Cell Function & Dysfunction Flashcards
Homeostasis
The control of composition of immediate environment and intracellular Millie within a narrow range of physiological parameters
Adaptation
Can occur when cells are under physiological or pathological (injury) stimuli; cells achieve a new steady sate that is compatible with their viability in a new environment
Reversible injury
Cell is able to adapt or heal from injury.
Cells can either adapt to stress or die.
Irreversible injury
Injury is too severe; affected cells die An acute stress cannot be overcome. Common causes are: Viruses, ischemia, radiation, toxic chemicals, extreme temperatures. Usual series - coagulative necrosis
Cell injury
Occurs when adaptive mechanisms aren’t sufficient to maintain homeostasis.
Results when environmental insults raise beyond ability of cell to adapt
Not an “all or nothing” response
Causes of cell stress/injury
- Hypoxia
- Ischemia
- Chemical insult
- Infections
- Immunological
- Genetic
- Nutritional
- Endocrine
- Physical
- Aging
Hypoxia injury
Deficient oxygen levels; lack of O2 cells.
Especially organ transplants.
Big deal for mitochondria
*expensive tissues (cardiac, kidney, nervous, muscle)
Ischemia injury
Deficient blood flow.
Since arterial vessels bring O2 to cells, pathways.
Especially organ transplants
Chemical insult injury
Drugs, alcohol, heavy metals
Liver is often affected
Ex: acetaminophen (hepatic necrosis)
alcohol (fatty liver, hepatitis, cirrhosis)
Infection injury
Viruses, bacteria, parasites, fungi
May operate through release of toxins or cause long term inflammation
Immunological injury
Damage caused by immune reactions. Anaphylaxis & loss of immune tolerance results in auto-immune disorders. Stressful on the body overall. Act on cell and release histamine.
Genetic injury
Gene defects, chromosomal anomalies.
Heritable or environment damage to genes and chromosomes.
Can be chronic
Ex: sickle cell
Nutritional injury
Deficiency or excess in nutrients (too little iron, vitamin deficient, protein deficient, calorie deficient, excess lipid intake - increase atherosclerosis).
Can be chronic
Endocrine injury
Increases or decreases in hormonal activity.
Stress hormones, growth factors.
Ex: cortisol (diverts glucose from brain to skeletal muscle = limiter memory)
Can be chronic
Physical injury
Mechanical trauma, thermal damage, radiation damage.
Ex: UV rays
Can be chronic
Aging injury
Injury occurs via programmed cell death or toxin build up. Failure of components, free radical build up, etc.
Cells become less and less efficient as they age.
Is more chronic
Labile
Epithelium tissues that replace themselves quickly
Ex: tongue cells
Cellular respnose to stress/injury
Results when environment insults raise beyond ability of cell to cope.
Cell attempts to respond (not an all or nothing)
The stronger/longer the injury = more damage done
Response of cell depends on type, status, genetic makeup. (ex: ischemia in muscle, cardiac = 20 mins, skeletal = 2 hours)
Either reversible (allows repair) or irreversible (cell necrosis)
Cellular swelling always occurs
Types of reversible cell injury
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
Cellular swelling
Cytoplasmic volume increases due to increased water volume as a response to injury.
Cell becomes incapable of controlling ion concentrations
Loss of homestasis occurs
Ex: at the organ level, this appears as pallor or weight increase
Cellular swelling
Also called “hydropic change”.
Atrophy
Shrinkage on size of the cell by loss of substance.
Clinically, decreased size or function level of structure.
Reflects in size decrease at cellular level.
Occurs in regions of persistent injury.
*A retreat to smaller size in attempt to survive
Ex: brain tissue in Alzheimer’s dementia
Frequent in heart, brain, skeletal, muscle, kidneys
Hypertrophy
Increase in cell size with heightened functional capacity.
Response to trophic (growth) signals or increased demands.
Clinically, increased size of organ.
Results from increased synthesis of structural proteins and organelles
“Good hypertrophy” - normal physiological response to demand
“Bad hypertrophy” - pathological response to injury
Causes of atrophy
Occurs in regions of persistent injury (chronic inflammation, vascular insufficiency, disuse, incomplete ischemia, reduced blood flow, denervation of muscles, interruption of hormones to cells)
Hyperplasia
Increase in cell number, often seen with hypertrophy.
Hormonal stimulation usually influences.
Ex: gravid uterus, estrogen levels at puberty yield hyperplasia of endometrial uterine cells; glandular epithelium of great cells), tumors.
Mostly occurs due to excessive growth factor stimulation, but can also be normal growth (like an embryo).
(warts due to viruses, wound healing, callus, etc.)
Metaplasia
Conversion of an already differentiated cell the to a different cell type due to injury.
A cell type sensitive to a particular stress is replaced by a cell type that is better adapted to handle it.
Ex: tobacco irritation in bronchi - bronchi normally lined with ciliated columnar epithelium, then replaced by squamous epithelium to provide protection
(occurs as a precursor of neoplastic conversions)
Dysplasia
Change in cell size, shape, and organization.
Ex: Most frequently occurs hyper plastic squamous epithelia (epidermal actinic keratosis from sunlight) squamous metaplasia (bronchus).
Progresses from metaplasia
A preneoplastic phase prior to cancer
Causes of hypertrophy
Results from increased synthesis of structural proteins and organelles
Causes of hyperplasia
Hormonal stimulation usually influences.
Mostly occurs due to excessive growth factor stimulation.
Causes of metaplasia
When a cell cannot handle the adaptions of a stressor or injury.
Neoplastic conversions
Occurs in cells as a conversion of the immortalized cells to tumorigenic cells.
Seen in cancers of lung, cervix, stomach, bladder
Causes of dysplasia
Cells become abnormal in features due to such high stressors.
Neoplastic conversions
Occurs in cells as a conversion of the immortalized cells to tumorigenic cells.
Seen in cancers of lung, cervix, stomach, bladder
Coagulative necrosis
Generally
Common sequence leading to cell death from insults
Histologic characteristics similar regardless of causes
Normally, cytosol calcium ion concentration is hypotonic relative to the extracellular environment, but here - an influx of Ca2+ occurs causing necrosis.
Irreversible cell injury
Point of no return
Eventually, injury affects oxidative phosphorylation and thus stops supplies of ATP synthesis.
Plasma membrane is affected.
1. Inability to reverse mitochondrial dysfunction
2. Profound losses in plasma membrane function
These injuries can take minutes or hours, depending on cell type
Coagulative necrosis
Steps & mechanisms
Ca2+ influx sets stage for destruction of organelles by lysosomes.
1. cell injury
2. loss of plasma membrane integrity
3. influx of Ca2+ (calcium homeostasis disrupted)
4. lysosomal digestion of the cell & it’s organelles
5. denaturation of proteins in the cell
The outline of cell remains, but it is dead.
Typical mechanism of cell death = MI & hypoxic cell death
Calcium homeostasis for cell injury
*flowchart
SO IMPORTANT!
The cystolic free Ca++ concentration is kept about 10x lower than the concentration of Ca++ in the extracellular environment.
Most intracellular Ca++ is kept sequestered in mitochondria and in E.R.
During cell injury, come is released into the cytosol and causes damage to the organelles.
Types of irreversible cell injury
- coagulative necrosis
- liquefactive necrosis
- fat necrosis
- caseous necrosis
- fibrinoid necrosis
- apoptosis
Liquefactive necrosis
Clinical result is commonly abcess
Same sequence of events as coagulative necrosis, BUT result is digestion of dead cells.
Typically seen in brain
Occurrences in large areas can yield cavities or cysts
Fat necrosis
Specifically seen in adipose tissue
Most common in pancreatitis or trauma
Unique feature - presence of triglycerides; digestive enzymes that are normally only in pancreatic duct and small intestine.
The triglycerides are released from injured pancreatic acinar cells and ducts into the extra-cellular spaces.
Digestion of pancreas and surrounding adipose cells ensues.
Caseous necrosis
Lesions seen in tuberculosis
Dead cells remain indefinitely in tissue as:
amorphous, coarse, granular, eosinophilic debris.
Unlike coagulative necrosis, the cells do not retain cellular outlines but they also don’t liquify.
Fibrinoid necrosis
In injured blood vessels, accumulation of plasma proteins causing intensely eosinophilic epithelial walls.
Apoptosis
Programmed cell death.
Activation of a genetically programmed “suicide pathway”
Ex: fetal hands and feet, apoptosis results in separation of web-like paddles into distinguished fingers/toes
Calcification
A normal event during bone formation.
Ca ion entry to dying cells is also frequent.
Two major types: dystrophic & metastatic
Types of calcification
- Dystrophic calcification
2. Metastatic calcification
Dystrophic calcification
Localized manifestation
Macroscopic deposition of calcium salts in injured tissues.
Occurs with Ca deposition from circulation or intestinal fluid into injured cells.
Grossly as sandlike grains or rock hard material.
May occur in mitral or aortic valves. The inflexibility leads to impeded blood flow;
Ex: atherosclerotic coronary arteries this lead to narrowing of lumen
Metastatic calcification
Systemic manifestation via blood
Deranged calcium metabolism.
Associated with hypercalcemia or increased serum calcium concentration.
Can cause calcification of alveolar septa of lung, renal tubules, blood vessels.
Ex: hyperparathyroidism (PTH increases Ca ion levels) or
Vitamin D intoxication (promotes Ca ion uptake)
Cellular aging
Normal process but represents progressive accumulation of sublethal injury that compromises cellular function.
May lead to cell death or a diminished capacity to respond to injury.
Cellular aging
Causes & effects
A number of processes decline with age:
Mitochondrial oxidative phosphorylation
Protein synthesis (ribosomes detach from rough ER)
Repair of chromosomal damage.
Free radical damage
*Due to both internal molecular clock AND extrinsic stressors (wear and tear).
Free radical damage
Free radicals are chemical species with a single, unpaired electron in the outer orbit.
They cause aging/injury by:
Causing lipid changes in the plasma membrane
Modifying protein synthesis
Cause lesions in DNA (DNA usually dictates protein synthesis)
Free radical “debate”
Whether they can be neutralized or not.
Evidence exists they can be neutralized by antioxidants (vitamins A & E), but does this actually add up to a decrease in the rate of cellular aging?
Effects of Ca2+ imbalances or irregulation
ATP decrease
plasma membrane loss
chromatin damage
cytoskletetal disassembly
Mitochondrial oxidative phosphorylation
effect/causes of cellular aging
protein synthesis
effect/causes of cellular aging
ribosomes detach from rough endoplasmic reticulum
repair of chromosomal damage
effect/causes of cellular aging
