ISCHEMIA, INFARCTION, SHOCK

AND EDEMA
ISCHEMIA
 A condition of inadequate blood supply to an area of tissue leading
to hypoxia.
 M/c cause of cell injury in clinical medicine.
 Three harmful effects of ischemia:
 Hypoxia-

Oxygen deprivation.
Most important factor for ischemic tissue damage of very
active cells.
Eg. muscles
 Malnutrition-

Blood contains glucose and amino acids that could be

metabolised by the amount of oxygen it contain, hence it is of
less importance.
 Failure to remove waste products-
Accumulation of metabolites is the most explanatory pain in
muscle ischemia
 General causes:–
 Inadequate cardiac output
But not all tissues are equally affected because of
redistribution of available blood.
 Symmetrical gangrene of extremities is an occasional
manifestation
 Local causes:-
 Obstruction of arterial flow.
 Extensive venous and capillary damage
Mechanism of Ischemic cell injury
 Mammalian cells have developed protective responses to deal with
hypoxic stress.
 Induction of transcription factor called hypoxia-inducible factor-
1 (HIF-1)
Promotes new blood vessel formation
Stimulates cell survival pathways and
Enhances glycolysis
INFARCTION
 An area of ischemic necrosis caused by:
 occlusion of either arterial supply or venous drainage.
 Roughly 40% of all deaths are caused by cardiovascular disease:
 myocardial or
 cerebral infarction
 Pulmonary infarction: also a common complication
 Bowel infarction: Fatal
 Arterial thrombosis or arterial embolism underlies vast majority of
infarction.

 Less common causes:

 Local vasospasm
 Hemorrhage into an atheromatous plaque
 Extrinsic vessel compression (e.g. by tumor)
 Other uncommon causes:
 Torsion of a vessel (e.g. in testicular torsion or bowel volvulus)
 Traumatic vascular rupture
 Vascular compromise by edema (e.g. anterior compartment
syndrome)
 Entrapment in a hernia sac.
 Venous thrombosis can cause infarction
 More likely in organs with a single efferent vein (e.g., testis and
ovary).
 MORPHOLOGY

 Classified according to:

 Color

 Presence or absence of infection

 Can be either:
 Red (hemorrhagic)
 White (anemic) and
 May be
 Septic

 Bland.
 Red infarct

 Occur in:
 Venous occlusions
Testicular torsion
 Loose, spongy tissues (where blood can collect in the infarcted zone)
Lung

 Tissues with dual circulations

Lung and small intestine
 Tissues previously congested by sluggish venous outflow
 Flow reestablished to a site of previous arterial occlusion and necrosis
Following angioplasty of an arterial obstruction
 White infarct

 Occur with:
 Arterial occlusions
 In solid organs with end-arterial circulation (e.g. heart, spleen,
and kidney)
 Wedge-shaped
 With occluded vessel at apex
 Periphery of the organ forming the base
 Fresh infarcts are poorly defined and slightly hemorrhagic
 Over a few days:
 Margins become better defined by a narrow rim of congestion
attributable to inflammation.
 With further passage of time, arterial occlusions in organs without a
dual blood supply:
 Progressively paler
 More sharply defined
 Extravasated red cells in hemorrhagic infarct are phagocytosed by
macrophages (hemosiderin laden macrophages)
 Dominant histologic characteristic: Ischemic coagulative necrosis.
 Vascular occlusion occurred shortly (minutes to hours)- histologic
changes may be absent
Hemosiderin laden macrophages
 Coagulative necrosis

 Normal

 Coagulative necrosis
 Takes 4 to 12 hours for dead tissue to show microscopic evidence of
frank necrosis.
 Ultimately replaced by scar.
 Brain is an exception to these generalizations that central nervous
system infarction results in liquefactive necrosis.
Liquefactive necrosis
 Septic infarction

 Occurs when:
 Infected cardiac valve vegetations embolize
 When microbes seed necrotic tissue.
 Infarct is converted into an abscess, with a correspondingly greater
inflammatory response
Factors That Influence Development of an
Infarct.
 Vascular occlusion:
 Cause effects ranging from virtually nothing to tissue
dysfunction
 Necrosis sufficient to result in death.
 Variables that influence outcome of vascular occlusion are:
I. Anatomy of vascular supply
II. Rate of occlusion
III. Tissue vulnerability to hypoxia
IV. Hypoxemia
EDEMA
 Accumulation of excessive body fluid in interstitial space or serous
body cavity (effusions), a pathological process caused by diseases.
 Depending on severity and location, may have minimal or profound
effects.
 Normally,
 Tendency of vascular hydrostatic pressure to push water and salt
out of capillaries into interstitial space is balanced by tendency of
plasma colloid osmotic pressure to pull water and salt back into
vessels.
Regulation of Fluid Distribution
 Pathophysiology

 Increased Hydrostatic Pressure

 Decreased Plasma Colloid Osmotic Pressure
 Sodium and Water Retention
 Lymphatic Obstruction
Other Categories of Edema

1. Pitting edema:
When interstitial fluid pressure
rises leading to free fluid
accumulation.
2. Non-pitting edema:
When tissue cells are swelled
not the interstitium or when the
interstitium becomes clotted with
fibrinogen so that it can’t move
freely.
 Features of Edema Fluid

Transudates:
 An ultrafiltrate of blood plasma
that results from osmotic or
hydrostatic imbalance across
the vessel wall without an
increase in vascular
permeability.
 Has low protein content.
 Low specific gravity.
Exudate:
 An extravascular fluid d/t
increased permeability of
blood vessels following injury.
 Has high protein content.
 High specific gravity.
 Contains cellular debris.
 Clinical Consequences

 Cardiac or renal disease

 Impairement of wound healing.
 Pulmonary edema due to LVF, renal failure.
 Brain edema.
 Morphology

 Easily recognized grossly

 Microscopically:
 Clearing and separation of extracellular matrix (ECM)
 subtle cell swelling
 M/c seen in subcutaneous tissues, lungs and brain.
 Periorbital edema:
 Edema resulting from renal dysfunction
 often appears initially in parts of body containing loose connective
tissue, such as eyelids
 Pulmonary edema:
 lungs are often two to three times their normal weight
 On c/s: Frothy, blood-tinged fluid (mixture of air, edema, and
extravasated red cells)
 Brain edema:
 can be localized or generalized depending on the nature and
extent of the pathologic process or injury
 Swollenbrain exhibits narrowed sulci and distended gyri,
compressed by unyielding skull.
Pulmonary edema
Shock
 State of circulatory failure that impairs tissue perfusion and leads to cellular
hypoxia.
 Cellular injury: Reversible
 Prolonged shock leads to irreversible tissue injury and can be fatal.
 May complicate:
 Severe hemorrhage
 Extensive trauma or burns
 Myocardial infarction
 Pulmonary embolism
 Microbial sepsis.
 Causes fall into three general categories:
 Hypovolemic shock
 Cardiogenic shock
 Septic shock
 Other:
 Anaphylactic shock
 Neurogenic shock
Clinical Presentation

 Tachycardia and tachypnea

 Weak, thready pulses
 Hypotension
 Cool and clammy skin
 Mental status changes
 Decreased urine output
 Stages of Shock
 An initial non progressive phase:
 during which reflex compensatory mechanisms are
activated and perfusion of vital organs is maintained.
 A progressive stage:
 during which tissue hypoperfusion and onset of
worsening circulatory and metabolic imbalances occur
including acidosis.
 An irreversible stage:
 that sets in after the body has incurred cellular and tissue
injury so severe that even if hemodynamic defects are
corrected, survival is not possible.
 Morphology

 Cellular and tissue effects of shock are essentially those of hypoxic

injury
 Caused by a combination of hypoperfusion and microvascular
thrombosis
 Any organ can be affected (brain, heart, kidneys, adrenals, and
gastrointestinal tract) are most commonly involved.
 Fibrin thrombi can form in any tissue but typically are most readily
visualized in kidney glomeruli.
 Adrenal cortical cell lipid depletion is akin to that seen in all
forms of stress and reflects increased use of stored lipids for steroid
synthesis.
 Lungs are resistant to hypoxic injury in hypovolemic shock
occurring after hemorrhage, sepsis or trauma can precipitate diffuse
alveolar damage leading to so-called “shock lung.”
 Except for neuronal and cardiomyocyte loss, affected tissues can
recover completely if the patient survives.
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