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CELLULAR INJURY MORPHOLOGY
When conditions for cells living are changed these cells also alter themselves to survive through a
process called adaption which entails cellular processes such as hypertrophy-increase in cell size,
atrophy-decrease in cell size, hyperplasia- increase in the number of cells and even metaplasia which is
the conversion of one differentiated cell type to another. There however the cells reach a stage wherethe cells are so severely stressed (through excessive exposure to inherently damaging agents) adaption
is no longer sufficient, resulting in cell injury. Cell Injury may either be reversible or irreversible.
Reversible cellular injury is as it name states reversible provided that the stimulus causing the injury is
removed at an appropriate time. The hallmarks of cellular injury are reduced oxidative phosphorylation,
adenosine triphosphate (ATP) depletion, and cellular swelling. There are two patterns associated with
reversible cell injury which are:
1) Cellular swelling
2) Fatty change
Cellular swelling is usually the first manifestation of almost all forms of injury to cells. It appears when
cells are unable to maintain their ionic and fluid homeostasis and is the result of loss of function of
plasma membrane energy dependent ion pumps such as sodium, potassium pump. It is a difficult
morphological change to see with a light microscope but is quite recognizable when viewing an entire
organ. When many cells are affected in an organ, it causes increased tugor, increased weight of the
organ as well as some pallor (which is a reduced amount of oxyhaemoglobin in the skin or mucous
membrane). When examined microscopically, small clear vacuoles may be seen within the cytoplasm
which represents distended and pinched-off segments of the endoplamic reticulum. This morphological
pattern is also termed as hydropic change or vacuolar degeneration. This swelling is reversible provided
that the stimulus is removed.
IN CELLULAR SWELLING, AT GROSS EXAMINATION, THE AFFECTED ORGAN IS ENLARGED, PALE AND SOFT.
MICROSCOPICALLY, THE CELLS ARE ENLARGED, WITH A CLEAR CYTOPLASM (DUE TO THE PRESENCE OF SMALL
CLEAR OR PALE VACUOLES, WITH INDISTINCT SHAPE AND LIMITS) AND A NORMAL NUCLEUS IN CENTRAL
POSITION; BLOOD CAPILLARIES ARE COMPRESSED, EXPLAINING THE ORGAN'S PALLOR.
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Normally stainable fat is present only in adipose tissue. In cell injury due to hypoxia or poisoning, lipid
droplets, membrane bound in rough endoplasmic reticulum RER and Golgi complex - (liposomes) or non-
membrane bound, may be present. Fatty change is commonly seen in the liver in alcoholism due to
impaired lipoprotein synthesis. In starvation - due to increased mobilisation of adipose tissue and
excessive supply of fatty acids to liver choline deficiency due to reduced lipoprotein synthesis. Usually
heart, liver, kidney and skeletal muscle are affected by this type of cellular injury. Under the light
microscope small fat vacuoles can be seen in affected cells, the small vacuoles may then join to form
larger vacuoles consequently causing the nucleus to be pushed to the periphery. In an organ is viewed
with fatty change a greasy, yellow appearance is observed. If the stimulus causing this cellular injury is
removed this morphological change will be reversed.
LIVER CELLS SHOWING FATTY CHANGE
If the stimulus causing the cell injury persists, there reaches a point where the cells cannot recover. In
ischemic tissues such as the myocardium, certain structural changes (e.g., amorphous densities in
mitochondria, indicative of severe mitochondrial damage) and functional changes (e.g., loss of
membrane permeability) are indicative of cells that have suffered irreversible injury. Irreversibly injured
cells invariably undergo morphologic changes that are recognized as cell death. There are two types of
cell death, necrosis and apoptosis, which differ in their morphology, mechanisms, and roles in disease
and physiology.
Necrosis
Necrosis is quite a common pattern of morphological change witnessed after cell death and is usually
related to cell injury or cell death caused by external agents e.g chemicals, hypoxia and infectiousagents.
Necrosis is the more common pattern of morphologic changes seen after cell death and is usually
related to cell injury/death caused by external agents e.g. chemicals, hypoxia, and infectious agents.
These changes occur as a result of:
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1. Enzymatic digestion of the cell (intracellular and extracellular enzymes)
2. Denaturation of proteins
These changes take hours to be seen with the light microscope, but ultrastructural changes can be seen
with the electron microscope within minutes. The main features seen with the light microscope
involving individual cells are:
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Apoptosis
Apoptosis, from Greek apo apart and ptossi for fallen, means fallen apart. It is a process of
programmed cell death of single cells scattered in a population of healthy cells. It is equated
with cell suicide, eliminates cells that are worn out or produced in excess. It is a physiological
process involving, controlled cell destruction and is involoved in normal cell deletion and
renewal.
Stages:
a. cells appear to initiate their own death by stimulation of endogeneous enzymes
resulting in cell shrinkage. This is brought about by disruption of the cytoskeletondisruption and clumping of nuclear DNA, wrinkling of cell membrane, in addition to,
condensation of cytoplasmic organelles.
Following this stage, the nucleus breaks down into spheres, dividing cell into spheres,
that is, membrane covered fragments.
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As the membrane changes during this process, the degradation process is completed,
with the engulfing of the apoptotic cell parts with surrounding phagocytic cells.
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* Apoptotic cells are recognised as eosinophilic bodies and do not elicit inflammatory reaction. The loss
of cells in disorders such as Alzheimers disease and Parkinsons disease does not induce inflammation.
Apoptosis is thought to be responsible for hormone dependent involution of tissues, death of immunecells, cell death by cytotoxic Tcells. It is also linked to several pathologic processes, as a determinant in
the growth of cancers and in cell death associated with viral infections, for example: Hepatitis B and C,
as well as, mild thermal injury and radiation injury.
* Apoptosis is associated with organ development and modelling in the embryo, physiological atrophy
and involution and maintenance of organ size in the adult.
* It is seen in liver in viral hepatitis, diphtheritic myocarditis, cell death in irradiation and in tumor
growth and leukemia.