Reversible and Irreversible Injury

Dr. E. Okon
● Adaptation allows cells or tissues to respond to
increased or decreased demand and thereby
revert to a state of homeostasis, but adaptation
can only go so far.
● When an injurious stimulus is severe or the cell
has exceeded its ability to adapt, cell injury
occurs.
●
● Reversible injury, the cell has the potential to
return to normal structure and function if the
injurious stimulus is withdrawn.
● Irreversible cell injury leads to cell death by
necrosis or apoptosis.
● Oxygen deprivation is extremely deleterious to cells.
● Insufficient oxygen delivery to tissue is called hypoxia
● Insufficient blood supply to tissues is called ischemia
● Cells are vulnerable to hypoxia in proportion to their oxygen
requirements:
– Metabolically highly active cells are most vulnerable.
● Ischemic injury is localized to the tissue normally supplied by
the blocked-off vessel
– An area of cells that have died due to decreased blood flow is called an
infarct. Infarcts are most commonly caused by obstruction of arteries
● A thrombus is a blood clot that forms in a blood vessel
as a result of activation of the coagulation
mechanism.
– It is composed of layers of fibrin and entrapped blood cells.
● An embolus is any particulate object that travels in the
bloodstream from one site to another.
● Most commonly arises from a thrombus but may be
composed of other substances such as bone marrow,
fat, air, or cancer tissue.
● Trauma, infection, and immune reactions are
other common causes of acute injury. Trauma
disrupts cells by direct physical force; the
effects are dependent on the site injured and
nature of the force applied.
● Immunologic mechanisms are an important part
of the inflammatory reaction and also contribute
to the damage produced by inflammation
●
● A sudden insult is called an acute injury.
● Chronic injury refers to injury that is prolonged
in duration.
● Whether the injury is acute or chronic, cells will
eventually die.
● 2 types of cell death: Necrosis & Apoptosis
● Necrosis is the death of cells or tissue as a
result of an irreversible, exogenous injury.
 Types of Necrosis
● Coagulation necrosis is most commonly caused
by anoxia, whether it is generalized or
ischemic.
– Coagulation process evolves slowly, over a number
of days, producing the characteristic preservation of
cell and tissue outlines until the later stages of the
process
● Liquefaction necrosis is most commonly caused
by certain types of bacteria, known as pyogenic
bacteria.
● Pyogenic bacteria attract neutrophils into the
area and the enzymes released by the
neutrophils liquefy the dead tissue. The
resultant thick, creamy mixture of dead tissue
and neutrophils is called pus or purulent
exudate
● Caseous necrosis is most commonly caused by
Mycobacterium tuberculosis, the bacterium that
causes tuberculosis, or by certain types of
fungi.
● The causative organisms are attacked by large
numbers of lipid-containing macrophages.
Necrosis of these macrophages produces a
solid, amorphous, cheesy material.
● Enzymatic fat necrosis
● injury to the pancreas and surrounding adipose
tissue as a result of leakage of that organ’s
digestive enzymes,
● produces chalky, yellow-white nodules
somewhat resembling caseous necrosis. T
● Gangrenous necrosis (gangrene) is coagulation
necrosis with superimposed decomposition by
bacteria.
● It is similar to postmortem decomposition
except that only a portion of the body is dead
● Apoptosis, often referred to as “programmed
cell death.” Unlike necrosis, it is not
accompanied by any evidence of inflammation.
● It results from the activation of specific genes
following appropriate stimuli.
● The cell is induced to dismantle its metabolic,
synthetic and genetic machinery secondary to a
specific internal or external message
● Apoptotic cell death is not necessarily an
indication of injury. Any cells that have outlived
their usefulness are eliminated via apoptosis.
● Apoptosis also occurs normally in tissues that
are continuously proliferating, such as the
mucosa of the gastrointestinal tract.
● apoptosis regulates normal functions or
developmental sequences.
● The most powerful stimulus for apoptosis under
pathologic conditions is irreparable damage to
DNA by radiation or chemotherapy
Necrosis
 Inflammation
● Inflammation is a defense mechanism that
protects the body from injury and promotes
repair.
 Acute Inflammation
● Acute inflammation consists of a tightly coordinated sequence
of vascular and cellular events.
● Vascular phase results in increased blood flow to the injured
area and increased vascular permeability so that water,
electrolytes, and serum proteins leak into the tissue spaces.
● Cellular phase, leukocytes, predominantly neutrophils and
monocytes, move from the blood into the tissue at the site of
injury.
● Vascular and cellular phases produce the cardinal signs of
inflammation: redness, swelling, heat, pain, and loss of
function.
 Sequence of Events in Acute
Inflammation
● Vascular phase - small vessels at the site of tissue injury dilate and
become leaky.
● Mast cells, which typically reside close to blood vessels, are
stimulated to release histamine, a molecule that causes smooth
muscle cells in the walls of small vessels to relax. The caliber of
small blood vessels at the site of tissue injury immediately increases
in response to histamine. This causes the flow of blood within the
vessel lumen to become sluggish. Pooling of blood in the vascular
bed is called stasis, and is the reason that injured tissue appears red.
● Histamine also causes the blood vessels to become leaky, so that
large proteins and water escape from the vessels into the tissue. This
causes edema or swelling of the tissue at the site of injury.
● Cellular phase of inflammation, white blood cells (leukocytes) leave
the circulatory system, move to the site of injury, and become
activated.
● Neutrophils and macrophages.
●
They move from their normal central location in the bloodstream to
the periphery as the venule dilates and the flow of blood slows.
●
This is called margination. The marginated leukocytes then stick to
the endothelial cells (adhesion), crawl between endothelial cells into
the tissue (emigration), and finally move through the tissue to the
site of injury via chemotaxis.
●
Chemotaxis is the movement of white blood cells in response to a
chemical gradient.