CELL INJURY PATHOLOGY

7/29/2019 CELL INJURY PATHOLOGY

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Components Of CellInjury

By

Dr.A.Sridhar

MPT(Neurology)



• What is Cell injury?



Cell injury

• When the cell is exposed to an injurious agent

or stress, a sequence of events follows that is

loosely termed as CI



• What are adaptive response?

• What are the consequences due to cell injury?



• Hypertrophy

• Hyperplasia

•

Atrophy• Metaplasia



Cellular Changes and its types



Myocyte Changes



Hypertrophy

• An increase in the size of cells resulting in

increase in the size of the organ.

• Examples of P & P



Hyperplasia

• Characterized by an increase in cell number

• Types

– hormonal hyperplasia

• proliferation of the glandular epithelium of the female

breast at puberty and during pregnancy

– compensatory hyperplasia

• hyperplasia that occurs when a portion of the tissue isremoved or diseased



Guess ?



Atrophy

•

Shrinkage in the size of the cell by the loss of cell substance

• Causes

–

decreased workload – loss of innervation

– diminished blood supply

–

inadequate nutrition – loss of endocrine stimulation

– aging



Guess ?



Metaplasia

• Reversible change in which one adult cell type

(epithelial or mesenchymal) is replaced by

another adult cell type

• cells sensitive to a particular stress are

replaced by other cell types better able to

withstand the adverse environment

• Smokers



Guess ?



Autophagy

• is the process in which the starved cell eats its

own components in an attempt to find

nutrients and survive.



Autophagy



Cell injury and cell death



Patterns Of Cell Death

• There are two principal patterns of cell death:

1- Necrosis and

2- Apoptosis



Mechanism of cell injury

• ATP production



MECHANISM OF CELL INJURY

1. DEPLETION OF ATP:

. ATP depletion and decreased ATP synthesis areassociated with both hypoxic and chemical

(toxic) injury .

. ATP is required for many synthetic and

degradative processes within the cell.



MECHANISM OF CELL INJURY cont.

• ATP is produced in two ways.

A- The major pathway is oxidative

phosphorylation of adenosine diphosphate.

B-The second is the glycolytic pathway , which

generate ATP in absence of oxygen using

glucose derived from body fluids or from

glycogen




Effects of depleted ATP

a) The activity of the plasma membrane

energy-dependent sodium pump is reduced.

It causes sodium to accumulate intracellularly

and potassium to diffuse out of the cell

causing cell swelling, and dilation of the

endoplasmic reticulum.




b) If oxygen supply to cells is reduced, as inischemia, oxidative phosphorylation ceasesand cells rely on glycolysis for energy

production (anaerobic metabolism) resultingin depletion of glycogen stores.

Glycolysis results in the accumulation of lacticacid which reduces the intracellular pH,resulting in decreased activity of many cellularenzymes.




c) Failure of the Ca2+ pump leads to influx of Ca2+, with damaging effects on numerouscellular components

d) Ribosomes detach from the RER andpolysomes breakdown into monosomes,leading to reduction in protein synthesis.Ultimately, irreversible damage tomitochondrial and lysosomal membranesoccurs, and cell undergoes necrosis




e) In cells deprived of oxygen or glucose,

proteins may become misfolded, and trigger

the unfolded protein response leading to cell

injury and even death.




2- Mitochondrial Damage:

. Mitochondria are important targets for all

types of injury, including hypoxia and toxins.




- Cells have defense systems to prevent injury

caused by these products.

- An imbalance between free radical-

generating and radical-scavenging systems

results in oxidative stress causing cell injury .




Free radical-mediated damage are seen in

- chemical and radiation injury

- ischemia-reperfusion injury- cellular aging, and

- microbial killing by phagocytes.




- Free radicals are chemical species that have single unpairedelectron in an outer orbit.

- They are initiated within cells in several ways:

a) Absorption of radiant energy (e.g., ultraviolet light, x-rays).

b) Enzymatic metabolism of exogenous chemicals or drugs .




c) The reduction-oxidation reactions that occur during normal metabolic processes. During normal respiration, smallamounts of toxic intermediates are produced; these includesuperoxide anion radical (O2-), hydrogen peroxide (H2O2),and hydroxyl ions (OH).

d) Transition metals such as iron and copper

e) Nitric Oxide (NO), an important chemical mediatorgenerated by various cells, can act as a free radical.



Necrosis

Necrosis is the type of cell death that occurs

after ischemia and chemical injury

Necrosis is always pathologic



Apoptosis

• Apoptosis occurs when a cell dies through

activation of an internally controlled suicide

program.

• Apoptosis is designed to eliminate unwanted

cells during embryogenesis and in various

physiologic processes and certain pathologic

conditions



APOPTOSIS

• Apoptosis is programmed cell death.

• It is a pathway of cell death that is induced by a tightlyregulated intracellular program in which cells destined to die

activate their own enzymes to degrade their own nuclearDNA, nuclear proteins and cytoplasmic proteins.

• The cell's plasma membrane remains intact, but its structureis altered in such a way that the apoptotic cell sends signal to

macrophages to phagocytose it.



Features of Necrosis and Apoptosis

Feature Necrosis ApoptosisCell size Enlarged (swelling) Reduced (shrinkage)

Nucleus Pyknosis→ karyorrhexis→

karyolysis

Fragmentation into

nucleosome-size

fragmentsPlasma membrane Disrupted Intact; altered structure,

especially orientation of

lipids

Cellular contents Enzymatic digestion; may

leak out of cell

Intact; may be released in

apoptotic bodies

Adjacent inflammation Frequent No

Physiologic or pathologic

role

Invariably pathologic

(culmination of irreversible

cell injury)

Often physiologic, means

of eliminating unwanted



Causes of Cell Injury

• Hypoxia

• Physical Agents – Mechanical trauma,

– Burns,

– Deep cold

– Sudden changes in atmospheric pressure, – radiation, and electric shock

• Chemical Agents and Drugs

• Infectious Agents e.g. bacteria, fungi, viruses and

parasites.• Immunologic Reactions.

• Genetic Derangements.

• Nutritional Imbalances



Cellular and biochemical sites of

damage in cell injury



Functional and morphologic consequences of

decreased intracellular ATP during cell injury.



THE MORPHOLOGY OF CELL AND

TISSUE INJURY



A normal cell and the changes in reversible

and irreversible cell injury (necrosis).



Cellular Aging

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CELL INJURY PATHOLOGY