Chapter 4 - Cell Injury, Aging, and Death Flashcards
What are cells and their function?
- They are active participants in the environment
- Adjust structure/function to accommodate change/demands/stress to maintain homeostasis
- Physiologic stress or pathologic stimuli result in ADAPTATION
Explain cellular injury
- Types
Occurs when cell cannot maintain homeostasis in the face of injurious stimuli
- Severity of injury determines response
Types
- Adapted Cell
- Reversible Injured Cell
- Irreversible Injured Cell
- Apoptosis or necrosis
- Dead Cell
Explain the mechanism of cell injury
1) Depletion of ATP
2) Mitochondrial Damage
3) Influx of intracellular Ca and loss of Ca homeostasis
4) Accumulation of oxygen-derived free radical (oxidative stress)
5) defects in membrane permeability
Define reversible cell injury
Reversible: Cell swelling develops when cells are incapable of fluid & ion homeostasis; fatty change accumulation of lipid vacuoles in the cytoplasm
1) Hydropic Swelling:
- Accumulation of water due to malfunction of Na/K pump (increase of Na within cell) or loss of ATP
- Dilated ER, swollen MC, large/pale cytoplasm
- Increase in size/weight of organs (megaly)
Hypoxia > ATP production decrease > Na/H2O in & K out; osmotic pressure increase > distended/rupture of organelles > hydropic degeneration
What is are reversible cell injuries?
1) Hydropic Swelling (Kidney):
- Accumulation of water due to malfunction of Na/K pump (increase of Na within cell) or loss of ATP
- Dilated ER, swollen MC, large/pale cytoplasm
- Increase in size/weight of organs (megaly)
Hypoxia > ATP production decrease > Na/H2O in & K out; osmotic pressure increase > distended/rupture of organelles > hydropic degeneration
2) Intracellular Accumulations (Fatty Liver)
- Excess accumulation of substances inside the cell leading to toxicity, immune response, and taking up of cellular space
- Pigments/particles appear because the cell is unable to degrade them
3) Limiting Protein Damage
- Increased synthesis of chaperones to correct protein
- Decrease translation of proteins
- Activate ubiquitin-proteasome to degrade unfolded proteins
- Activate caspases = apoptosis
What is cellular adaptation?
The cell’s ability to escape and protect itself from injury
- Common in disease states
What are 5 types of cellular adaptation responses?
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
Define and describe Atrophy
Cells shrink and reduce their functions in response to normal and injurious factors (DISUSE)
- Causes: Disues, denervation, ischemia, nutrient starvation, aging, etc.
- Results: reduced ER, MC, and myofilaments (results from decreased functional demand or chronic ischemia)
- Ex. Broken bone - muscles suffers
Define and describe Hypertrophy
Increase in cell mass accompanied by augmented functional capacity in response to physiological and pathophysiologic demands
- Usually result from increased functional demand
- Cause: increase cellular protein content or workload, and hormonal stimulation
- Ex. Cells unable to undergo meiosis
Define and describe Hyperplasia
Increase in functional capacity related to increase in cell number due to mitotic division
- Usually result from increased functional demand
- Often accompanies hypertrophy
- Cause: increase physiologic demand and hormonal stimulation, persistent cell injury, and chronic irritation of epithelial cells
- Ex. Endometrial lining
Define and describe metaplasia
Replacement of one differentiated cell type with another
- result from persistent injury
- Cause: adaptation to persistent injury, with replacement of a cell type that is better suited to tolerate injurious stimulation
- Fully reversible when injurious stimulation is removed
Define and describe Dysplasia
Disorganized appearance of cells because of abnormal variations in size, shape, and arrangement
- result from persistent injury
- Atypical hyperplasia: an adaptive effort gone astray
- Significant potential to transform into cancerous cells
- Severe and involves thickness of epithelial (carcinoma in situ)
Define Irreversible Cell Injury
Two basic processes:
- Denaturation of protein
- Enzymatic digestion of cell components
Define Necrosis
- Pathlogic cell death; consequence of schema or toxic injury (severe or prolonged injury)
5 Types of Necrosis
1) Heart (Coagulative)
- Most common
- Arises from ischemic injury @ metabolic acidosis in tissues (hypoxia)
- Dead cells - gel-like
- Ex. Heart, kidney, adrenal glands
2) Brain (Liquefactive)
- When dead tissue dissolves into liquid
- Liquification of lysosomal enzymes
- Formation of abscess or cyst
3) Lung (Caseous)
- Damage second to tuberculosis
- Clumpy cheese - cellular details are gone
4) Pancreas (Fat)
- Death of adipose tissue in breath, pancreas, abdominal structures
- Result of trauma
- Chalky soap like
- Triglycerides digested and free fatty acids precipitate as Ca-salts
5) Gangrene
- Cellular death of large area of tissue
- Result from interruption of blood supply (hypoxia injury)
- Abundance of bacteria determines severity
- Dry: black dry skin separated by line of health tissue
- Wet: internal organs due to anaerobic bacteria, liquid/cold/swollen black appearance (liquefactive)
- Gas: infection of necrotic tissue of anaerobic bacteria; gas bubble
Phases of Necrosis
Two Phases:
1) Pyknosis: shrinkage of nucleus with marked clumping of chromatin
2) Karyolysis: loss of nuclear membrane followed by rupturing
Processes following cell death (necrosis)
- Cellular self-digestion (autolysis)
- Dense clumped (degeneration of chromatin)
- Disruption of plasma & organelle membranes
Define Apoptosis
Programmed cell death - does not cause inflammation; occurs in response to injury that does not directly kill the cell
- Not always a pathologic process: animals need to get rid of cells and cells need to die in an orderly manner
- Activates suicide response
- Main components are caspases
What are the 2 pathways of apoptosis?
1) Mitochondrial (Intrinsic) Pathway
- cell injury > Mitochondrial pathway becomes dysfunctional > produces cytochrome c and proteins that initiate cascades > executioner caspases > endonuclease activation = membrane bleb = apoptotic body = phagocyte
2) Death Receptor (Extrinsic) Pathway
- Receptor-ligane interactions > adaptor proteins > initiator caspases > executioner caspases > breakdown of cytoskeleton > membrane bleb = apoptotic body = phagocyte
Aetiology of schema and hypoxic injury
- Hypoxia often caused by ischema which is the most common cause of cell injury
- Combination of disruption of oxygen supply with accumulation of metabolic waste
Define and explain hypoxia
- Inadequate oxygenation
- Most common cause of cell injury
- Usually due to schema
- Chemical & acid-base imbalances
- May be reversible if O2 restored
- Death if not
Define and explain ischemia
- restriction of blood supply causing shortage of O2 and glucose needed for cellular metabolism
- leads to lactic acidosis
- ## death occurs when plasma, MC, and Lysosomal membranes are damaged
What is ischemia-reperfusion injury
- Ca-overlead
- formation of free radicals
- subsequent inflammation
Hypoxic Injury Induced by Ischemia
Best example
- Reversible change in response to injury
- Still have chance to rescue cell
- See that organelles (ER) become distended = effects protein synthesis = deposition of lipids (Intra-cell-accumulations)
What is nutritional deficiency?
Results from:
- Poor intake
- Altered absorption
- Impaired circulatory system
Causes:
- Poverty
- Chronic alcoholism
- Acute/chronic illness
What is nutritional excesses
Results from:
- Excessive intake
- BMI greater than 27kg/m2 (health risk)
- BMI greater than 30kg/m2 (obesity)
Infectious and immunologic injury…
- Bacteria and viruses can injure cells in a variety of ways depending on their virulence
- Added injury may occur indirectly by triggering body’s immune response
- Bacteria rarely gets direct access to the cell
- Release toxins:
- Exotoxins – constantly released as long as bacteria is alive
- Endotoxins – contains in bacteria and are released after death of bacteria (most detrimental)
- These toxins might actually have generally effect on the body or may trigger a particular type of organ
Viruses are notorious for entering the cell and mingling/reprograming the DNA (cell) for their own proliferation
- May live for a while within cell or destroy immediately
- We can use long duration virus for treatments (benefit)
Parasites – fit profile of both protozoa and metazoa
- Might actually have access inside the cell or might live among cells in various tissues
- May be destructive and cause death
- Ex. Malaria
Fungi – symbiotic relationship
- Both partners benefit esp. in individuals with low immunology
- Ex. Yeasts
Chemical Injury
Toxic chemicals or poisons cause injury directly or by being metabolized into reactive chemicals to the body
- Dose related
Physical and mechanical injury
Factors
- Extremes in temperature
- Abrupt changes in atmospheric pressure
- Mechanical deformation
- Electricity
- Ionizing radiation
Radiation induced injury
Ionizes H2O into H+ & OH-
- OH- attaches to DNA & prevents cell reproduction
- DNA mutations
- Splits into free radicals = destroys cell via necrosis
Radiation sicknesses…
- Dermatitis
- Sterility
Cellular Basis of Again
Cumulative result from two factors cause cellular and molecular damage:
- Progressive decline in proliferation and reparative capacity of cells
- Exposure to environmental factors
Responsible mechanisms
- DNA damage
- Reduced proliferative capacity of stem cells
- Accumulation of metabolic damage
Cellular Theories
1) Free radical theory
- if a cell produces too much excessive amounts of free radical ions = become detrimental = damages organelles and cell itself
2) Programmed senescence theory
- Cells undergo only so many proliferations
- Cancer cells are able to over come shortening of telomeres (via telomerase)
- Repairs caps = proliferate indefinitely
Physiologic Changes of Aging
- Age-related decrease in functional reserve
- Inability to adapt to environmental demand
Somatic Death
- Death of the entire organism
- No inflammation or immunologic response occurs prior to death
- General features: cessation of respirations and heartbeat
- Presence of stiffened muscles throughout body after death (rigor mortis); then flaccid
- Release of lytic enzymes in body tissues: postmortem autolysis
- Determination of “brain death” as proof of somatic death
