HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

PATHOLOGY REVIEWER

If superficial: varicose veins saphenous veins local

congestion, pain, rarely embolize
1. Advanced age, bed rest and immobilization
2. CHF
3. Trauma, surgey, burns
4. Puerperal and post- partum
5. tumor
Disseminated intravascular coagulation
- not a dse but a complication
o microthrombi diffuse circulatory insufficiency
o rapid concurrent consumption of platelet and
coagulation factors serious bleeding
o

Deep vein thrombosis occurs in

Refers to the widespread fibrin thrombi in the

microcirculation, caused by variety of disorders

******* NOTHING FOLLOWS********

PATHOLOGY REVIEWER

How alterations of the normal blood flow can

cause thrombus formation?

This factor is important in causing thrombosis in

veins, cardiac chambers and arterial aneurysms;
hyperviscosity syndromes or deformed
erythrocytes.
Defined as any alteration of the coagulation
pathways that predisposes to thrombosis; occurs
less frequently
What is the most common heritable
hypercoagulable states?
Administration of the unfractionated heparin
induces circulating antibodies that cause platelet
activation and endothelial cell injury
Platelet activation of patients with antibodies
against anionic, phospholipids
Common morphology of thrombus

Thrombi that may also form on heart valves

Fate of thrombus

Deep veins thrombus

Arterial thrombi
Venous thrombi

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER
a. Disrupts laminar flow and bring platelets into contact
with the endothelium
b. Prevents dilution of the activated clotting factors by
free- flowing blood
c. Retard inflow of clotting factor inhibitors and permit
build- up of thrombi
d. Promote endothelial cell activation
stasis

Hypercoagulability

Factor V gene mutations

Heparin- induced thrombocytopenia syndrome

Anti- phospholipid antibody syndrome

a.
b.
c.
d.

Aortic or cardiac thrombi- typically non- occlusive

Smaller arterial thrombi- usually occlusive
All begins at site of endothelial injury
Venous thrombi- occur is sites of stasis and are
occlusive
e. At sites of origin- firmly attached
f. Arterial thrombi- extend retrograde from attachment
point; venous extend following the direction of the
blood flow
g. May create an embolus
h. Cardiac and arterial thrombi are gray- red and tend to
have gross and microscopic laminations (lines of
Zahn) produced by pale layers of platelets and fibrin
alternating with red- cell rich lines.
i. Venous thrombosis- red- blue cast of vein lumen
Infective endocarditis- caused by bacteria or fungi
(vegetation)
Sterile vegetation- non- bacterial
Verrucous endocarditis (libman- Sacks)
If the patient survives the immediate effects;
a. Propagation- causing complete vessel obstruction
b. Embolization- esp. the lungs
c. Dissolution- by fibrinolytic activity
d. Organization and recanalization- re- establishing blood
flow
e. Bacterial seeding (rarely) of the thrombus resulting to
mycotic aneurysm
Willl cause only congestion and edema of the lower
extremities, but once it becomes an emboli, it can cause death
Are less likely to embolize, local obstruction is more important
o Usually occurs in superficial or deep veins

PATHOLOGY REVIEWER

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

Why plasmin activity is restricted to sites of

thrombosis?

Plasmin activator inhibitors are increased by?

Anticoagulants that are activated by thrombin.
Anticoagulant that is activated by plasmin
Anticoagulant that is activated by
Anticoagulant that is activated by heparin- like
molecules on the endothelium
This anticoagulant converts inactive circulating
plasminogen into active plasma
This anticoagulant breaks down fibrin and
interferes with its polymerization
Acts as weak anticoagulants
Inhibits thrombin and other serine proteasesfactors 9a,10a,11a,12a
Inactivates factors 5a and 8a
Procoagulant that is activated by released platelet
granules
Activated by vWf
Activated by exposed collagen
Activated by thrombin
Thrombin and well as certain cytokines
This procoagulant catalyzes the final steps of the
cascade leading to the production of fibrin
This procoagulant release cytokines and other
procoagulant substaces
This refers to the inappriorate activation of blood
clotting in uninjured
Composed the Virchow triad? (primary influences
on thrombus formation)

b. Anti- thrombins in the presence of heparin- like

molecules on the endothelium inhibit thrombin and
other serine proteases- factors 9a, 10a, 11a and 12a
c. In the presence of thrombomodulin, thrombin activates
proteins C and S which in turn inactivates factors 5a
and 8a
d. Thrombin induces endothelial release of tissue
plasminogen activator (t- PA) which convert inactive
circulating plasminogen into active plasmin. Plasmin
breaks down the fibrin and interferes with its
polymerization resulting to fibrin split products that
also act as weak anticoagulants
e. Endothelium regulates anti-coagulation by releasing
plasminogen activator inhibitors; these block
fibrinolysis by inhibiting t- PA binding to fibrin
1. t- PA activates plasminogen when bound to a fibrin
meshwork
2. free plasmin is rapidly neutralized by serum alpha2
plasmin inhibitor
3. t-PA activity is blocked by plasminogen activator
inhibitor
Thrombin as well as certain cytokines cause intravascular
thrombosis accompanying severe inflammation
Protein C and S, t- PA
Fibrin split producst
t- PA
antithrombins
t- PA
Plasmin
Fibrin split products
Antithrombins
Protein C and S
Calcium, ADP, phospholipid complex
Platelet granules
Von willebrand factor
Fibrin
Thrombin
vWf
Thrombosis
1. Endothelial injury
2. Alteration =s in normal blood flow
3. Hypercoagulability

PATHOLOGY REVIEWER

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

The lining of the blood vessels that modulates

several, frequently opposing aspects of
hemostasis
The properties exhibited by a normal endothelium.
The properties exhibited by the endothelium after
an injury.
What determines whether the thrombus formation,
propagation or dissolution occurs
This blood component plays a central role in
normal hemostasis and thrombosis.
When platelet is activated, it involves the ___
This process acts as bridge between platelet
surface receptors and exposed collagen
The process adhesion is mediated by what
factor?
The genetic deficiency dse of vWf or to in a
platelet receptor
What are the two types of granules that occurs
secretion

Endothelium

A vitamin that is important factor in coagulation

cascade
This provides a site for calcium and coagulation
factor binding in the intrinsic clotting cascade
What do you call the the platelet adhering to other
platelets
The mechanism of platelet aggregation.

Calcium (result)

This refers to the sequence of conversions of

inactive proenzymes into activated enzymes
culminating in the generation of insoluble fibrin
from the soluble plasma protein fibrinogen
The intrinsic and extrinsic pathway converge at
what factor?
The intrinsic pathway is traditionally initiated by
activation of what factor?
What activates the extrinsic pathway?
Each step of the intrinsic and extrinsic pathways
result from _____

What enzyme catalyzes the final steps of the

cascade?
Most of the effects of thrombin are induced
What are the control mechanism of hemostasis
and thrombosis?

Exhibit anti- platelet, ant- coagulant and fibrinolytic properties

Exhibit procoagulation function
The balance between the anti- thrombotic and pro- thrombotic
activities
Platelet
shape change, secretion and aggregation
Adhesion
Adhesion
Bernard- sullier syndrome
a. Alpha granule expresses the molecule P- selectin and
contained coagulation and growth factors
b. Delta bodies or delta granules- contains adenosine
nucleotides (ATP, ADP)

Phospholipid comples
Platelet aggregation
Promoted by: ADP and the platelet vasoconstrictor product
Thromboxane A2
Creates: the primary hemostatic plug which is reversible
Coagulation cascade

Factor 10 (X)
Factor 12 (Hageman Factor)
Tissue factor
Complex composed of an enzyme, a substrate and a cofactor
(reaction accelerator) all held together by calcium ions on a
phospholipid complex
Thrombin
via thrombin receptors, very potent, even in a small amount
a. Factor activation is restricted to sites of exposed
phospholipids, factors are diluted by flow at sites
distant from the original injury and cleared by the liver
and tissue macrophages

PATHOLOGY REVIEWER

Moderate infections and higher LPS levels

Severe infection
2nd mediators in severe infection may cause

Organs affected most often

Organs and the corresponding morphology in
shock.

3 general phases of shock

HEMODYNAMICS.PART 2
What is hemostasis?

A pathologic state wherein there is inappropriate

activation of hemostatic mechanisms in uninjured
vasculature or thrombotic occlusion of a vessel
after relatively minor injury.
Thrombosis and hemostasis depends on three
components which are ___
Summary of the normal hemostasis.

Considered as the first response of the

endothelial tissue to injury.

The stage of coagulation cascade where exposed

endothelial ECM allows platelet adhesion and
activation which secrete products attracting more
platelet to forma temporary hemostatic plug.
The stage where tissue factor exposed by the site
of injury activates the coagulation cascade
thrombin generation conversion of fibrin into
insoluble fibrin solid, permanent plug

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER
Cytokine- induced secondary effectors become significant like
systemic effects of TNF and IL- 1
Septic shock, high- dose cytokines and secondary mediators
a. Systemic vasodilation
b. Diminished myocardial contractility
c. Widespread endothelial injury and activation ARDS
d. Activation of coagulation system DIC
Heart, brain, lungs, kidney, adrenals, GIT
Brain= hypoxic encephalopathy
Heart= areas of coagulation necrosis with subendocardial
hemorrhage, contraction- band necrosis or both kinds
Kidneys= extensive tubular ischemic injury causing oliguria,
anuria, and electrolyte imbalance
1. Initial non- progressive phase- reflex comepensatory
pathways are activated and perfusion of vital organs is
maintained
2. Progressive stage- tissue hypoperfusion and
metabolic imbalances etc
* peripheral pooling worsens cardiac output e
exacerbates endothelial anoxia DIC
3. Irreversible stage- the body has incurred cellular and
tissue injury that even if hemodynamics are corrected,
survival is not possible.
It is the normal physiologic process maintaining blood in a
fluid, clot- free state in normal vessels and inducing a rapid
and localized hemostatic plug at sites of vascular injury.
Thrombosis

1. Vascular endothelium
2. Platelets
3. Coagulation cascade
Endothelial injury platelet adhesion to the site of injury
(primary hemostasis) and recruit other platelets secrete
secretory granules recruit more platelet coagulation
cascade thrombin generation fibrinogen fibrin solid
permanent plug
Transient reflex neurogenic arteriolar vasoconstriction
augmented by endothelin (constrictor)
Primary hemostasis

Secondary hemostasis

PATHOLOGY REVIEWER

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

Factors that influence the development of an

infarct.

In infarct that is considered as an after shock or

systemic hypoperfusion
A morphology of infarct that occurs in venous
occlusions, loose tissues, tissues with dual
circulation and tissues previously congested
because of the sluggish venous outflow.
Observed in solid organs with end arterial
circulation.
In an infarct that is wedged- shape, what serves
as the base and apex?
The most dominant histologic characteristic of an
infarct.
Initial inflammatory responses is usually followed
by ___
What specific morphology is seen in a brain
infarct?
This infarction occur with embolization of infected
heart valve vegetations or when microbes seed
an area of necrosis.
What is shock?
Shock is the result of?
This is considered as the final common pathway
of many lethal events.
3 major categories of shock

Septic shock

This is released when cell walls are degraded and

this consist of toxic fatty acid (lipid A) core and a
complex of polysaccharide coat
Septic shock at low doses

a. Anatomic pattern of vascular supply- dual circulation

may tend to develop a collateral circulation, but with
end- arterial vessel, it may cause vessel obstruction
and eventually lead to infarction.
b. Rate of development of occlusion- slowly developing
occlusion may allow more time to develop collateral
circulation and the damage is less
c. Vulnerability to hypoxia- neurons for example, 3-4
mins of lack of blood supply may caused irreversible
damage, 20- 30 mins for the myocardium ad
fibroblasts in the myocardium is several hours
d. Oxygen content of the blood- conditions like anemia,
cyanosis or CHF can cause infarction
Watershed infarcts (necrosis at the places farthest from the
arterial supply)
Red infarcts

White infarcts
Apex is the occluded blood vessel; the base is the organ
periphery
Ischemic coagulative necrosis
A reparative response that in most cases eventually replaced
by a scar tissue
Liquefactive necrosis
Septic infarctions

A systemic hypoperfusion resulting from reduction in either

cardiac output or the effective circulating blood volume
Hypotension followed by impaired tissue perfusion and cellular
hypoxia
Shock
1. Low cardiac output- cardiogenic and hypovolemic
shock
2. Septic shock- caused by gm (-) bacteria
3. Neurogenic shock- with loss of vascular tone and
peripheral pooling
25- 75 % mortality
main cause of death in the ICU
70% is caused by gm (-) bacteria
Bacterial lipopolysaccharides (LPS)

Activates complement and monocytes macrophages

bacterial eradication

PATHOLOGY REVIEWER

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

This emboli causes decompression sickness,

obstetric complications
The morphology of this embolism are the
adipocytes within blood vessels
Complications of this embolism are pulmonary
disseminated intravascular coagulopathy
How many % of the pulmonary thromboembolism
is clinically silent?
Embolic obstruction of medium- sized arteries
may result to ____
When 60% of the pulmonary circulation is
obstructed with emboli may result to ___
This refers to the emboli in the arterial circulation
80% of systemic thromboembolism is from ___
How many percent of the systemic
thromboembolism is caused by MI and dilated
atria?
The 2nd most common cause of embolism
Occurs after fracture of the long bone
This syndrome is fatal in 10% causing sudden
pulmonary insufficiency 1- 3 days after injury with
20- 50% of the patients diffuse petechial rash
Describe the pathogenesis of the fat embolism
syndrome
Hallmark of diagnosing fat embolism.
Presence of air bubbles within the circulation that
causes obstruction.
For the air to be clinically significant, it should be
___ ml
This sickness is caused by sudden changes in
atmospheric temp
Mechanism of decompression sickness

The gas bubbles in skeletal muscle and joint

Gas bubbles in lungs
Treatment for decompression sickness
More chronic form of decompression sickness
This embolism is caused by the infusion of
amniotic fluid into maternal circulation
The classic findings of amniotic fluid embolism
If patient survives the initial crisis, what probably
might result to the patient?
An area of ischemic necrosis usually caused by
occlusion of the arterial supply (97% of the cases)
If venous drainage is the one occluded, what
might result?

Gas
Fat
Amniotic fluid
60- 80%
Pulmonary hemorrhage but not usually cause pulmonary
infarction due to collateral blood flow
Sudden death, right heart failure or cardiovascular collapse
Systemic thromboembolism
Cardiac mural thrombi
2/3 from the MI, 25% from the dilated atria, and the rest is
caused by aortic aneurysm, ulcerated atherosclerotic plaques,
valvular vegetations and parodixal emboli
Fat embolism
Microscopic fat globules
Fat embolism syndrome

Mechanical obstruction local platelet and erythrocyte

aggregation and release of the fatty acid toxic injury to
endothelium
Identifying microvascular fat globules
Air embolism
100 ml
Decompression sickness
Air breathed from a atmp. pressure high amount of gas
dissolved in blood and tissues rapid ascent
(depressurization) gasses bubble out of solution
The bends
The chokes
Repressurizing the individual followed by slow decompression
Caisson dse; ischemic necrosis
Amniotic fluid embolism
Fetal squamous cells, mucin, lanugo hair, venix caseosa fat in
the maternal pulmonary microcirculation
Pulmonary edema occurs
Infarction
It may cause infarction but more often only congestion due to
opening of bypass channels

PATHOLOGY REVIEWER

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

Mechanism of edema in decreased osmotic

pressure

Microscopic morphology of the edema.

Edema of what organ results to increased size
and weight and separation of parenchymal
elements
This edema morphology is typical in in leftventricular failure
This edema is often prominent in loose connective
tissue matrix e.g. eyelids
Localized to sites of injury (abscess, neoplasm) or
may generalized
Generalized brain edema
Refers to the extravasation of blood because of
vessel rupture
This type of hemorrhage is usually due to
vascular injury such as trauma, atherosclerosis, or
inflammatory/ neoplastic erosion of the vessel
This bleeding occurs with chronic congestion
Groups of hemorrhage

Larger (> 3mm) hemorrhages associated with

similar pathologies as well as trauma, vasculitis
and increased vascular fragility
Minute 1- 2 mm hemorrhages of the skin, mucous
membranes or serosal surfaces, with increased
intravascular pressure, low platelet count,
defective fxn and clotting factors deficits
These are subcutaneous hematomas (>1-2 cm)
commonly known as bruise and follows after a
trauma
Erythrocytes are degraded by
Illustrate how bruise develops

Clinically, hemorrhage depends on ___

Refers to aby intravascular solid, liquid, or
gaseous mass carried by the blood to a site
distant from its point or origin

How many % of thrombi becomes an emboli?

Common embolus materials
4 types of embolism

Type of embolism that has a morphology of fetal

squames, lanugo hairs within blood vessels

Reduces the movement of fluid into vessels due to loss of

albumin such as nephrotic syndrome. Exacerbated by salt and
water retention and net movement is into the interstitium
Subtle cell swelling with separation of ECM
Edema of the solid organs

Pulmonary edema (lungs enlarged by 2- 3x)

Subcutaneous edema
Brain edema
Brain is grossly swollen with narrowed sulci and distended gyri
flattened against the skull.
Hemorrhage
Rupture of the large artery and veins

Capillary bleeding
1. Petechiae
2. Purpura
3. Ecchymoses
4. Large accumulations of blood in the body
Purpura

petechiae

ecchymoses

Macrophages
Hemoglobin bilirubin and biliverdin hemosiderin (goldenbrown) changes of color of the bruise
volume and rate of blood loss
Embolism

99%
Fat, gas bubbles, atherosclerotic debris, tumor fragments,
bone marrow, foreign bodies
1. Thromboembolism
2. Fat
3. Gas
4. Amniotic fluid
Amniotic fluid

HEMODYNAMIC DISORDERS: THROMBOSIS AND SHOCK

Dr. WALTER

PATHOLOGY REVIEWER

.
QUESTIONS

The active process with augmented blood flow

caused by arteriolar dilatation.
What happens to tissue with hyperemia?
What is congestion?
Isolated venous obstruction may cause ____
Systemic venous obstruction causes _____
What is cyanosis?
Stasis of deoxygenated blood long enough can
cause?
Morphology of hyperemia and congestion.

This morphology is commonly associated with

edema
Chronic congestion is characterized by ____

In chronic congestion of the lungs, it typically

involves ___
Differentiate acute and chronic lung congestion

Congestion of the liver usually involves ____

Differentiate acute and chronic congestion of the
liver.

The condition of increased in fluid in the interstitial

tissue spaces or body cavities
What are the two pathologic categories of
edema?
Non- inflammatory causes

Increased hydrostatic pressure causes fluid to __

this obstruction blocks the removal of the

interstitial fluid

ANSWERS

hyperemia
Tissues are redder owing to engorgement with oxygenated
blood
The passive process caused by impaired outflow from a tissue.
local congestion
CHF
The red blue color of the tissue when by prolonged and
deoxygenated hemoglobin accumulates
Hypoxia cell death
a. Acute congestion
b. Capillary bed congestion
c. Chronic congestion
Capillary bed congestion
Capillary rupture hemorrhage
Breakdown of RBC hemosiderin- laden macrophages
Tissue appears: BROWN
Parenchymal cell atrophy or death with scaring may be
present
Common in: LIVER and LUNGS
Left- sided heart failure
Acute: engorged capillaries and septal edema with transudate
in the air spaces
Chronic: edematous to fibrotic septa, presence of hemosiderinladen macrophages which are considered as heart- failure
cells
Right- sided heart failure or with hepatic vein or SVC
obstuction
Acute: distention of central veins and sinusoids
Chronic: red- brown central region of hepatic lobules (nutmeg
liver)
Microscopic: cenrilobular necrosis
With severe long- standing congestion: hepatic fibrosis
(cardiac cirrhosis)
Edema (may be localized or systemic)
Non- inflammatory (yields protein- poor transudate)
Inflammatory (yields protein- rich exudate)
a. Increased hydrostatic pressure
b. Decreased osmotic pressure
c. Primary sodium retention
d. Lymphatic obstruction
Fluid to get out of the vessels, CHF is the most common cause
of systemic edema
Lymphatic obstruction