MID 2163PATHOLOGY
TOPIC 2:CELL INJURY AND
ADAPTATIONS
CELLCELL
Cell
Basic structural and functional unit in human body
Human contain almost 100 trillion cellsDifferent cells in tissues constantly interact
with each other = cell-cell and cell-matrix
Cell3 principle components
– Plasma membrane– Nucleus– Cytoplasm
10ORGANELLES
CYTOSKELETON
CENTROSOME
CILIA & FLAGELLA
RIBOSOME
ENDOPLASMIC RETICULUM
GOLGICOMPLEX
LYSOSOME
PEROXISOME
PROTEASOME
MITOCHONDRIA
3 MAIN GROUPS OF CELLS
Labile cells(unstable)
Rapid proliferation and cell turnover
e.g: gut lining & epithelial cells
Stable cells
Slow proliferation and cell turnover
e.g: hepatocytes
Permanent cells Not able to proliferate e.g: neurons
CELL CELL INJURYINJURY
Cell InjuryCells are active participants in their
environment– constantly adjusting their structure &
function to accommodate changing demands and extracellular stresses
Cells tend to maintain their normal condition = homeostasis
Cell InjuryCells encounter physiologic stresses or
pathologic stimuli = undergo adaptation– achieving a new steady state and preserving
viability and function
Ultimate fate of a cell (once exposed to a harmful stimulus) depends on the type, severity & duration of the stimulus and also the type of cells
Cell InjuryExample:
– Brain cells, heart cells susceptible to hypoxia and ischemia
– liver cells susceptible to chemical injury– Calf muscle tolerates 2-3h of ischemia– Cardiac muscle dies in 20-30 min
Cell InjuryCell exposed to injurious agents, the
possible outcomes are:i. The cell may adapt to the situationii. The cell may require reversible injuryiii. The cell may obtained irreversible injury and
may die
CAUSES(internal)
Enzyme defects (genetic) e.g. glactosemia
Ischaemia = reduced blood
supply
Deficiency of vitamins,
hormones etc
Immune-mediated mechanisms
CAUSES(externally)
Physical e.g: mechanical trauma, atmospheric pressure,
thermal, U.V. light, Ionising radiation
Microbial agents: bacteria, viruses,
fungi
Chemical agents & toxins
e.g: paraquat
Nutritional e.g: lead posoning
Cell InjuryInjury to a certain component in cell will lead
to its dysfunctionThe cellular components that are prone to
injury are:→ Plasma membrane→ Mitochondria→ Nucleus→ Lysosomes
Plasma MembraneFunctions:
– Maintain integrity of cell– Contact with extracellular environment =
cell surface receptors– Passage of ions (through permeable
channels) & complex molecule (pinocytosis or phagocytosis)
Plasma MembraneIf the cell injured, blebs of the cellular plasma
membrane noted– Focal extrusion of the cytoplasm– Cell detach from the membrane
Contact with extracellular environment = cell surface receptors
Passage of ions (through permeable channels) & complex molecule (pinocytosis or phagocytosis)
Plasma MembraneEffects of plasma membrane injury:
– Loss of structural integrity - cause cell to rupture and die
– Loss of function - water enters cells and cause cloudy swelling hence electrolyte imbalance within cell
– Deposition of lipofuscin (brown atrophy) - brown pigments deposited within cytoplasm eg in myocardial cells and liver cells
Mitochondria
Main sites of energy production for cellular activities
Disorder of energy production affects all cellular functions
– Mitochondria swell, dissipation of energy gradient & impairment of mitochondrial volume – amorphous densities rich in phospholipid may appear = reversible
Nucleus Contains DNA - controls all cellular activities
– Action of at least 1000 genes – Each encodes a protein with structural, enzymatic
or control functions
Damage to DNA (esp in dividing cells) – Effective repair mechanisms but severe damage
usually leads to cell death by apoptosis
GERM CELL SOMATIC CELL
Germ Cell DNA Damage
Spermatogonia / Oocytes
Severe damage to chromosomal structurePrevention of conceptionEarly abortion
Less severe damage to groups of genes or single genesDevelomental abnormalitiesHereditary diseaseSusceptibility to disease
Somatic Cell DNA Damage
All cells in our body
Acquired during life Damage to stem cell
Example: - development of cancer cells through activation of oncogens or loss of tumor supressor genes
Nucleus Effects of DNA abnormalities:
– Failure of synthesis of structural proteins – Failure of mitosis – Failure of growth-regulating proteins – Failure of enzyme synthesis
LysosomesMembrane bound organelles contain
hydrolytic enzymes– Responsible for digestion and disposal of
complex substances
Disorder may lead to escape of enzymes or to cellular overloading (storage disorders)
Cell InjuryInjury may progress to:
1) Adaptation state• Mild/persistant injorious agents = recover to
normal state
2) Reversible injury• Respond to injury but recover
3) Irreversible injury• Cell respond to injury and cannot recover
(cell death)
Cell InjuryIf the adaptive capability is exceeded or if
the external stress is inherently harmful– cell injury develops!
Severe or persistent stress results in irreversible injury and death of the affected cells
Cell InjuryCells are stressed so severely
– no longer able to adapt – exposed to inherently damaging agents– suffer from intrinsic abnormalities
Different injurious stimuli affect many metabolic pathways and cellular organelles
CELL ADAPTATIONS
CELL ADAPTATIONS
Changes made by a cell in response to adverse environmental changes
➲REVERSIBLE CHANGES!
Cell Adaptations2 types of adaptations
1. Physiological adaptations: usually response of cells to normal
stimulation by hormones or endogenous chemical mediators
e.g: hormone-induced enlargement of the breast during pregnancy
1. Pathological adaptations: responses to stress that allow cells to
modulate their structure and function and thus escape injury
Cell Adaptations
Cells adapt by altering their pattern of growth– Hypertrophy– Hyperplasia– Atrophy– Metaplasia – Dysplasia
*Within certain limits injury is reversible, and cells return to a stable baseline
HypertrophyIncrease in the size of cells
– Increased workload increased protein synthesize and size & number of intracellular organells = increased organ's size
– Happen in cell that cannot be devide– Reaches limit no longer able to
compensate = failure & degeneration
Hypertrophy Example:
– Pathological: • enlargement of left ventricle in
hypertensive heart disease– Physiological:
• muscle increase in body builder
Hyperplasia
Increase in the number of cells– Resulting from increase in cell division –
happen in cell that can divide = mitosis– Compensatory (regeneration) &
hormonal (occurs mainly at organs that depend on estrogen)
Hyperplasia
Example:– Physiological:
• enlargement of breast during pregnancy
– Pathological: • endometrial hyperplasia
Atrophy
Decrease in the size of cells– Reduced functional capacity, lead to
decrease size of organ• Formation of autphagic vacuoles
contain cellular debris from degraded organelles
AtrophyLoss of cell substances due to
decrease workload loss of innervation diminished blood supply inadequate nutrition loss of endocrine stimulation
Atrophy
Examples:– Physiological:
• reduced activity of old age = decrease in size of skeletal muscle, brain and testis
• Thymus atrophy during early childhood– Pathological:
• Trauma to a supply nerve root = skeletal muscle markedly riduced in size following loss of innervation
Normal Adult 82 y.o = atrophy
Metaplasia
Replacement of one differentiated tissues by another differentiated tissues– adaptive substitution - able to withstand the
adverse environment = reversible!– Altered differentiation pathway of tissue stem
cells
May result in reduced functions or increased propensity for malignant transformation.
Metaplasia
Example:– Squamous metaplasia – replacement of
another type of epithelium with squamous epithelium
– Osseus metaplasia – replacement of connective tissue by bone
Dysplasia
Abnormality of development– Morphological transformation – increased in rate
of cell division & incomplete maturation of resultant cells
– High nuclear to cutoplasmic ratio
Early neoplastic processExample:
– Epithelial dysplasia of the cervix – detected by a pap smear