3. Objectives
• At the end of the class students are expected to
know about;
Know mechanism of edema,
Causes of hemorrhage,
Understand different types of shock,
Know about Virchow's triads of thrombosis.
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4. Introduction
• The health of cells and organs critically depends on
an unbroken circulation to deliver oxygen and
nutrients and to remove wastes.
• However, the well-being of tissues also requires
normal fluid balance
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5. Con’t…
• Changes in vascular volume, pressure, or protein
content, or alterations in endothelial function, all
affect the net movement of water across the vascular
wall.
• Such water extravasation into the interstitial spaces
is called edema.
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6. Con’t…
• Clotting at inappropriate sites (thrombosis) or
migration of clots (embolism) obstructs blood flow
to tissues and leads to cell death (infarction).
• Conversely, inability to clot after vascular injury
results in hemorrhage;
• Local bleeding can compromise regional tissue
perfusion, while more extensive hemorrhage can
result in hypotension (shock) and death.
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7. 1. Edema
• Approximately 60% of lean body weight is water;
two thirds of this water is intracellular, and
the remainder is found in the extracellular space,
mostly as interstitial fluid (only about 5% of total
body water is in blood plasma).
• The term edema signifies increased fluid in the
interstitial tissue spaces.
• Anasarca is a severe and generalized edema with
profound subcutaneous tissue swelling.
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8. Con’t…
• In general, the opposing effects of vascular
hydrostatic pressure and plasma colloid osmotic
pressure are the major factors that govern
movement of fluid between vascular and interstitial
spaces.
• Either increased capillary pressure or diminished
colloid osmotic pressure can result in increased
interstitial fluid === Edema.
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9. Con’t…
• Edema is most easily recognized grossly;
• Although any organ or tissue in the body may be
involved, edema is most commonly encountered in
subcutaneous tissues, the lungs, and the brain.
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10. Con’t…
Subcutaneous edema
• may have different distributions depending on the
cause.
• The edema distribution is typically influenced by
gravity and is termed dependent edema
• Edema of the dependent parts of the body (e.g., the
legs when standing, the sacrum when recumbent)
is a prominent feature of congestive heart failure,
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11. Con’t…
• Edema as a result of renal dysfunction or nephrotic
syndrome is generally more severe than cardiac
edema and affects all parts of the body equally.
It may, however, initially manifest itself in tissues
with a loose connective tissue matrix, such as the
eyelids;
Periorbital edema is a characteristic finding in
severe renal disease.
• Pitting edema= depression when pressure applied
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13. 2. Hemorrhage
• Hemorrhage, defined as the extravasation of blood
from vessels, is most often the result of damage to
blood vessels or defective clot formation.
• Hemorrhage may be manifested in a variety of
patterns, depending on the size, extent, and location
of bleeding.
• Hemorrhage may be external or may be enclosed
within a tissue;
• Accumulation of blood within tissue is referred to as
a hematoma.
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14. Con’t…
• 1- to 2-mm hemorrhages into skin, mucous membranes
are denoted as petechiae
• Slightly larger (≥3 mm) hemorrhages are called
purpura.
• Larger (>1 to 2 cm) subcutaneous hematomas are called
ecchymoses
• Large accumulations of blood in the body cavities are
called;
Hemothorax (in pleural cavity ),
Hemopericardium (in pericardial cavity ),
Hemoperitoneum ( in peritoneal cavity), or
hemarthrosis (in joints).
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15. Con’t…
• The clinical significance of hemorrhage depends on
the volume and rate of bleeding.
• Rapid loss of up to 20% of the blood volume or slow
losses of even larger amounts may have little impact
in healthy adults;
• Greater losses, however, may result in hemorrhagic
(hypovolemic) shock.
• The site of hemorrhage is also important;
Bleeding that would be trivial in the subcutaneous
tissues may cause death if located in the brain.
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16. Con’t…
• Finally, chronic or recurrent external blood loss
(e.g., due to peptic ulcer or menstrual
bleeding)frequently cause iron deficiency anemia as
a consequence of a loss of iron in hemoglobin.
• By contrast, iron is efficiently recycled from
phagocytosed red cells, so internal bleeding (e.g., a
hematoma) does not lead to iron deficiency.
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17. 3. Shock
• Shock is a state in which diminished cardiac output
or reduced effective circulating blood volume
impairs tissue perfusion and leads to cellular
hypoxia.
17
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20. A. Hypovolemic shock
• Definition: This is shock caused by reduced blood
volume.
•Causes of hypovolumic shock include:
a)Haemorrhage
b)Diarrhoea & vomiting
c)Burns
d)Trauma
20
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21. • Hypovolumic shock is the most common type of
shock in clinical medicine .
•A normal healthy adult can lose 550ml (10% of blood
volume) without significant symptoms.
•But loss of 25% or more of the blood volume
(N=1250ml) results in significant hypovolemia.
21
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22. B. Cardiogenic shock
• Definition: This is shock that results from severe
depression of cardiac performance.
• It primarily results from pump failure [myocardial
failure].
• Example of causes of cardiogenic shock :
–Acute Myocardial Infarction (MI)
–Cardiac Myopathy
22
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23. C. Distributive shock
• Definition: Distributive shock refers to a group of
shock subtypes caused by peripheral vasodilatation
despite normal or high cardiac output.
• Causes of distributive shock
1.Septic shock – the commonest among the group
2.Neurogenic shock
3.Anaphylactic shock
4.Endocrine shock
23
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24. Septic shock
• Caused by the host response to bacterial, viral or
fungal infections.
• Systemic inflammatory condition characterized by
Endothelial cell activation,
Tissue edema,
Disseminated intravascular coagulation, and
Metabolic derangements
24
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26. Stages of Shock
• Non progressive stage- reflex compensatory
mechanisms are activated and perfusion of vital
organs is maintained
• Progressive stage : tissue hypoperfusion and onset
of worsening circulatory and metabolic imbalances,
including lactic acidosis
• Irreversible stage: cellular and tissue injury severe
,survival is not possible
26
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27. 4. Hemostasis and Thrombosis
• Normal hemostasis comprises a series of
regulated processes that culminate in the
formation of a blood clot that limits bleeding
from an injured vessel.
• The pathologic counterpart of hemostasis is
thrombosis, the formation of blood clot
(thrombus) within non-traumatized, intact
vessels.
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30. Con’t..
• The pathologic opposite to hemostasis is thrombosis;
• Thrombosis can be considered as an inappropriate
activation of normal hemostatic processes,
such as the formation of a blood clot (thrombus) in
uninjured vasculature or thrombotic occlusion of a
vessel after relatively minor injury.
• Both hemostasis and thrombosis are regulated by three
general components—
the vascular wall,
platelets, and
the coagulation cascade.
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31. Thrombosis
• Three primary influences predispose to thrombus
formation, the so-called Virchow’s triad:
(1) Endothelial injury;
(2) Stasis or turbulence of blood flow; and
(3) Blood hypercoagulability
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33. 1. Endothelial Injury
• It has the dominant influence; endothelial injury by
itself can lead to thrombosis.
• It is particularly important for thrombus formation
occurring in the heart or in the arterial circulation,
• Thus, thrombus formation within the cardiac
chambers (e.g., following endocardial injury due to
myocardial infarction), or
• at sites of traumatic or inflammatory vascular injury
(vasculitis) is largely due to endothelial injury.
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34. 2.Alterations in Normal Blood Flow/Stasis
• Turbulence contributes to arterial and cardiac
thrombosis by causing;
o endothelial injury or dysfunction
o as well as by forming countercurrents and local
pockets of stasis;
stasis is a major factor in the development of venous
thrombi
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35. • Normal blood flow is laminar such that the platelets
flow centrally in the vessel lumen, separated from the
endothelium by a slower-moving clear zone of
plasma.
• Stasis and turbulence therefore
(1) disrupt laminar flow and bring platelets into contact
with the endothelium;
(2) prevent dilution of activated clotting factors by fresh
flowing blood;
(3) retard the inflow of clotting factor inhibitors and
permit the build-up of thrombi; and
(4) promote endothelial cell activation, predisposing to
local thrombosis, leukocyte adhesion
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36. 3. Hypercoagulability
• Hypercoagulability contributes less frequently to
thrombotic states.
• It is defined as any alteration of the coagulation
pathways that predisposes to thrombosis.
• The causes of hypercoagulability may be primary
(genetic) and secondary (acquired) disorders
- Example: pregnancy , HIV/AIDS, Cancer …
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37. • Thrombi may develop anywhere in the
cardiovascular system:
within the cardiac chambers;
on valve cusps; or
in arteries, veins, or capillaries.
• They are of variable size and shape, depending on
the site of origin and the circumstances leading to
their development.
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38. • Arterial or cardiac thrombi usually begin at a site of
endothelial injury (e.g., atherosclerotic plaque) or
turbulence (vessel bifurcation);
• venous thrombi characteristically occur in sites of
stasis.
• An area of attachment to the underlying vessel or
heart wall, frequently firmest at the point of origin,
is characteristic of all thromboses.
• The propagating tail may not be well attached and,
particularly in veins, is prone to fragmentation,
creating an embolus.
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39. Arterial thrombi :
• are usually occlusive;
• the most common sites, in descending order,
Coronary A,
Cerebral A, and
femoral arteries.
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40. Fate of the Thrombus
• Thrombi undergo some combination of the
following four events in days to weeks
1. Propagation. The thrombus may accumulate more
platelets and fibrin (propagate), eventually leading
to vessel obstruction.
2. Embolization. Thrombi may dislodge and travel to
other sites in the vasculature (eg to lung ).
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41. 3. Dissolution. Thrombi may be removed by
fibrinolytic activity
4. Organization and recanalization. Thrombi may
induce inflammation and fibrosis (organization) and
may eventually become recanalized; that is,
may reestablish vascular flow, or
may be incorporated into a thickened vascular wall
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Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously monitors and adjusts to conditions in the body and its environment. Hemodynamics explains the physical laws that govern the flow of blood in the blood vessels.
Hyperemia is an active process resulting from arteriolar dilation and increased blood inflow, as occurs at sites of inflammation or in exercising skeletal
muscle. Hyperemic tissues are redder than normal because of engorgement with oxygenated blood.
Congestion is a passive process resulting from impaired outflow of venous blood from a tissue. It can occur systemically, as in cardiac failure, or locally as a consequence of an isolated venous obstruction.
Major pathogenic pathways in septic shock. Microbial products (PAMPs, or pathogen-associated molecular patterns) activate endothelial cells
and cellular and humoral elements of the innate immune system, initiating a cascade of events that lead to end-stage multiorgan failure. Additional details are
given in the text. DIC, Disseminated vascular coagulation; HMGB1, high mobility group box 1 protein; NO, nitric oxide; PAF, platelet activating factor; PAI-1,
plasminogen activator inhibitor 1; TF, tissue factor; TFPI, tissue factor pathway inhibitor
Normal hemostasis. (A) After vascular injury, local neurohumoral factors induce a transient vasoconstriction. (B) Platelets bind via glycoprotein
Ib (GpIb) receptors to von Willebrand factor (VWF) on exposed ECM and are activated, undergoing a shape change and granule release. Released ADP
and thromboxane A2 (TXA2) induce additional platelet aggregation through platelet GpIIb-IIIa receptor binding to fibrinogen, and form the primary
hemostatic plug
. (C) Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization,
“cementing” the platelets into a definitive secondary hemostatic plug. (D) Counterregulatory mechanisms, mediated by tissue plasminogen activator
(t-PA, a fibrinolytic product) and thrombomodulin, confine the hemostatic process to the site of injury.
