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 fluidIncreased capillary pressure Diminished colloid osmotic pressure

Fluid accumulationMovement of water into tissues (or body

cavities) exceeds drainage Abnormal increase in interstitial fluid

within tissues Edema

Fluid collections in the different body cavitiesHydrothoraxHydropericardiumHydroperitoneum (ascites)

AnasarcaSevere and generalized edemaWidespread subcutaneous tissue

swelling

TransudateEdema caused by:

Increased hydrostatic pressure Reduced plasma protein

Typically a protein-poor fluidHeart failure, renal failure, hepatic

failure, and certain forms of malnutrition

Inflammatory edemaProtein-rich exudateResult of increased vascular

permeability

LymphedemaImpaired lymphatic drainageTypically localizedCauses

Chronic inflammation with fibrosis Invasive malignant tumors Physical disruption Radiation damage

Certain infectious agentsParasitic 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 extremityComplicate surgical removal and/or

irradiation Breast and associated axillary lymph

nodes • Breast cancer

MorphologyEdema is easily recognized grosslyMicroscopic examination

Clearing and separation of the extracellular matrix

Subtle cell swelling

Most commonly seen:Subcutaneous tissues, lungs, and brain

Subcutaneous edemaDiffuse or more conspicuous in regions

with high hydrostatic pressuresDistribution is influenced by gravity

Dependent edema• Legs when standing, the sacrum when

recumbent

Subcutaneous edemaPitting edema

Finger pressure over substantially edematous subcutaneous tissue

Displaces the interstitial fluid and leaves a depression

Edema secondary to renal dysfunctionAffect all parts of the bodyManifests in tissues with loose connective

tissue matrix (eyelids) Periorbital edema

• Characteristic finding in severe renal disease

Soft tissue edemaImportant because it signals underlying

cardiac or renal diseaseImpairs wound healing or the clearance of

infection

Pulmonary edemaLungs are often two to three times their

normal weightSectioning yields frothy, blood-tinged

fluid Mixture of air, edema, and extravasated

red cellsCommon clinical problemMost frequently seen with left ventricular

failure

Pulmonary edemaLungs are often two to three times their

normal weightSectioning yields frothy, blood-tinged

fluid Mixture of air, edema, and extravasated

red cellsCommon clinical problemMost frequently seen with left ventricular

failure

Brain edemaLocalized or generalized Depending on the nature and extent of

the pathologic process or injuryGeneralized edema

Brain is grossly swollen with narrowed sulci

Distended gyri show evidence of compression against the unyielding skull

Brain edema Life-threateningSevere 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

HyperemiaActive 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 processReduced outflow of blood from a tissueSystemic

Cardiac failure

Congestion Local

Isolated venous obstructionDusky reddish-blue color (cyanosis)

Red cell stasis Accumulation of deoxygenated

hemoglobin

Long-standing chronic passive congestionLack 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

MorphologyCut 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

MorphologyMicroscopic examination

Chronic pulmonary congestion • Septa are thickened and fibrotic• Alveoli often contain numerous hemosiderin-

laden macrophages Heart failure cells

MorphologyAcute hepatic congestion

Central vein and sinusoids are distended Centrilobular hepatocytes can be frankly

ischemicChronic passive hepatic congestion

Centrilobular regions are grossly red-brown• Areas are accentuated against uncongested

parenchyma• Nutmeg liver

MorphologyMicroscopic 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 disordersCollectively called hemorrhagic

diatheses

Distinct patterns of tissue hemorrhageHemorrhage 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)

PurpuraSlightly larger (≥3 mm) hemorrhagesAssociated with many of the same

disorders that cause petechiae Secondary to trauma, vascular

inflammation (vasculitis), or increased vascular fragility (amyloidosis)

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EcchymosesLarger (>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 cavityHemothoraxHemopericardiumHemoperitoneumHemarthrosis (in joints)

Normal hemostasisConsequence of tightly regulated

processes Maintain blood in a fluid state in normal

vesselsPermit the rapid formation of a

hemostatic clot at the site of a vascular injury

ThrombosisPathologic counterpart of hemostasisInvolves blood clot (thrombus) formation

Both hemostasis and thrombosis involve three components: Vascular wall (particularly the

endothelium)PlateletsCoagulation cascade

Endothelial cells Key players in the regulation of

homeostasisExhibit antiplatelet, anticoagulant, and

fibrinolytic propertiesAfter injury or activation

Acquire numerous procoagulant activitiesActivated by infectious agents,

hemodynamic forces, plasma mediators, and cytokines

Antiplatelet effectsIntact 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 effectsEndothelial cells

Also elaborate adenosine diphosphatase• Degrades adenosine diphosphate (ADP)• Further inhibits platelet aggregation

Anticoagulant effectsMediated 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 effectsMediated 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 effectsHeparin-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 effectsEndothelial cells synthesize tissue-type

plasminogen activator (t-PA) Protease that cleaves plasminogen to form

plasmin• Plasmin cleaves fibrin to degrade thrombi

Platelet effectsEndothelial 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 effectsResponse 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 effectsEndothelial 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 activationResults 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 hemostasisForming the hemostatic plug that

initially seals vascular defectsProviding a surface that recruits and

concentrates activated coagulation factors

Function depends on several glycoprotein receptorsContractile cytoskeletonTwo 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 receptorsTwo 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 changeSecretion (release reaction)Aggregation

Mediated largely via interactions with vWFActs 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 receptorsInitiate an intracellular protein

phosphorylation cascade Leads to degranulation

Various agonists can bind platelet surface receptorsRelease 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 activationAppearance 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 aggregationFormation of the primary hemostatic

plug Initial wave of aggregation is

reversible

Concurrent activation of the coagulation cascadeGenerates thrombinStabilizes 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 plugThrombin converts fibrinogen to fibrin in

the vicinity of the platelet plug• Cements the platelets in place

Noncleaved fibrinogenImportant 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

Part 2

Third arm of the hemostatic process Amplifying series of enzymatic

conversionsEach step proteolytically cleaves an

inactive proenzyme into an activated enzyme Culminates in thrombin formation

Thrombin is the most important coagulation factorCan act at numerous stages in the process

Conclusion of the proteolytic cascadeThrombin 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 assayAssesses 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

effectsMost effects of thrombin occur through

its activation of a family of protease activated receptors (PARs) Belong to the seven-transmembrane G

protein-coupled 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

anticoagulantsAntithrombins (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 anticoagulantsProteins C and S

Vitamin K-dependent proteins Act in a complex that proteolytically

inactivates factors Va and VIIIaTFPI 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 fibrinConfers an overall procoagulant effectProduction is increased by thrombin as

well as certain cytokines

Three primary abnormalities that lead to thrombus formation (called Virchow's triad):Endothelial injuryStasis or turbulent blood flowHypercoagulability of the blood

Particularly important for thrombus formation in the heart or the arterial circulationNormally high flow rates might otherwise

impede clotting by preventing platelet adhesion and washing out activated coagulation factors

Endothelial cell injuryThrombus 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,

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 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 flow-induced 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 states Any alteration of the coagulation

pathways that predisposes to thrombosisDivided into primary (genetic)Secondary (acquired) disorders

Of the inherited causes of hypercoagulabilityMost common

Point mutations in the factor V gene Prothrombin gene

Elevated levels of homocysteine Contribute to arterial and venous

thrombosis Prothrombotic effects of

homocysteineMay be due to thioester linkages formed

between homocysteine metabolites and a variety of proteins, including fibrinogen

Rare inherited causes of primary hypercoagulabilityDeficiencies of anticoagulants

Antithrombin III, protein C, or protein S Present with venous thrombosis and

recurrent thromboembolism beginning in adolescence or early adulthood

Acquired thrombophilic statesHeparin-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 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 formsPrimary 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

causeArterial or cardiac thrombi

Begin at sites of turbulence or endothelial injury

Venous thrombi Occur at sites of stasis

Focally attached to the underlying vascular surfaceArterial thrombi tend to grow retrograde

from the point of attachmentVenous thrombi extend in the direction

of blood flow

Gross and microscopic laminationsLines 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 lumenMural thrombi

Abnormal myocardial contraction• Arrhythmias, dilated cardiomyopathy, or

myocardial infarction• Endomyocardial injury (myocarditis or

catheter trauma)

Arterial thrombi Frequently occlusiveMost common sites

Coronary, cerebral, and femoral arteriesConsist of a friable meshwork of

platelets, fibrin, red cells, and degenerating leukocytes

Usually superimposed on a ruptured atherosclerotic plaque

Venous thrombosis (phlebothrombosis) Invariably occlusiveThrombus forming a long cast of the

lumenThrombi form in the sluggish venous

circulationContain more enmeshed red cells

Red, or stasis, thrombiVeins of the lower extremities are most

commonly involved (90% of cases)

Postmortem clotsMistaken for antemortem venous thrombiGelatinous 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

Firmer Focally attachedGross and/or microscopic lines of Zahn

VegetationsThrombi on heart valves Blood-borne bacteria or fungi

Adhere to previously damaged valves (rheumatic heart disease)

Directly cause valve damage Infective endocarditis

VegetationsSterile vegetations

Nonbacterial thrombotic endocarditisSterile, verrucous endocarditis

Libman-Sacks endocarditis

Survival of the initial thrombosisEnsuing 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, 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 channelsDVTs are asymptomatic in approximately

50% of affected individualsRecognized 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 consumptionFibrinolytic mechanisms are activated

Initially thrombotic disorderEvolve into a bleeding catastrophe

EmbolusDetached intravascular solid, liquid, or

gaseous mass that is carried by the blood to a site distant from its point of origin

ThromboembolismRare 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 emboliLeg or pelvic veins

Large emboli Sudden death

Lodging • Major branches of pulmonary arteries• Saddle emboli

Acute cor pulmonale

Small emboliMinimal symptomsException

Inadequate bronchial circulation • Symptoms

Causes of emboliImmobilized individualsHypercoagulable state (primary vs.

secondary)Heart failure

Pathophysiologic response

Clinical significance

Extent of pulmonary artery obstruction

Size of occluded vessel

Number of emboli

Status of the cardiovascular system

Release of vasoactive factors

Pathophysiologic consequencesRespiratory compromise Hemodynamic compromise

Adequate cardiovascular functionBronchial artery compensation

Hemorrhage without infarction

Infarction Inadequate circulationRare in young

Clinical course Cardiopulmonary resuscitation

Electromechanical dissociation• Electrocardiogram has a rhythm• No pulses are palpated

Survival (post-sizable pulmonary embolus) Mimics myocardial infarction

DiagnosisSpiral CTOther diagnostic methods

Ventilation perfusion scanning

Pulmonary angiography Duplex ultrasonography•Deep vein thrombosis

PreventionMajor clinical problem Prophylactic therapy

Early ambulation Stockings Anticoagulation Filter

TreatmentThrombolysis Anticoagulation

Gross examinationParenchyma

75% of all infarcts affect the lower lobes Greater than 50%--multiple lesions Wedge shaped Hemorrhagic

Fibrinous pleural exudateScarEmbolus

http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=714&viewer=java&lay=&jpg=493

Microscopic examinationIschemic necrosis

Alveolar walls, bronchioles, and vesselsInfected 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 circulationCoalesce 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 bendsRapid formation of gas bubbles within

skeletal muscles and supporting tissues in and about joints

The chokesGas 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 embolismOminous complication of labor and the

immediate postpartum periodSudden 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 eventsIncluding 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 shockSeptic shock

Depend on the precipitating insult Hypovolemic and cardiogenic shock

Patient presents with hypotension Weak, rapid pulse; tachypnea; and cool,

clammy, cyanotic skin

Septic shockSkin 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 acidosis