YOUNAS MASIH NEW LIFE COLLEGE OF NURSING KARACHI Patho-pharma Trauma and cell injury unit-iv-b

YOUNAS MASIHNEW LIFE COLLEGE OF NURSING

KARACHI

Patho-pharmaTrauma and cell injury

unit-iv-b

Cell injury

When the cell is exposed to an injurious agent or stress, a sequence of events follows that is loosely termed cell injury.

Cell injury is reversible up to a certain point

If the stimulus persists or is severe enough from the beginning and is dangerous , the cell reaches a point of no return and suffers irreversible cell injury and ultimately cell death.

Overview

Cell injury

Reversible : Cell swelling develops when cells are

incapable of fluid an ion homeostasis (↓ed function of ATP dependant pumps).

Fatty change the accumulation of lipid vacuoles in the cytoplasm.

Irreversible cell injuryDenaturation of protein

Enzymatic digestion of cell components

Cell death

it is the ultimate result of cell injury and it can be classified as

1- Necrosis (is always pathologic) occurs after chemical or ischemia

2- Apoptosis(when a cell dies through activation of an internally controlled suicide program. )

Mechanism of cell injury

Depletion of ATP

Mitochondrial Damage

Influx of Intracellular Calcium and Loss of Calcium

Homeostasis

Accumulation of Oxygen-Derived free radical

(Oxidative stress)

Defects in Membrane Permeability

Physical agents

Nutritional imbalance


1. DEPLETION OF ATP: . ATP depletion and decreased ATP synthesis

are associated with both hypoxic and chemical (toxic) injury.

. ATP is required for many synthetic and degradative processes within the cell.


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 in ischemia, oxidative phosphorylation ceases and cells rely on glycolysis for energy production (anaerobic metabolism) resulting in depletion of glycogen stores. Glycolysis results in the accumulation of lactic acid which reduces the intracellular pH, resulting in decreased activity of many cellular enzymes.


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

d) Ribosomes detach from the RER and polysomes breakdown into monosomes, leading to reduction in protein synthesis. Ultimately, irreversible damage to mitochondrial and lysosomal membranes occurs, and cell undergoes necrosis


2- Mitochondrial Damage:. Mitochondria are important targets for all

types of injury, including hypoxia and toxins.Mitochondria can be damaged by :A- Increases Ca2+ B- Oxidative stressC- Breakdown of phospholipids,D- Lipid breakdown products.


3.INFLUX OF INTRACELLULAR CALCIUM & LOSS OF CALCIUM HOMEOSTASIS.

. Ischemia causes an increase in cytosolic calcium concentration. Increased Ca2+ in turn activates a number of enzymes, e.g.

- ATPases (thereby hastening ATP depletion),

-Phospholipases (which cause membrane damage),

- Proteases (which break down both membrane and cytoskeletal proteins), and

-Endonucleases (which are responsible for DNA and chromatin fragmentation).


4. ACCUMULATION OF OXYGEN-DERIVED FREE RADICALS (OXIDATIVE STRESS)

- Small amounts of partially reduced reactive oxygen forms are produced as a byproduct of mitochondrial respiration.

- Some of these free radicals can damage lipids, proteins, and nucleic acids.

- They are referred to as reactive oxygen species


- Free radicals are chemical species that have single unpaired electron 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, small amounts of toxic intermediates are produced; these include superoxide anion radical (O2-), hydrogen peroxide (H2O2), and hydroxyl ions (OH).


Defects In Membrane Permeability:- In ischemic cells, membrane damage may be

the result of ATP depletion and calcium-modulated activation of phospholipases.

- It can also be damaged directly by certain bacterial toxins, viral proteins etc.

- Physical mechanism- Extreme temperature - Mechanical forces


Extreme temperature Extreme heat and cold causes cell injury

(43 -46 C)It causesVascular injuryIncreasing Cell metabolismInactivation of the enzymesDisruption of the cell membrane


Exposure to low temperature Increases blood viscosity and promotes blood

vessels constrictionDecreases blood flow that may lead towards

hypoxic injuryInjury from freezing

Ice crystal formationBlood flow is decreasedThis leads to capillary stasis and thrombosisEdema is caused by the increased capillary

permeability


Nutritional imbalancesExcess and deficiencies

Problems like “beriberi”, pellagra” and scurvy are caused by nutritional imbalances

APOPTOSIS AND ITS SIGNIFICANCE

Number of cells inn the body are maintained by the cell death and cell proliferation

Significance In normal physiological process:Destruction of the cells during embryonic

developmentDeath of the immune cells Cell death in proliferating cells

APOPTOSIS AND ITS SIGNIFICANCE

ExamplesSeparation of webbed fingers and toes in

developing embryoApoptosis controls the number of auto

reactive T cells in the thymusPathological process

Suppression of this process is an indicator of the neoplastic growth

It is associated with the cell death by viral infections, thermal and radiationinjury

http://www.phschool.com/science/biology_place/biocoach/biomembrane1/solutions.html

http://www.nursingcenter.com/lnc/ce_articleprint?an=00152258-201301000-00010

http://www.nursingcenter.com/lnc/cearticle?tid=1157503

http://www.yournursingtutor.com/hypertonic-iv-solutions/







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YOUNAS MASIH NEW LIFE COLLEGE OF NURSING KARACHI Patho-pharma Trauma and cell injury unit-iv-b