CELLULR
ADAPTATION, CELL
INJURY AND CELL
DEATH.
DR(Med) YOLANDA ASHIE
KNUST-KSMD
OBJECTIVES
• Identify the various types of cellular adaptation
• Describe the conditions leading to these adaptive
changes.
• Categorize injurious agents and their resultant
effects on the cell.
• Describe the cellular changes in necrosis and
apoptosis.
Remember!
CELL
TISSUE
ORGAN
ORGAN SYSTEM
ORGANISM
Cellular
Differentiation and
Cell Types
Differentiation is the
process by which cells
become specialized to
perform distinct
functions. E.g. cardiac
cells, nerve cells,
fibroblasts, epithelial
cells, erythrocytes,
osteocytes, etc.
CELL TYPES
CHARACTERISTIC
EXAMPLE
LABILE CELLS
Continuously replicating.
Squamous epithelia of
skin and mucous
membranes,
haematopoietic cells,
epithelia of ducts of
glands, gastrointestinal
tract and genitourinary
tract
Mostly quiescent. Can
proliferate due to cell loss
or injury.
Cells of the liver, kidney,
glands; mesenchymal
cells(fibroblasts,
endothelial cells, smooth
muscle cells, etc)
No proliferative ability
Cardiac cells, skeletal
cells and neurons
Cells can be classified into
three main categories based
on their replicative
STABLE CELLS
potential:
PERMANENT
CELLS
Types of Injurious Agents
Nonlethal injurious stimuli to the cells such as increased physiological
demands, hormonal stimulation, chronic irritation, malnutrition and
physical disuse usually result in Cellular adaptations.
Infections, ischaemia, chemical injuries, ionizing radiation, and
oxidative stress will result in Reversible or Irreversible cell injury.
Metabolic alterations and chronic injury culminates in
Intracellular accumulations.
Cellular aging/senescence.
CELLULAR
ADAPTATION
Reversible changes in the
structure and function of cells
in response to external stresses.
HYPERTROPHY
An increase in the size of the cells and
thus function. Caused by increased
functional demand or hormonal/growth
factor stimulation.
• Physiologic hypertrophy: e.g.
exercised-induced cardiac hypertrophy.
• Pathologic hypertrophy: e.g. left
ventricular hypertrophy of heart
secondary to hypertension, bladder
hypertrophy from lower urinary tract
obstruction, and compensatory
hypertrophy of kidney after unilateral
nephrectomy.
HYPERPLASIA
Increase in the number of cells and size of
the organ. Occurs in labile/stable cells.
Triggered by increased functional demand,
hormonal/growth factor stimulus. Usually
coexists with hypertrophy.
Types:
• Physiologic: e.g. female breast in puberty
and pregnancy, also uterine hyperplasia in
pregnancy. Hepatic hyperplasia post
lobectomy(compensatory).
• Pathologic: e.g. Benign prostatic
hyperplasia, endometrial hyperplasia
ATROPHY
Decrease in cell size and number and
thus function and structure of organ.
Types:
• Physiologic; e.g. during embryogenesis
and postpartum shrinkage of uterus.
• Pathologic; results from a decreased
workload, nutritional deficiency,
ischaemia, undernutrition,
denervation, pressure effects, and loss
of hormonal stimulation. E.g. loss of
muscle mass and strength after
immobilization in a cast, endometrial
atrophy.
Endometrial atrophy
METAPLASIA
A reversible change from one
adult/matured cell type to another
matured cell type in response to a
chronic persisting irritation or
inflammation. Involves the
differentiation of stem cells.
Examples include Barrett’s
oesophagus due to GERD and
squamous metaplasia of the
respiratory epithelium in chronic
smokers. These metaplastic cells are
better able to withstand the
persistent stress and irritation.
• NB: Dysplasia is usually not regarded as a true adaptation. It is an
abnormal/disordered growth of cells displaying atypical features and
mostly become precursors of malignancy.
CELLULAR
INJURY &
CELL DEATH
CAUSES OF CELL INJURY
1. Physical agents: extremes of temperature, mechanical
trauma, changes in atmospheric pressure, electrical shock
and radiation injuries.
2. Chemical agents: environmental pollutants, alcohol,
poisons(arsenic, cyanide, mercuric salts), hypertonic
concentrations saline or glucose , therapeutic agents.
3. Infectious agents: viruses, helminths, prions, bacteria,
fungi,etc.
4. Immunologic reactions: autoimmune disease and
anaphylactic reactions.
5. Nutritional deficiencies: protein-energy malnutrition,
vitamin deficiencies, obesity, etc.
6. Genetic abnormalities: haemoglobinopathies, inborn
errors of metabolism, misfolded proteins, congenital
disorders.
Mechanisms of
Cell Injury
1.
Formation of free radicals
2.
Hypoxia and ATP depletion
3.
Disruption of intracellular calcium
homeostasis
Reversible cell injury
Biologicial functions and structural integrity of the cell is maintained
in the face of stressors and also because the offending agent is
withdrawn before fatal damage ensues.
Features include depleted ATP due to reduction in oxidative
phosphorylation, cellular swelling resulting from defective ion pumps
and swelling of ER and mitochondrion and fatty change.
Irreversible cell injury
Persistence of stressors or injurious agents renders cells depleted of
reserves, and adaptive mechanisms fail to maintain integrity of cell.
Eventually there is breakdown of the cellular components resulting in
death.
Cellular death can occur via the process of Necrosis or Apoptosis.
NECROSIS
• Persistent or intense injury results in severe damage
to the cells with loss of membrane
integrity(denaturation of membrane proteins) and
release of lysosomal enzymes(enzymatic digestion of
cellular components).
• Cellular debris from necrosis further elicits
inflammation.
Patterns of Necrosis
1.
Coagulative necrosis: the necrotic tissue is firm with a maintained architecture.
Vascular occlusion leading to ischaemia of all organs, except the brain, results in
coagulative necrosis(Infarct).
2.
Liquefactive necrosis: results from digestion of cell debris by the action of leukocytes.
Tissue becomes a liquid viscous mass and may form pus. In the brain, hypoxic injury
results in liquefactive necrosis.
3.
Caseous necrosis: commonly found in necrotizing granulomatous lesions caused by TB
infection. The area of necrosis is easily friable rendering a cheese-like appearance.
4.
Fat necrosis: usually results from traumatic injury to areas of fat deposition such as
breast. In acute pancreatitis, the release of pancreatic enzyme, lipase, results in the
digestion of surrounding fat. The fatty acids combine with calcium to produce chalky
white deposits(fat saponification), characteristic of this condition.
5.
Gangrenous necrosis: usually describes a necrotic limb resulting from lack of blood
supply. Bacterial superinfection leads to liquefactive necrosis and is termed Wet
gangrene.
6.
Fibrinoid necrosis: occurs in blood vessels as a result of immune complex reactions
with the deposition of fibrin with the wall of the vessels(vasculitis).
APOPTOSIS
• A programmed cell death mediated by a well-regulated mechanism targeted at eh
cellular DNA and proteins.
• Physiologic apoptosis occurs in:
Embryogenesis
Involution of hormone dependent tissues when hormone is withdrawn, e.g. ovarian
follicular atresia or endometrial atrophy in menopause.
Cell loss in proliferating polpulations, e.g. loss of epithelial cells in intestinal crypts to
maintain homeostasis
Loss of potentially harmful self-reactive lymphocytes.
COMPARISON BETWEEN APOPTOSIS AND
NECROSIS
APOPTOSIS
NECROSIS
Occurs in single or few groups of cells
Numerous cells or groups of cells affected at a time
Progresses from reversible to irreversible
Irreversible once initiated
Passive process
Active process dependent of ATP
Destruction of cell membrane and organelles
Formation of apoptotic bodies(membrane bound
cellular components)
References and Resources
5.
Robbins and Cotran pathologic basis of diseases, 9th Edition.
https://images.search.yahoo.com/search/images;_ylt=AwrEtymIx61l9.kQEQBXNyoA;_ylu=Y29s
bwNiZjEEcG9zAzEEdnRpZAMEc2VjA3BpdnM-?p=cell+tissu+organisation&fr2=pivweb&type=C210US91075D20160906&fr=mcafee#id=95&iurl=https%3A%2F%2Fimgnm.mnimgs.com%2Fimg%2Fstudy_content%2Flp%2F2%2F7%2F6%2F606%2F974%2F2104%2F
2156%2FLP_2.7.6.1.2.1.1_Ruchika_html_38370136.png&action=click
https://s3.studentvip.com.au/notes/40555-sample.pdf?v=1601901269
https://medicine.nus.edu.sg/pathweb/wp-content/uploads/2019/06/normal-uterus-21024x662.jpg
http://www.patologia.cm.umk.pl/atlas/reproductive/female/complexatypia/img/large/2.jpg
6.
https://www.duncansportspt.com/2018/01/unexplained-body-pain/
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