There are two main patterns of cell death: necrosis and apoptosis. Necrosis is characterized by cell swelling and membrane rupture, releasing cellular contents. Apoptosis involves cell shrinkage and intact membranes, with nuclear fragmentation. Cell injury can result from hypoxia, depletion of ATP, calcium influx, oxidative stress, and free radical damage. Specific mechanisms include impaired sodium/potassium pumping and protein synthesis, mitochondrial damage, and lipid peroxidation. This leads to loss of organelles and cellular digestion.

2. Mechanisms of Cell Injury

4. There are two Patterns Of Cell death
Features Necrosis Apoptosis
Cell Size (Enlarged(swelling (Reduced(shrinkage
Nucleus Pyknotic  Karyorrhexis Fragmentation into nucleosome size
 Karyolysis fragments
Plasma Disrupted Intact; altered structure, especially
Membrane orientation of lipids
Cellular Enzymatic digestion; may Intact; may be released in apoptotic
Content leak out of cell bodies
Adjacent Frequent No
inflammation
Physiologic Often physiologic, means of
and Pathologic eliminating unwanted cells; may be
role Invariably pathologic pathologic after some forms of cell
injury, especially DNA damage

5. : ( Oxygen Deprivation (Hypoxia( 1
Hypoxia is an extremely important and
.common cause of cell injury and cell death
Hypoxia is inadequate oxygenation of the( 1
.blood due to cardio respiratory failure
Loss of the oxygen-carrying capacity of the( 2
blood, as in anemia or carbon monoxide
poisoning
Depending on the severity of the hypoxic
.state, cells may adapt, undergo injury, or die

6. Hypoxia
. Most common cause of cell injury
. Hypoxia : inadequate oxygenation of tissue( 1
. MAJOR CAUSES OF HYPOXIA
. Ischemia: decreased arterial blood flow to tissues
. Most common cause of hypoxia
Ex: Atherosclerosis in coronary arteries due to
. deposition of lipid in intima of blood vessels
Hypoxemia: decrease in the amount of oxygen dissolved in
: plasma. Seen in
Atelectasis, pulmonary embolus and interstitial fibrosis
. of lung
Hemoglobin related abnormalities
Anemia
Carbon monoxide poisoning (CO has high affinity for
(. hemoglobin
Will get HEADACHES

7. Causes of cellular injury
Physical agents: mechanical trauma, burns, frostbite,( 2
sudden changes in pressure, radiations, electric shock
Chemical agents: poisons (toxins), insecticides, CO,( 3
asbestos, alcohol, tobacco, glucose, salt, oxygen
Infectious agents: Viruses , rickettsiae, bacteria, fungi,( 4
parasites
Immunologic reactions: anaphylaxis, autoimmune( 5
.disease
Nutritional imbalances: protein calorie deficiency, vitamin( 6
(deficiencies, excess food intake (obesity, atherosclerosis
Genetic derangements: congenital malformations,( 7
abnormal proteins (hemoglobinopathies), abnormal or absent
(.enzymes (storage disorders

8. :By Depletion of ATP( 1
Mechanisms of Cell Injurya( The activity of the plasma membrane energy-
dependent sodium pump (Na+,K+-ATPase( is
reduced. diminished ATP concentration and
enhanced ATPase activity, causes sodium to
accumulate intracellular and potassium to diffuse
out of the cell. isosmotic gain of water, cause cell
swelling, & dilation of the endoplasmic reticulum
b( oxidative phosphorylation ceases and cells
rely on glycolysis for energy glycogen stores are
rapidly depleted. accumulation of lactic acid and
inorganic phosphates from the hydrolysis of
phosphate esters. This reduces the intracellular
pH, resulting in decreased activity of many
..cellular enzymes
, +c( Failure of the Ca2+ pump leads to influx of Ca2
Damaging effects on numerous cellular components
d( detachment of ribosome from the rough
endoplasmic reticulum and dissociation of
polysomes into monosomes, with a
.consequent reduction in protein synthesis
e( proteins may become misfolded, the
unfolded protein response that may lead to cell
.injury and even death

9. oxidative phosphorylation↓
Ischemia
ATP↓↓
↓ Na pump ↑Glycolysis Ribosomal Detachment
Influx of Na, H2O ↓ Glycogen ↑ Lactic acid ↓ Protein
+
Ca2& Synthesis
Efflux of K
↓ pH
Cell Swelling
ER swelling
Loss of microvilli Nuclear chromatin
Membrane blebs clumping

10. 2) MITOCHONDRIAL DAMAGE
Mitochondria are
important targets for
virtually all types of
,injurious stimuli
hypoxia and toxins( 1
a( increases of
,+cytosolic Ca2
b( by oxidative
, stress
c( by breakdown of
phospholipids
through the
phospholipase A2
and sphingomyelin
pathways, and by
d(lipid breakdown
products

11. INFLUX OF INTRACELLULAR CALCIUM( 3
AND LOSS OF CALCIUM HOMEOSTASIS
The enzymes known to
be activated by calcium
include
a) ATPases (thereby
hastening ATP
(, depletion
b) phospholipases
(which cause membrane
(, damage
c) proteases (which
break down both
membrane and
cytoskeletal proteins(,
and
d) endonucleases
(which are responsible
for DNA and chromatin
(fragmentation

12. ACCUMULATION OF OXYGEN-DERIVED FREE RADICALS( 4
(Reactive Oxygen Species (OXIDATIVE STRESS
The reduction-oxidation reactions that occur during normal metabolic **
process. During normal respiration, molecular oxygen is sequentially
.reduced by the addition of four electrons to generate water
Reactive Oxygen Species : toxic intermediates are produced; these include**
superoxide anion radical (O2-(, hydrogen peroxide (H2O2(, and hydroxyl ions
. (OH(.this free can damage lipids,protiens, and nucleic acids
:Cells have defence system against to prevent injury by free radicals
Antioxidants either block the initiation of free radical formation or( 1
inactivate and terminate radical damage(scavenging system(. Examples are
.the lipid-soluble vitamins E , A , Vit C and glutathione in the cytosol
Enzymes: which breaks down H2O2,superoxide O2- helps in protecting ( 2
against the bad effects of free radicals e.g. Catalase, Superoxide dismutase,
.glutathion peroxidase
An imbalance between free radical generating and radical scavenging **
.system leads to oxidative stress causing cell injury

15. :Free Radical- mediated damage are seen in
Chemical and Radiation Injury( 1
Ischemia- Reperfusion Injury( 2
Cellular aging and( 3
.Microbial Killing by Phagocytes( 4
: The effects of these reactive species are
Lipid peroxidation of membranes results in*
extensive membrane, Organellar and cellular damage
Oxidative modification of proteins resulting protein*
.fragmentation
Lesions in DNA are responsible for aging and *
malignant transformation of cells

16. Mitochondrial dysfunction*
Loss of membrane phospholipids *
Plasma membrane damage results in loss of
osmotic balance and influx of fluids and ions,
as well as loss of proteins, enzymes,
coenzymes, and ribonucleic acids. The cells
may also leak metabolites, which are vital for
the reconstitution of ATP, thus further
depleting net intracellular high-energy
. phosphates
Injury to lysosomal membranes results in*
leakage of their enzymes into the cytoplasm
and activation of these enzymes. Lysosomes
contain RNases, DNases, proteases,
phosphatases, glucosidases, and
cathepsins. Activation of these enzymes
leads to enzymatic digestion of cell
components, resulting in loss of
ribonucleoprotein, deoxyribonucleoprotein,
, and glycogen
.and the cells die by necrosis
Cytoskeletal abnormalities*