CHAPTER 4

Hemodynamic Disorders,
Thromboembolism, and Shock
Hemostasis is the process of blood clotting that prevents excessive bleeding
after blood-vessel damage
o Inadequate hemostasis  hemorrhage, and if massive and rapid 
hypotension, shock and death

Inappropriate clotting (thrombosis) or migration of clots (embolism) can

iueobstruct blood vessels causing ischemic cell death (infarction)

HYPEREMIA AND CONGESTION – locally increased blood

volume in the organ or tissue due to hemodynamic disorders

Hyperemia is an active process resulting from arteriolar dilation and

increased blood inflow as occurs at sites of inflammation (pathologic) or in
exercising (physiologic) skeletal muscle
o Tissues are redder than normal (erythema)

Congestion is a passive process resulting from decreased outflow of venous

blood from a tissue as in cardiac failure
o Tissues are blue-red colour (cyanosis)
o Chronic congestion can lead to:
 parenchymal cell death and secondary tissue fibrosis
  Edema
 Focal hemorrhages

Look at the different

morphological features of acute lung conjestion, chronic lung congestion;

MORPHOLICAL CHANGES
ACUTE CHRONIC ACUTE HEPATIC CHRONIC HEPATIC
PULMONARY PULMONARY CONJESTIONS CONJESTIONS
CONJESTIONS CONJESTIONS

 Engorged  Thickened and  Central vein and  Central regions of

alveolar fibrotic septa sinusoids are hepatic lobules are red-
capillaries  Numerous distended with blood brown and slightly
 Very often septal hemosiderin-laden  Sometimes necrosis depressed (oweing to
edema macrophages (also of centrally located cell loss)  nutmeg
 Focal intra- called heart failure hepatocytes liver
alveolar cell)  Peripheral areas of
hemorrhage  Peripheral hepatic lobules
hepatocytes may yellowish (because of
develop fatty change fatty change)
 Much firmer due to
fibrosis

EDEMA
 an abnormal increase in interstitial fluid; fluid collections in intercellular
spaces and different body cavities
 Types
o Focal or generalized
o Inflammatory or non-inflammatory
 Extravascular fluid can also collect in body cavities  effusions. Examples
include effusions in:
o Pleural cavity  hydrothorax
o Pericardial cavity  hydropericardium
o Peritoneal cavity  hydroperitoneum or ascites
(The term "edema" refers to the abnormal accumulation of fluid in the
interstitial spaces of tissues or in body cavities. Effusion, on the other hand,
specifically refers to the collection of fluid in body cavities such as the pleural,
pericardial, or peritoneal cavities. Effusions are a subset of edema, occurring
within the confines of these cavities.)

 Anasarca is a severe generalized edema marked by profound swelling of

subcutaneous tissues and accumulation of fluid in body cavities
 Excess edema is removed by lymphatic drainage and is returned to the blood
stream through the thoracic duct
 The edema fluid that accumulates in the setting of increased hydrostatic
pressure or reduced intravascular colloid typically is a protein-poor
transudate; by contrast, because of increased vascular permeability,
inflammatory edema fluid is a protein-rich exudate with a high specific
gravity.

CAUSES OF
EDEMA 

INCREASED HYDROSTATIC PRESSURE

Causes of Increased Hydrostatic Pressure

 Increases in hydrostatic pressure are mainly caused by disorders that impair
venous return
 Localized - causes include deep venous thrombosis (DVT) causing edema in
affected limbs.
 Generalized - in congestive heart failure leading to systemic edema.

Mechanisms in Congestive Heart Failure

 Congestive heart failure reduces heart's pumping ability, causing venous
congestion.
 Increased capillary hydrostatic pressure in tissues, leading to fluid leakage.
 Reduced cardiac output triggers renal sodium and water retention (secondary
hyperaldosteronism). The heart struggles to increase cardiac output which
sets up a cycle of fluid retention, increased venous pressure, and worsening
edema.

Management of Generalized Edema

Strategies for generalized edema management:
 Diuretics to remove excess sodium and water.
 Salt restriction to reduce water retention.
 Aldosterone antagonists to block the effects of aldosterone.

REDUCED PLASMA OSMOTIC PRESSURE

Reduction of plasma albumin concentrations leads to decreased colloid osmotic
pressure of the blood and loss of fluid from the circulation

Causes of Reduced Plasma Osmotic Pressure:

 Nephrotic Syndrome: This syndrome, characterized by leaky glomerular
capillaries in the kidneys, results in the loss of albumin and other proteins in
the urine, leading to generalized edema.
 Liver Disease (e.g., Cirrhosis): Severe liver disease can reduce albumin
synthesis, contributing to reduced plasma osmotic pressure.
 Protein Malnutrition: Inadequate protein intake can lead to lower albumin
levels.

Consequences of Reduced Albumin:

Reduced albumin levels lead to a stepwise sequence of events:
 edema, decreased blood volume, reduced kidney perfusion, and secondary
hyperaldosteronism.
 Hyperaldosteronism results in increased salt and water retention by the
kidneys  which worsens edema

LYMPHATIC OBSTRUCTION
Edema may result from lymphatic obstruction that compromises resorption
(removing) of fluid from interstitial spaces.

Causes of Lymphedema
Lymphedema commonly results from conditions such as inflammation or
tumors. These conditions can obstruct the flow of lymphatic fluid, leading to
swelling.

Examples:
Filariasis: This parasitic infection can lead to massive edema in the lower
extremities and external genitalia, a condition known as "elephantiasis." It does
so by causing fibrosis in inguinal lymphatic vessels and nodes.
Breast Cancer: Breast cancer can infiltrate and obstruct superficial lymphatics,
causing edema in the overlying skin. This results in a characteristic "peau
d’orange" appearance, resembling orange peel.
Therapeutic Complications: Lymphedema can also occur as a complication of
therapy. For instance, women with breast cancer who undergo axillary lymph
node removal or radiation therapy may experience lymphatic disruption and
severe lymphedema in the arm.

SODIUM AND WATER RETENTION

Sodium and water retention can lead to can lead to edema by increasing
hydrostatic pressure (because of expansion of the intravascular volume – means
more blood) and reducing plasma osmotic pressure.

CLINICAL FEATURES
Variability in Effects: Edema can range from being a minor annoyance to a
rapidly fatal condition.

Subcutaneous Edema:

 Important for recognizing underlying cardiac or renal diseases.

 Can impair wound healing and the body's ability to clear infections when
significant.

Pulmonary Edema:
 Commonly associated with left ventricular failure.
 ls seen in renal failure, acute respiratory distress syndrome, and lung
inflammatory and infectious disorders.
 Interferes with normal breathing, hinders oxygen diffusion, and promotes
infection within the lungs.
 Complications pneumonia, respiratory distress, longstanding-death

Brain Edema:
 Life-threatening condition
 Severe brain swelling can cause herniation (extrusion) through the foramen
magnum.
 Increased intracranial pressure can compress the brain stem's vascular
supply, potentially leading to death due to injury to vital centers controlling
functions like respiration.

MORPHOLOGY

Gross Inspection: Edema is easily recognizable through visual examination. It

appears as swelling and can be observed by the naked eye.

Microscopic Examination: Microscopic examination reveals clearing and

separation of the extracellular matrix (ECM) elements within the affected tissue.

Common Sites of Edema:

 Subcutaneous tissues
 Lungs
 Brain
 Dependent Edema:

Edema is most pronounced in body parts located farthest below the heart, where
hydrostatic pressures are highest. Thus, edema typically is most pronounced in
the legs with standing and the sacrum with recumbency, a relationship termed
dependent edema. This is known as "dependent edema."

Pitting Edema:
When pressure is applied to edematous subcutaneous tissue, it displaces
interstitial fluid, leaving a depression that can be indented by finger pressure.

Specific Types of Edema:

 Edema resulting from renal dysfunction or nephrotic syndrome often
first manifests in loose connective tissues, such as the eyelids, causing
periorbital edema.
 Pulmonary edema leads to increased lung weight and contains frothy fluid
consisting of air, edema fluid, and red blood cells.
 Brain edema can be localized or generalized, depending on the nature and
extent of the underlying pathological process or injury. With generalized
edema, the gyri of the brain swell and flatten against the skull, narrowing the
sulci.

HEMORRHAGE
Defined as the extravasation (leakage) of blood from vessels and is most often
the result of damage to blood vessels or defective clot formation

Causes of Hemorrhage:

 Capillary bleeding can occur in chronically congested tissues.

 Trauma, atherosclerosis, and inflammatory or neoplastic (related to tumor
growth) erosion of blood vessel walls can also lead to hemorrhage.
  Hemorrhagic Diatheses: refer to conditions or disorders that predispose
individuals to bleeding tendencies or a propensity for hemorrhage
(bleeding). These disorders have diverse causes, including inherited or
acquired defects in vessel walls, platelets, or coagulation factors, which
are necessary for proper blood clotting.

Clinical Features of Hemorrhages:

 Large bleeds into body cavities are described variously according to
location— hemothorax, hemopericardium, hemoperitoneum, or
hemar- throsis (in joints). Extensive hemorrhages can occasionally
result in jaundice from the massive breakdown of red cells and
hemoglobin.
 Petechiae: Minute (1 to 2 mm) hemorrhages into skin, mucous
membranes, or serosal surfaces. Causes include low platelet counts,
defective platelet function, and loss of vascular wall support.
 Purpura: Slightly larger (3 to 5 mm) hemorrhages that can result from
various disorders, including those causing petechiae, trauma, vascular
inflammation (vasculitis), and increased vascular fragility.
 Ecchymoses: Larger (1 to 2 cm) subcutaneous hematomas, commonly
referred to as bruises. The color changes in a bruise result from the
enzymatic conversion of hemoglobin to bilirubin and eventually
hemosiderin.

Clinical Significance:
The clinical significance of a hemorrhage depends on the volume of blood lost
and the rate of bleeding. The site of hemorrhage is also critical; bleeding in the
brain, for example, can be life-threatening. Chronic or recurrent external blood
loss can lead to iron deficiency anemia due to the loss of iron in hemoglobin,
while internal bleeding (e.g., a hematoma) does not lead to iron deficiency
because iron is efficiently recycled from phagocytosed red cells.

HEMOSTASIS AND THROMBOSIS

NORMAL HEMOSTASIS
Hemostasis involves platelets, clotting factors and endothelium that occurs at
the site of vascular injury and culminates in the formation of blood clot, which
prevents or limits the extent of bleeding

Below is the sequence of events leading to hemostasis at a site of vascular

injury:

Arteriolar Vasoconstriction:
 Immediate vasoconstriction of arterioles occurs in response to vascular
injury. This reduces blood flow to the injured area, significantly
diminishing hemorrhage. It is mediated by reflex neurogenic mechanisms
and local secretion of vasoconstrictors like endothelin.

Primary Hemostasis - Formation of the Platelet Plug:

 Endothelial disruption exposes subendothelial factors, including von
Willebrand factor (vWF) and collagen, which promote platelet
adherence and activation.

 Activated platelets undergo a dramatic shape change and release

secretory granules that recruit additional platelets.
  Aggregation of platelets results in the formation of a primary hemostatic
plug.

Secondary Hemostasis - Deposition of Fibrin:

 Vascular injury exposes tissue factor at the injury site.
 Tissue factor (membrane-bound procoagulant glycoprotein) activates
factor VII, initiating a cascade of reactions leading to thrombin
generation.
 Thrombin cleaves fibrinogen into insoluble fibrin, forming a fibrin
meshwork.
 Thrombin is also a potent platelet activator, leading to further platelet
aggregation.
 Secondary hemostasis consolidates the initial platelet plug.

Clot Stabilization and Resorption:

 Polymerized fibrin and platelet aggregates undergo contraction, forming a

solid, permanent plug that prevents further hemorrhage.
 Counterregulatory mechanisms, such as tissue plasminogen activator (t-
PA) produced by endothelial cells, limit clotting to the site of injury.
Normal endothelial cells express
anticoagulant factors that inhibit
platelet aggregation, coagulation, and
promote fibrinolysis. However, when
activated or injured, this balance shifts,
and they adopt procoagulant activities,
including the activation of platelets and
clotting factors.

PLATELETS
Function: Platelets play a crucial role
in hemostasis by forming the primary
plug that initially seals vascular defects
and by providing a surface for binding
and concentrating activated
coagulation factors.

Structure: Platelets are disc-shaped,

anucleate cell fragments originating
from megakaryocytes in the bone
marrow. They possess glycoprotein
receptors, a contractile cytoskeleton, and two types of cytoplasmic granules: α-
granules and dense (or δ) granules.

Granules Content: α-Granules contain various proteins involved in

coagulation (e.g., fibrinogen, coagulation factor V), wound healing (e.g.,
fibronectin, platelet factor 4), and growth factors (e.g., PDGF, transforming
growth factor-β). Dense granules contain ADP, ATP, ionized calcium,
serotonin, and epinephrine.

Platelet Activation Sequence:

 Adhesion: Platelets adhere to subendothelial connective tissue

constituents (e.g., vWF and collagen). vWF acts as a bridge between
platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen.
 Shape Change: Platelets rapidly change shape from smooth discs to
spiky "sea urchins" with increased surface area. This change is
accompanied by increased affinity of glycoprotein IIb/IIIa for fibrinogen.
 Secretion (Release Reaction): Platelet activation involves the secretion
of granule contents, triggered by factors like thrombin and ADP.
Thrombin activates platelets through protease-activated receptors (PAR).
ADP release leads to recruitment and additional platelet activation.
 Platelet Aggregation: Conformational changes in glycoprotein IIb/IIIa
during activation allow binding of fibrinogen, which bridges adjacent
platelets and leads to their aggregation.
 Platelet Contraction: Platelets contract, dependent on the cytoskeleton,
consolidating the aggregated platelets.
 Thrombin: Concurrent activation of thrombin stabilizes the platelet plug
by causing further platelet activation and aggregation, promoting
 irreversible platelet contraction. Thrombin also converts fibrinogen into
insoluble fibrin, cementing the platelets in place and creating the
definitive secondary hemostatic plug.

Additional Components: Hemostatic plugs may also contain entrapped red

blood cells and leukocytes due to the adherence of leukocytes to P-selectin
expressed on activated platelets.

IMPORTANT!

Summary

 Endothelial injury exposes the

underlying basement membrane
ECM; platelets adhere to the ECM
primarily through the binding of
platelet GpIb receptors to VWF.
 Adhesion leads to platelet
activation, an event associated with
secretion of platelet granule
contents, including calcium (a
cofactor for several coagulation
proteins) and ADP (a mediator of
further platelet activation);
dramatic changes in shape and
membrane composition; and
activation of GpIIb/IIIa receptors.
 The GpIIb/IIIa receptors on
activated platelets form bridging
crosslinks with fibrinogen, leading
to platelet aggregation.
 Concomitant activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.
COAGULATION CASCADE

From page 104 – 106

I skipped :’)

ENDOTHELIUM

Antithrombotic Properties of Endothelium:

The endothelium's role in maintaining hemostasis is crucial, as it helps prevent
inappropriate clot formation, propagation, or dissolution. This balance between
anticoagulant and procoagulant activities of endothelium is essential in
determining clotting outcomes.

Platelet Inhibitory Effects:

Barrier Function: Intact endothelium serves as a barrier that shields platelets

from subendothelial components such as von Willebrand factor (vWF) and
collagen. Release of Inhibitory Factors:
 Prostacyclin (PGI2): Endothelium produces prostacyclin, which inhibits
platelet activation and aggregation.
 Nitric Oxide (NO): Nitric oxide released by endothelial cells also
inhibits platelet activity.
 Adenosine Diphosphatase: This enzyme degrades ADP, a potent
activator of platelet aggregation.
  Thrombin Regulation: Endothelial cells can bind and modulate the
activity of thrombin, a potent platelet activator.

Anticoagulant Effects:

 Coagulation Factor Shielding: Normal endothelium protects

coagulation factors from tissue factor in vessel walls.
 Expression of Anticoagulant Factors: Endothelial cells express
multiple factors that actively oppose coagulation, including:
 Thrombomodulin: Binds thrombin, rendering it unable to activate
coagulation factors and platelets. Instead, thrombin activates protein C,
which, with protein S as a cofactor, inhibits coagulation factors Va and
VIIIa.
 Endothelial Protein C Receptor: Binds protein C and contributes to the
inhibition of coagulation.
 Heparin-like Molecules: These molecules on the endothelial cell surface
activate antithrombin III, which then inhibits various coagulation factors.
 Tissue Factor Pathway Inhibitor (TFPI): Requires protein S as a
cofactor and binds and inhibits tissue factor/factor VIIa complexes.
Fibrinolytic Effects:
 Tissue Plasminogen Activator (t-PA): Normal endothelial cells synthesize
tissue plasminogen activator (t-PA), a key component of the fibrinolytic
pathway, which plays a role in dissolving blood clots.

THROMBOSIS
Causes of intravascular thrombosis: (VIRCHOW’S TRIAD!)
 Endothelial injury
  Stasis or turbulent blood flow
 Hypercoagulabity
Saddle embolus and massive embolus??

ENDOTHELIAL INJURY

Prothrombotic Alterations in Endothelial Activation:

 Activated endothelial cells downregulate key modulators like
thrombomodulin, sustaining thrombin activation.
  This, in turn, stimulates platelets and exacerbates inflammation through
protease-activated receptors (PARs).
 Endothelial activation also reduces the expression of other anticoagulants
like protein C and tissue factor pathway inhibitor, promoting a
procoagulant state.

Anti-fibrinolytic Effects:
 Activated endothelial cells release plasminogen activator inhibitors (PAI),
limiting fibrinolysis and downregulating tissue-type plasminogen
activator (t-PA), favoring clot development.

ABNORMAL BLOOD FLOW

Turbulence (chaotic blood flow) contributes to arterial and cardiac thrombosis

by causing endothelial injury or dysfunction, as well as by forming
countercurrents and local pockets of stasis.

Turbulent and Stagnant Blood Flow in Clinical Settings:

Ulcerated Atherosclerotic Plaques: These plaques not only expose

subendothelial extracellular matrix (ECM) but also cause turbulent blood flow,
increasing the risk of thrombosis.

Abnormal Aortic and Arterial Dilations (Aneurysms): Aneurysms create

local stasis in blood flow, making them fertile sites for thrombosis.

Acute Myocardial Infarction: Focally noncontractile myocardium results from

acute myocardial infarction. Ventricular remodeling after remote infarction can
lead to aneurysm formation. In both cases, local blood stasis makes cardiac
mural thrombi more likely.

Mitral Valve Stenosis: Mitral valve stenosis, often occurring after rheumatic
heart disease, leads to left atrial dilation. When combined with atrial fibrillation,
the dilated atrium promotes stasis and is a prime location for thrombus
development.

Hyperviscosity Syndromes (e.g., Polycythemia Vera): Conditions like

polycythemia vera increase resistance to blood flow, causing small vessel stasis,
which raises the risk of thrombosis.

Sickle Cell Anemia: Deformed red cells in sickle cell anemia cause vascular
occlusions, leading to stasis and an increased predisposition to thrombosis.

HYPERCOAGULABILITY

Hypercoagulability refers to an abnormally high tendency of blood to clot, often

due to alterations in coagulation factors.
Primary (Inherited) Hypercoagulability:
  Factor V Leiden Mutation: Specific factor V mutation found in 2% to
15% of white individuals. Renders factor V resistant to protein C's
inhibitory action, increasing the risk of venous thrombosis.
 Prothrombin Gene Variant: A single-nucleotide substitution in the
prothrombin gene's 3'-untranslated region increases prothrombin
transcription and the risk of venous thrombosis.
 Elevated Homocysteine: High levels of homocysteine are associated
with both arterial and venous thrombosis, potentially due to thioester
linkages formed with various proteins, including fibrinogen.
 Deficiencies of Anticoagulants: Rare inherited deficiencies of
anticoagulants like antithrombin III, protein C, or protein S increase the
risk of venous thrombosis, usually in adolescence or early adulthood.

Secondary (Acquired) Hypercoagulability:

 Various clinical settings can lead to secondary hypercoagulability,

including stasis or vascular injury in conditions such as cardiac
failure or trauma.
 Conditions like oral contraceptive use and pregnancy can elevate
hepatic synthesis of coagulation factors, contributing to
hypercoagulability.
 Disseminated cancers release procoagulant tumor products, predisposing
to thrombosis.
 Advanced age is linked to increased platelet aggregation and reduced
release of PGI2, promoting hypercoagulability.
 Heparin-Induced Thrombocytopenia (HIT) Syndrome:
Autoantibodies develop in response to heparin treatment, leading to a
 prothrombotic state and thrombocytopenia. Newer low-molecular-weight
heparins induce antibodies less frequently.
 Anti-Phospholipid Antibody Syndrome: Also known as the lupus
anticoagulant syndrome, it causes recurrent thromboses, repeated
miscarriages, and other clinical manifestations. Antibodies interfere with
phospholipids and promote a hypercoagulable state through uncertain
mechanisms.

Note: Anti-phospholipid antibody syndrome can be primary (occurring

without other autoimmune disorders) or secondary (associated with
autoimmune diseases like lupus). It's treated with anticoagulation and
immunosuppression.

MORPHOLOGY OF THROMBI

 Thrombi can form anywhere in the cardiovascular system.

 Arterial or cardiac thrombi usually develop at sites with endothelial injury
or turbulence, while venous thrombi often occur at sites of stasis.
 Arterial thrombi grow in a retrograde direction from the point of
attachment, whereas venous thrombi extend in the direction of blood flow.
 Thrombi can be distinguished by the presence of lines of Zahn, which are
grossly and microscopically apparent laminations composed of alternating
pale platelet and fibrin layers and darker red cell-rich layers.
o These lines of Zahn are only found in thrombi that form in flowing
blood, allowing the distinction of antemortem thrombosis from
postmortem clots.
 Thrombi that occur in heart chambers or the aortic lumen are termed mural
thrombi and can result from abnormal myocardial contraction or
 endomyocardial injury (e.g., myocarditis or catheter trauma), while
ulcerated atherosclerotic plaques and aneurysmal dilation can promote
aortic thrombosis. – (aortic thrombi originates from aorta itself whereas
mural thrombi in aorta is secondary -get it?)
 Arterial thrombi are typically occlusive and rich in platelets, often
associated with ruptured atherosclerotic plaques or other vascular injuries.
 Venous thrombi are almost always occlusive and may propagate some
distance toward the heart, giving rise to emboli; they are characterized by
a higher proportion of enmeshed red cells and are often referred to as red or
stasis thrombi.
 At autopsy, postmortem clots can be distinguished from venous thrombi by
their gelatinous appearance, dark red dependent portion, yellow upper
portion, and lack of attachment to the vessel wall.
 Thrombi on heart valves are termed vegetations and can be caused by
bacterial or fungal infections (infective endocarditis) or sterile conditions
in hypercoagulable states (nonbacterial thrombotic endocarditis) or
autoimmune diseases like systemic lupus erythematosus (Libman-Sacks
endocarditis).

I skipped end of page 110 and whole of page

111

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

 Sudden or insidious onset

 Can be seen in obstetric complications, advanced malignancy etc.
 Widespread microvascular thrombosis consumes platelets and coagulation
proteins and SIMULTANEOUSLY fibronolytics are activated
o Therefore excessive clotting and bleeding co-exist!

EMBOLISM

An embolus is a detached intravascular solid, liquid or gaseous mass that is

carried by the blood from its point of origin to a distant site, where it often
causes tissue dysfunction and infarction
 Majority are from dislodged thrombus, therefore 
thromboembolism
 The primary consequence of systemic embolization is ischemic necrosis
(infarction) of downstream tissues, whereas embolization in the pulmonary
circulation leads to hypoxia, hypotension, and right-sided heart failure.

PULMONARY THROMBOEMBOLISM
These originate from deep venous thromboses (DVT) (mainly deep leg veins
located proximal to the popliteal fossa) and are the most common form of
thromboembolic disease.
Path of emboli: Fragmented thrombi from DVTs are carried through
progressively larger channels and typically pass through the right side of the
heart before lodging in the pulmonary vasculature.
Variability: Depending on their size, a PE can occlude the main pulmonary
artery, get lodged at the bifurcation of the right and left pulmonary arteries
(saddle embolus), or enter smaller branching arterioles.
Multiple emboli: Often, multiple emboli can occur, either sequentially or as a
shower of smaller emboli from a single large thrombus. Patients who have had
one pulmonary embolus are at an increased risk of having more.
Paradoxical embolism: Rarely, an embolus can pass through an atrial or
ventricular defect and enter the systemic circulation.

Clinical and pathological features:

 Most pulmonary emboli (60%–80%) are small and clinically silent. Over
time, they can undergo organization and become incorporated into the
vascular wall, sometimes leaving bridging fibrous webs.
 On the other end of the spectrum, a large embolus that blocks a major
pulmonary artery can cause sudden death.
 Embolic obstruction of medium-sized arteries and subsequent rupture of
downstream capillaries can lead to pulmonary hemorrhage. Pulmonary
infarction is rare in such cases because the area also receives blood
through an intact bronchial circulation (dual circulation).
 In cases where bronchial artery perfusion is diminished, such as in the
setting of left-sided cardiac failure, a similar embolus can result in a
pulmonary infarct.
 Embolism to small end-arteriolar pulmonary branches usually causes
infarction.
 Multiple emboli occurring over time can lead to pulmonary
hypertension and right ventricular failure, known as cor pulmonale.

SYSTEMIC THROMBOEMBOLSIM

Origin of Systemic Emboli:

 About 80% of systemic emboli arise from intracardiac mural thrombi.
 o Two-thirds of these are associated with left ventricular infarcts.
 Another 25% are associated with dilated left atria, often due to conditions
like mitral valve disease.
 The remaining systemic emboli can originate from sources such as aortic
aneurysms, thrombi on ulcerated atherosclerotic plaques, fragmented
valvular vegetations (covered in Chapter 11), or the venous system in
cases of paradoxical emboli.
Destination of Systemic Emboli:
 Unlike venous emboli, which often lodge in the lungs, arterial emboli can
travel to various parts of the body.
o Common sites of arteriolar embolization include the lower
extremities (about 75%) and the central nervous system
(approximately 10%).
o Less common targets for embolization are the intestines, kidneys,
and spleen.
The consequences of embolization depend on factors like
 the size of the occluded vessel,
 the presence of collateral blood supply
 the tissue's vulnerability to oxygen deprivation.

SKIPPED PAGE 113 and 114 FAT EMBOLISM,

AMNIOTIC FLUID EMBOLISM AND AIR EMBOLISM
INFARCTION AND SHOCK LEFT
The stages of shock

The stages of shock are typically categorized into four main phases:

. Initial or Non-Progressive Stage (Compensated Shock):

• This stage is characterized by the body's initial response to a
shock-inducing event.
• The body activates compensatory mechanisms to maintain
blood pressure and tissue perfusion.
• Signs and symptoms may be subtle, such as increased heart
rate and mild vasoconstriction.
• Oxygen and nutrients are redirected to vital organs.
. Non-Progressive or Compensated Shock:
• In this stage, the body's compensatory mechanisms are no
longer sufficient to maintain adequate tissue perfusion.
• Cellular oxygen demand exceeds supply, and anaerobic
metabolism begins, leading to lactic acidosis.
• Clinical signs become more evident, including increased heart
rate, rapid breathing, and altered mental status.
• Treatment at this stage can still reverse shock and prevent
progression.
. Progressive Stage:
• During this phase, shock continues to worsen as compensatory
mechanisms fail.
• Widespread tissue hypoxia and organ dysfunction occur.
• Hemodynamic instability is marked by a severe drop in blood
pressure, weak pulses, and cool, clammy skin.
• Immediate intervention is critical to prevent irreversible
damage.
. Refractory Stage:
• The refractory stage represents the most advanced and severe
form of shock.
• Organ failure is extensive, and even aggressive medical
intervention may not reverse the process.
• Mortality rates are high at this stage, and death is a significant
risk.