Cell injury and inflammation Flashcards
Phases of Healing
- hemostatis and degeneration
- inflammation
- proliferaion and migration
- remodeling and maturation
Adaptation
the extent to which the cell is able to alter mechanisms and regain homeostasis in the altered environment
What does reversible injury depend on?
- mechanism of injury
- length of time the injury is present w/o intervention
- severity of injury
mild injury
leads to sublethal alterations, may be reversible
moderate or severe injury
lead to lethal alterations, likely irreversible – lead to cell death
Ischemia
Causes: occurs when blood flow is insufficient to maintain cell homeostasis and metabolic function. Due to reduction in blood flow or increase in metabolism in tissue beyond capacity of arterial vascular system.
Suffocation, pneumonia, atherosclerosis, thrombus, anemia
partial (hypoxia), or total (anoxia) reduction in O2 supply –> loss of aerobic metabolism –> reduction in ATP synthesis –> accumulation of ions and fluid –> cell swell –> compromised function
Infectious Agents
-bacteria, viruses, mycoplasmas, fungi. rickettsiaw, protozoa, prions and helminths may cause cell injury or death.
how does bacterial infections cause cell injury?
invading tissue and releasing exotoxins and endotoxins that can cause cell lysis and degradation of extracellular matrix.
Injury can result from inflammatory/ immunologic reactions induced by bacteria in host.
Ex: clostridial organisms that cause gas gangrene, tetanus, botulism, clostridium tetani
Causes of Cell injury
Ischemia
infectious agents
immune reactions
genetic factors
nutritional factors
physical factors
chemical factors
What is sepsis?
when microorganisms or their toxins are present in blood
may lead to septic shock when cardiovascular system collapse
How does viruses cause cell injury?
-cytopathic effect: found with RNA. Kill from within by disturbing various cellular processes or disrupt integrity of nucleus and plasma membrane
- indirect cytopathic effect mediated by immune mechanisms: virally encoded proteins become inserted into plasma membrane of host cell, alter permeability of cell membrane to ions. Loss of ionic barrier lead to cell swell and death
DNA virsues kill by intergrating into cellular genome
When the immune system is compromised or if the number of invading microorganisms overwhelm the immune system what occurs?
disease
Immune reactions
overzealous in its activity leading to hypersensitivities ranging from mild allergy to life threatening anaphylactic reactions or autoimmune disorders
What are the mechanisms by which the immune system can lead to cell injury or death?
antibody attachment, complement activation, and activation of inflammatory cells
-allergies caused by highlevels of specific antibodies (IgE) on surface of specialized cells (mast and basophils which release histamine)
Chemical factors
- substances that can injure cell directly
ex: heavy metals - substances that require metabolic transformation into the toxic agent
ex:acetaminophen, carbontetrachloride
-overdose
Production of Reactive oxygen species (ROS)
-formation of free radicals
Free Radicals
An integral part of metabolism and formed continously
ex: body natural process: the by product during process of using O2 and food to produce energy
Unpaired electrons
-when normal O2 atoms lose one of their four paired electrons
-chain reaction
Exert positive or negative effects
If produced in excess amts –> oxidative stress -> cell injury/death
(oxidative stresses caused by free radicals are factors in > 90% of lifestyle related disease)
Free radicals central to damaging effects can lead to CVD, diabetes, cataracts, Parkinsons, pre mature aging
Oxidation- The Chain Reaction
oxidation as a by product of metabolism damages cell membranes, leading to intrinsic cellular damage, a part of the normal aging process
Other causes of free radical formation
Exposure to toxic chemicals
exposure of high level of oxygen
irradiation
UV
Fluorescent ligjt
pollutants
tobacco smoke
pesticides
drug overdose
heat stress
reperfusion injury
prolonged exercise
Antioxidants
-neutralize the extra free radicals and stop chain reaction
What is endogenous antioxidants?
enzymatic (scavengers) and non-enzymatic defense mechanisms are present within cells to perform function of antioxidants detoxifying ROS and protecting cells from type of injury.
What is exogenous antioxidants?
Can be obtained from outside body through diet.
- 200 found in food or plant substances
What level of intensity is good to strengthen antioxidant defense?
moderate PA and exercise.
intense or porlonged, strenuous exercise (esp in sedentary person) leads to oxidative stress and may be harmful
Genetic Factors
- alterations in structure or # of chromosomes that induce multiple abnormalities
- down syndrome: 3rd chromosome in 21st pair - single mutations of genes that cause changes in amt or functions of proteins
-sickle cell anemia, low density lipoprotein receptor deficiency, and alpha antitrypsin deficiency - multiple gene mutations that interact with environmental factors to cause multifactorial disorders
-hypertension and type 2 diabetes
Mechanical Factors
- soft tissues are influenced by history of recent physical stresses so that the accumulation of individual stresses can cause injury
-Trauma (bone fracture or ligament rupture)
-Other causes of tissue injury
repeated episodes of moderate-magntiude force
-slow degradation of tissue tolerance
-low loads sustained over a long time
What is physical stress theory?
proposes that the change in the relative level of physical stress cause a predictable adaptive response in all biologic tissue
typical tissue response to physical stress:
-decrease stress tolerance (atrophy)
-maintenance
-increased stress tolerance (hypertrophy)
-injury
-death
a decrease in mechanical stress can be detrimental as it relates to bone health.
What determines the type and extent of tissue damage?
Characteristics of load (rate, compression, forces (torsion, shear)
, along with properties of affected tissue
What determines inflammatory response in mechanical factors?
time elapsed since injury
extent of tissue damage
Nutritional Factors
-imbalance in essential nutrients
1. excessive nutrient intake (leads to obesity and its many complications)
2. dietary deficiency (quantity and quality of foods)
- marasmus
-abnormal levels of vitamins or minerals (deficiency of iron leads to anemia)
Marasmus or protein malnutrition (kwashiorkor)
interfere with protein synthesis to replace cell proteins lost through normal catabolism, through growth, and in preparation for cell replication (Essential for healing processes)
Physical Factor
Blunt or penetrating trauma
-massive brain contusion, injury to internal organs and soft tissues, and blood loss may lead to immediate mortality
-survivors may die later of infections and multiple organ failure
Extremes of physical agents such as temp (burn or frostbite), radiation (irradiation therapy for cancer) electricity
-motor vehicles accident
Psychosocial Factors
Fear, tension, anxiety may influence individual threshold values for tissue adaptation and injury
Cellular Aging
Aging and age related changes can significantly influence homeostasis and recovery process
-mitochondrial DNA is prime target for age related changes
What is the presences of lipofuscin?
age associated change in the subcellular structure (lysosomes) of post mitotic cells.
Aging pigment granule that is found in high concentrations in old cells.
Theories of Cellular Aging
More than 300 theories exist
Mechanism
-decreased capacity to respond to stress -> progressive decline in homeostatic balance -> pathology
Pathological changes associated with aging vary from person to person but usu. consist of reduced functional reserve caused by atrophy of tissue or organs
the effects of exercise training on cellular aging: intervention
Types of cell injury
Reversible
Irreversible
Reversible Cell injury (sublethal)
Normal cell structure and function can return after removal of stressor or injurious stimulus.
Acute:
Impairment of ion homeostasis within cell –> increased intracellular levels of sodium and calcium –> influx of interstitial fluid into cell causes cell volume swelling within cytosol, mitochondria, ER –> less energy generates, cell metabolism slows –> plasma membrane blebs are formed seal off and detach from cell surface
(cellular swelling, accumulation of fluid in ER, release of ribosomes and formation of membrane blebs)
Cellular adaptations in chronic cell injury
sublethal stress remains over time then alterations or adaptations takes place in affected cells.
Adaptations allows cell to function in altered environment and avoid injury.
Common cellular adaptations to chronic cell injury
change in size, number, function increase cell ability to survive.
-atrophy
-hyperplasia
-metaplasia
-dysplasia
Atrophy
reduction in cell size and organ size.
Hypertrophy
increase in size of cell or organ.
can occur with increase functional demands placed on cells with increased hormonal input.
pure hypertrophy occur only in heart and striated muscles b/c organs consits of cells cant divide
hyperplasia
increase in number of cells, leading to increase organ size.
tissues that have cells that can divide, presence of excessive functional demands cause increase in cell numbers.
pure hyperplasia: due to hormonal stimulation (prolonged estrogen cause endometrium to become thick) or chronic stimulation (pressure on skin induce hyperplaisa and forms callus)
metaplasia
a change in cell morphology and function resulting from conversion of one adult cell type to another.
ex: change from ciliated to stratified in smokers
Dysplasia
increase in cell numbers that is accompanied by altered cell morphology and loss of histologic organization
intracellular accumulations or storage in reversible cell injury
are increases in the storage of lipids, proteins, carbohydrates, or pigments within the cell that occur as result of an overload of various metabolites or exogenous material.
Ex: when liver is sublethally injured, lipid accumulates within hepatocyte
irreversible cell injury
-synonymous with cell death
-cell death result from apoptosis or necrosis
apoptosis
programmed cell death
-typically not associated with inflammatory response
necrosis
active process of degradation of dead cells
end point of pathologic process that results in lethal, irreversible cel injury
What are the hallmarks of lethally injured cells?
alterations in cell nucleus, mitocondria, lysosomes and rupture of cell membrane
What is inflammatory process responsible for?
removal of injurious agent
removal of cellular debris
initiation of healing process
Inflammation
the process initiate after cell injury through several mechanisms
-amt, type, severity of inflammatory reactions are dependent on amt, type and severity of injury
Purpose:
removal of injurious agent, removal of cellular debris, and initiation of healing process
Normally, inflammation has a protective role and generally beneficial to body, however whether in acute or chronic stage ( and with all of its components), it can be detrimental and potentially cause damage even death to adjacent healthy tissue
Four cardinal signs/symptoms of inflammation
Erythema and Heat : vasodilation and increase blood flow
Edema: fluid and cells leaking from local blood vessels into extravascular spaces
Pain: direct trauma, chemical meditation by bradykinesis, histamines, serotonin;internal pressure secondary to edema; swelling of nerve endings
Characteristics of acute inflammation
vasodilation: increased blood flow with resultant heat and redness (erythema)
increased capillary permeability
clotting: permits passage of plasma proteins and leukocytes into extravascular space (site of injury) –> edema
Loss of fluid –> slower blood flow, higher concentration of RBS in small vessels and increased blood viscosity
migration of leukocytes from the microcirculation: accumulation in the focus of injury and activation to eliminate offending agent –> swelling
edema
fluid and cells leaking from local blood vessels into the extravascular spaces
