By Muhammad Aurang zeb For Nursing Allied health Sciences in health and Medicine

1. TRAUMA AND CELLULAR INJURY
Pathophysiology
By: Muhammad Aurangzeb
MPH, BSN
Instructor
KHYBER MEDICAL UNIVERSITY PESHAWAR
October 29th 2017

2. OBJECTIVES
• Define cell injury.
• Explain the process of cell injury.
• Discuss reversible and irreversible cell injury.
• Describe the mechanism of cell injury.
• Discuss cell death, Mechanisms and types of
necrosis, Mechanisms and significance of
apoptosis.

3. Cellular adaptation
• Cells are the structural and functional units of
tissues and organs. They are capable of
adjusting their structure and functions in
response to various physiological and
pathological conditions. This capability is
called cellular adaptation.

4. Cellular adaptations include:
• Atrophy--shrinkage of cells
• Hypertrophy--increase in the size of cells
which results in enlargement of the organs
• Hyperplasia--increased number of cells in an
organ or tissue
• Metaplasia-transformation or replacement of
one adult cell type with another

5. Trauma
• Trauma is an injury (such as a wound) to living
tissue caused by an extrinsic agent
or
• Trauma is injury or damage caused by physical
harm from an external source.

6. Cell Injury
• If the cells fail to adapt under stress, they
undergo certain changes called cell injury. The
affected cells may recover from the injury
(reversible) or may die (irreversible).

7. Reversible cell injury
• It denotes pathologic changes that can be
reversed when the stimulus is removed or if
the cause of injury is mild.
• IRREVERSIBLE CELL INJURY
• It denotes pathologic changes that are
permanent and cause cell death.

8. Mechanism of cell injury
• There are several pathogenic mechanisms
through which cell injury can take place. One
or more than one of the following biochemical
reaction may be involved.
• 1. Impaired cell membrane function.
• 2. Decreased energy production.
• 3. Genetic alteration
• 4. Metabolic derangement.

9. Causes of Cell Injury
• Hypoxia
• physical agents
• chemical agents
• infections agents
• immunologic reactions
• genetic defects
• nutritional imbalances

10. Hypoxia
• Lack of oxygen due to,
• Ischemia due to arterial occlusion.
• Inadequate oxygenation of blood secondary to
pulmonary disease.
• Loss of oxygen carrying capacity of blood as in
anemia.
• Decreased tissue perfusion as occurs in
hypotension,shock and cardiac failure.

11. Physical agents
• Trauma, radiation, electric shock.
• Extremes of temperatures.
• Sudden change in atmospheric pressure.

12. Chemical Agents
• Glucose or salt in hypertonic concentration.
• Oxygen in high concentration.
• Poison insecticide.

13. Infections agents
• Bacteria, viruses, fungi, parasites.
• Immunologic Reaction
• Anaphylactic reaction, autoimmune disease.

14. Genetic defects
• Congenital malformation, sickle cell anemia.
• Nutritional Imbalances
• Hypovitaminosis, Protein caloric malnutrion.

15. Free Radicals
• Oxygen derived free radicals are chemical
species with a single unpaired electron in an
outer orbit.
• When generated in cells, they rapidly attack
and degrade nucleic acids and membrane
molecules.

16. Generation of free radicals
• Free radical may be generated with in cell by,
• Normal metabolism (oxidation reduction)
• Oxygen toxicity.
• Ionizing radiation
• Drugs and chemicals.
• Cellular aging
• Acute inflammation

17. Mechanism of cell injury by free radicals
• Lipid Peroxidation of membrane resulting in
cellular and mitochondrial membrane
damage.
• DNA damage.
• Loss of enzymatic activity by promoting cross
linking of protein.

18. Reversible cell injury
• Hypoxia affects mitochondria that results in
decreased synthesis of ATP. As a result
changes develop in cell structure which are
reversible if oxygen supply is restored.
• 1. Cellular swelling.
• 2. Desegregation of ribosomes and failure of
protein synthesis.
• 3. Reduction intracellular pH.
• 4. Appearance of myelin figures and cell
blebs.

19. Irreversible cell injury
• Irreversible/Necrosis:
The changes are produced by enzymatic
digestion of dead cellular elements,
denatunation of proteins and autolysis (by
lysosomal enzymes)
• Cytoplasm - increased eosinophilia
• Nucleus - nonspecific breakdown of DNA
leading to pyknosis (shrinkage), karyolysis
(fading) and karyorrhexis (fragmentation).

20. Necrosis
• After death the cell shows no change initially
then within a few hours autolysis occurs and
the cell shows morphological changes by
which cell death can be recognized.
• Necrosis refer to a sequence of morphologic
changes that follow cell death in living tissue.

21. Conti..
• The morphologic changes caused by the
progressive degradative action of enzymes on
dead cells is called necrosis.

22. Mechanism of Necrosis
• Two processes cause the basic morphologic
changes of necrosis.
• Enzymatic degradation of cell.
• Denaturation of protein.

23. Cell Death
• Death of cells occurs in two ways:
• Necrosis--(irreversible injury) changes
produced by enzymatic digestion of dead
cellular elements
• Apoptosis--vital process that helps eliminate
unwanted cells--an internally programmed
series of events effected by dedicated gene
products

24. Patterns of Necrosis In Tissues or Organs
• As a result of cell death the tissues or organs display
certain macroscopic changes:
• Coagulative necrosis: the outline of the dead cells
are maintained and the tissue is somewhat firm.
Example: myocardial infarction
• Liquifactive necrosis: the dead cells undergo
disintegration and affected tissue is liquified.
Example: cerebral infarction.

25. Cont…
• Caseous necrosis: a form of coagulative necrosis
(cheese-like). Example: tuberculosis lesions.
• Fat necrosis: enzymatic digestion of fat. Example:
necrosis of fat by pancreatic enzymes.
• Gangrenous necrosis: Necrosis (secondary to
ischemia) usually with superimposed infection.
Example: necrosis of distal limbs, usually foot and
toes in diabetes.

26. Apoptosis
• This process helps to eliminate unwanted cells by an
internally programmed series of events effected by
dedicated gene products. It serves several vital
functions and is seen under various settings.
• During development for removal of excess cells
during embryogenesis
• To maintain cell population in tissues with high
turnover of cells, such as skin, bowels.
• To eliminate immune cells after cytokine depletion,
and autoreactive T-cells in developing thymus.

27. Cont..
• To remove damaged cells by virus
• To eliminate cells with DNA damage by
radiation, cytotoxic agents etc.
• Hormone-dependent involution -
Endometrium, ovary, breasts etc.
• Cell death in tumors.

28. Morphology of Apoptosis
• Shrinkage of cells
• Condensation of nuclear chromatin peripherally
under nuclear membrane
• Formation of apoptotic bodies by fragmentation of
the cells and nuclei. The fragments remain
membrane-bound and contain cell organelles with or
without nuclear fragments.
• Phagocytosis of apoptotic bodies by adjacent
healthy cells or phagocytes.
• Unlike necrosis, apoptosis is not accompanied by
inflammatory reaction

29. Cont..
• Apoptosis goes through several complex
phases. To put it simply, abnormal
mitochondrial membrane permeability is a
crucial event which allows escape of
cytochrome-c into the cystosol which, in turn,
activates proteolytic enzymes (caspases)
leading to the execution of the process. The
final phase is the removal of dead cell
fragments by phagocytosis without
inflammatory reactions.

30. REFERENCES
• McCance L.Katheryn and Huether E.Sue
(2002),THE BIOLOGIC BASIS FOR DISEASE IN
ADULTS AND CHILDREN,Ed 4th ,Chapter 2,
Page 43-80.
• Danish Inam Mohammad(2009), SHORT
TEXTBOOK OF PATHOLOGY ,Ed 4th ,Chapter 2
and 6, Page 3-19 and 54-57.