Chapter 2 Flashcards
1
Q
Homeostasis
A
Ability to maintain internal conditions
2
Q
Stress
A
Strain exerted on a system
3
Q
Stress in the body can be from…
A
Temp pH, o2/CO2, nutrient availability, hormones, etc
4
Q
Endogenous stress factors
A
Hereditary or congenital stressors
5
Q
Exogenous stress factors
A
Environmental stressors like infectious particles, toxins, etc
6
Q
Range of tolerance
A
Parameter which the body systems function normally
7
Q
Ranges of resistance
A
Ranges above and below the range of tolerance
At these ranges, adaptations and compensatory mechanism will start
If not returned to normal range, irriversible injury will occur
8
Q
Compensation
A
Alternation in function that temporarily masks the loss of optimal conditions
Survival mechanism
Occurs in allostatic ranges
9
Q
Allostasis
A
Range where compensatory mechanism occur
10
Q
Allostatic overload
A
Beyond allostatic range, where compensations fail
11
Q
Example of compensatory mechanisms
A
Vasoconstriction to compensate for reduced BP due to heart failure
Increased erythropoietin’s to compensate for reduced O2 at high altitudes
12
Q
Decompensation
A
Deterioration of compensatory mechanisms
13
Q
Example of decompensation
A
Heart failure
- compensatory effect: vasoconstriction
Decompensation
- leads to evaluated afterload on failing heart which results in decompensated cardiac output
This progressively worsens heart failure
Compensatory effects worsen the original trigger if used for too long
14
Q
Exhaustion
A
Where Decompensation is overwhelmed
Leads to crisis
15
Q
Crisis
A
Divergence of conditions from homeostatic range where tissues die
16
Q
Tissue adaptations are the result of changes such as
A
Energy use
Growth
Cell division
17
Q
Labile tissues
A
Tissues with a high rate of cell division and short life span
Eg, blood cells, epithelium
18
Q
Stable tissues
A
Slow to be replaced, can divide faster if needed.
Eg. Osteocytes, hepatocytes
19
Q
Permanent tissues
A
Tissues that enter G0 phase during maturation
- no longer divide
Eg. Neurons, skeletal and cardiac muscle
20
Q
G1 phase
A
Cell metabolically active
Organelles and cytoplasmic components duplicate
Centrosome replication begins
21
Q
S phase
A
DNA replication
22
Q
G2 phase
A
Cell grows more
Proteins and enzymes synthesized
Centrosome replication complete
23
Q
Atrophy
A
Decrease in cell volume and number
24
Q
Physiological atrophy
A
Atrophy of uterus after pregnancy
25
Pathological atrophy
Atrophy of muscle due to nerve damage
26
Cellular mechanism behind atrophy
Decreased protein synthesis
Reduced number/size of mitochondria
Increased rate of autolysis
27
Atrophied tissue is sometimes replaced with:
Connective tissue and or adipose tissue
28
Hypertrophy
Increase in cell volume
Due to increase demand placed on tissue
29
Mechanism behind hypertrophic
Binding of growth factors to receptors
Leads to intracellular signally and increased RNA and protein synthesis
30
Physiological hyper trophy
Increase in muscle size when lifting weights
31
Pathological hypertrophy
Common in the heart due to chronic hypertension
Increase in myocardial mass leading to faster fatigue
32
Hyperplasia
Increase in number of cells due to increase in rate of division
33
Physiological hyperplasia
Sex organ growth during puberty
Expansion of uterus during pregnancy
34
Compensatory hyperplasia occurs where…
Tissues have lost mass due to death
Liver toxicity can lead to death of hepatocytes. Compensatory hyperplasia leads to their replacement to get back to normal liver size
35
Pathological hyperplasia
Abnormal proliferation of cells
Eg. Imbalance in estrogen/progesterone leads to hyperplasia of endometrial epithelium leading to endometriosis or heavy menstrual bleeding
36
Aplasia
Absence of cell division
37
Physiological aplasia example
Cardiac or skeletal muscle cells
Permanent tissues that no longer divide
38
Pathological aplasia
Aplastic anemia
Loss of production of blood cells due to exposure of bone marrow to toxins
39
Metaplasia
Reversible replacement of one type of adult cell by another
Considered adaptation to hostile environment
Common in areas with chronic stress of epithelial cells
40
Metaplasia example (pathological)
Respiratory epithelium (ciliated columnar) replaced by stratified squamous to overgrow damage from smoking
Leads to inability to remove mucus and irritants (no cilia and goblet cells)
41
Since metaplasia is often caused by exposure to chronic stress…
It is sometimes a precursor to tumour development
42
Dysplasia
Abnormal cellular form
Appears disorganized (size shapes and arrangements)
Driven by persistent injury
Abnormal nuclei, staining, shaped cells
43
Dysplasia is a manifestation of….
Decompensation, rather than adaption
44
Metaplasia and dysplasia can signal
Pre neoplastic (precancerous) state
45
5 types of cellular adaptions
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
46
Cellular adaptation cause by decreased demand or chronic ischemia
Atrophy
47
Cellular adaptation caused by increased function demend (2)
Hypertrophy
Hyperplasia
48
Cellular adaptation cause by persistence injury (2)
Metaplasia and dysplasia
49
Cell injury events (what thing happen when a cell is injured)
ATP production loss, leaky membranes, lack of protein synthesis, swollen nuclei with loss of DNA integrity
50
Reversible cell injury
Cell can repair and re establish normal function
51
Irriversible cell injury
Cell repair does not re establish normal function
Leads to reduced function or death
52
Cell injury causes (6)
Deficiency (most common)
Intoxication (most common)
Infectious
Immunological
Physical injury
Chemical injury
53
Deficiencies
Type of cell injury caused by lack of required substance
Eg. Hypoxia, Ischemia
54
Hypoxia
Reduced o2 in the tissues
Often caused by ischemia
55
Reduced o2 in tissue (hypoxia) leads to…
Reduced cellular respiration, meaning reduced ATP production
This causes slowed activity of Na/K ATPase, which leads to accumulation of Na in cell which leads to swelling (osmosis)
56
Decompensation of glycolysis (when aerobic respiration is not possible)
Accumulation of lactic acid in cells and bloodstream, leading to acidosis
57
Ischemia
Insufficient blood from to the tissues
Can lead to infarction (tissue necrosis)
58
Ways arterial occlusions can form
Thrombosis
Embolus (object like fat)
Stenosis (narrowing of lumen)
59
Where ischemia is gradual, _______ occurs, leading to…
Inflammation, leading to phagocytes releasing ROS leading to cell damage
60
Oxidative phosporylation
Process where oxygen is used to transfer energy from bonds in energy substrates to ATP
Extremely effective, but exposures the body to reactive oxygen derivatives
61
What does decreased ATP production lead to (3)
Decreased protein synthesis
- due to detachment of ribosomes
Clumping of chromatin
- due to anaerobic glycolysis creating lactic acid and lowering pH
Cellular swelling
- due to decreased work of Na/K pump, leading to lots of Na in the cell, then osmosis of water into cell
62
Intoxications
Type of cell injury caused
- endogenous - toxin came from within
- exogenous - from outside
63
Oxidative stress and the resulting oxidative cellular injury
Mechanism leading to many age related diseases.
Oxidative phosphorylation
64
Oxidation of the cells (due to oxidative stress) results in…
Alteration of the structure of proteins, lipids, nucleic acids
- leads to functional changes in the cell
Free radicals and ROS alter structure by displacing bonds in these molecules
65
Oxidation “agents”
Free radicals and Reactive oxygen species
66
Diseases resulting from oxidative injury
Atherosclerosis, some cancers, cataracts, aging process
67
Free radicals (what are they, how can they be formed)
Highly unstable molecules that have unpaired elections. Steal electrons form others which causes the others to be unstable
Can be formed from other chemicals in ways such as radiation exposure
68
Lipid oxidization results in
Membrane leakiness, cell swelling
Snowball effect, mitochondrial membrane leakage leads to loss of function = less ATP = more Na in cell = swelling (osmosis)
69
Protein oxidation leads to
Loss of secondary and tertiary structures = loss of function s
70
DNA oxidation lead to…
Gene damage
71
Reperfusion injury after ischemia (what is it, what has it been linked to)
Further damage that occurs after blood flow is restored
Been linked to:
- formation of ROS
- increased intracellular calcium (bad)
- inflammation
72
Leakage of cytochrome C into cytoplasm (due to ROS damage on mitochondrial membranes) triggers:
Cell apoptosis
73
What do anti oxidants do
React with free radicals to make them stable
74
Types of anti oxidants (2)
Exogenous
- vitamin A, C, E
Endogenous
- neutralize free radicals produced by metabolism
75
An important indicator of a cells ability to detox ROS is:
It’s ratio of oxidized glutathione to reduced glutathione
76
Glutathione reductase
Converts oxidized glutathione to reduced glutathione (this ratio helps detox ROS in cells)
77
Organelle response to injury: lysosomes
Heterophagy, autophagy
78
Organelle response to injury: smooth ER
Induction of protein processing
79
Organelle response to injury:
Mitochondria
Number, size, shape, FUNCTION
80
Organelle response to injury: nucleus
Karyolysis (breakdown)
Karyorrhexis (change of size)
Pyknosis (shrinkage)
81
Immunologic injury (how can inflammation/cells of the immune system cause damage)
Inflammation can produce injurious products over time
Cells of the immune system create ROS to defend invaders, but ROS will eventually damage our cells
82
Physical injury (a few examples)
Frostbite (cytoplasmic fluid freezes, killing cells)
Burns destroy tissue
Radiation can break chemical bonds and generate freer radicals that damage our cells
83
Direct chemical injury
Heavy metals can be directly toxic
Or
Chemicals can become toxic after metabolization (acetaminophen)
84
Accumulations (infiltrations) (2)
Accumulation of substances in cells can be an indication of injury or result in cell injury
Can be classified as:
- excess normal substance
Or
- accumulation of abnormal substances due to a faulty metabolism / cannot be degraded by the cell
85
Why do normal substances accumulate in the cells (examples)
Hormonal dysregulation (diabetes mellitus)
Metabolic disturbances from toxins (fatty accumulation in liver)
Genetics
86
Most common reason for abnormal substance buildup in cells
Uptake of exogenous molecules the cell cannot metabolize
87
Lipid accumulation (what happens, waht is the effect)
Fat accumulates in the ER and golgi due to lipid metabolism disorders
Fat disrupts function of organelles
- cells/organ enlarges
- can lead to necrosis and impairment of organ function
88
Glycogen accumulation (why does it occur)
Diabetes mellitus
- glycogen buildup in liver, heart, kidney parts
89
Protein accumulation (what happens) (ex of diseases caused)
Misfolded proteins can accumulate in all types of cells or extracellular matrix
Diseases caused
- emphysema, cystic fibrosis, Alzheimer’s, etc
90
Calcium accumulation (likely most important to know)
(What happens when this happens?)
Includes two types of calcification (mentioned in other slides)
Enzymatic function is exacerbated and membrane and nucleus damage occurs
This is because Ca is a cofactor for many enzymes
91
Dystrophic calcification (buildup of calcium, where does it occur and why)
Occurs in dying o dread tissue when calcium serum levels and metabolism are normal
Occurs in chronically irritated muscle tissues and tumors
Happens in almost everyone with age
92
Metastatic calcification (what is it, why does it happen)
Calcium is deposited in normal tissues due to excessive amounts in the body
Caused by dyregulated parathyroid hormone (which regulates calcium), abnormal bone resorption, excess vitamin D
93
Flow chart of increased intracellular calcium
Excess calcium leads to activation of enzymes
This causes:
- reduced ATP due to ATPase activation
- nuclear damage due to endonuclease activation
- membrane damage due to phospholipase and protease activation
94
Pigment accumulation (waht colours are from waht) (3)
Yellow (lipofuscin)
- thought to be due to fat metabolites
- not considered very toxic
- happens in old people
Black (melanin)
- can accumulate in conditions like melanomas
Bruise pigments (bilirubin, hemosiderin, biliverdin)
- common where blood vessels are ruptured
95
Hyaline accumulation
Result of viral infections, excess production of basement membrane substance
96
Necrosis
Cell death
Leads to inflammatory response due to leakage of intracellular content
- leakage of digestive enzymes form lysosomes cause negrosis in nearby cells (chain reaction)
ALWAYS pathological
Leaves a mess
97
Apoptosis
Programmed cell death that involves activation of metabolic pathways resulting in cell suicide
No leakage of contents - no mess
Get phagocytize by other cells
No inflammation
Can be physiological OR pathological
98
What leads to necrosis?
Influx of Na, Ca, and water due to membrane distortions
Leads to leakage of lysosomal enzymes which eat the cell organelles
- once mitochondria falls, cell dies
- nucleus changes (shrinks/dies)
99
Types of necrosis (4)
Coagulative
Colliquative
Fatty
Gangrene
100
Coagulative necrosis
Most common (seen in heart and kidneys)
Tissue appearance firm and opaque (egg white)
- this is due to lack of blood supply or chemical injury
Caseation may occur
- tissue goes crumbly (cheese like) typical in tb granulomas
101
Colliquative (liquefaction) necrosis
Usually in brain due to fatal injury of neurons
- Glia release lysosomal enzymes that digest tissue
Pus like, has fluid pockets
102
Fatty necrosis occurs in…
Pancreas and breasts due to release of lipases which digest triglycerides
These triglycerides release fatty acids which combine to saponify the tissue (look like soap)
103
Gangrene
Type of necrosis where bacterial action is present
Coagulative (dry)
Liquifactive (wet)
104
Dry gangrene (why it occurs, characteristics)
Occurs because of reduction of blood flow to extremities (frostbite, small artery disease)
Has slow spread, no infection, and a line of demarcation is present around the area
105
Wet gangrene (why it occurs, characteristics)
Bacterial infection is present
- smells awful
Cold, swollen, pulselessness area
Spread is rapid and lacks line of demarcation
106
Gas gangrene (cause, what happens)
Cause by clostridia infection usually in large traumatic wounds like bullets n stuff
Organisms digest deep connective tissue rapidly
- gas bubbles are caused by fermentation of tissue
Can cause shock and intravascular coagulation
Can kill you pretty quick (hours)
- due to potent exotoxins
107
Apoptosis types (2)
Developmental
- fetal development (removal of interdigital web)
Self sacrifice
- done by cells with damaged genetic material, organelles, or if it receives death signals
- beyond repair, kills itself
108
Apoptotic pathways
Extrinsic and intrinsic
These end up combining into the common apoptotic pathway
109
Common apoptotic pathway
Activation of executioner caspases that breakdown cytoskeleton and activate endonucleases
Leads to formation of apoptotic bodies that will be phagocytized
110
Extrinsic apoptotic pathway (2)
Cells are signalled to die by cytotoxic T cells due to presence of an abnormal gene or virus
- cell surface receptors are used to communicate death signal
Under normal circumstances, the cell receives survival signals from the ECM. Absence of these leads to apoptosis
111
Intrinsic apoptotic pathways
Cell initiates self destruction as a result of injury
Pathway involves increased mitochondrial membrane permeability
- this allows cytochrome C into the cytoplasm which will activate initiator caspases (network cell death)
112
When do the pathways merge in apoptosis (ex and intrinsic)
After executioner caspases the pathways from the common pathways
113
Aging at an organism level features…
A loss of adaptive responses to stress
Cells lose capacity to divide, maintain ATP production, and maintain structural integrity
114
Cell senescence
Overall decline in function of cells, particularly cell division
115
Factors contributing to cellular aging (2)
Genetic
Environmental
116
Genetic factors that contribute to cellular aging (2)
DNA repair defects
- accumulation of mutations
Genetic abnormalities
- abnormal cellular aging
Both of these lead to replicative senescence
- this leads to reduced ability to produce new cells, promoting cellular aging
117
Environmental factors that contribute to cellular aging (2)
Environmental insults
- lead to ROS induced damage
Reduces proteasome activity
- leads to accumulation of damaged proteins and organelles
Both of these lead to replicative senescence, which causes reduced ability to produce new cells
- contributes to aging
118
“Common pathway” in cellular aging
Both genetic and environmental factors pathways meet at:
Replicative senescence, leading to reduced ability to produce new cells
- leads to cellular aging
119
Telomeres and aging
Cells require telomeres to divide
Every time they divide, telomeres shorten
When they become too short, cell division stops
120
Telomerase
Enzyme that adds telomere length to chromosomes as cells divide
Allows cells to divide basically infinite times
Present in stem cells, germ cells, and cancer cells
121
Glycation
Non enzymatic addition of glucose molecules to proteins
Results in loss of normal protein function
Happens particularly in collagen (ECM, dermis, joints)
Age related tissue injury
122
Hutchinson-Gilford progeria syndrome
Condition caused by extremely fast aging caused by nucleus mutations
Signs appear early (baldness, large head, atherosclerosis, insulin resistant diabetes)
No treatment, death usually before 10
123
Werner syndrome
Signs of aging appear during teen years
- rare to survive past 50
Inherited
- mutations where gene that codes for Werner protein can’t unwind DNA To perform repair
