EDEMA: TYPES AND PATHOPHYSIOLOGY

DR TOSIN ALADE
INTRODUCTION

• Normal fluid homeostasis involves maintaining vessel wall integrity, intravascular pressure, and
osmolarity within physiological range.
• Normally, as blood passes through capillary beds, proteins are retained within the intravascular
space and there is little net movement of water and electrolytes into the interstitial space which are
drained by lymphatics.
• The movement of water between vasculature is controlled by opposing effects of VASCULAR
HYDROSTATIC PRESSURE & PLASMA COLLOID OSMOTIC PRESSURE.
• Hydrostatic pressure is more at the arteriolar end while oncotic pressure is more at the venous end.
DEFINITION; EDEMA

• EDEMA is an abnormal accumulation of fluid in the interstitium located beneath the skin and
body cavities.
• Accumulation of fluid in body cavities is known as EFFUSIONS.
• Effusions can occur in;
• Pleural cavity (hydrothorax(plasma fluids), haemothorax(blood), chylothorax( lymph))
• Pericardial space ((hydropericardium, haemopericardium)
• Peritoneal cavity (hydroperitoneum or ascites)
• Edema fluid may be inflammatory or non inflammatory.
• Inflammatory edema: Also called exudate occurs as a result of increases vascular permeability
caused by inflammatory mediators. Exudate are protein-rich fluid.
• Non-inflammatory edema: Also called transudate occurs as a result of systemic defect.
Transudates are protein-poor fluids.
PATHOPHYSIOLOGY OF EDEMA

• EDEMA results from an increased movement of fluid from the intravascular to the
interstitial space due to an abnormal increase in the hydrostatic pressure or decreased
movement of water from the interstitium into the capillaries or lymphatic vessels.
AETIOLOGY/CAUSES

Any of the following factors can result in the formation of edema

• Increased hydrostatic pressure
• Reduced plasma osmotic pressure
• Lymphatic obstruction
• Sodium and water retention
• Inflammation.
INCREASED HYDROSTATIC PRESSURE

An increase in hydrostatic pressure are mainly caused by disorders that impair(prevent) venous
return. These include;
• Congestive cardiac failure
• Constrictive pericarditis
• Liver cirrhosis
• Venous obstruction
• Lower extremity inactivity with prolonged dependency
REDUCED PLASMA OSMOTIC PRESSURE

• Albumin accounts for almost half of the total plasma protein that exerts colloid osmotic pressure.
• Therefore, conditions that results in reduced synthesis or increased loss of albumin from the
circulation would lead to a significant decrease in the colloid osmotic pressure.
The conditions include:
• Liver cirrhosis
• Protein-losing glomerulopathies ( nephrotic syndrome)
• Malnutrition
• Protein-losing gastroenteropathies.
SODIUM AND WATER RETENTION

Increased salt retention, with associated water retention causes both increase in hydrostatic pressure
(due to intravascular fluid volume expansion) and diminished vascular osmotic pressure (due to
dilution).
• Excessive salt intake with renal insufficiency
• Increased tubular reabsorption of sodium
• Renal hypotension
• Increased renin-angiotensin-aldosterone secretion.
LYMPHATIC OBSTRUCTION

• Edema may result from lymphatic obstruction that compromises resorption of fluid from
interstitial space.
• Trauma, fibrosis invasive tumors and infectious agents can all disrupt lymphatic vessels and
impair the clearance of interstitial fluid, resulting in Lymphedema in the affected part of the body.
Lymphatic obstruction can occur in:
• Inflammation
• Neoplastic
• Postsurgical
• Postirradiation
INFLAMMATION

• Acute inflammation\
• Chronic inflammation
• Angiogenesis.
CLASSIFICATION OF EDEMA

Edema can be classified into

• Generalized or localized
• Pitting or non-pitting
• Organ specific
GENERALIZED EDEMA

• GENERALIZED EDEMA/ ANASARCA is a condition characterized by widespread swelling 0f

the skin due to effusion of fluid into the extracellular space involving the abdomen, arms, legs,
face and feet.
CAUSES
• Congestive heart failure
• Nephrotic syndrome
• Cirrhosis of liver
LOCALISED EDEMA

A medical condition in which the swelling is confined to a particular part/organ in the body
CAUSES
• Trauma
• Infection
• Lymphatic obstruction
• Venous obstruction e.g. thrombosis
PITTING EDEMA

• Cutaneous edema is referred to as ‘pitting’ when, after pressure is applied to a small area, the
indentation persists after the release of the pressure.
• It occurs as a result of water retention caused by an increase in hydrostatic pressure or decrease in
oncotic pressure.
CAUSES
• Pregnancy in some women
• Thrombophlebitis
• Insect bites e.g Bee
NON-PITTING EDEMA

• This is observed when the indentation does not persist.

CAUSES
• Lymphedema
• Lipedema
• Inflammation.
OTHER TYPES OF OEDEMA
• Dependent edema
• Its distribution is often influenced by gravity (e.g., it
appears in the legs when standing and the sacrum
when recumbent)
• PULMONARY EDEMA
• Pulmonary edema is the accumulation of fluids in the lungs due to the
blockage of the pulmonary veins.
• Periorbital edema
• Edema resulting from renal dysfunction often appears initially in parts
of the body containing loose connective tissue, such as the eyelids
HYPEREMIA AND CONGESTION
• Both refers to an increase in blood volume within a tissue, they have
different underlining mechanisms.
• HYPEREMIA is an active process resulting from arteriolar dilation and
increase in blood inflow.
• It’s associated with inflammation and could be seen in exercising of
skeletal muscles.
• CONGESTION is a passive process resulting from impaired outflow of
venous blood from tissue.
• It can occur systemically as a result from cardiac failure or locally from
obstructed venous outflow.
• It gives a blue appearance as a result from cyanosis [deoxygenated
blood]
• If persistent, it can result in inadequate tissue perfusion, elevated
intravascular pressure, oedema rupture of capillaries production of
focal haemorrhage and parenchymal cell death.
• Congested tissues take on a dusky reddish-blue color (cyanosis) due
to red cell stasis and the presence of deoxygenated haemoglobin.
• Acute pulmonary congestion exhibits engorged alveolar capillaries,
alveolar septal edema, and focal intraalveolar hemorrhage.
• chronic pulmonary congestion, in congestive heart failure, the septa
are thickened and fibrotic, and the alveoli often contain numerous
hemosiderin-laden macrophages called heart failure cells
• Acute hepatic congestion, the central vein and sinusoids are
distended.
• Chronic passive hepatic congestion, the centrilobular regions are
grossly red-brown and slightly depressed (because of cell death) and
have a nutmeg liver appearance.
• Hemosiderin-laden macrophages, and variable degrees of hepatocyte
dropout and necrosis are seen here.
SIGNS AND SYMPTOMS OF
EDEMA
Swelling
Puffiness of ankles, face, eyes
Aching body part and stiff joints
Weight gain
Decreased urination
Visual anomalies.

SW PADV
CLINICAL SIGNIFICANCE
• Subcutaneous oedema
• Signal underlying disease
• Impair wound healing and
• Clearance of infection
• Pulmonary oedema
• impede oxygen diffusion,
• Secondary bacterial infection
• Cerebral oedema
• Herniation
• Compressed brain stem vascular supply
RECAP ON EDEMA
Edema is the result of the movement of fluid from the vasculature into
the interstitial spaces -transudate or exudate.
• CAUSES:
■ Increased hydrostatic pressure (e.g., heart failure)
■ Decreased colloid osmotic pressure e.g., liver disease, protein
malnutrition, nephrotic syndrome
■ Increased vascular permeability (e.g., inflammation
■ Lymphatic obstruction (e.g., infection or neoplasia)
■ Sodium and water retention e.g., renal failure
HEMORRHAGE
• Hemorrhage is the release of blood into the extravascular space
• Hemorrhage can be external or enclosed within a tissue called a
hematoma.
• Petechiae are minute, 1-2mm hemorrhage in the skin, mucous
membranes, or serosal surfaces. These occur with increased
intravascular pressure, low platelet count or defective platelet
function
• Purpura are >3mm hemorrhage. Can result from trauma, local
vascular inflammation
• Ecchymoses are > 1-2cm subcutaneous hematomas i.e. bruises. Can
be due to trauma, it can also be exacerbated by other bleeding
disorder
• Large accumulation of blood in the body cavities are called
hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis
(joint) depending on the location.
Significance of hemorrhage
• VOLUME - Greater blood losses resulting hemorrhage (hypovolemic )
shock
• LOCATION – Bleeding that would be inconsequential when located in
in subcutaneous tissues may cause death when located in the brain.
• Chronic blood loss e.g. peptic ulcer disease, heavy menstrual
bleeding, cancer) can result in iron deficiency anemia
Hemostasis.
The process of preventing blood loss from a vessel or organ of the body
is termed hemostasis.
-coined from 2 Greek words:- HEME(BLOOD) and STASIS(HALTING)
meaning ‘Halting of the Blood’
-Normal hemostasis is a consequence of tightly regulated processes
that maintain blood in a fluid state in normal vessels, yet also permit
the rapid formation of a hemostatic clot at the site of a vascular
injury.
Summary of sequence of events that
occur at the site of vascular injury.
• A brief period of arteriolar vasoconstriction mediated by reflex
neurogenic mechanisms and augmented by the local secretion of
factors such as endothelin, it is a transient(short) effect.
• Endothelial injury exposes highly thrombogenic subendothelial
extracellular matrix (ECM), facilitating platelet adherence and
activation. Activation of platelets leads to other rxns. This is the process
of primary hemostasis.
• Tissue factor is also exposed at the site of injury. Also known as factor III
and thromboplastin, It acts in conjunction with factor VII as the major in
vivo initiator of the coagulation cascade, eventually culminating in
thrombin generation.
• Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating
a fibrin meshwork, and also induces additional platelet recruitment
and activation. This sequence, secondary hemostasis, consolidates
the initial platelet plug.
• Polymerized fibrin and platelet aggregates form a solid, permanent
plug to prevent any further 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.
Disorders of hemostasis.
• It should be recalled that the normal hemostatic response involves
the blood vessel wall, the platelets, and the clotting cascade.
• Hemorrhagic diatheses:- Abnormally increased or extended bleeding
due to an otherwise adequate cause or a generalized propensity to
bleed in the absence of an adequate cause
• Most of these disorders are typically associated with locally increased
intravascular pressure, low platelet counts (thrombocytopenia),
defective platelet function, or clotting factor deficiencies.
• Bleeding could be due to one or combination of the
following:-
• Vessel wall abnormalities
• Reduced platelet numbers-Thrombocytopenia.
• Defective platelet function.

ASSIGNMENT…
THROMBOSIS
• Thrombosis is the formation of a solid mass [thrombus] in a blood
vessel
• A thrombus consists of aggregates of coagulated blood containing
platelets, fibrin and entrapped blood cells.
• Thrombi can develop anywhere in the cardiovascular and vary in size
and shape depending on site and underlying cause.
• They are focally attached to the underlying vascular surface,
particularly at the point of initiation.
AETIOLOGY
Three primary abnormalities can lead to thrombus formation and the
constitute VIRCHOW’S TRIAD:
• Endothelial injury
• Stasis or turbulent blood flow
• Hypercoagulability of the blood
ENDOTHELIAL INJURY
• Intact endothelial cells have properties which prevent thrombus
formation and these include:
• Antiplatelet effect; NO, prostaglandin 11, Adenosine diphosphatase
• Anticoagulant effect; thrombomodulin, heparin-like molecules
• Fibrinolytic effect; t-PA
ENDOTHELIAL INJURY
Endothelial injury may be due to;
• Physical damage
• Endothelial dysfunction [activation]
PHYSICAL ENDOTHELIAL INJURY
• This leads formation of a thrombus in the heart or arterial circulation
characterized by platelet adhesion and aggregation.
CAUSES
• HEART
• In the heart chambers; Myocardial infarction
• In the heart valves [vegetations]; Infective endocarditis, CHD, SLE
• ARTERIES
• Ulcerated atherosclerotic plague
• Vasculitis
PHYSICAL ENOTHELIAL INJURY
• CAPILLARIES
• Acute inflammatory lesions
• Vasculitis
MECHANISM
Physical injury to/loss of endothelium exposes thrombogenic
subendothelial ECM and this leads to the adhesion of platelets at the
site of injury. vWF and TF released promote platelet aggregation and
also coagulation
ENDOTHELIAL DYSFUNCTION
[ACTIVATION]
• Endothelial dysfunction is an alteration in the normal endothelium
characterized by imbalance between the prothrombotic and
antithrombotic activities of the endothelium
CAUSES
• Hypertension
• Diabetes
• Turbulent blood flow
• Metabolic disorders; hypercholesterolemia, hypercystinemia
• Toxins; bacteria endotoxins, toxins from cigarettes
ENDOTHELIAL DYSFUNCTION
[ACTIVATION]
MECHANISM
Endothelial dysfunction can disturb the balance between
prothrombotic and antithrombotic activities of the endothelium by;
• Synthesizing more procoagulative factors like platelet adhesion
molecules, tissue factor and PAIs
OR
• Synthesizing less anticoagulant effectors like thrombomodulin, PGI2,
t-PA
STASIS OR TURBULENT BLOOD
FLOW
• The normal flow of blood is laminar in which the platelets [and other
blood cells] are flowing centrally and are separated from the
endothelium by the plasma.
• Abnormal blood flow seen in turbulent [disturbed] blood flow can
lead to thrombus formation in the heart and arteries.
• Abnormal blood flow seen in stasis leads to thrombus formation in
the vein
STASIS OR TURBULENT BLOOD
FLOW
CAUSES
• Ulcerated atherosclerotic plaques
• Aortic and arterial dilations called aneurysms
• Acute myocardial infarctions
• Rheumatic mitral valve stenosis with atrial fibrillation
• Hyperviscosity [polycythemia, rubra vera, HbSS]
STASIS OR TURBULENT BLOOD
FLOW
MECHANISM
• Promoting endothelial injury/activation and increasing procoagulant
activities
• Bringing the platelets in contact with the endothelium
• Prevents cleansing and dilution of activated clotting factors by fresh
flowing blood
• Prevents flowing in of clotting factors inhibitors
HYPERCOAGULABILITY
[THROMBOPHILIA]
• Hypercoagulability can be loosely defined as any disorder of the blood
that predisposes to thrombosis
• It plays a particularly important role in venous thrombosis
CAUSES
• Primary [genetic]
• Secondary [acquired]
MORPHOLOGY
• Generally, thrombi grossly and microscopically show alternating pale
and dark laminations called lines of Zahn.
• The pale layer is composed of platelet and fibrin deposits
• The darker layer is red cell- rich
FATE OF THROMBOSIS
• Dissolution
• Organization and recanalization
• Propagation
• Embolization
FATE OF THROMBOSIS
• 1)Dissolution ;if a thrombus is newly formed, activation of fibrinolytic
factors my lead to its rapid shrinkage and complete resolution
• 2)Organization; older thrombi become organized by the in growth of
endothelial cells, smooth muscles and fibroblasts
FATE OF THROMBOSIS
• 3) PROPAGATION The thrombus may enlarge in size due to more and
more deposition from the constituents of flowing blood. In this way, it
may ultimately cause obstruction of some important vessel.
• 4) THROMBOEMBOLISM The thrombi in early stage and infected
thrombi are quite friable and may get detached from the vessel wall.
These are released in part or completely in blood-stream as emboli
which produce ill-effects at the site of their lodgment
CLINICAL CORRELATES
• Decrease blood supply to tissue or organ – ischemic injury
• Thrombo-embolisation
• The clinical presentation depends on the involved site
VENOUS THROMBOSIS
• Superficial venous thrombosis (Thrombophlebitis)
• due to inflammation
• Saphenous vein due to varicosity,
• Rarely embolize
• Cause oedema congestion, infection and ulceration of the overlying skin.
CLINICAL CORRELATES
• Deep venous thrombosis (Phlebothromosis)
• Due to stasis
• commonly affect the popliteal, femoral, and iliac vein
• May be asymptomatic or cause local pain and oedema.
• Embolize often causing pulmonary infarction.
• Arterial and Cardiac thrombosis
• Major causes: Atherosclerosis myocardial infarction
• Prone to embolization- brain, Kidney and spleen
EMBOLISM
• Embolism refers to any solid, liquid or gaseous mass carried by blood
flow to a site distant from its origin.
• Most arise from thrombi hence the term thromboembolism
• Rare form includes fat droplets, gas bubbles, atherosclerotic debris,
tumour fragments, bone marrow, or foreign body
• Emboli lodges in vessels too small to permit further passage, resulting
in partial or complete vascular occlusion and ischemic necrosis
(infarction)
INFARCTION
ASSIGNMENT