EDEMA
- an abnormal increase in
interstitial fluid within tissues
Anasarca - a severe and
generalized edema with
widespread subcutaneous tissue
swelling
Transudate - protein-poor fluid
caused by increased hydrostatic
pressure or reduced plasma protein
Exudate - protein-rich caused by
increased vascular permeability
Pathophysiologic Categories of
Edema (Causes)
INCREASED HYDROSTATIC
PRESSURE
Impaired venous return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or
compression Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with
prolonged dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation
REDUCED PLASMA OSMOTIC
PRESSURE
(HYPOPROTEINEMIA)
Protein-losing glomerulopathies
(nephrotic syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
Albumin - the major plasma protein
nephrotic syndrome - important
cause of albumin loss
LYMPHATIC OBSTRUCTION
Inflammatory
Neoplastic
Postsurgical
Postirradiation
SODIUM RETENTION
Excessive salt intake with renal
insufficiency
Increased tubular reabsorption of
sodium
Renal hypoperfusion
Increased renin-angiotensin-
aldosterone secretion
INFLAMMATION
Acute inflammation
Chronic inflammation
Angiogenesis
Factors influencing fluid
transit across capillary walls
Capillary hydrostatic pressure
Osmotic pressure
* increased hydrostatic pressure or
diminished plasma osmotic
pressure will cause extravascular
fluid to accumulate
Morphology:
Subcutaneous edema
edema seen in subcutaneous
tissues, the lungs, and the brain
- diffuse in regions with high
hydrostatic pressures
- signals potential underlying
cardiac or renal disease
Dependent edema
- influenced by gravity (e.g., the
legs when standing, the sacrum
when recumbent)
Pitting edema
-edematous subcutaneous tissue
displaces the interstitial fluid and
leaves a depression when pressed
HYPEREMIA AND
CONGESTION
Hyperemia - an active process in
which arteriolar dilation leads to
increased blood flow
Congestion - a passive process
resulting from reduced outflow of
blood from a tissue
Morphology:
Acute pulmonary congestion
- microscopically exhibits engorged
alveolar capillaries often with
alveolar septal edema and focal
intra-alveolar hemorrhage
Chronic pulmonary congestion
- the septa are thickened and
fibrotic
Heart failure cells
- hemosiderin-laden macrophages
Acute hepatic congestion
- the central vein and sinusoids are
distended
Chronic passive hepatic
congestion
- the centrilobular regions are
grossly red-brown and slightly
depressed
Nutmeg liver
- uncongested tan liver
HEMORRAGE
- the extravasation of blood into
the extravascular space
Hemorrhagic diatheses
- increased tendency to
hemorrhage
Distinct Pattern of Tissue
Hemorrhage
Hematoma
- accumulation of blood
external or within in the
tissue
Petechiae
- Minute 1- to 2-mm
hemorrhages into skin,
mucous membranes, or
serosal surfaces
- assoc. with increased
intravascular pressure, low
platelet counts
(thrombocytopenia), or
defective platelet function
(as in uremia).
Purpura
- Slightly larger (3 mm)
hemorrhages
- secondary to trauma,
vascular inflammation
(vasculitis), or increased
vascular fragility (e.g., in
amyloidosis).
Ecchymoses
- Larger (>1 to 2 cm)
subcutaneous hematomas
Red-blue color
hemoglobin (24hrs.)
Blue-green bilirubin
(48-72hrs.)
Gold-brown
hemosiderin (3-5days)

HEMOSTASIS AND
THROMBOSIS
Hemostasis opposite of
hemorrhage
- stoppage of bleeding
Thrombosis - blood clot
(thrombus) formation within intact
vessels
3 Components:
1. Vascular wall (endothelium)
2. Platelets
3. Coagulation cascade
General sequence of events in
hemostasis
Arteriolar
vasoconstriction - local
secretion of factors such as
endothelin
Endothelin - a potent
endothelium-derived
vasoconstrictor
Primary hemostasis
(Platelet adherence and
activation) formation of a
hemostatic plug
Secondary hemostasis
(Tissue factor activation)
Tissue Factor -a.k.a factor III
and thromboplastin
- membrane-bound
procoagulant glycoprotein
synthesized by endothelial
cells
Factor VII - the major in vivo
initiator of the coagulation cascade
Thrombin cleaves
circulating fibrinogen into insoluble
fibrin
Formation of permanent
plug
- counter-regulatory
mechanisms (e.g., tissue
plasminogen activator, t-PA)
are set into motion to limit
the hemostatic plug to the
site of injury
t-PA a fibrinolytic product
Endothelium
- key players in the regulation of
homeostasis
- exhibit antiplatelet, anticoagulant,
and fibrinolytic properties
Antithrombotic Properties
Antiplatelet effects
Prostacyclin (PGI2) and nitric oxide
- potent vasodilators and
inhibitors of platelet aggregation
- produced by the endothelial
cells impede platelet adhesion
Anticoagulant effects
- mediated by endothelial
membrane-associated heparin-like
molecules, thrombomodulin, and
tissue factor pathway inhibitor
Heparin-like molecules cofactor
that enhance the inactivation of
thrombin and several other
coagulation factors by the plasma
protein antithrombin III
Thrombomodulin acts indirectly;
binds to thrombin and converts it
from a procoagulant into an
anticoagulant via its ability to
activate protein C
Protein C - inhibits clotting by
inactivating factors Va and VIIIa
Tissue factor pathway inhibitor
(TFPI) - a cell surface protein that
directly inhibits tissue factorfactor
VIIa and factor Xa activities
Fibrinolytic effects
Tissue-type plasminogen activator
(t-PA) - a protease that cleaves
plasminogen to form plasmin
Plasmin - cleaves fibrin to degrade
thrombi
Prothrombotic Properties
Platelet effects
von Willebrand factor (vWF) - an
essential cofactor for platelet
binding to matrix elements
Procoagulant effects
- In response to cytokines
(e.g., tumor necrosis factor
[TNF] or interleukin-1 [IL-1])
or bacterial endotoxin,
endothelial cells synthesize
tissue factor
Antifibrinolytic effects
Plasminogen activator (PAIs) - limit
fibrinolysis; favor thrombosis.
* intact, nonactivated endothelial
cells inhibit platelet adhesion and
blood clotting. Endothelial injury or
activation, however, results in a
procoagulant phenotype that
enhances thrombus formation
Platelets
- disc-shaped, anucleate cell
fragments that are shed from
megakaryocytes
-Granules - contain fibrinogen,
fibronectin, factors V and VIII,
platelet factor 4 (a heparin-binding
chemokine), platelet-derived
growth factor (PDGF), and
transforming growth factor- (TGF-
)
Dense (or ) granules - contain
ADP and ATP, ionized calcium,
histamine, serotonin, and
epinephrine
On contact with collagen and
adhesive glycoprotein,
platelets undergo:
Platelet adhesion to ECM
von Willebrand disease - genetic
deficiency of vWF
Bernard-Soulier syndrome -
deficiency of glycoprotein Ib (GpIb),
the receptor for vWF
Secretion
Adenosine diphosphate (ADP) - a
potent activator of platelet
aggregation
Platelet aggregation
 - follows adhesion and
granule release
Thromboxane A2 (TxA2) - an
important platelet-derived stimulus
that amplifies platelet aggregation
Glanzmann thrombasthenia -
inherited deficiency of GpIIb-IIIa
Prostaglandin PGI2 (prostacyclin) -
inhibits platelet aggregation and is
a potent vasodilator
Coagulation Cascade
Extrinsic pathway - required the
addition of an exogenous trigger
- most physiologically
relevant pathway for coagulation
occurring when vascular damage
has occurred
Intrinsic pathway - only required
exposing factor XII (Hageman
factor) to thrombogenic surfaces
Factor IX - can be activated either
by factor XIa or factor VIIa
Tissue factor pathway inhibitor
(TFPI) - inhibits the activation of
factors X and IX by factor VIIa
Prothrombin time (PT) - assesses
the function of the proteins in the
extrinsic pathway (factors VII, X, II,
V, and fibrinogen)
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)
3 Categories of endogenous
anticoagulation
1.) Antithrombins - inhibit the
activity of thrombin and other
serine proteases, including factors
IXa, Xa, XIa, and XIIa
2.) Proteins C and S - vitamin K
dependent proteins that act in a
complex that proteolytically
inactivates factors Va and VIIIa
3.) Tissue factor pathway inhibitor
(TFPI)
Thrombosis
3 primary abnormalities that
lead to thrombus formation
(called Virchow's triad):
1.) Endothelial injury
2.) Stasis or turbulent blood
flow
- Promote endothelial
activation
- Disrupt laminar flow
- Prevent washout and
dilution of activated clotting factors
Turbulence - contributes to
arterial and cardiac thrombosis by
causing endothelial injury or
dysfunction
Stasis is a major contributor
in the development of venous
thrombi
3.) Hypercoagulability of the
blood
- a.k.a Thrombophilia
Divide into:
primary (genetic
secondary (acquired)
* Of the inherited causes of
hypercoagulability, point mutations
in the factor V gene and
prothrombin gene are the most
common.
Leiden mutation - mutation in
factor V
Heparin-induced thrombocytopenia
(HIT) syndrome - occurs following
the administration of
unfractionated heparin
Antiphospholipid antibody
syndrome - previously called the
lupus anticoagulant syndrome
* Arterial or cardiac thrombi
usually begin at sites of turbulence
or endothelial injury; venous
thrombi characteristically occur at
sites of stasis
* arterial thrombi tend to grow
retrograde from the point of
attachment, while venous thrombi
extend in the direction of blood
flow
lines of Zahn - apparent
laminations in thrombi
mural thrombi - Thrombi occurring
in heart chambers or in the aortic
lumen
vegetations - thrombi on heart
valves
Fate of the Thrombus
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
Clinical Consequences
Venous Thrombosis
(Phlebothrombosis)
Arterial and Cardiac
Thrombosis
Atherosclerosis is a major cause of
arterial thrombosis
Disseminated Intravascular
Coagulation (DIC)
- the sudden or insidious onset of
widespread fibrin thrombi in the
microcirculation
- a.k.a Consumption coagulopathy
EMBOLISM
Embolus - a detached
intravascular solid, liquid, or
gaseous mass that is carried by the
blood to a site distant from its point
of origin
Pulmonary embolism
 - In more than 95% of cases,
PEs originate from leg deep vein
thromboses (DVTs)
Systemic thromboembolism -
refers to emboli in the arterial
circulation
Fatty and marrow Embolism -
characterized by pulmonary
insufficiency, neurologic symptoms,
anemia, and thrombocytopenia
Air Embolism
Decompression sickness - occurs
when individuals experience
sudden decreases in atmospheric
pressure
the bends - painful condition of the
joints
Caisson disease - a more chronic
form of decompression sickness
Amniotic fluid embolism - an
ominous complication of labor and
the immediate postpartum period
INFARCTION
Infarct - an area of ischemic
necrosis caused by occlusion of
either the arterial supply or the
venous drainage
Morphology:
Red infarcts (hemorrhagic)
- occur (1) with venous
occlusions (e.g., ovary), (2) in loose
tissues (e.g., lung) (3) in tissues
with dual circulations (e.g., lung
and small intestine) (4) in tissues
previously congested by sluggish
venous outflow, and (5) when flow
is re-established to a site of
previous arterial occlusion and
necrosis
White infarcts (anemic)
- occur with arterial
occlusions in solid organs with end-
arterial circulation (e.g., heart,
spleen, and kidney)
Ischemic coagulative necrosis
- dominant histologic
characteristic of infarction
Septic infarctions
- occur when infected cardiac
valve vegetations embolize or
when microbes seed necrotic tissue
- infarct is converted into an
abscess
Factors That Influence
Development of an Infarct
Nature of the vascular
supply
Rate of occlusion
development
Vulnerability to hypoxia
Oxygen content of blood
SHOCK
-the final common pathway
for several potentially lethal clinical
events
- characterized by systemic
hypotension due either to reduced
cardiac output or to reduced
effective circulating blood volume
- consequences are impaired
tissue perfusion and cellular
hypoxia
3 Major Types of Shock
1.) Cardiogenic shock
- results from low cardiac
output due to myocardial pump
failure
2.) Hypovolemic shock
- results from low cardiac
output due to the loss of blood or
plasma volume
3.) Septic shock
- results from vasodilation
and peripheral pooling of blood
Neurogenic shock - result of loss of
vascular tone and peripheral
pooling of blood (anesthetic
accident or a spinal cord injury)
Anaphylactic shock - denotes
systemic vasodilation and
increased vascular permeability
caused by an IgEmediated
hypersensitivity reaction
Septic shock - associated with
severe hemodynamic and
hemostatic derangements
- most frequently triggered
by gram-positive bacterial
infections, followed by gram-
negative bacteria and fungi
- older synonym of
endotoxic shock
Major factors:
Inflammatory mediators
Endothelial cell activation
and injury
3 major sequelae in
endothelial cell activation by
leukocytes:
1. thrombosis
2. increased vascular
permeability
3. vasodilation
Metabolic abnormalities
Immune suppression
Organ dysfunction
Superantigens- polyclonal T-
lymphocyte activators that induce
the release of high levels of
cytokines
Stages of shock
An initial nonprogressive
phase
- reflex compensatory
mechanisms are activated and
perfusion of vital organs is
maintained
Progressive stage
- characterized by tissue
hypoperfusion and onset of
worsening circulatory and
metabolic imbalances
Irreversible stage
- sets in after the body has
incurred cellular and tissue
injury so severe that even if the
hemodynamic defects are
corrected, survival is not
possible
Clinical Consequences
* In hypovolemic and cardiogenic
shock the patient presents with
hypotension; a weak, rapid pulse;
tachypnea; and cool, clammy,
cyanotic skin. In septic shock the
skin may initially be warm and
flushed because of peripheral
vasodilation.

/mla MD-2