Hemodynamic Disorders,

Thrombosis, and Shock

Dr. Samadara Siriwardena
BDS, MPhil, PhD, MD Oral Path

Dept of Oral Pathology

Normal body
composition
Water composes about 60% of total body

mass
3 body compartments containing H2O:
Intracellular
Interstitial
Plasma

= 70%
= 25%
= 5%

Edema
The term edema signifies increased fluid in

the interstitial tissue spaces;

Fluid collections in different body cavities are

variously designated hydrothorax,

hydropericardium, or hydroperitoneum (the
last is more commonly called ascites).

Pathophysiology of
Edema
Anatomic
structures which
drain excess
interstitial fluid
into venous blood:

Lymphatics

Hydrostatic
pressure

Plasma colloid
oncotic pressure

Two opposing
major factors
governing fluid
movement between
vascular and
interstitial space:

Either increased capillary pressure or diminished

colloid osmotic pressure can result in increased

interstitial fluid.
As extravascular fluid accumulates, the increased
tissue hydrostatic and plasma osmotic pressures
eventually achieve a new equilibrium, and water reenters the venules.
Excess interstitial edema fluid is removed by
lymphatic drainage, ultimately returning to the
bloodstream via the thoracic duct
Lymphatic obstruction (e.g., due to scarring or tumor)
can also impair fluid drainage and cause edema.
Sodium retention due to renal disease can also cause
edema

Edema
Exudate - increased vascular permeability,
inflammatory edema is a protein-rich exudate
with a specific gravity that is usually greater
than 1.020
Transudate- volume or pressure overload, or

under conditions of reduced plasma protein, is

typically a protein-poor transudate; it has a
specific gravity less than 1.012.

Increased Hydrostatic
Pressure
Localized increases in intravascular pressure

can result from impaired venous return

ex. lower extremity deep venous thrombosis
can cause edema restricted to the distal
portion of the affected leg.
Generalized increases in venous pressure,
with resultant systemic edema, occur most
commonly in congestive heart failure ,
affecting right ventricular cardiac function.

Clinical manifestations of
edema
Clinical Signs

Bilateral symmetrical edema of skin

& subcutis of both legs below knees
in 57-year-old man whose only
complaint is shortness of breath

Unilateral edema of one arm in a 60year-old female with a mastectomy

scar on that side

Most Likely Cause(s)

Increased hydrostatic
pressure in veins due to
congestive heart failure

Lymphatic obstruction

Reduced Plasma Osmotic Pressure

Albumin is the serum protein most responsible for

maintaining intravascular colloid osmotic pressure;

reduced osmotic pressure occurs when albumin is
inadequately synthesized or is lost from the circulation.
An important cause of albumin loss is the nephrotic
syndrome, in which glomerular capillary walls become
leaky; patients typically present with generalized edema.
Reduced albumin synthesis occurs in the setting of
diffuse liver diseases (e.g., cirrhosis;) or due to protein
malnutrition.
In each case, reduced plasma osmotic pressure leads to a
net movement of fluid into the interstitial tissues with
subsequent plasma volume contraction.

Lymphatic Obstruction
Impaired lymphatic drainage and consequent

lymphedema is usually localized;

it can result from inflammatory or neoplastic
obstruction. For example, the parasitic infection
filariasis can cause extensive inguinal lymphatic and
lymph node fibrosis. The resultant edema of the
external genitalia and lower limbs can be so massive
as to earn the appellation elephantiasis.
Cancer of the breast can be treated by resection
and/or irradiation of the associated axillary lymph
nodes; the resultant scarring and loss of lymphatic
drainage can cause severe upper extremity edema.

Inflammatory Lymphatic
Obstruction
Filariasis
A parasitic infection

which leads to lymphatic

and lymph node fibrosis
in the inguinal region
resulting in edema of the
external genitalia and
lower extremity called
ELEPHANTIASIS

Sodium and Water

Retention
Salt retention can also be a primary cause of

edema. Increased salt-with the obligate

accompanying water-causes both increased
hydrostatic pressure (due to expansion of the
intravascular volume) and reduced vascular
osmotic pressure.
Salt retention can occur with any compromise
of renal function

EDEMA INCREASED
HYDROSTATIC
PRESSURE
CongestiveHeartFailure
Ascites
VenousObstruction

INCREASED
PERMEABILITY
Inflammation

Summary
HEART
LIVER
KIDNEY

DECREASED
ONCOTIC
PRESSURE
NephroticSyndrome
Cirrhosis
ProteinMalnutrition

LYMPHATIC
OBSTRUCTION
Inflammatory
Neoplastic

Edema Fluid
Exudate
Inflammatory

Transudate
High hydrostatic Cause
pr.

High

Low

Protein content

>1.020)

<1.012)

Specific gravity

Rich

Absent

Inflammatory
cells

Summary
Edema is extravasation of fluid from vessels into

interstitial spaces; the fluid may be protein poor

(transudate) or may be protein rich (exudate).Edema
results from any of the following conditions:
Increased hydrostatic pressure, caused by a
reduction in venous return (as in heart failure)
Decreased colloid osmotic pressure, caused by
reduced concentration of plasma albumin (due to
decreased synthesis, as in liver disease, or increased
loss, as in kidney disease)
Lymphatic obstruction that impairs interstitial fluid
clearance (as in scarring, tumors, or certain
infections)
Primary renal sodium retention (in renal failure)
Increased vascular permeability (in inflammation)

Subcutaneous Edema
Edema of the

subcutaneous tissue is
most easily detected
Grossly (not
microscopically)

Push your finger into it

and a depression
remains
pitting edema

Edema

Dependent Edema is a prominent feature

of Congestive Heart Failure; in legs if

standing or sacrum in sleeping patient
Periorbital edema is often the initial

manifestation of Nephrotic Syndrome,

while late cases will lead to generalized
edema.

Pulmonary Edema
is most frequently seen in Congestive Heart

Failure
May also be present in renal failure, adult

respiratory distress syndrome (ARDS),

pulmonary infections and hypersensitivity
reactions

Pulmonary Edema
The Lungs are

typically 2-3 times

normal weight
Cross sectioning
causes an
outpouring of
frothy,
sometimes bloodtinged fluid
It may interfere
with pulmonary
function

Normal lung

Pulmonary Edema

Pulmonary Edema
Clinical Correlation
May cause death by interfering with Oxygen
and Carbon Dioxide exchange
Creates a favorable environment for

infection

Brain Edema
Trauma, Abscess, Neoplasm, Infection

(Encephalitis)

Brain Edema
Clinical Correlation

For extra fluid has

no space
Herniation into the

foramen magnum
leads to death

Clinical Correlation of Edema

The effect of edema may be just annoying to fatal

condition.
It usually points to an underlying disease.
However, it can impair wound healing or clearance

of infection.
Creates a favorable environment for infection.
May cause death by interfering with Oxygen and

Carbon Dioxide exchange.

Hemodynamic
terminology
Hyperemia : locally increased blood

caused by arteriolar dilation with

augmented inflow, as in a working muscle
or acute inflammation
Congestion: locally increased blood due
to impaired venous outflow (lungs in heart
failure)

Hemostasis overview
Normal hemostasis
Maintain blood fluid within vessels
Induce rapid localized plug at injury site
Thrombosis
Formation of blood clot within vessel
(appropriately or inappropriately)
Three components which regulate normal

hemostasis / thrombosis:
Vascular wall, Platelets, Coagulation cascade

Hyperemia
Hyperemia and congestion:
Both indicate a local increased volume of blood
in a particular tissue
Hyperemia:
an active process resulting from augmented
blood flow due to arteriolar dilation
Examples:

sites of inflammation
skeletal muscle during exercise

The affected tissue is redder than normal

because of engorgement with oxygenated blood

Congestion:
a passive process resulting from impaired
venous return out of a tissue
It may occur:
systemically, as in cardiac failure
locally, resulting from an isolated venous obstruction

The tissue has a blue-red color (cyanosis):

as worsening congestion accumulation of
deoxygenated hemoglobin in the affected tissues

Congestion (continued):
Chronic passive congestion:
Is a long-standing congestion
The stasis of poorly oxygenated blood causes:
Chronic hypoxia degeneration or death of
parenchymal cells subsequent tissue fibrosis
Capillary rupture small foci of hemorrhage
phagocytosis and catabolism of the erythrocyte
debris accumulations of hemosiderin-laden
macrophages

Liver with chronic passive

congestion and
hemorrhagic necrosis. A,
Central areas are red and
slightly depressed
compared with the
surrounding tan viable
parenchyma, forming a
"nutmeg liver" pattern
(so called because it
resembles the alternating
pattern of light and dark
seen when a whole
nutmeg is cut). B,
Centrilobular necrosis with
degenerating hepatocytes
and hemorrhage

Hemorrhage
Extravasation of blood from vessels into the

extravascular space
Hemorrhagic diatheses :
increased tendency to hemorrhage (usually

with insignificant injury) occurs in a wide

variety of clinical disorders

 Hematoma:
any accumulation within tissue that results
from a hemorrhage
Large accumulations of blood in body cavities

are called (according to location):

Hemothorax
Hemopericardium
Hemoperitoneum
Hemarthrosis

Causes:
Trauma
Atherosclerosis
Inflammatory erosion of vessels wall
Neoplastic erosion of the vessel wall

Purpura :
Slightly larger (3- to 5-mm) hemorrhages
can be associated with:
many of the same disorders that cause petechiae
Trauma
vasculitis
increased vascular fragility
Ecchymoses:
Larger (1- to 2-cm) subcutaneous hematomas (bruises)

A, Punctate petechial hemorrhages of the colonic mucosa, a

consequence of thrombocytopenia.
B, Fatal intracerebral hemorrhage. Even relatively inconsequential
volumes of hemorrhage in a critical location, or into a closed space (such
as the cranium), can have fatal outcomes.

20% rapid loss of blood shock

Greater loss, but slow

impact

may have little

Hemostasis and thrombosis

Vasoconstriction

Hemostasis sequence 1

Primary Hemostasis (platelet plug)

Hemostasis sequence 2
Secondary Hemostasis (fibrin clot)

Thrombosis and antithrombotic events

Dualistic endothelial cell

function
Procoagulant (favors
thrombosis)

Green
molecule?

Anticoagulant (inhibits
thrombosis)

vWF

Orange
molecul
e?

AT III

Platelet response to injury

Platelets encounter extravascular matrix

molecules: collagen, proteoglycans,

fibronectin
Platelets
respond in three phases:
Adhesion
1 =
Secretion (release reaction)

2 =
Aggregation

3 =

Platelet adhesion and aggregation

Deficient Gp1b
receptor on platelets
for vWF:
Bernard-Soulier
syndrome
Deficient Gp IIb-IIIa
complex:
Glanzmann
thrombasthenia

Deficient von Willebrands factor:

Von Willebrand disease

Coagulation Cascade: 3
component

Central role of thrombin

Functions:
1) Formation of
fibrin
2) Induce platelet
aggregation
3) Activates
endothelium
4) Activation of
lymphocytes &
monocytes

Fibrinolytic system:
restriction of clotting to local
site of injury

Application: Lab
evidence of DIC?
(3 nonmorphologic
abnormalities)
1) prolonged PT
2) elevated D-dimer
3) thrombocytopenia

One RBC
morphologic
abnormality?
(not sensitive or
specific)

histocytes
Fig. 4-12, Pathologic Basis of

Thrombosis: a clot within

vessel
Predisposing factors: Virchows triad
Endothelial Injury

Trauma,
atherosclerosis,
vasculitis

Atherosclerosis,
aneurysms,
valvular heart
disease

Abnormal
blood flow

Hypercoagulability

Inherited or
acquired

Blood clot

Venous thrombosis
Most common location?
Most serious complication?

Deep leg veins (pelvic veins 2nd)

Pulmonary embolization

Disseminated intravascular
coagulation (DIC)
Not a primary disease, but complication of

diseases with widespread activation of thrombin

Pathophysiology:
fibrin-platelet thrombi in microcirculation, with

concurrent consumption of platelets and coagulation

proteins.
RBCs may be torn and fragmented by fibrin thrombi.
Diffuse activation of fibrinolysis, generating increased
FDPs & D-dimer (lab evidence DIC)

Treatment: diagnose and treat underlying

disease; buy time (not cure) with administration

of platelets and fresh frozen plasma

Morphology
Thrombi can develop anywhere in the cardiovascular

system
The size and shape of a thrombus depend on the site
of origin and the cause.
Arterial or cardiac thrombi typically begin at sites of
endothelial injury or turbulence; venous thrombi
characteristically occur at sites of stasis.
Thrombi are focally attached to the underlying
vascular surface; arterial thrombi tend to grow in a
retrograde direction from the point of attachment,
while venous thrombi extend in the direction of blood
flow (thus both tend to propagate toward the heart).
The propagating portion of a thrombus tends to be
poorly attached and therefore prone to fragmentation,
generating an embolus.

Thrombi can have grossly (and microscopically)

apparent laminations called lines of Zahn;

these represent pale platelet and fibrin layers
alternating with darker erythrocyte-rich layers.
Such lines are significant only in that they
represent thrombosis in the setting of flowing
blood; their presence can therefore potentially
distinguish antemortem thrombosis from the
bland nonlaminated clots that occur in the
postmortem state (see also below).
Although such lines are typically not as
apparent in veins or smaller arteries (thrombi
formed in sluggish venous flow usually resemble
statically coagulated blood), careful evaluation
generally reveals ill-defined laminations

Arterial thrombi are frequently occlusive and are

produced by platelet and coagulation activation;

they are typically a friable meshwork of platelets,
fibrin, erythrocytes, and degenerating leukocytes.
Although arterial thrombi are usually superimposed
on an atherosclerotic plaque, other vascular injury
(vasculitis, trauma) can be involved.
Venous thrombosis (phlebothrombosis) is almost

invariably occlusive, and the thrombus can create

a long cast of the lumen; venous thrombosis is
largely the result of activation of the coagulation
cascade, and platelets play a secondary role.

Postmortem clots can sometimes be mistaken

at autopsy for venous thrombi.

Postmortem "thrombi" are gelatinous, with a dark
red dependent portion where red cells have
settled by gravity, and a yellow "chicken fat"
supernatant,
They are usually not attached to the underlying
wall.
In contrast, red thrombi are firmer and are focally
attached, and sectioning reveals strands of gray
fibrin.

Thrombi on heart valves are called

vegetations. Bacterial or fungal blood-borne

infections can cause valve damage,
subsequently leading to large thrombotic
masses (infective endocarditis,).
Sterile vegetations can also develop on
noninfected valves in hypercoagulable states,
so-called nonbacterial thrombotic
endocarditis.

Fate of the Thrombus

If a patient survives the initial thrombosis, in the

ensuing days or weeks thrombi undergo some

combination of the following four events:
1. Propagation. Thrombi accumulate additional
platelets and fibrin, eventually causing vessel
obstruction.
2. Embolization. Thrombi dislodge or fragment and are
transported elsewhere in the vasculature.
3. Dissolution. Thrombi are removed by fibrinolytic
activity.
4. Organization and recanalization. Thrombi induce
inflammation and fibrosis (organization). These can
eventually recanalize (re-establishing some degree of
flow), or they can be incorporated into a thickened
vessel wall.

Dissolution is the result of fibrinolytic

activation, which leads to rapid shrinkage and

even total lysis of recent thrombi.
With older thrombi, extensive fibrin
polymerization renders the thrombus
substantially more resistant to proteolysis, and
lysis is ineffectual.
This is clinically significant because
therapeutic administration of fibrinolytic
agents (e.g., t-PA in the setting of acute
coronary thrombosis) is generally effective
only within a few hours of thrombus formation.

Older thrombi become organized by the ingrowth of

endothelial cells, smooth muscle cells, and fibroblasts

into the fibrin-rich clot.
Capillary channels are eventually formed.
Although the channels may not successfully restore
significant flow to many obstructed vessels,
recanalization can potentially convert a thrombus into
a vascularized mass of connective tissue.
Eventually, with contraction of the mesenchymal cells
only a fibrous lump may remain to mark the original
thrombus site.
Occasionally, instead of organizing, the center of a
thrombus undergoes enzymatic digestion, presumably
because of the release of lysosomal enzymes from
trapped leukocytes and platelets.

Clinical Correlations
Venous versus Arterial Thrombosis
Thrombi are significant because they cause

obstruction of arteries and veins and are

potential sources of emboli.
Venous thrombi can cause congestion and
edema in vascular beds distal to an obstruction,
but they are most worrisome for their capacity
to embolize to the lungs and cause death.
Conversely, while arterial thrombi can embolize
and even cause downstream tissue infarction,
their role in vascular obstruction at critical sites
(e.g., coronary and cerebral vessels) is much
more significant clinically.

Venous Thrombosis (Phlebothrombosis)

Most venous thrombi occur in the superficial or

deep veins of the leg. Eg: varicosities. Such

superficial thrombi can cause local congestion,
swelling, pain, and tenderness along the course
of the involved vein, but they rarely embolize.
Nevertheless, the local edema and impaired
venous drainage do predispose the overlying
skin to infections from minor trauma and to the
development of varicose ulcers.

Deep venous thrombosis can occur with stasis

Cardiac failure is an obvious reason for stasis in the venous

circulation. Trauma, surgery, and burns usually result in reduced

physical activity, injury to vessels, release of procoagulant
substances from tissues, and/or reduced t-PA activity.
There are many influences contributing to the thrombotic
propensity of peripartum and postpartum states; in addition to
the potential for amniotic fluid infusion into the circulation
during parturition, late pregnancy and the postpartum period
are associated with hypercoagulability.
Tumor-associated procoagulant release is largely responsible for
the increased risk of thromboembolic phenomena seen in
disseminated cancers
Regardless of the specific clinical setting, advanced age, bedrest, and immobilization increase the risk of deep venous
thrombosis because reduced physical activity diminishes the
milking action of muscles in the lower leg and so slows venous
return.

Cardiac and Arterial Thrombosis

Atherosclerosis is a major initiator of

thromboses, because it is associated with loss

of endothelial integrity and abnormal vascular
flow.
Rheumatic heart disease can cause atrial
mural thrombi due to mitral valve stenosis,
followed by left atrial dilation and concurrent
atrial fibrillation.

Embolism
Definition: detached intravascular solid,

liquid, or gaseous mass carried by blood to a

site distant from its origin.
Types:
Thromboembolism:> 99% of all emboli
Fat or marrow: post-trauma to bones
Cholesterol: after invasive vascular procedures,

presenting as hematuria or renal insufficiency due

to multiple renal microinfarctions
Tumor: from neoplasms invading vessels
Foreign body: intravenous devices/ drug abuse
Thromboembolism : 1/50,000 deliveries; mortality

>80% with complications of pulmonary edema/DIC

Pulmonary thromboembolism

Occlusion of
small artery
results in
what type of
infarction?
Occlusion large pulmonary artery

hemorrhagic

Pulmonary thromboembolism
200,000 deaths/year in US
Many are clinically silent if small
Saddle: thrombus occluding main p. artery at bifurcation
Paradoxical : thromboembolus originating in veins, passing

through atrial or ventricular septal defect, into arterial side

Sudden death: likely if >60% pulmonary circulation is
obstructed with emboli (acute right heart failure)
haemorrhage: results from occlusion of medium-sized vessels

(dual bronchial blood supply prevents infarction)

Infarction: results from occlusion of small end arteries or

arterioles

Systemic Thromboembolism
Systemic thromboembolism refers to emboli in the arterial

circulation.
Most (80%) arise from intracardiac mural thrombi, most are
associated with left ventricular wall infarcts
The remainder originate from aortic aneurysms, thrombi on
ulcerated atherosclerotic plaques, or fragmentation of valvular
vegetations.
A very small fraction of systemic emboli appear to arise in veins
but end up in the arterial circulation, through interventricular
defects. These are called paradoxical emboli.
In contrast to venous emboli, which tend to lodge primarily in one
vascular bed (the lung), arterial emboli can travel to a wide
variety of sites; the site of arrest depends on the point of origin of
the thromboembolus and the relative blood flow through the
downstream tissues.
The major sites for arteriolar embolization are the lower
extremities (75%) and the brain (10%),

Fat Embolism
Microscopic fat globules can be found in the

circulation after fractures of long bones (which

contain fatty marrow) or after soft-tissue
trauma.
Typically, the symptoms appear 1 to 3 days
after injury, with sudden onset of tachypnea,
dyspnea, and tachycardia.
Neurologic symptoms include irritability and
restlessness, with progression to delirium or
coma.

The pathogenesis of fat emboli syndrome

probably involves both mechanical obstruction

and biochemical injury.
Fat microemboli occlude pulmonary and
cerebral microvasculature; vascular occlusion
is aggravated by local platelet and
erythrocyte aggregation.
This pathology is further exacerbated by free
fatty acid release from the fat globules,
causing local toxic injury to endothelium.

Air Embolism
Gas bubbles within the circulation can

obstruct vascular flow (and cause distal

ischemic injury) almost as readily as
thrombotic masses can.
Air may enter the circulation during obstetric
procedures or as a consequence of chest wall
injury.
Generally, more than 100 mL of air are
required to produce a clinical effect; bubbles
can coalesce to form frothy masses
sufficiently large to occlude major vessels.

A particular form of gas embolism, called decompression

sickness, occurs when individuals are exposed to sudden

changes in atmospheric pressure.
Scuba and deep-sea divers, and underwater construction
workers are at risk. When air is breathed at high pressure
(e.g., during a deep-sea dive), increased amounts of gas
(particularly nitrogen) become dissolved in the blood and
tissues.
If the diver then ascends (depressurizes) too rapidly, the
nitrogen expands in the tissues and bubbles out of
solution in the blood to form gas emboli that can induce
focal ischemia in a number of tissues, including brain and
heart.

Amniotic Fluid Embolism

Amniotic fluid embolism is a grave but fortunately

uncommon complication of labor and the immediate

postpartum period (1 in 50,000 deliveries).
It has a mortality rate in excess of 20% to 40%.
The onset is characterized by sudden severe dyspnea,
cyanosis, and hypotensive shock, followed by seizures
and coma. If the patient survives the initial crisis,
pulmonary edema typically develops, along with (in half
the patients) disseminated intravascular coagulation
(DIC), due to release of thrombogenic substances from
amniotic fluid.
The underlying cause is entry of amniotic fluid (and its
contents) into the maternal circulation via a tear in the
placental membranes and rupture of uterine veins.

Infarction
An infarct is an area of ischemic necrosis caused by

occlusion of either the arterial supply or the venous

drainage in a particular tissue.
Nearly 99% of all infarcts result from thrombotic or
embolic events, and almost all result from arterial
occlusion.
Occasionally, infarction may also be caused by other
mechanisms, such as local vasospasm, expansion of an
atheroma secondary to intraplaque hemorrhage, or
extrinsic compression of a vessel (e.g., by tumor).
Although venous thrombosis can cause infarction, it more
often merely induces venous obstruction and congestion.

Morphology
Infarcts are classified on the basis of their

color (reflecting the amount of hemorrhage)

and the presence or absence of microbial
infection.
Therefore, infarcts may be either red
(hemorrhagic) or white (anemic) and may be
either septic or bland.

Red infarcts
Occur
1. with venous occlusions (such as in ovarian torsion);
2. in loose tissues (such as lung) that allow blood to collect

in the infarcted zone;

3. in tissues with dual circulations such as lung and small
intestine, permitting flow of blood from an unobstructed
parallel supply into a necrotic area (such perfusion not
being sufficient to rescue the ischemic tissues);
4. in tissues that were previously congested because of
sluggish venous outflow;
5. when flow is re-established to a site of previous arterial
occlusion and necrosis (e.g., fragmentation of an occlusive
embolus or angioplasty of a thrombotic lesion).

White infarcts
occur with arterial occlusions or in solid

organs (such as heart, spleen, and kidney),

where the solidity of the tissue limits the
amount of hemorrhage that can seep into the
area of ischemic necrosis from adjoining
capillary beds
All infarcts tend to be wedge shaped, with
the occluded vessel at the apex and the
periphery of the organ forming the base

In solid organs, the relatively few

extravasated red cells are lysed, with the

released hemoglobin remaining in the form of
hemosiderin.
Thus, infarcts resulting from arterial
occlusions typically become progressively
more pale and sharply defined with time.
In spongy organs, by comparison, the
hemorrhage is too extensive to permit the
lesion ever to become pale.
Over the course of a few days, however, it
does become firmer and browner, reflecting
the accumulation of hemosiderin pigment.

Spleen

Septic infarctions
occur when bacterial vegetations from a heart

valve embolize or when microbes seed an

area of necrotic tissue.
In these cases the infarct is converted into an
abscess, with a correspondingly greater
inflammatory response
The eventual sequence of organization,
however, follows the pattern previously
described.

Factors That Influence Development

of an Infarct
Vascular occlusion can have no or minimal

effect, or can cause death of a tissue or even

the individual.
The major determinants of the eventual
outcome include
1. the nature of the vascular supply,
2. the rate of development of the occlusion,
3. vulnerability to hypoxia,
4. and the oxygen content of blood.

Nature of the Vascular

Supply
The availability of an alternative blood supply is the most

important determinant.
For example, as mentioned above, lungs have a dual
pulmonary and bronchial artery blood supply; thus,
obstruction of small pulmonary arterioles does not cause
infarction in an otherwise healthy individual with an intact
bronchial circulation.
Similarly, the liver, with its dual hepatic artery and portal
vein circulation, and the hand and forearm, with their dual
radial and ulnar arterial supply, are all relatively resistant to
infarction.
In contrast, renal and splenic circulations are end-arterial,
and obstruction of such vessels generally causes infarction.

Rate of Development of Occlusion

Slowly developing occlusions are less likely to

cause infarction because they provide time for

the development of alternative perfusion
pathways.

Vulnerability to Hypoxia
The susceptibility of a tissue to hypoxia

influences the infarction.

Neurons undergo irreversible damage when
deprived of their blood supply for only 3 to 4
minutes.
Myocardial cells, though hardier than neurons,
are also quite sensitive and die after only 20
to 30 minutes of ischemia.
In contrast, fibroblasts within myocardium
remain viable after many hours of ischemia.

Oxygen Content of Blood

The partial pressure of oxygen in blood also

determines the outcome of vascular occlusion.

Partial flow obstruction of a small vessel in an
anemic or cyanotic patient might lead to
tissue infarction,

Infarction, gross
features

Lung, acute hemorrhagic

infarction (note wedge-shape)

Kidney, remote healed

infarction (fibrous scar)

Shock
Def.: systemic hypoperfusion due to reduced

cardiac output or reduced effective blood volume.

Major causes:
Cardiogenic

: myocardial pump failure

Hypovolemic :loss blood/plasma volume

Septic
Neurogenic

: systemic microbial infection

: spinal cord injury

Anaphylactic : generalized IgE-mediated hypersensitivity

response, with widespread vasodilation, increased

capacitance, & increased vascular permeability

Shock: 3 most common types

Septic shock
25-50% mortality rate, >100,000 deaths/yr.
Increasing incidence (intensive care,

invasive procedures, longer lifespan, more

immunocompromised patients)
70% cases produced by which type of
bacteria ? Gram negative
Endotoxins : lipopolysaccharides (LPS) released
when bacterial cell walls are degraded by
inflammation or therapy.

Cytokine cascade in Gramnegative sepsis

Produced by:

macrophages

Produced by:

macrophages

Produced by:
macrophages

Clinical sequelae of sepsis

NO = nitric oxide
PAF = platelet-activating
factor

Stages of shock
Nonprogressive phase
Reflex mechanisms activated and perfusion of
vital organs maintained
Progressive stage
Persistent tissue hypoperfusion leads to
widespread hypoxic cell damage, metabolic
acidosis, prolonged vasodilation
Irreversible stage
Severe cellular injury with multiorgan failure,
dominated by renal, lungs, heart