Session 3: Cellular responses to stress and noxious stimuli

Session 3: Cellular responses to stress and noxious stimuli

• Alex Simon (MD)

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Learning tasks

Learning tasks

At the end of this session, students are expected to be able to:

Identify critical intracellular systems that are susceptible to injury.

Identify factors which influence cellular responses to injury.

Explain forms of cellular responses to injury.

Explain how tissues respond to injury using heart as an example.

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Introduction

Introduction

Cells are active participants in their environment, constantly adjusting their structure and function to accommodate changing demands and extracellular stresses.

Cells normally maintain a steady state called homeostasis in which the intracellular milieu is kept within a fairly narrow range of physiologic parameters.

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Cellular systems susceptible to injury

Cellular systems susceptible to injury

Genetic apparatus of the cell (DNA).

Mitochondria (site for ATP production).

Protein synthesis (Ribosomes detachment from endoplasmic reticulum).

Cell membranes.

Plasma membrane

Organelle membrane (lysosomes, mitochondrial).

Cytoskeleton.

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Factors influence cellular responses to injury

Factors influence cellular responses to injury

The cellular response to injury depends on

Type of injury.

Duration of injury.

Nature (pattern) of injury.

Severity and intensity of injury.

Type of cell injured.

The cell's metabolic state (basal cellular metabolism).

The cell's ability to adapt.

Blood and nutrient supply to tissues.

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Forms of cellular responses to injury

Forms of cellular responses to injury

When a cell is exposed to an injurious agent the possible outcomes are:

The cell may adapt to the situation.

They cell may acquire a reversible injury.

The cell may obtain an irreversible injury.

The cell may die.

The cell may die via one of two ways: either by necrosis or by apoptosis.

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Slide 7

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Overview of cellular adaptations

Overview of cellular adaptations

As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation.

Adaptations occur in order to achieve a new steady state and preserve viability and function of cells.

If the adaptive capability is exceeded or if the external stress is inherently harmful, cell injury develops.

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Overview of cellular injury

Overview of cellular injury

For mild injury, reversible cell injury occurs.

If the injurious stimulus is removed, the cells can return to a stable baseline.

However, if the stress is severe, persistent and rapid in onset, it results in irreversible injury and death of the affected cells.

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Overview of cellular death

Overview of cellular death

Cell death is one of the most crucial events in the evolution of disease in any tissue or organ.

There are two types of cell death: necrosis and apoptosis.

Ischemia, infections, toxins, and immune reactions cause necrosis type of cell death.

Cell death is also a normal and essential process in embryogenesis, the development of organs, and the maintenance of homeostasis (apoptosis type of cell death).

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Cellular responses to stress:Heart as an example

Cellular responses to stress:Heart as an example

Myocardium subjected to persistent increased load, as in hypertension or with a narrowed (stenotic) valve, adapts by undergoing hypertrophy.

An increase in the size of the individual cells and ultimately the entire heart.

This generate the required higher contractile force.

If the increased demand is not relieved, or if the myocardium is subjected to ischemia (from an occluded coronary artery), the muscle cells may undergo injury.

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Cellular responses to stress:Heart as an example

Cellular responses to stress:Heart as an example

Myocardium may be reversibly injured if the stress is mild or the coronary arterial occlusion is incomplete or sufficiently brief.

Reversibly injured myocytes are not dead and may resemble normal myocytes morphologically.

However, they are transiently noncontractile, so even mild injury can have a significant clinical impact.

It may undergo irreversible injury and cell death (infarction) after complete or prolonged occlusion.

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Cellular responses to stress:Heart as an example

Cellular responses to stress:Heart as an example

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Cellular responses to stress:Descriptions for previous slide

Cellular responses to stress:Descriptions for previous slide

Yellowish white area in the bottom right muscle indicates ischaemic coagulative necrosis.

In the example of myocardial hypertrophy (lower left), the left ventricular wall is thicker than normal.

Reversibly injured myocardium shows reversible changes like cellular swelling and fatty change (upper right).

In the specimen showing necrosis (lower right) the transmural light area in the posterolateral left ventricle represents an acute myocardial infarction.

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Key points

Key points

Stresses and injury affect not only the morphology but also the functional status of cells and tissues.

Cellular responses to injury include: cellular adaptation, reversible & irreversible cell injuries and cell death.

Myocardium adapts by undergo hypertrophy after persistent increased load.

Myocytes undergo irreversible injury and cell death (infarction) after complete or prolonged ischemia.

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Evaluation

Evaluation

Why do cells respond to stress and noxious agents?

Mention five (5) factors which cellular response to injury depends on.

What are the critical intracellular systems that are susceptible to injury?

List two (2) stimuli which affect myocytes.

Explain how heart respond to stress and noxious stimuli.

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References

References

Bezabeh M.; Tesfaye A.; Ergicho B. et al (2004): General pathology lecture notes for Health Sciences students. Ethiopia Public Health Training Initiative. Pg. 14.

Kumar V.; Abbas A. K.; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, China. Pg. 1-3.

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