Pathology cell injury

1. Cell injury
Pre by Lect: MR Muhammad Imran Khan
Lecturer MLT department suit

2. When the limits of adaptive responses are
exceeded cell injury occurs or when the cell
cannot adapt to new environment, initially
reversible, then irreversible leading to cell
death.
Reversible cell injury.
Pathological changes that can be reversed when
stimulus or stress is removed or mild injury.
Irreversible cell injury.
Pathological changes that are permanent and
cause cell death.

3. Example
Low dose of toxic / briefly duration of ischemia _
reversible injury
Long dose of toxic / long duration of ischemia_
irreversible injury
Skeletal muscle in the leg accommodate complete
ischemia for 2-3 hours without irreversible injury
Cardiac muscale dies after 20-30 mintes

4. causes
Hypoxia
Physical agents
Chemical agents
Microbiologic agents
Immunologic reaction
Genetic defects
Nutritional imbalance

5. Lack of oxygen in the tissue. Causes are
..ischemia . Loss of blood supply due to artery occulusion.
Pulmonary disease
Loss of oxygen carrying capacity of blood
Decrease tissue perfusion as occure hypotension , shock
and cardaic failure.
Physical agents
Trauma , radiation , electric shock , extreme temperature,
sudden change in atm pressure all have wide ranging
effects on cells.

6. Chemical agents
Glucose or salt in hypertonic concentration
Poisons
Insecticides , carbon monoxide , alcohol
Drugs
Microbiological agents
Bacteria , viruses , fungi, parasites
Genetic defects
Congenital malformation, sickle cell anemia, down syndrome
Nutritional imbalances
Under nutrition, over nutrition
Immunological
Protective mechanism, fight our own cell as enemy they
produce auto immune response

7. Target of cell injury
1. Mitochondria (site of ATP generation)
2. Cell membrane
3. Protein synthesize
4. Cytoskeleton
5. DNA

8. Process of cell injury

9. Morphological changes of cell

10. Mechanisms of cellular injury
 Energy depletion (ATP)
 Mitochondrial permeability transitions
 Rise in cytosolic calcium concentration
 Free radicals, reactive (activated) oxygen species
(ROS) oxidize membrane lipids
 Plasma membrane damage and permeability
changes
 DNA and protein structural damage

11. Causes of hypoxia
Ischemia
 Atherosclerosis
hardened lumpy plaque of lipid, lymphocytes and
foam cells
 Thrombosis
◦ thrombus = lump: clot of coagulated blood that
forms within a blood vessel
 Embolism
◦ embolos = stopper: clot or gas bubble that
travels from site of formation to block a small
vessel.
Hypoxemia
Causes: decrease inspiration (high altitude)
Hypoventilation due to respiratory distress
Ventalation defect

12. ATP DEPLETION - HYPOXIA/ISCHAEMIA
 Mitochondria - reduced oxidative phosphorylation,
this is the aerobic mechanism which need oxygen.
 Cell membrane - reduced sodium pump.
 Sodium and water enter the cell; potassium exits.
 Increase osmolority inside the cell.
 Pull of water inside the cell.
 Endoplasmic reticulum dilates, the cell swells,
blebs appear.
 Anaerobic glycolysis occurs with loss of glycogen,
accumulation of lactic acid, acid pH which
interferes with enzymes.

13.  Failure of the calcium pump leads to influx of Ca++
into the cell, activate various enzymes to the
detriment of the cell.
 Activate the number of enzymes which is so
danger and destroyed the cell.
 RER loses ribosomes and protein synthesis falls -
structural proteins (membranes,cytoskeleton) and
enzymes.

15. IMPORTANCE OF CALCIUM
 Influx of calcium to the cytosol comes from the
extracellular fluid and stores in mitochondria and
endoplasmic reticulum.
 Ca++ activates phospholipases (damages cell
membranes),proteases (damages cell membranes
and cytoskeleton) and endonucleases (damages
DNA).
 This is one of the main mechanisms of cell death,
either through severe damage to membranes of
lysosomes and leakage of lysosomal enzymes or
triggering apoptosis.
 Occurs particularly in hypoxia and ischaemia and
with certain toxins. Preventing the rise in Ca++ or
restoring to normal levels prevents cell death.

17. Reversible ischemic injury
 Reduced oxygen tension inhibits ATP production
and increases glycolysis, anaerobic respiration
 Increased glycolysis decreases pH, denatures
proteins, activates acid proteases and
phosphatases
 ATP depletion inhibits active transport of ions
across membranes
 Decreased ion transport flattens ion gradients and
disrupts osmotic gradients
 Disrupted osmosis results in swelling
 Swelling smoothes endoplasmic reticular
membranes, decreases protein synthesis,
disperses cytoskeletal ultra structure
 Nuclei remain intact and cells may restore integrity

18. Irreversible ischemic injury—infarction
 Infarction localized area of necrosis in a tissue
results from hypoxia, secondary to ischemia
 Swollen cells have altered cytosolic pH, [Ca++],
[Na+]
 Proteins denatured by increased acidity and ionic
environment
 Cytoplasmic [Ca++] normally 1000 – 10000 times
less than extracellular and organellar
concentrations
 Loss of ATP-dependent Ca++ transport allows
influx from mitochondria, ER, extracellular fluid
 Ca++ activates degradative enzymes
 Phospholipase A, ribonucleases, proteases
degrade membranes, ribosomes, structural

20. THE IMPORTANCE OF FREE RADICALS
 Free radicals have a single unpaired electron in the
outer orbit or another term for free redical is
reactive oxygen species(ROS).
 Are usually derived from oxygen to produce
reactive oxygen species, superoxide, hydroxyl
radicals,H2O2,etc.
 Are normally produced during cellular respiration.
ROS are generated by normal physiologic
reduction oxidation reaction, ultravoilet light, x.ray
and ionizing reaction.
 Produced in excess, they react with, and damage
proteins, lipids, carbohydrates, nucleic acids.
 These damaged molecules may themselves be
reactive species with a chain reaction being set up

21. Free radicals cause lipid peroxidation in cell
membranes, oxidation of amino acids and proteins
resulting in fragmentation, and protein-protein
cross linkages. Altered proteins are acted on by
the proteosomes with further cell damage , DNA
fragmentation.

23. Cell death
 Cell death – is an irreversible change in the cell a
 We can distinguish two different types of cell death,
that differ one from another in many aspects,
particularly
in morphologic changes
in pathogenesis
These are
necrosis
Apoptosis

24. Necrosis
Death of groups of contiguous cells in tissue or organ
or the cell is killed “murder”
Necrosis is the most common pattern of cell death .
Causes of necrosis are trauma or demage.
it.s involve large group of cell. Necrosis is always
pathological process. In necrosis inflammation
occure in the body.

25. Types of necrosis
◦ Coagulative necrosis
◦ Liquefactive necrosis
◦ Caseous necrosis
◦ Fat necrosis
◦ Gangrene necrosis

26. Coaglative necrosis
Keep the shape but lose the nuclie.
 Cells have died but the basic shape and
architecture of the tissue endures
 Most common manifestation of ischaemic necrosis
in tissues.
 this pattern of necrosis-most commonly results
from sudden severe ischemia (is encountered
mostly in solid organs, such as kidney, heart,
spleen, adrenal glan
 focus)
 The best example is mycordial infartion.

27. Coagulative necrosis

28. Liquefactive necrosis
Complete enzymatic degradation of the tissue.
 Complete dissolution of necrotic tissue.
 Most commonly due to massive infiltration by
neutrophils (abscess formation).
◦ Release of reactive oxygen species and
proteases
 Liquefaction is also characteristic of ischaemic
necrosis in the brain.
 characteristic of ischemic necrosis of brain,
pancreas
 also common in bacterial lesions - due to activity of
enzymes of bacterial and leukocytic origin good
example of liquefactive necrosis is brain infarction

30. Caseous necrosis
another distinctive type of necrosis that is a
combination of coagulative and liquefactive
necrosis. It is encountered in tuberculousis.
 Tissue architecture is abolished and viable cells
are no longer recognizable.
 Characteristically associated with the
granulomatous inflammation of tuberculosis. Also
seen in some fungal infections.

32. Fat necrosis
 Results from the action of lipases released into
adipose tissue.
◦ pancreatitis, trauma.
 Free fatty acids accumulate and precipitate as
calcium soaps (saponification).
◦ These precipitates are grossly visible as pale
yellow/white nodules
 Microscopically, the digested fat loses its cellular
outlines. There is often local inflammation

33. Fat necrosis

34. Gengrene necroses
Due to ischemia or infection.
Toe and diabetec.
 dry gangrene
 wet gangrene
 gas gangrene

35. APOPTOSIS
Its designation „apoptosis“- it is a word from Greek
language, which originally refers to falling of leaves
from trees in the autumn.
Apoptosis means the cell kill it.s self(suicide)
programmed cell death.
In apoptosis some thing force to cell to suicide due
to external factor or internal factor.it.s involve one
cell or small group of cell.apoptosis could be
physiological or pathological.
Sequence of events in apoptosis
1- elevation of cellular calcium and rapid reduction
of volume of the cell

36. 3- fragmentation of DNA and marked condensation
of both nucleus and cytoplasm
4- formation of apoptotic bodies- small apoptotic
bodies are composed of fragments of nuclei with
condensed chromatin.
 5- apoptotic bodies are rapidly phagocytosed
by epithelial cells in neibourghood or by
macrophages - cell dying by apoptosis are
recognized and phagocytosed soon after initiation
of apoptosis.

37. Morphological changes
Cell size reduced (shrinkage ) in apoptosis.
Fragmentation of nucleus size.
Cell membrane intact in apoptosis.
Intact may be release apoptotic bodies.
No inflammation occure in apoptosis.

38. Physiological apoptosis
Seperation of finger in embryogenesis
Hormonal withdrawal breast and uterus
Atrophy
some time not enough have apoptosis causes
Cancer
Auto immune disease

39. Final thought…
Our lives are filled with joys and strife,
And what is death but part of life?
Will come the day that we must die,
And leave behind those learning why.

40. THANK YOU