BETHY S HERNOWO

The health and well being of cells and tissue

depends not only on intact circulation to
deliver oxygen, also on normal fluid
homeostasis.
Abnormalities in either blood supply or fluid
balance are result in morbidity/mortality.
The pathologies include edema, vascular
congestion, hemorrhage, thrombosis,
embolism, infarction and shock.
EDEMA
Approximately 60% of lean body weight is water,
two thirds of which is intracellular and one third is
extracellular.
Edema signifies increased fluid in the interstitial
tissue space.
In general caused by vascular hydrostatic pressure
and plasma colloid osmotic pressure.
Pathophysiologic Categories of Edema
Increased Hydrostatic Pressure :
•Impaired heart failure (Congestive heart failure,Constrictive
pericarditis,Ascites)
•Arteriole Dilatation (Heat, Neurohumoral dysregulation)

Reduced Plasma Osmotic Pressure (Hypoproteinemia):

•Protein-losing glomerulopathies (nephrotic syndrome)
•Liver cirrhosis (ascites)
•Protein-losing gastroenteropathy

Lymphatic Obstruction :
(Inflammatory, neoplastic, postsurgical and post radiation)
Sodium Retention :
•Excessive salt intake with renal insufficiency
•Increased tubular reabsorption of sodium

Inflammation :
(Acute and chronics inflammation)
 Systemic edema in heart failure

Malnutrition
↓ Hepatic Synthesis
Nephrotic Syndrome

Heart Failure ↓ Plasma oncotic pressure

↑ CVP ↑ COP ↓ Blood volume

↑ Capillary ↓ Effective arterial ASCITES

Pressure blood volume Other effusions

↑ Renal vasoconstriction ↑ Renin

↑ Tubular ↓ GFR ↑ Aldosteron

reabsorption
of Na + H2O ↑ Angiotensin II ↑ Renal Na ↑ ADH
reabsorption

↑ Renal retention ↑ Renal retention

of Na + H2O of water
↑ Plasma volume

↑ Transudation

EDEMA
Morphology
Substle cell swelling, with clearing and separation of
the extracellular matrix element.
Most commonly encountered in subcutaneous
tissues, the lungs and the brain.
Subcutaneous edema maybe diffuse or occur
where hydrostatic pressure are greatest. Ex. Edema
in CHF
Edema resulting from hypoproteinemia is
generally more severe & diffuse, it is most evident
in loose connective tissue
Edema in solid organs result in increased size &
weight
Brain edema may be localized to sites of injury or
maybe generalized
HYPEREMIA AND CONGESTION

Indicate a local increase volume of blood in

particular tissue.
Hyperemia is an active process due to augmented
blood inflow caused by arteriolar dilatation or
inflammation.
Congestion is an passive process resulting from
impaired outflow from a tissue.
ology
In acute congestion vessel are distended, organ are
grossly hyperemic
In chronic congestion capillary rupture may cause focal
hemorrhage, subsequent erythrocytes breakdown result
s in hemosiderin-laden macrophage. Parenchymal cell
atrophy or death may also present
Grossly tissue s appear brown, contracted & fibrotic
Example:
Acute pulmonary congestion : alveolar capillaries
engorged with blood. Chronic pulmonary
congestion : thickened and fibrotic septa, and
alveolar space contain hemosiderin-laden
macrophage.
Acute hepatic congestion : central vein and
sinusoids distended with blood and central
hepatocytes degeneration. Chronic passive
congestion : centrilobular necrosis and
hemosiderin – laden macrophages.
HEMORRHAGE
Indicate extravasation of blood because of vessel
rupture.
Rupture of a large artery or vein, is almost due to
vascular injury, including trauma, atherosclerosis,
inflammatory and neoplastic erosion of the vessel
wall.
The referred accumulation known as
hematoma.
Ø 1-2 mm into skin, mucous membranes or
serosal surface are called petechiae.
Ø ≥ 3mm called purpura.
Larger/> 1 to 2 cm called ecchymosis.
Erythrocytes degraded and phagocytosed by
macrophages.
Large accumulations : hemothorax,
hemopericardium, hemoperitoneum, and
hemarthrosis.
Erythrocytes in hemorrhages are degraded by
macrophages
The hemoglobin is converted to bilirubin (red-blue
color)& biliverdin (blue-green color) and eventually to
hemosiderin (golden brown color), accounting for the
characteristic color changes in bruise
Clinical significance of hemorrhage depends on the
volume & rate of blood loss
Greater loss > 20% of blood result in hypovolemic
shock
HEMOSTASIS & THROMBOSIS
Normal hemostasis accomplish two important
functions : (1) maintain blood in a fluid and (2) rapid
and localized hemostasis plug at a site of vascular
injury.
Both hemostasis and thrombosis depend on : vascular
wall, platelets and the coagulation cascade.
Normal Hemostasis
A. Vasoconstriction
Injury reflex neurogenic mechanism and local secretion
endothelin factors vasoconstrictor.
B. Primary Hemostasis
Exposes highly thrombogenic subendothelial extracellular
matrix activated platelets secretory granules

hemostatic plug.
C. Secondary Hemostasis
Exposes tissue factors conjunction with platelet factors
activate coagulation cascade. Thrombin convert fibrinogen to
insoluble fibrin deposition fibrin platelet plug
enlargement.
D. Thrombus and Antithrombotic Events
Polimerized fibrin and platelet agregates permanent
plug to prevent any further hemorrhage.
After injury, there is a characteristic hemostatic
response:
Reflex neurogenic arteriolar vasoconstriction is
augmented by endothelin
Platelet adhesion & activation are promoted by
exposed subendothelial extracellular matrix (ECM)
Activation of the coagulation cascade is driven by
tissue factor, a membrane-bound lipoprotein
procoagulant factor synthesized by endothelium &
exposed after injury
Activation of counter-regulatory mechanism ex.
Tissue plasminogen activator (t-PA) restrict the
hemostatic plug to site of injury
 Endothelium
Endothelial cells (EC) modulate several aspects of
hemostasis including antiplatelet, anticoagulant &
fibrinolytic properties.
After injury or activation endothelial cells exhibit
procoagulation function
The balance between EC anti- and prothrombotic
activities determines whether trombus formation,
propagation, or dissolution
 Platelet
Crucial for normal hemostasis & thrombosis
After vascular injury, platelets encounter ECM constituents
(collagen, proteoglycans, fibronectin & other adhesive
glycoproteins) normally sequestered beneath an intact
endothelium.
Platelets than undergo activation involving adhesion &
shape change, release secretion and aggregation
 Platelet
Platelet-ECM adhesion is mediated through von Willebrand
factor acting as a bridge between platelet receptors &
exposed collagen
Platelet granule secretion (release reaction) occurs shortly
after adhesion. granules express P-selectin adhesion
molecules & contain coagulation factors
Platelet aggregation is promoted by ADP and tromboxane
A2
 Platelet
Platelet aggregation creates primary hemostatic plug,
which is reversible. Activation of the coagulation
cascade generates thrombin & fibrin to form an
irreversibly fused mass of platelets & fibrin constituting
the secondary hemostatic plug
Erythrocytes & leucocytes also aggregate in
hemostatic plug.
Thrombosis
Thrombus formation (Virchow’s Triad) :
Endothelial Injury

Thrombosis

Abnormal Hypercoagulability
Blood Flow
 Thrombosis

1. Endothelial injury is dominant and can cause

thrombosis. Thrombosis result from exposed
subendothelial ECM & tissue factor, adherence
platelets & depletion of prostaglandin I2 and PAIs
2. Alteration in normal blood flow can cause thrombosis.
Normal blood flow is laminar, disrupt of this flow
bring platelets into contact with the endothelium
3. Hypercoagulability contributes less frequently to
thrombotic states but is important in certain states
Morphology
Arterial thrombi are usually occlusive,
superimposed on an atherosclerotic plaque,
adherent to the arterial wall and gray-white,
composed of platelets, fibrin, erythrocytes and
degenerating leukocytes.
Venous thrombosis almost in variable occlusive,
contain more erythrocytes (red thrombi).
Thrombi may also form on heart valves. In infective
endocarditis organism from large infected
thrombotic masses causing underlying valve
damage & systemic infection
 Fate of the Thrombus

If a patient survive the immediate effects of a thrombus,

some combination occurs:
Propagation causing complete vessel obstruction
Embolization to other sites in the vasculature is especially
common with lower extremity venous thrombi embolizing
to the lung
Dissolution by fibrinolytic activity
Organization & recanalization, reestablishing flow by
ingrowth on endothelial cells
EMBOLISM
Is a detached intravascular solid, liquid or
gaseous that is carried by the blood to a site
distant from its point of origin.
99% from dislodged thrombus (thrombo
embolism).
Caused disturbance vessel passage
partial/complete vascular occlusion
ischemic necrosis distal tissue/infarction.
Type of Embolism
1. Pulmonary Thromboembolism
95% from deep leg vein thrombi above the
level knee. May occlude the main pulmonary
artery, Bifurcation (saddle embolus) and
smaller branching arterioles.
2. Systemic Thromboembolism
Gain access to systemic circulation
(paradoxical embolism). 80% arise from
intracardiac mural thrombi, 2/3 associated
with left ventricular wall infarcts and another
with dilated left atria. Cause infarction of
tissue due to obstructed vessel.
3. Fat Embolism
Microscopic fat globules in circulation after
fractures of long bone (rare by soft tissue trauma
and burns). Fat released by marrow and enter
the circulation via rupture of marrow vascular
sinusoids or of venules. Begin 1 to 3 days after
injury with sudden tachypne, dyspnea and
tachycardia. The microscopic found fat
microglobules.
4. Air Embolism
Gas bubbles within the circulatory can
obstruct vascular flow. In excess of 100 cc is
required to have a clinical effect. Induce
focal ischemia in a number of tissues.
5. Amniotic Fluid Embolism
Complication of labor and the imme-diate
postpartum period. Cause of amniotic fluid
embolism (squamous epithelial cell from
fetal skin, lanugo hair, fat from vernix
caseosa and mucin derived from the fetal
respiratory or gastrointestinal tract) into
maternal sirculation.
INFARCTION
Is an area ischemic necrosis caused by
occlusion of either the arterial supply or the
nervous drainage in a particular tissue.
Classified on the basis of their color :
Red infarcts (hemorrhagic) : venous
occlusions, loose tissue, dual circula- tion,
previously congested.
White infarcts (anemia) : arterial occlusion or
in slid organ.
Wedge-shaped with occlusion vessel, overlying
fibrinous exudate, irregular lateral margin, poorly
defined and slightly hemorrhagic.
In solid organ, extravasated red cells and lysed,
released hemoglobin to hemosiderin.
In spongy organs, hemorrhage too extensive and
became pale.
No demonstrable histologic in minutes to
hours. In 12 to 18 hours only present a
hemorrhage.
Within 1 or 2 days occurs necrotic material,
gradual degradation dead tissue, phagocytosis
cellular debris by neuthrophils and
macrophages.
Septic infarct occurs by fragmentation of a
bacterial vegetation and converted into an
abcess.
Factors That Influence Development of an
Infarct
i. The nature of the vascular supply.
ii. Rate of development of the occlusion.
iii. Vulnerability of a given tissue to hypoxia.
iv. Oxygen content of the blood.
SHOCK
Shock or cardiovascular collapse, is the final
common pathway for a number of potentially
lethal clinical events.
Constitutes systemic hypoperfusion owing to
reduction either in cardiac out put or in the
effective circulating blood volume.
End result : hypotension, impaired tissue
perfusion and cellular hypoxia/anoxia.
Three Major Types of shock
Type of Shock Clinical Examples Principal Mechanisms

CARDIOGENIC Myocardial infarction Failure of myocardial pump owing to

Ventricular rupture intrinsic myocardial damage, extrinsic
Arrhytmia pressure, or obstruction to outflow
Cardiac tamponade
Pulmonary embolism

HYPOVOLEMIC Hemorrhage Inadequate blood of plasma volume

Fluid loss

SEPTIC Overwhelming microbial Peripheral vasodilatation and pooling

infections of blood; endothelial activation/injury;
Gram positive septicemia leukocyte-induced damage; DIC ;
Fungal sepsis activation of cytokine cascades
Superantigens
Neurogenic shock, e.g. in the setting of anesthetic
accident or spinal cord injury. Loss of vascular
tone and peripheral pooling of blood.
Anaphylactic shock, initiated by a gene-ralized
IgE-mediated hypersensitivity response, is
associated with systemic vasodilatation and
increase vascular permeability.
Stages of Shock
1. An initial nonprogressive phase during which
reflex compensatory mechanisms are
activated and perfusion of vital organs is
maintained.
2. A progressive stage characterized by tissue
hypoperfusion and onset of worsening
circulatory and metabolic imbalances
including acidosis.
3. 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.
Morphology
Shock characterized by failure of multiple
organ systems.
At brain tissue called ischemic encephalopathy.
The heart undergo focal or widespread
coagulation necrosis, subendocardial
hemorrhage or contraction band necrosis.
The kidneys typically exhibit extensive tubular
ischemia injury (ATN) with oliguria, anuria and
electrolyte disturbances.
The lung seldom affected shock because
resistant to hypoxic injury. Unless at septic
shock, occurs diffuse alveolar damage (shock
lung).
The gastrointestinal tract : patchy mucosal
hemorrhages and necroses (hemorrhage
enteropathy).
The liver : fatty changed and central
hemorrhagic necrosis.