Edema and Infarction

Dr S.Sulochana
Professor of pathology
SIMATS
• The Greek word oedema means swelling.
• Oedema is defined as abnormal and excessive accumulation of “free fluid” in
the interstitial tissue spaces and serous cavities.
• Free fluid in body cavities: called as effusion
Example- ascites (if in the peritoneal cavity),
• hydrothorax or pleural effusion (if in the pleural cavity), and hydropericardium
or pericardial effusion (if in the pericardial cavity).
• Free fluid in interstitial space: termed as oedema, the fluid lies free in the
interstitial space between the cells and can be displaced from one place to
another.
• oedema in the subcutaneous tissues, momentary pressure of finger produces
a depression known as pitting oedema.
• non-pitting or solid oedema in which no pitting is produced on pressure e.g. in
myxoedema, elephantiasis.
Oedema may be of 2 main types:
1. Localised - limited to an organ or limb
e.g. lymphatic oedema, inflammatory oedema, allergic oedema,
pulmonary oedema, cerebral oedema etc.
2. Generalised (anasarca or dropsy) - it is systemic in distribution,
particularly noticeable in the subcutaneous tissues e.g. renal oedema,
cardiac oedema, nutritional oedema.
Depending upon fluid composition, oedema fluid may be:
• Transudate such as in oedema of cardiac and renal disease; or
• Exudate such as in inflammatory oedema.
PATHOGENESIS OF OEDEMA or
classification of edema
Oedema is caused by mechanisms that interfere with normal
fluid balance of plasma, interstitial fluid and lymph flow.
The following mechanisms may be operating singly or in
combination to produce oedema:
1.Decreased plasma oncotic pressure
2. Increased capillary hydrostatic pressure
3. Lymphatic obstruction
4. Tissue factors (increased oncotic pressure of interstitial
fluid, and decreased tissue tension)
5. Increased capillary permeability
6. Sodium and water retention.
1. DECREASED PLASMA ONCOTIC PRESSURE
2. The plasma oncotic pressure exerted by the total amount of plasma proteins
tends to draw fluid into the vessels normally.
• A fall in the total plasma protein level (hypoproteinaemia of less than 5 g/dl,
mainly hypoalbuminaemia)--results in lowering of plasma oncotic pressure --
 it can no longer counteract the effect of hydrostatic pressure of blood.
• -- results in increased outward movement of fluid from the capillary wall and
decreased inward movement of fluid from the interstitial space causing oedema
Examples
• Oedema of renal disease e.g. in nephrotic and nephritic syndrome.
• ii) Ascites of liver disease e.g. in cirrhosis of the liver.
• iii) Oedema due to other causes of hypoproteinaemia e.g. in protein-losing
enteropathy.
2. INCREASED CAPILLARY HYDROSTATIC PRESSURE
• The hydrostatic pressure of the capillary is the force that
normally tends to drive fluid through the capillary wall into
the interstitial space by counteracting the force of plasma
oncotic pressure.
• A rise in the hydrostatic pressure at the venular end of the
capillary which is normally low (average 12 mmHg) to a level
more than the plasma oncotic pressure results in minimal or
no reabsorption of fluid at the venular end, consequently
leading to oedema
• Oedema of cardiac disease e.g. in congestive cardiac failure,
constrictive pericarditis.
• ii) Ascites of liver disease e.g. in cirrhosis of the liver.
• iii) Passive congestion e.g. in mechanical obstruction due to
thrombosis of veins of the lower legs, varicosities, pressure
by pregnant uterus, tumours etc.
• iv) Postural oedema e.g. transient oedema of feet and
ankles due to increased venous pressure seen in individuals
whose job involves standing for long hours such as traffic
constables,bus drivers,doctors and nurses.
3.LYMPHATIC OBSTRUCTION
Normally, the interstitial fluid in the tissue spaces escapes by way of
lymphatics.
Obstruction to outflow of these channels causes localised oedema,
known as lymphoedema
Examples:
• Removal of axillary lymph nodes in radical mastectomy for carcinoma
of the breast causing lymphoedema of the affected arm.
• ii) Pressure from outside on the main abdominal or thoracic duct due to
tumours, effusions in serous cavities etc may produce lymphoedema.
• At times, the main lymphatic channel may rupture and discharge chyle
into the pleural cavity (chylothorax) or into peritoneal cavity (chylous
ascites)
• iii) Inflammation of the lymphatics as seen in filariasis
(infection with Wuchereria bancrofti) results in chronic
lymphoedema of scrotum and legs known as elephantiasis,
a form of non-pitting oedema.
• iv) Occlusion of lymphatic channels by malignant cells may
result in lymphoedema.
• v) Milroy’s disease or hereditary lymphoedema is due to
abnormal development of lymphatic channels.
• It is seen in families and the oedema is mainly confined to
one or both the lower limbs
4. TISSUE FACTORS
• The two forces acting in the interstitial space—oncotic pressure of the
interstitial space and tissue tension, are normally quite small and
insignificant to counteract the effects of plasma oncotic pressure and
capillary hydrostatic pressure respectively.
• However, in some situations, the tissue factors in combination with
other mechanisms play a role in causation of oedema (Fig. 4.3,E).
These are :
• i) Elevation of oncotic pressure of interstitial fluid as occurs due to
increased vascular permeability and inadequate removal of proteins
by lymphatics.
• ii) Lowered tissue tension as seen in loose subcutaneous tissues of
eyelids and external genitalia.
5. INCREASED CAPILLARY PERMEABILITY
An intact capillary endothelium is a semipermeable membrane which
permits the free flow of water and crystalloids but allows minimal
passage of plasma proteins normally.
However, when the capillary endothelium is injured by various
‘capillary poisons’ such as toxins and their products (e.g. histamine,
anoxia, venoms, certain drugs and chemicals), the capillary
permeability to plasma proteins is enhanced due to development of
gaps between the endothelial cells, causing leakage of plasma proteins
into interstitial fluid.
This causes reduced plasma oncotic pressure and elevated oncotic
pressure of interstitial fluid, consequently producing oedema
Examples
• Generalised oedema occurring in systemic infections, poisonings,
certain drugs and chemicals, anaphylactic reactions and anoxia.
• ii) Localised oedema A few examples are :
• infammatory oedema as seen in infections, allergic reactions, insect-
bite, irritant drugs and chemicals.
• It is generally exudate in nature.
• Angioneurotic oedema is an acute attack of localised oedema
occurring on the skin of face and trunk and may involve lips, larynx,
pharynx and lungs. It is possibly neurogenic or allergic in origin
• SODIUM AND WATER RETENTION
• The mechanism of oedema by sodium and water retention in
extravascular compartment is best described in relation to
derangement in normal regulatory mechanism of sodium and water
balance. Natrium (Na) is the Latin term for sodium.
• Normally, about 80% of sodium is reabsorbed by the proximal
convoluted tubule under the influence of either intrinsic renal
mechanism or extra-renal mechanism while retention of water is
affected by release of antidiuretic hormone
• Intrinsic renal mechanism is activated in response to sudden
reduction in the effective arterial blood volume
(hypovolaemia) e.g. in severe haemorrhage.
• Hypovolaemia stimulates the arterial baroreceptors present
in the carotid sinus and aortic arch which, in turn, send the
sympathetic outflow via the vasomotor centre in the brain.
• As a result of this, renal ischaemia occurs which causes
reduction in the glomerular filtration rate, decreased
excretion of sodium in the urine and consequent retention
of sodium
• Extra-renal mechanism involves the secretion of aldosterone, a sodium-
retaining hormone, by the reninangiotensin-aldosterone system.
• Renin is an enzyme secreted by the granular cells in the juxta-glomerular
apparatus.
• Its release is stimulated in response to low concentration of sodium in the
tubules.
• Its main action is stimulation of the angiotensinogen which is α2-globulin or
renin substrate present in the plasma.
• On stimulation, angiotensin I, a decapeptide, is formed in the plasma which is
subsequently converted into angiotensin II, an octapeptide, in the lungs and
kidneys by angiotension converting enzyme (ACE).
• Angiotensin II stimulates the adrenal cortex to secrete aldosterone hormone.
• Aldosterone increases sodium reabsorption in the renal tubules and
sometimes causes a rise in the blood pressure
ADH mechanism
• Retention of sodium leads to retention of water secondarily under
the influence of anti-diuretic hormone (ADH) or vasopressin.
• This hormone is secreted by the cells of the supraoptic and
paraventricular nuclei in the hypothalamus and is stored in the
neurohypophysis (posterior pituitary).
• The release of ADH is stimulated by increased concentration of
sodium in the plasma and hypovolaemia.
• Large amounts of ADH produce highly concentrated urine.
• Thus, the possible factors responsible for causating oedema by excessive
retention of sodium and water in the extravascular compartment via
stimulation of intrinsic renal and extra-renal mechanisms as well as via
release of ADH are i) Reduced glomerular filtration rate in response to
hypovolaemia.
• ii) Enhanced tubular reabsorption of sodium and consequently its
decreased renal excretion.
• iii) Increased filtration factor i.e. increased filtration of plasma from the
glomerulus.
• iv) Decreased capillary hydrostatic pressure associated with increased
renal vascular resistance. The examples of oedema by these mechanisms
are as under: i) Oedema of cardiac disease e.g. in congestive cardiac
failure. ii) Ascites of liver disease e.g. in cirrhosis of liver. iii) Oedema of
renal disease e.g. in nephrotic and nephritic syndrome.
Cardiac Oedema
• Generalised oedema develops in right-sided and congestive cardiac
failure.
• Pathogenesis of cardiac oedema is explained on the basis of the
following mechanisms (Fig. 4.5):
• 1. Reduced cardiac output causes hypovolaemia which stimulates
intrinsic-renal and extra-renal hormonal (reninangiotensin-aldosterone)
mechanisms as well as ADH secretion resulting in sodium and water
retention (as discussed above) and consequent oedema.
• 2. Due to heart failure, there is elevated central venous pressure which
is transmitted backward to the venous end of the capillaries, raising the
capillary hydrostatic pressure and consequent transudation; this is
known as back pressure hypothesis.
• 3. Chronic hypoxia may injure the capillary endothelium causing
increased capillary permeability and result in oedema; this is called
forward pressure hypothesis.
• However, this theory lacks support since the oedema by this mechanism
is exudate whereas the cardiac oedema is typically transudate.
• In left heart failure, the changes are, however, different. There is venous
congestion, particularly in the lungs, causing pulmonary oedema rather
than generalised oedema.
• Cardiac oedema is influenced by gravity and is thus characteristically
dependent oedema i.e. in an ambulatory patient it is on the lower
extremities, while in a bed-ridden patient oedema appears on the
sacral and genital areas. The accumulation of fluid may also occur in
serous cavities.
Morphology

• Grossly, the affected organ is enlarged and heavy with tense

capsule.
• Microscopically, the oedema fluid separates the connective
tissue fibres of subcutaneous tissues.
• Depending upon the protein content, the oedema fluid may
appear homogeneous, pale, eosinophilic, or may be deeply
eosinophilic and granular
Haemodynamics
Infarction
Def :
• An area of ischemic necrosis caused by
occlusion of either the arterial supply or the
venous drainage.
• 40% of death in US is due to tissue infarction,
• Myocardial , cerebral, pulmonary, bowel
infarction and ischemic necrosis of lower
extremities(gangrene)
Aetiopathogenesis:

• All infarcts result from thrombotic or embolic arterial occlusions.

Other mechanisms causing infarction are
• Local vasospasm
• Hemorrhage into an atheromatous plaque, or
• Extrinsic vessel compression( by tumor)
Rare causes
• Torsion of a vessel(testicular torsion or bowel volvulus)
• Traumatic rupture or vascular compromise by edema(anterior
compartmental syndrome) or
• Entrapment in a hernia sac.
Infarcts caused by venous thrombosis are in organs with a single
efferent vein (testis and ovary)
Morphology:
Types ;
1.According to color
Red (hemorrhagic ) or
White (pale or anemic)
2. Presence or absence of infection
Septic or
Bland
Red infarcts occur
1.With venous occlusions (ovary)
2.In loose tissues (eg;lung)where blood can collect in the infarcted
zone.
3.In tissues with dual circulation (eg; lung and small intestine) that
allow blood flow from an unobstructed parallel supply into a
necrotic zone
4.In tissues previously congested by sluggish venous
outflow, and
5.When flow is re-established to a site of previous
arterial occlusion and necrosis (eg, following
angioplasty of an arterial obstruction)
White infarcts;
• Occur with arterial occlusions in solid organs with end
arterial circulation.(eg; heart , spleen and kidney),and
• Where tissue density limits the seepage of blood from
adjoining capillary beds into the necrotic area.
Shape ;
• Wedge-shaped, with the occluded vessel at the apex and
the periphery of the organ forming the base.
• Acute infarcts are poorly defined and slightly
hemorrhagic
• Infarcts resulting from arterial occlusions in organs
without dual circulation typically become paler and more
sharply defined.
• Infarct in lung are hemorrhagic
• Extravaged red cells in haemorrhagic infarcts are
phagocytosed by macrophages ,which converts heme iron
to hemosiderin.
• Small haemorrhagic infarcts don’t grossly impart any
colour to the tissue.
Microscopic
• Ischmic coagulative necrosis.
• If the vascular occlusion has occurred minutes to hours – no
changes
• 4 to 12hrs ,tissue shows frank necrosis.
• Acute inflammation is present within few hours and well defined
within 1 to 2 days along the margins of infarcts.
• In stable or labile tissues ,parenchymal regeneration occur at the
periphery, the underlying stromal architecture is preserved.
• Most infarcts are replaced by scar, except brain ,infarction results
liquefactive necrosis
Septic infarcts occur when
• Infected cardiac valve vegetations embolize or when microbes seed
necrotic tissue.
• These infarcts are converted into an abscess.
Factors that influence development of an Infarct
1.the nature of the vascular supply
2. the rate at which the occlusion develops
3.vulnerability to hypoxia
4.the oxygen content of the blood.
1.the nature of the vascular supply
Dual blood supply is important one to determine vessel occlusion
will cause damage
E,g ;
1.lungs- pulmonary and bronchial artery blood supply, provides
protection from thrombo-embolism induced infarction.
2.Liver –hepatic artery and portal vein circulation
3. Hand and fore arm- radial and ulnar artery circulation
Renal and spleenic circulations are end – arterial, and vascular
obstruction causes tissue death.
Rate of occlusion development;
• Slowly developing occlusions are less likely to cause infarction,because
they provide time to develop alternate perfusion pathways.
• E,g; three coronary arteries with collateral circulation with minimal
functional flow.
• If one of the coronary artery or larger coronary artery is occluded slowly,
flow within the collateral circulation increase to prevent infarction
Vulnerability to hypoxia
• Neurons –deprived of blood supply for 3 to 4 mts ,irreversible damage
• Myocardial cells die after 20 to 30 mts of ischemia
• Fibroblasts within myocardium remain viable even after many hours of
ischemia.
Oxygen content of blood
• partial occlusion of a small vessel in normal individual is no effect, but in
anaemic or cyanotic patients might cause infarction.
Red infarct White infarct
1.haemorrhagic infarct 1.Pale or anemic infarct
2.either arterial or venous 2.caused by arterial
occlusion occlusion.
3.In organs with dual 3.In organs with end
blood supply arterial occlusion.
4.Loose tissue which 4.Solid organs
allow blood to collect 5.Spleen
5.sites; ovary(venous kidney
occlusion) heart
Lung (loose tissue)
Intestine(dual supply)
 6.Wedge shaped.Apex
6. Gross ; formed by the occluded
Well circumscribed, firm, vessels and periphery of
dark red the area forms the base of
7.Microscopic the wedge.
Coagulative necrosis. Well demarked, pale,
borders are dark red.
7.Coagulative necrosis
With dense inflammatory
infiltrate at the junction of
the normal and infarcted
area
Thank you