Hemodynamic Disorders,

Thrombosis, and Shock

Dr Dagnaw
April 21,2018
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).
 Anasarca is a severe and generalized
edema with profound subcutaneous tissue
swelling.
 There are several pathophysiologic
categories of edema ;
1. Inflammatory
2. Non inflamatory
 Noninflammatory causes of edema
Increased Hydrostatic Pressure

Impaired venous return

Congestive heart failure

Constrictive pericarditis

Ascites (liver cirrhosis)

 Venous obstruction or compression
B
Thrombosis

External pressure (e.g., mass)

Lower extremity inactivity with prolonged dependency

Arteriolar dilation

Heat
Reduced Plasma Osmotic Pressure (Hypoproteinemia)

Protein-losing glomerulopathies (nephrotic syndrome)

Liver cirrhosis (ascites)

Malnutrition

Protein-losing gastroenteropathy
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
HYPEREMIA AND
CONGESTION
 The terms hyperemia and congestion both
indicate a local increased volume of blood in
a particular tissue.
 Hyperemia is an active process resulting
from augmented blood flow due to arteriolar
dilation (e.g., at sites of inflammation or in
skeletal muscle during exercise).
 The affected tissue is redder than normal
because of engorgement with oxygenated
blood.
 Congestion is a passive process resulting
from impaired venous return out of a
tissue. It may occur systemically, as in
cardiac failure, or it may be local,
resulting from an isolated venous
obstruction.
 The tissue has a blue-red color (cyanosis),
especially as worsening congestion leads
to accumulation of deoxygenated
hemoglobin in the affected tissues .
HEMORRHAGE
 Hemorrhage is extravasation of blood from
vessels into the extravascular space. capillary
bleeding can occur under conditions of
chronic congestion; an increased tendency to
hemorrhage occurs in a wide variety of
clinical disorders collectively called
hemorrhagic diatheses.
 Rupture of a large artery or vein results in
severe hemorrhage, and is almost always due
to vascular injury, including trauma,
atherosclerosis, or inflammatory or
neoplastic erosion of the vessel wall.
 Hemorrhage can be external or can be
confined within a tissue; any
accumulation is referred to as a
hematoma.
 Hematomas can be relatively insignificant
(e.g., a bruise) or can involve so much
bleeding as to cause death (e.g., a massive
retroperitoneal hematoma resulting from
rupture of a dissecting aortic aneurysm.
 Petechiae
 Purpura
 Ecchymoses
 Hemothorax
 Hemopericardium
 Hemoperitonium
 Hemoarthroses
HEMOSTASIS AND
THROMBOSIS
 Normal hemostasis is a consequence of
tightly regulated processes that maintain
blood in a fluid, clot-free state in normal
vessels while inducing the rapid formation of
a localized hemostatic plug at the site of
vascular injury.
 The pathologic form of hemostasis is
thrombosis; it involves blood clot (thrombus)
formation in uninjured vessels or thrombotic
occlusion of a vessel after relatively minor
injury.
 Both hemostasis and thrombosis involve
three components:
1. the vascular wall
2. platelets, and
3. the coagulation cascade.
Normal Hemostasis
 After initial injury a brief period of
arteriolar vasoconstriction occurs mostly
as a result of reflex neurogenic
mechanisms and is augmented by the
local secretion of factors such as
endothelin (a potent endothelium-derived
vasoconstrictor).
 Endothelial injury also exposes highly
thrombogenic subendothelial extracellular
matrix, allowing platelets to adhere and be
activated.
 Activation of platelets results in a
dramatic shape change (from small
rounded disks to flat plates with markedly
increased surface area) and release of
secretory granules.
 Within minutes the secreted products have
recruited additional platelets
(aggregation) to form a hemostatic plug;
this is the process of primary hemostasis.
 Tissue factor is also exposed at the site of
injury. Also known as factor III and
thromboplastin, tissue factor is a
membrane-bound procoagulant
glycoprotein synthesized by endothelium.
It acts in conjunction with factor VII as
the major in vivo pathway to activate the
coagulation cascade, eventually
culminating in thrombin generation.
 Thrombin cleaves circulating fibrinogen
into insoluble fibrin, creating a fibrin
meshwork deposition. Thrombin also
induces further platelet recruitment and
granule release. This secondary
hemostasis sequence lasts longer than the
initial platelet plug.
 Polymerized fibrin and platelet aggregates
form a solid permanent plug to prevent
any additional hemorrhage. At this stage
counter-regulatory mechanisms (e.g.,
tissue plasminogen activator, t-PA) are set
into motion to limit the hemostatic plug to
the site of injury.
Coagulation Cascade
 The coagulation cascade constitutes the
third component of the hemostatic process
and is a major contributor to thrombosis.
 The coagulation cascade is essentially an
amplifying series of enzymatic
conversions; each step in the process
proteolytically cleaves an inactive
proenzyme into an activated enzyme,
eventually culminating in thrombin
formation; thrombin is the most important
enzyme regulating the coagulation
process.
 Thrombin converts the soluble plasma
protein fibrinogen into fibrin monomers
that polymerize into an insoluble gel; this
gel encases platelets and other circulating
cells in the definitive secondary
hemostatic plug.
 The blood coagulation scheme has been
traditionally classified into extrinsic and
intrinsic pathways that converge with the
activation of factor X .
 The extrinsic pathway is the most
physiologically relevant of the two in driving
coagulation after vascular damage; it is
activated by tissue factor (also known as
thromboplastin or factor III), a membrane-
bound lipoprotein expressed at sites of
injury.
 The clinical pathology lab assesses the two
pathways using two standard assays:
prothrombin time (PT) and partial
thromboplastin time (PTT).
Thrombosis
 Pathogenesis
 There are three primary influences on
thrombus formation (called Virchow's
triad):
(1) endothelial injury,
(2) stasis or turbulence of blood flow, and
(3) blood hypercoagulability
 Endothelial Injury
It is particularly important for thrombus
formation occurring in the heart or in the
arterial circulation, where the normally high
flow rates might otherwise hamper clotting
by preventing platelet adhesion or diluting
coagulation factors.
 Thus, thrombus formation within the
cardiac chambers (e.g., after endocardial
injury due to myocardial infarction), over
ulcerated plaques in atherosclerotic
arteries, or at sites of traumatic or
inflammatory vascular injury (vasculitis)
is largely a function of endothelial injury.
Alterations in Normal Blood Flow

 Turbulence contributes to arterial and cardiac

thrombosis by causing endothelial injury or
dysfunction, as well as by forming
countercurrents and local pockets of stasis;
 stasis is a major contributor to the
development of venous thrombi. Normal
blood flow is laminar, such that platelets
flow centrally in the vessel lumen, separated
from the endothelium by a slower moving
clear zone of plasma.
 Hypercoagulability
Hypercoagulability generally contributes
less frequently to thrombotic states but is
nevertheless an important component in the
equation. It is loosely defined as any
alteration of the coagulation pathways that
predisposes to thrombosis, and it can be
divided into primary (genetic) and
secondary (acquired) disorders .
EMBOLISM
 An embolus is a detached intravascular solid,
liquid, or gaseous mass that is carried by the
blood to a site distant from its point of
origin.
 Virtually 99% of all emboli represent some
part of a dislodged thrombus, hence the
term thromboembolism.
 Rare forms of emboli include fat droplets,
bubbles of air or nitrogen, atherosclerotic
debris (cholesterol emboli), tumor fragments,
bits of bone marrow, or foreign bodies such
as bullets.
 Inevitably, emboli lodge in vessels too
small to permit further passage, resulting
in partial or complete vascular occlusion.
The consequences of thromboembolism
include ischemic necrosis (infarction) of
downstream tissue.
 Pulmonary Thromboembolism
In more than 95% of cases, venous emboli
originate from deep leg vein thrombi above
the level of the knee (described above).
They are carried through progressively
larger channels and pass through the right
side of the heart before entering the
pulmonary vasculature.
 Depending on the size of the embolus, it may
occlude the main pulmonary artery, impact across
the bifurcation (saddle embolus), or pass out into
the smaller, branching arterioles.
 They eventually become organized and become
incorporated into the vascular wall; in some cases,
organization of the thromboembolus leaves
behind a delicate, bridging fibrous web.Sudden
death, right ventricular failure (cor pulmonale), or
cardiovascular collapse occurs when 60% or
more of the pulmonary circulation is obstructed
with emboli.
 Systemic Thromboembolism
Systemic thromboembolism refers to emboli in
the arterial circulation. Most (80%) arise from
intracardiac mural thrombi, two-thirds of which
are associated with left ventricular wall infarcts
and another quarter with dilated left atria (e.g.,
secondary to mitral valve disease). The
remainder originate from aortic aneurysms,
thrombi on ulcerated atherosclerotic plaques,
or fragmentation of valvular vegetations .
 Fat embolism
 Air embolism
 Amniotc fluid embolism
SHOCK
 Shock gives rise to systemic hypoperfusion; it
can be caused either by reduced cardiac
output or by reduced effective circulating
blood volume.The end results are
hypotension, impaired tissue perfusion, and
cellular hypoxia.
 Impaired perfusion is responsible for
cellular injury that causes
maldistribution of blood flow, further
compromising cellular perfusion; the
latter ultimately causes multiple organ
failure (MOF) and, if the process is not
interrupted, leads to death.
 Clinical shock is usually accompanied
by hypotension (i.e., a mean arterial
pressure [MAP] <60 mmHg in
previously normotensive persons).
 There are three general categories of
shock:
1. cardiogenic,
2. hypovolemic, and
3. septic
1. Cardiogenic shock results from failure of
the cardiac pump. This may be caused by
myocardial damage (infarction),
ventricular arrhythmias, extrinsic
compression (cardiac tamponade), or
outflow obstruction (e.g., pulmonary
embolism).
2. Hypovolemic shock results from loss of
blood or plasma volume. This may be caused
by hemorrhage, fluid loss from severe burns,
or trauma.
3. Septic shock is caused by microbial
infection. Most commonly this occurs in the
setting of gram-negative infections (endotoxic
shock), but it can also occur with gram-
positive and fungal infections.
Notably, there need not be systemic
bacteremia to induce septic shock; host
inflammatory responses to local
extravascular infections may be sufficient.
 Shock tends to evolve through three
general stages.
 An initial nonprogressive stage during which
reflex compensatory mechanisms are
activated and perfusion of vital organs is
maintained
 A progressive stage characterized by tissue
hypoperfusion and onset of worsening circulatory
and metabolic imbalances .
 An irreversible stage that 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 Course
The clinical manifestations of shock
depend on the precipitating insult. In
hypovolemic and cardiogenic shock, the
patient presents with hypotension; a weak,
rapid pulse; tachypnea; and cool, clammy,
cyanotic skin.
 In septic shock, however, the skin may be
warm and flushed as a result of peripheral
vasodilation.
 The prognosis varies with the origin of
shock and its duration. Thus, 80% to 90%
of young, otherwise healthy patients with
hypovolemic shock survive with
appropriate management, whereas
cardiogenic shock associated with
extensive myocardial infarction, or gram-
negative sepsis carries a mortality rate of
75%, even with care that is state of the
art.