patoloji-ders-notlari

Title

Serdar Balcı

General Mechanisms of Cell Injury

Serdar BALCI

Homeostasis

What if homeostasis is not preserved

Figure 1-1 from Robbins and Cotran Pathologic Basis of Disease 8 th _ ed, _

Adaptations

Reversible

Functional and structural responses

More severe physiologic stresses

Pathologic stimuli

**A new steady state is achieved. **

Continue to function

Type of adaptations

If cell cannot adapt

If adaptive capability is exceeded

Or the stress is very harmfull

If stress is severe

Persistent

Rapid onset

Irreversible Injury

Cell Death

ALTERED PHYSIOLOGICAL STIMULI SOME NONLETHAL INJURIOUS STIMULI

Stimulus Adaptation
Increased demand, increased stimulation (e.g., by growth factors, hormones) Hyperplasia, hypertrophy
Decreased nutrients, decreased stimulation Atrophy
Chronic irritation (physical or chemical) Metaplasia

Adapted from Table 1-1, from Robbins

REDUCED OXYGEN SUPPLY CHEMICAL INJURY MICROBIAL INFECTION

Stimulus Injury
Acute and transient Acute reversible injury Cellular swelling fatty change
Progressive and severe (including DNA damage) Irreversible injury → cell death Necrosis Apoptosis
   

Adapted from Table 1-1, from Robbins

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Stimulus Response
Metabolic alterations, genetic or acquired; chronic injury Intracellular accumulations; calcification
Cumulative sublethal injury over long life span Cellular aging

Cardiac muscle cells

**Increased demand **

to pump more and MORE

Decrease O 2 __ supply__

**Increased demand **

to pump more

Atherosclerosis

ischemia

Muscle adapts

Increases functional units (proteins)

Adapts→hypertrophy

Cell cannot aford the demand

Ischemia

Cell death

Remember!

Adaptation is good. But for a certain time.

Adapted cell is functioning, but not as good as it used to be.

Adapted cell is more vulnerable to injury.

Adaptations

CELL INJURY AND CELL DEATH

Cell injury

Occurs;

So severe stress → unable to adapt

Exposed to inherently damaging agents, intrinsic anomalies

Reversible cell injury

Early, mild forms

Reversible when damage is removed

No severe membrane damage

No nuclear dissolution

Cell death

  Necrosis Apoptosis
Cell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis, karyorrhexis, karyolisis Fragmantation into nucleosome size fragmants
Plasma membrane Disrupted Intact, orientation of lipids are altered
Cellular contents Enzymatic digestion, may leak out of cell Intact, may be released in apoptotic bodies
Adjacent inflammation frequent none
  Pathologic, irreversible cell injury Physiologic (eliminate unwanted cells)
Pathologic (DNA, protein damage)

Necrosis

Apoptosis

nuclear dissolution

**without complete loss of membrane integrity. **

Reasons:

deprivation of growth factors

DNA or proteins are damaged beyond repair

many normal functions and is not necessarily associated with pathologic cell injury

no inflammatory response

CAUSES OF CELL INJURY

Causes of Cell Injury

Oxygen deprivation

Chemical agents

Infectious agents

Immunologic reactions

Genetic factors

Nutritional imbalances

Physical agents

**Aging **

O2 deprivation

Chemical agents

Infectious agents

Viruses

Rickettsiae

Bacteria

Fungi

Protozoa

Tape worms, flukes

Immunologic ractions

Autoimmune reactions

Exaggerated reactions

Genetic factors

Defect in proteins

Deficiency

Malfunction

Accumulation

Susceptibility to external stimuli

Nutritional imbalances

Physical agents

Trauma

Heat

Radiation

Electric

Atmospheric pressure

Aging

Decreased replication, repair and destruction capability

Error accumulation in DNA

Protein accumulation