Altered Cells And Tissues Flashcards
1
Q
Cellular Adaptation
A
-Cells adapt to changes (stressors) in their environment
-They increase glucose absorption when their glucose stores are low
-They initiate repair mechanisms when they are damaged
-When cells are damaged they can either adapt or die
2
Q
Cell Injury Common Causes
A
-inadequate oxygen
-chemical, thermal, or physical agents
-ionizing radiation
-toxins
-microbes
-inflammation and immune reactions
-nutritional imbalance
-genetic and metabolic defects
-aging
3
Q
Cell Injury - Inadequate Oxygen
A
-Usually result of ischemia
-Inadequate blood flow doesn’t just effect oxygen delivery but also transport of glucose for fuelling cells and removal of metabolic waste products like CO2
4
Q
Cell Injury: Physical, Thermal, Chemical
A
-These can be anything from a high speed MVA to frostbite to industrial accidents
5
Q
Cell Injury: Ionizing Radiation
A
-X ray or gamma rays may damage DNA or cause proteins to midfield in the cell
6
Q
Cell Injury: Toxins
A
-Depending on the toxin, they can damage enzyme pathways in your cells or destroy the membranes of your cells
7
Q
Cell Injury: Microbes
A
Could be bacteria, yeasts, moulds, and viruses
8
Q
Cell Injury: Inflammation and immune reactions
A
-If you have an autoimmune disease that causes your own antibodies to cross react and attack your own cells
9
Q
Cell Injury: Nutritional Imbalances
A
-This can be considered anything from scurvy due to lack of vitamin C to chronic excess sugar in your diet leading to type 2 diabetes
10
Q
Cell Injury: Genetic and Metabolic Defects
A
-Some genetic diseases cause the accumulation of abnormal products, which can damage cells
11
Q
Cell Injury: Age
A
-aging causes progressive, mild injury that ultimately leads to cell death directly or renders cells less able to withstand other forms of injury
12
Q
Cell Injury
A
-Injury may occur anywhere within the body’s structural hierarchy
-Genes influence how we react to injury
-Impaired health may result from the inflammation and repair process that follows injury
-Cells will react differently based on different injuries
13
Q
If cytoskeleton is damaged ..
A
Then cell with make an enzyme or increase it’s concentration to repair it
14
Q
If DNA is damaged..
A
Then the cell will run another program to make a different enzyme to detect the change and correct it
15
Q
If damage is too extensive ..
A
-or not enough raw materials are around like glucose, oxygen, amino acids, etc
-then cell isn’t going to be able to fix itself
-May result in inflammation or even cell death
16
Q
Examples Acute Mild Injury
A
Hydronic change
Steatosis
17
Q
Examples Chronic Mild Injury
A
Intracellular accumulations
Altered growth and differentiation
18
Q
Not all injured cells ___
A
Die
-some are able to survive but may exhibit physiological changes
-these changes may be reversible or permanent depending on type and extent of injury
19
Q
Whether or not cell injury is reversible depends on
A
-the duration and severity of injury or stress
-mild injuries produce visible, reversible changes in cells which reverts to normal when the cause of injury disappears
-long term mild injury or stress leads to changes that persist until the cause of the injury disappears
20
Q
Acute Mild Injury Causes
A
-Brief, visible cell change
21
Q
Most Common Cause of Acute Mild Injury
A
-Most common cause is brief hypoxia or anoxia though toxins may exert a similar effect
-Two most common types of injury or stress are 1) hydropic change 2) steatosis
22
Q
Hydropic Change
A
-Eg Congestive heart failure
-Occurs because of change in intracellular sodium concentration
-Normally extracellular sodium is higher than intracellular sodium
-This concentration difference is maintained by the sodium pump mechanism of cell membrane which constantly pumps sodium out of the cell as fast as it seeps in
-Lack of oxygen deprives pump of its energy (ATP) damaging this mechanism and allowing sodium to seep across the membrane and into the cytoplasm
-Because solutes attract water, a rise in intracellular solute (sodium) attracts water into the cytoplasm
23
Q
Hydropic change is ___
A
Reversible if the injurious situation is corrected
24
Q
Steatosis
A
-Eg Fatty Liver (accumulation of fat in the cell)
-Most common in liver cells because of the livers premier role in fat metabolism
-often in people who abuse alcohol
-now more common in young adults and children due to obesity
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Steatosis is ___
Reversible
-However chronic steatosis of the liver can progress to cirrhosis and liver failure
26
Common types of Chronic Mild Injury
-Two most common types of cell response to common mild injury or stress are intracellular accumulations and altered patterns of cell growth and differentiation
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Types of Intracellular Accumulations
-Cholesterol
-Protein
-Pigment
-Environmental Particles
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Intracellular Accumulations
-Water and fat accumulate within reversibly injured cells as a result of mild short term injury
-More prolonged injury is associated with other accumulations, including cholesterol, protein, pigment, and various environmental particles
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Intracellular Accumulations: Cholesterol
-Eg. Atherosclerotic artery
-Low density lipoproteins or very low density lipoproteins carry cholesterol from your liver to your fat cells
-if too much LDL or VLDL in your blood stream then can bind and buildup in areas they shouldn’t and begin narrowing arteries causing atherosclerosis
-still don’t know why this happens
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Intracellular Accumulations: Proteins
-Normal body proteins are long chains of amino acids that must be folded into appropriate shape for their function
-When they are damaged and fold inappropriately they may clump together and accumulate
31
Protein Accumulation Example
-Tau protein accumulation in Alzheimer’s disease
-Tau normally stabilizes microtubules which form the cytoskeleton in cells
-During cell stress or damage tau can be released, misfolded and bind to other tau molecules clumping together
-Too much clumps inside the cell and the cell can’t transmit neurotransmitters for instance and died, usually via apoptosis
-Theory for developing Alzheimer’s disease
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Other Protein Accumulation Examples
-Include most of the other Neuro degenerative disease
-Include: Huntington’s, Parkinsons, and ALS as well as many other diseases such as the buildup of alpha 1 antitrypsin in the liver of patients with genetic alpha 1 antitrypsin deficiency mutation which can result in in COPD and liver cirrhosis
33
Pigment Intracellular Accumulations
-Most widely occurring pigment accumulation is lipofuscin
-Golden brown substance most notable in long lived cells such as brain neurons, cardiac myositis, and liver hepatocytes
-It’s presence indicates wear and tear
-End result of fatty acid oxidation in lysosomes associated with many diseases from Parkinson’s to COPD
-It May be symptomatic of membrane damage, or damage to mitochondria and lysosomes
34
Other Pigment Accumulation Examples
-Bilirubin in jaundice (often due to liver diseases, gallstones, pancreatic tumours, etc)
-Melanin (used by skin keratinocytes to protect against UV damage; tanning)
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Cellular Accumulation Environmental
-Inhaled particles from cigarette smoke or air pollution accumulate in respiratory cells and bronchial lymph nodes and contribute to a variety of resp diseases
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Types of Altered Cell Growth and Differentiation
-Atrophy
-Hypertrophy
-Hyperplasia
-Metaplasia
-Dysplasia
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Altered Cell Growth and Differentiation
-Cells respond to chronic mild injury or stress including good stress of exercise by making certain adaptations
-When the source of the chronic injury or stress is removed, the cell, tissue, organ, or body part usually returns to normal
38
Cell Atrophy
-Decrease in cell number, size and work output
-Adaptation to diminished resources/ decreased demand or to increased stress as the dell shuts down its metabolic processes to conserve energy
-Normal part of life
-Eg. Observed when you stop exercising for an extended period of time
-Often reversible
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Examples Cell Atrophy Exercise
Stopping Exercise
-skeletal muscle cells are not required to do as much work as they used to
-adapt to this change in their environment by breaking down excess sarcomeres and organelles, resulting in decreased cell size and functional capacity
-whole muscle decrease in size and strength
-This response to decreased workload is referred to as DISUSE ATROPHY
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Examples Cell Atrophy: Main Cause
-Pathologic atrophy typically is the result of disuse or lack of normal physiological support
-Bodies of underfed children are atrophied
-Organs deprived of blood and nutrition it brings will atrophy
-paralyzed limbs atrophy from disuse
-thyroid and adrenal glands will atrophy if denied hormonal support from the pituitary
-If effect cells decrease their size and energy requirements during these circumstances as a means of survival
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Atrophy in the case of muscle cells …
Don’t necessarily die, they just shrink
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Atrophy Causes
-Disuse
-Denervation (neurogenic)
-Hormones
-Malnutrition
-Ischemia
-Aging
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Atrophy: Denervation
-Also known as neurogenic atrophy
-Affects the nerves connected to the muscles rather than the muscles themselves
-Nerve damage much harder to treat and will not reverse with exercise
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Common causes of nerve damage
-Alcohol abuse
-Toxins
-Injury
-Diseased that affect the nerves that engage in muscle movement (ALS, Polio, Carpal tunnel syndrome =thenar atrophy, Spinal cord injury)
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Atrophy: Hormones
-Uterine atrophy is a type of atrophy due to loss of endocrine signalling
-Estrogen stimulates uterine smooth muscle hypertrophy and it’s loss causes atrophy
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Atrophy: Malnutrition
-May be result of insufficient total caloric intact (starvation) or insufficient intake of one or more particular nutrients (such as lack of protein)
-Effects include changes in body mass, poor wound healing, severe weight loss (cachexia) and organ failure
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Atrophy: Ischemia
-Eg. Ateriovenous fistula, abnormal connection or passageway between an artery and vein
-usually but not always congenital
-Eg. Common example peripheral artery disease
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Atrophy: Aging
-Aging is associated with changes in body composition and energy and protein metabolism that are due both to direct effects of aging and age related diseases
-Loss of lean body mass is associated with loss of strength, immune function, pulmonary function, and with increased disability and mortality
49
Hypertrophy
-Opposite of atrophy
-Increased cell size and functioning due to the increased size of individual cells
-Most often seen in muscle because muscle tissue has few stem cells which means that muscle cannot meet increased demand by growing new cells, must adapt by cell enlargement
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Hypertrophy: muscle increased use
-In addition to increased use, muscle hyperatrophies in response to endocrine stimulation
-Males tend to have more skeletal muscle mass than females because of the presence of male sex hormone testosterone
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Testosterone stimulates
Skeletal muscle to Hypertrophy
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Hyperatrophy: abnormal (pathologic)
-Not all hyperatrohphy is normal
-Eg. Cardiac muscles response to hypertension
-systemic high BP increases the amount of work the left ventricle must do to force open the aortic valve and eject blood into the aorta
-Systemic hypertension increases the afterload on the heart
-Cardiac muscle cells in the left ventricle respond to increased workload by Hypertrophying
-Result = larger and stronger cardiomyocytes are capable of contracting with greater force, and the left ventricle as a whole can generate enough pressure to overcome afterload and eject blood into the aorta -hypertensive hearts have much thicker left ventricles than healthy hearts, indicating the cardiac muscle hypertrophy has occurred
-At some point if hypertension is not treated and continues to worsen, the cardiac muscle cells stop hypertrophying and results in left heart failure which can be fatal
53
Hypertrophy: epithelial and connective tissue cells
-Not only limited to muscle cells
-under certain circumstances epithelial and connective tissue cells are capable of increasing in size and functional capacity
-Eg. If one kidney is surgically removed or rendered inactive, the remaining kidney enlarges to compensate for the loss
54
Hyperplasia
-Increase in cell number in an organ or tissue
-Adaptation to increased workload and/or endocrine stimulation
-Often reversible
-Enlargement of tissue or organ owing to an increase in the number of cells
-Only occurs in cells capable of mitosis such as epithelial and connective tissue cells
-Same signals that stimulate hypertrophy also stimulate hyperplasia = both occur in the same cell at the same time
-Occurs under both normal and abnormal circumstances
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Two most common types of normal hyperplasia
-Hormonal and compensatory
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Hormonal Hyperplasia
-Breast and uterine hyperplasia observed during puberty and pregnancy are stimulated by high concentrations of estrogen
-Estrogen also stimulates uterine smooth muscle hypertrophy (so in pregnancy both are happening)
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Hyperplasia Compensatory
-Regeneration of tissue after it is removed or diseased
-Eg. Liver regeneration = when a liver is partially resected, mitotic activity in the remaining hepatocytes begins as early as 12 hours later, eventually restoring the liver to its normal weight
-Eg. Binge drinking kills cells that can rebuild over time
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Most pathologic hyperplasias are due to…
Excessive hormonal and growth factor stimulation
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Abnormal Hyperplasia
-During pregnancy endometrial hyperplasia due to high estrogen concentrations is a good thing
-When it happens otherwise it may not be = excessive estrogen production can cause endometrial hyperplasia in the uterus and abnormal menstrual bleeding
-Benign prostatic hyperplasia in males can obstruct urine flow
-Androgens such as testosterone promotes prostate cell proliferation and excess of that or dihydrotestesterone can cause this
-An estimated 50% of men have evidence of BPH by age 50 and 75% by age 80
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Hyperplasia Example Growth Factor
-Skin warts are an example of hyperplasia caused by growth factors produced by certain viruses such as papillomaviruses
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Hyperplasia and Cancer
-NOT THE SAME THING
-hyperplasia = increased cell proliferation
-cancer = increased cell proliferation
-Hyperplasia is strictly regulated adaptation to a particular stressor and is reversible
-Cancer is uncontrolled cell proliferation
-Removal of stressor that caused cancerous cell division does not result in reversal
62
Metaplasia
-Change from one cell type to another
-Only occurs in epithelium and mesenchyme (connective tissue)
-Often reversible
-Caused by chronic injury
-Most common in epithelium because epithelial cells are short lived and are always being replenished from stem cells
-Injured or stressed epithelial cells can mature into a different type of cell more suitable to existing conditions
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Metaplasia Pathology
-Few examples of normal physiologic Metaplasia
-Adaptation to an injurious stressor
-May be a precursor to dysplasia and cancer
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Metaplasia and respiratory system
-Epithelium in non-smokers is composed of ciliated simple columnar or pseudostratified epithelial cells
-In smokers this changes into stratified squamous epithelium = more durable tissue better suited to defend against noxious substances in smoke
-In this circumstance Metaplasia has survival advantages but protective mechanisms are sacrificed such as musics secretion and ciliary clearance = double edged sword
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Metaplasia and respiratory system chronic
-stressors that induced metaplasia of the resp epithelium May if not removed result in cancer
-squamous metaplasia in the resp epithelium epithelium often coexists with cancers composed of malignant squamous cells
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Metaplasia and Gastric Reflux
-Change occurs in chronic gastric reflux
-Normally esophagus is lined with stratified squamous epithelium
-In response to chronic exposure to stomach acid is replaced with more gastric or intestinal like simple columnar epithelium
-May only be a short term solution as the risk of esophageal cancer is increased if stressor is not removed
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Metaplasia and connective tissue
-Metaplasia also occurs in mesenchymal cells but less clearly as an adaptive response
-Metaplasia DOESNT just happen in epithlial cells
-Eg. Calcific tendonitis of the shoulder
-usually occurs in location of injury
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Dysplasia
-Abnormal cell growth
-Cells vary is size, shape, and organization
-Still considered “adaptive” because it is reversible
-literally means “disordered growth”
-also refer to pre-malignant change of cells
-Not invasive and is usually reversible
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What does dysplasia do
-Usually occurs in epithelial
-As uniform appearance and orderly arrangement of cells is replaced by haphazardly arranged, enlarged, distorted cells with large dark nuclei that reflect chromosomal chaos within
-Mileppost on the way to malignancy
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Dysplasia vs Metaplasia
Dysplasia: cell maturation and differentiation are delayed
Metaplasia: one mature, differentiated type replaced by cells of another mature, differentiated type
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Dysplasia associated with ..
-Often associated with chronic irritation and inflammation
-Often preceded by Metaplasia
-Strongly implicated as a precursor to cancer
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Dysplasia and Pap smear
-Looks at the dysplastic cell progression of the cervix which might result in cancer
-Triggered by HPV = epithelial cells begin to become dysplastic
-Their nucleus to cytoplasmic ratio changes and alters the ordered differentiation of the cells
-up until this becomes cancerous it is entirely reversible is stressor is removed
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Pap smear classifications
CIN: Cervical intraepithelial neoplasia
CIN1: mild and mild to moderate dysplasia
CIN2: moderate and moderate to severe dysplasia
CIN3: severe dysplasia and carcinoma In situ
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Dysplasia and cancer
-dysplasia is an adaptive process and does not necessarily mean cancer
-In many cases dysplastic cells revert to their former structure and function
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Severe injury causes
Cell death
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Two types of cell death
1. Necrosis
2. Apoptosis
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Cells die because of..
Injury or the passing of time
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Cells have a natural ..
Life span
-after living out their natural term of a few days, months, or a human lifetime they die by “natural suicide” in a carefully regulated orderly process called apoptosis
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Necrosis
-Pathological Cell Death
-Usually due to Ischemia/hypoxia/anoxia
-Often occurs in a contiguous block of cells
-There are 4 principal types:
Coagulative, liquefactive, caseous, fat
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Larger scale necrosis
-Rare
-Fibrinoid = rare form of necrosis caused immune complex deposition
-Gangrenous = essentially just a form of coagulative + liquefactive necrosis
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Coagulative Necrosis
-characterized by gel-like change in blocks of freshly dead cells
-most common type
-occurs in the infarcts, local blocks of necrotic tissue due to schema caused by impaired blood flow in the artery feeding the tissue
-Because the cells die in place without anatomic disruption, gross microscopic tissue is preserved despite the fact the tissue is dead
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Coagulative Necrosis Examples
-Solid organs like the liver, heart, and kidney are the most often affected
-Eg. Blockage of a coronary artery produces Ischemia in downstream heart muscle cells, resulting in a myocardial infarction
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Liquefactive Necrosis
-Cell death in which the dead tissue dissolves into fluid
-Occurs because dead cells are disrupted or dissolved
-Most frequently produced by bacterial infection
-Some bacteria incite severe cell damage and attract great numbers of WBC’s that release digestive enzymes to kill bacteria = in process dead cells are digester into liquid known as pus to form an abscess
-This may also happen in the brain due to focal or global brain Ischemia
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Caseous Necrosis
-Variant form of coagulative necrosis and limited liquefactive and obliterated cell detail
-Most common cause is tuberculosis infection
-Caseous means cheesy = the dead tissue appears off white, soft, pasty, and clumpy
-Caused by macrophages sealing off necrotic tissue and the granulatous formulation
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Fat Necrosis
-Specialized form of liquefactive necrosis that occurs only in fat
-Especially common around the pancreas, skin or any other fat including the breast
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Process of Fat Necrosis
-Pancreatic disease (such as inflammation or trauma) liberated pancreatic digestive enzymes that convert pancreatic fat into glycerol and fatty acids
-Fatty acids combined with calcium to form soap which traps calcium in tiny deposits in the injured tissue where it becomes visible on x rays
= pose a diagnostic challenge in breast cancer because breast cancers often contain calcium deposits
-These soaps appear as white chalky deposits
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Apoptosis
-Programmed natural cell death
-Cell wants to die
-Internal of external forces can active the mechanism
-Important in embryological development Eg. Webbed fingers
-Many pathologic processes also invoke
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Apoptosis activated by:
Internal forces: embryological development
External forces: pathological
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Apoptosis external forces
-External force activates “suicide” genes, inactivates other genes necessary for cell to sustain life, and manufactured its own lethal cocktail of suicide substances that attack cell structures
-Metabolism slows, and the cell shrivels and is ultimately ingested and digested by scavenger cells (macrophages)
-Some degenerative diseases, especially Alzheimer’s disease and other diseases of the nervous system may be caused by pathologic apoptosis
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Apoptosis Pathway
1) Cell receives an injury or signal to undergo apoptosis, in many cases the injury will be either damage to DNA or to the mitochondria, if it’s a cellular signal these will often be withdrawl of hormones or growth factors, or messaging and interaction with the immune system
2) the apoptosis pathway then triggers enzymes called caspases to activate and begin disassembly of the cell
3) the caspases activate a variety of degradation enzymes to start breaking down the organelles, cytoskeleton, and DNA of the cell
4) Finally phagocytes such as macrophages come along and clean up the leftover cellular bits
