Cell Death Flashcards
(42 cards)
Four Aspects of a Disease Process
1) ETIOLOGY or CAUSE (either genetic or acquired)
2) PATHOGENESIS
3) MORPHOLOGICAL CHANGES (structural alterations in cells or tissues that are characteristic of a disease or diagnostic etiologic process)
4) FUNCTIONAL DERANGEMENT AND CLINICAL MANIFESTATIONS (signs/symptoms)
What is Pathogenesis?
A sequence of events in cell’s response to etiologic agent, from initial stimulus to the ultimate expression of the disease
Stages of the Cellular Responses to Stress and Injurious Stimuli
1) Normal Cell (homeostasis)
2) if the cell under goes stress, than it can undergo ADAPTATION or if it is unable to adapt or simply undergoes injurious stimulus, cell injury occurs.
3) Cell injury can either be reversible or irreversible and if it is IRREVERSIBLE, cell death occurs
4) Cell death is either NECROSIS or APOPTOSIS
Types of Cellular Adaptations
- Hypertrophy
- Hyperplasia
- Atrophy
- Metaplasia
Hypertrophy
Reversible INCREASE IN CELL SIZE leading to INCREASED SIZE OF ORGAN or TISSUE
**NO NEW CELLS, JUST BIGGER ONES
Examples:
> normal production of sex hormones at puberty/pregnancy
> exogenous stimuli like anabolic steroid use
> endogenous stimuli (internal) such as overproduction of Thyroid stimulating hormone
> PATHOLOGICAL HYPERTROPHY (non-physiological) from excessive or prolonged stress
Hyperplasia
A reversible increase in the NUMBER of cells in an organ or tissue resulting in an increase in the size of an organ or tissue
may be precancerous and are often see concurrently in proliferating cells
Examples:
> hormonal increase in estrogen leads to increase in # of endometrial cells (pathologic if excessive)
> compensatory increase in mass after damage/resection
> increased functional demand - secondary polycythemia (like with sleep apnea)
> persistent cell injury - epithelial hyperplasia/hyperkeratosis
Mechanism of Hyperplasia
growth factor driven proliferation of mature cells
increased output of new cells from tissue stem cells
DILANTIN AND CYCLOSPORIN lead to hyperplasia in the CT of gums
Atrophy
Adaptive response to stress in which the cell/tissue shrinks in volume and shuts down its differentiated functions – reducing its energy needs
Results in a decrease in cell size and function (clinically seen as a decrease in the size or function of a tissue or organ)
Causes can be physiologic – due to decreased work load or endocrine stimulation (immobilized by cast, decreased size of uterus following child birth or disease)
Pathological – primarily due to denervation of muscle, diminished blood supply, nutritional deficiency. chronic injury
Mechanisms of Underlying Atrophy
Decreased metabolic activity reduces protein synthesis and increased protein degradation in cells
Shrinkage of cells/tissue/organ due to
- nutrient deficiency: activates a ubiquitin/proteasome pathway: ligases attach ubiquitin to proteins which target them to degradation in proteasomes
- autophagy: starved cell “eats” its own content to attempt to reduce nutrient demand to match supply
Metaplasia
Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type
Most common replacement is glandular columnar epithelium by squamous epithelium
IS A RESPONSE TO PERSISTENT INJURY
(smoking, GERD, chronic infection)
Mechanism underlying Metaplasia
Arises from re-programming stem cells or undifferentiated mesenchymal cells present in adult tissue due to local effectors (cytokines, growth factors)
Reversible Changes Induced by Injury
(reversible if damage is removed)
CHANGES IN ION CONCENTRATION AND WATER INFLUX
HYDROPIC SWELLING (light microscopic change)
FAT DROPLET FORMATION
Ultrastructural changes in Reversible injury
Plasma Membrane: blebs (outpouches) appear and there is a lose of microvili
Mitochondria: swells and may develop small amorphous densities
ER; dilates and ribosomes detach
Nucleus: chromatin clumping, break down of granular and fibrillar elements
Examples of Nuclear Changes
PYKNOTIC - nuclear condensation
(clumping) increases as the cell dies
KARYORREHEXIS - small pieces of the nucleus breaking off
KARYLOYSIS - breaking up of the nucleus totally
Hydropic Swelling
increase in cell volume characterized by a large amount of pale CYTOPLASM and a normally located nucleus
accumulation of sodium is what leads to increase in water content and the organ often becomes heavier and firmer
IS A REFLECTION OF ACUTE. REVERSIBLE, CELL INJURY (however can be irreversible if injury continues)
Necrosis
- Cells are unable to maintain membrane integrity
- Contents leak out
- Elicits an inflammatory response
• Cell contents are digested by cellular lysosomal enzymes and
inflammatory process
Coagulative Necrosis
The outline of the dead cells and architecture are maintained and the tissue is somewhat firm
- Protein denaturation (low pH) is the primary pattern
- Example: myocardial infarction
- Earliest tissue microscopic or gross evidence 4-12 hours after cell death, enzymes released immediately ~2hrs
Liquifactive necrosis
The dead cells undergo disintegration and affected tissue is liquefied
- Enzyme digestion by leukocyte hydrolases dominates
- Example: cerebral infarction or bacterial infection
- Evoked by bacterial or fungal infection
- White blood cells (neutrophils) have hydrolases which digest dead cells
- Abscess is formed when cells are killed and digested faster than
the repair process, leaving a cavity filled with leukocytes and fluid (pus = dead stuff and white blood cells ) - Also seen in cerebral infarcts – brain tissue liquefies – without an inflammatory response
Gangrenous necrosis
clinical term often involving both coagulative (due to ischemia) and liquifactive (due to infection) necrosis
Caseous necrosis
a form of coagulative necrosis (cheese-like)
associated with tuberculosis lesions
- Microscopic: granuloma
Fat necrosis
Enzymatic digestion of fat associated with pancreatitis
and leakage of enzymes into abdomen
- Occurs when activated pancreatic lipases are released into the pancreas and the peritoneal cavity
- Microscopic: necrotic fat cells
Fibrinoid necrosis
immunologically-mediated vasculitis in blood vessel
walls
Mechanisms of cell injury
ALL LEAD TO CELL DEATH DETECTABLE AT THE TISSUE LEVEL
Decrease in ATP production and mitochondrial damage
Entry of Ca2+ leading to an increase in mitochondrial permeability and/or activation of multiple cellular enzymes
Increase in ROS (reactive oxygen species) leads to damage to lipids, proteins, DNA
Membrane damage of either plasma membrane or lysosomal membrane leading to loss of cellular components (plasma) or enzymatic digestion of cellular components (lysosomal)
Protein Misfolding/DNA damage leading to activation of pro-apoptotic proteins
Mechanism of Cell Injury
- Cellular response to injury depends upon the nature of the injury, duration and severity
- Consequences of cell injury depend on the type, state, and adaptability of the injured cell
• Cell injury results from different biochemical mechanisms acting on
several essential cellular components
