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Bio 2192 - Cellular Response to Stress

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What is the key factor that leads to differences between cells?
Gene expression
What is the role of the 2 sets of genes in differentiated cells?
1 - run cell's basic life functions
2 - control differentiated traits
Define hematopoeisis
process of creating new RBCs
Define adaptation
Reversible, functional or structural responses to severe stress where altered steady states are achieved and survival & function are maintained
What are the 4 main forms of stress response?
1. Hypertrophy
2. Hyperplasia
3. Atrophy
4. Metaplasia
Hypertrophy
increase in cell size; due to increase in structural components
Examples of cells that undergo hypertrophy
skeletal muscle cells, heart muscle cells
Mechanism of hypertrophy
Mechanical sensors sense increase in workload; sensors activate growth factor (GF) & vasoactive agents; increase protein synthesis; hypertrophy
Physiological example of hypertrophy
Endometrial lining thickens due to hormone stimulation during pregnancy
Pathological example of hypertrophy
Cardiomyocte hypertrophy due to hypertension
Hyperplasia
increase cell number causing enlarged organ/tissue
Two types of hyperplasia
Hormonal & compensatory (tissue damage)
Example of hormonal hyperplasia
thickening of uterine wall
Example of compensatory hyperplasia
liver regeneration
What causes pathologic hyperplasia?
abnormal levels of hormones or growth factors
Examples of pathologic hyperplasia
Pathologic endometrial hyperplasia; benign prostate hyperplasia; papillomavirus
What distinguishes pathologic hyperplasia from cancer?
Cancer is uncontrolled; pathologic hyperplasia is reversible if stimulus removed; increased replication can lead to cancerous mutation
Atrophy
Decreased cellular size/number
Examples of physiologic atrophy
Ductus arteriosus (connects fetal hart to circulatory system); thyroglossal duct
Causes of pathological atrophy
Disuse atrophy, pressure atrophy, denervation atrophy, Ischemia atrophy, general malnutrition, lack of hormonal stimulation
Examples of general malnutrition
Marasamus (energy deficiency due to lack of nutrients); cachexia (wasting)
What is the main mechanism of atrophy?
Conserve energy by reducing all unnecessary activities & decreasing size
What two factors are involved in atrophy?
Protein degradation & autophagy
Metaplasia
reversible replacement of one differentiated cell with another
Example of metaplasia
Ciliated columnar epithelial cells in smoker's respiratory tract replaced by squamous epithelial (more resistant)
_____ & _____ can lead to neoplasia
Metaplasia & dysplasia
Define anaplasia
structural differentiation loss within cell/group of cells (aggressive form of cancer)
Define Aplasia
organ or part missing
Define hypoplasia
decreased number of cells
Define neoplasia
abnormal proliferation
Define dysplasia
change in cell/tissue phenotype
Define prosoplasia
development of new cell function
Cell's response depends on _____ & _____ of stress
Intensity & duration
What are the two types of cell death?
Necrosis & apoptosis
Necrosis is an _______ process
Uncontrolled
Apoptosis is a ______ process
Controlled
What causes necrosis?
Ischemia or toxins
Apoptosis is also known as _____
programmed cell death
Necrosis causes an ______ response
Inflammatory
Apoptosis does not cause an _______ response
Inflammatory
Is Necrosis pathological or physiological?
Pathological
Is Apoptosis pathological or physiological?
Both
What are 8 causes of cell injury?
Hypoxia, ischemia, physical agents, chemical agents & drugs, infectious agents, immunological reactions, nutritional imbalances, genetic derangements
Define hypoxia
decreased oxygen to cell
Why is oxygen so important for cells?
production of ATP
Define ischemia
lack of blood supply to tissue; no oxygen or nutrients; more severe than hypoxia
What does mitochondrial damage lead to?
Increased mitochondrial membrane permeability; leakiness allows cytochrome C to escape and trigger apoptosis
What does increased cytoplasmic calcium lead to?
Uncontrolled activation of several enzymes; increased leakiness of mitochondrial membrane
Cell membrane damage leads to loss in ____________ __________ of the membrane
selective permeability
What does lysosomal membrane damage lead to?
Leakage of enzymes into cytoplasm; triggers necrosis
List the 6 biochemical mechanisms of cell injury
1. Failure to generate ATP
2. Mitochondrial damage
3. Calcium influx
4. Free radicals
5. Defects in Cell membrane permeability
6. Damage to DNA & proteins
Oxidative damage to lipids results in....
membrane leakiness
Oxidative damage to proteins results in...
Change in protein function; affects membranes & enzymes
Oxidative damage to DNA results in....
affects cell integrity
How long does it take for electron microscopes to detect cell damage?
minutes to hours
How long does it take high microscopes to detect cell damage?
hours to days
Reversible damage is characterized by _____ & ______
Swelling & fatty change
Two events that constitute transition from "Reversible" to "Irreversible" cell damage
1. Damage to mitochondria that cannot be repaired
2. Malfunctioning/leaky cell membranes
Two forms of COPD
Chronic bronchitis & emphysema
Define chronic bronchitis
defined clinically; persistent cough with excessive mucous
Define emphysema
defined morphologically; permanently enlarged airspaces to terminal bronchioles
Necrosis due to effects of ______ _____ ______
escaped lysosomal enzymes
Define autolysis
digestion of cellular structures by cell's own enzymes
What happens if debris not cleaned up quickly after being broken down?
Calcium salt formation
Common features of necrosis
More eosinophilic, appear spongy due to empty spaces, calcified
Define karyolysis
nucleus paler than normal when stained
Pyknosis
nucleus shrinks & stains darker
Karyorrhexis
after undergoing some degree of pyknosis, nucleus breaks up
Reperfusion injury
injury due to allowing blood flow back to tissue
Reasons for reperfusion injury
1. Accumulation of ROS
2. Ischemia produces some inflammation
3. Complement cascade may contribute to cell damage
Tissue patterns of necrosis
1. Coagulative
2. Liquefactive
3. Caseous
4. Fat
What is the most common pattern of necrosis?
Coagulative necrosis
What is coagulation necrosis characterized by?
Denaturation of proteins; cell/tissue framework preserved
What does liquefactive necrosis involve?
Complete digestion of cell; most commonly associated with cell death due to bacteria
What is caseous necrosis?
form of coagulative necrosis; associated with TB; "cottage cheese; affected area surrounded by border of inflammatory cells
What is fat necrosis most associated with?
Acute pancreatitis
What causes gangrene?
insufficient blood supply
Define dry gangrene
cutting off of arterial blood flow to extremities (ex: frost bite); Coagulative necrosis, slow spread, absence of infection; line of demarcation
Define wet gangrene
area infected by bacteria; liquefactive necrosis; no line of demarcation; rapid spread
Define gas gangrene
due to clostridia infection; causes myonecrosis; shock/death may rapidly follow
Morphology of apoptosis
Cells shrink, chromatin condenses, cytoplasmic blebs & apoptotic bodies, phagocytosis
Apoptosis: Extrinsic Pathway
Immune cell communicates with target cell via cells surface receptors; target cells express Fas (death receptor); FasL binds to Fas to activate caspase cascade (caspar 8)
Apoptosis: Intrinsic Pathway
if damage beyond repair, cell signals suicide; orchestrated by pro- & anti-apoptotic molecules; pro replace anti leading to mitochondria membrane permeability, triggering cascade cascade
What are two anti-apoptotic molecules?
Bcl-2 & Bcl-x
What are two pro-apoptotic molecules?
Bad & Bax
What two phases make up the apoptotic pathway?
Initiation & execution
Activation of caspase cascade
Initiation cascade 8&9 cleave & activate execution cascade 3&6; execution cascades cleave & activate endonucleases & proteases
What is a caspase?
enzyme that cleaves at cysteine and aspartic acid
What is an example of membrane alteration?
movement of phosphatidylserine from interior membrane to exterior, recognized by annexin V = apoptosis
What is the condition when lipids accumulate in parenchymal cells?
Steatosis/fatty change
What is the main organ involved in fat metabolism?
liver
Most common causes of lipid accumulation in liver
Alcohol, diabetes, obesity, protein malnutrition
Define xanthoma
masses formed by cholesterol accumulation in macrophages (foam cell); sign of hyperlipidemia
What occurs when calcium is deposited at sites of cell damage & death?
dystrophic calcification
What occurs when calcium deposited in normal tissue?
Metastatic calcification; due to hypercalcemia
Known changes occurring at cellular level that influence aging
1. Decreased cellular replication
2. Accumulation of ROS & free radicals
What is the function of telomeres?
Postpone erosion of genes
What enzyme increases telomere length?
Telomerase