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