Block 1 Flashcards
Where does disease begin?
within the cell; collective response of organism determines the disease
What is a cell? What are its features?
minimal structural/functional unit of the body, bonded by plasma membrane, autonomous
- Shape: spheroidal, discoid, columnar, pyramidal, spindle
- Polarity: apical (external) vs. basolateral (internal); directed transport, membrane specialization
- Size: usually microscopic, some elongated (neurons)
- Number: # determines size
- Organelles: ribosomes, ER, mitochondria, Golgi apparatus
- Nucleus: usually solitary; stains BLUE
What are the 4 cell types?
- Epithelial: covers all body surfaces; skin, and lining of organs; most common
- Muscle: contractile~shorten to generate force
- Nervous: excitable~change in membrane voltage (electrical impulses)
- Mesenchymal: cells in ECM~connective; multipotent stem cells
–> collagen, fibrous tissue, elastin; non-living substance between cells
What is the life cycle of a cell?
Some cells are transitory, others last a lifetime (intestinal–>skin–>brain)
1. Embryonal stage: active division, large nuclei (embryonic cells, stem cells)
2. Maturity stage: maximal differentiation in form and function (nervous, muscle cells)
3. Regression (senescence): waning of function, degeneration
4. Death: usually apoptosis (programmed cell death)
**cell populations in tissue are controlled by the balance of stem cell output vs. differentiation, senescence, and death
What is tissue? What are the 4 types?
similar cells organized for common function; arise from embryonic germ layers (ectoderm~ext, mesoderm~mid, endoderm~int)
- Epithelial: the lining of GI tract, organs, skin; squamous, columnar, cuboidal in simple (1 layer), stratified (multiple layers), or pseudostratified (staggered)
- Muscle: cardiac (striated, involuntary) = heart, smooth (involuntary) = line walls of hollow viscera/ducts/blood vessels, skeletal (striated, voluntary) = “flesh” of musculoskeletal system
- Mesenchymal: perform connecting, binding, supporting functions; includes fat, bone, tendons, blood elements
- Nerve: brain, spinal cord, nerves; neurons, glia, Schwann; waves of excitation
What is an organ? What are the two main components of an organ?
the aggregate of tissues (2+) arranged in characteristic plan for independent function; contain fibrous framework, capsule, and independent blood supply
- Parenchyma: essential, characteristic, and functional cells in an organ
- Stroma: internal, auxiliary, supporting tissue (capsule)
What is a system?
the set of organs that collaborate in carrying out related/interconnected functions
11 of them: nervous, digestive, cardiovascular, genitourinary (renal), endocrine, immune, respiratory, musculoskeletal, reproductive, sensory, integumentary
What is a network?
synchronized interaction between systems (protein-protein, gene-regulatory, metabolism, signaling)
What is disease? What is the difference between disease and etiology?
an emergent property: body’s response to cascading of disruptions when adaptive response is inadequate
etiology: underlying event/injury that initiates the disease process
Injury: any perturbation that upsets (even transiently) the normal homeostasis
What is adaptation? Adaptation vs. disease?
a change that preserves the viability/function of a cell
ex) muscular hypertrophy
uterine bleeding is normal during menstruation, increase in BP with age, hyperbilirubinemia in newborn
What are the cells’ responses to injury?
Altered steady state or point of no return
Reactive changes
1. Death: several pathways (common from injury, adaptation, and development)
2. Atrophy: loss of vital capacity, shrinkage
3. Hypertrophy: increase capacity, enlarged
4. Degeneration: diminution of viability
Growth disturbance
1. Hyperplasia: increase in cell number in tissue (calluses)
2. Metaplasia: substitution of one adult type cell for another adult type cell (lungs)
3. Dysplasia: accumulation of less mature cells, incomplete differentiation
4. Neoplasia: “new growth”, loss of growth control, NOT REVERSIBLE (cancer)
What are the two types of inflammatory responses?
- innate: immediate, less specific, acute inflammation
- Adaptive: delayed, very specific, chronic inflammation
Why do so many diverse kinds of injury often cause the same disease?
The biological response repertoire is limited → Quantitative alterations (1 of the 8 reactions)
Why was there so much variability in COVID-19 symptoms? What systems are interacting to create this disease?
immune response and resilience of individuals varies because of genetics, prior exposures, vaccination, co-morbid conditions
excessive immune response damages tissues: cytokine storm, excessive neutrophil (clots damage lung cells)
What are the types of cell death?
Accidental: sudden, unexpected, acute
1. Necrosis
Regulated: physiologic reactions in an orderly matter in response to injury, signal, etc.
1. Apoptosis
2. Necroptosis
3. Ferroptosis
4. Autophagy
5. Senescence
What is cell death?
irreversible event characterized by the loss of ability of a cell to maintain isolation from its environment = breach or fragmentation of the plasma membrane
substances reequilibrate when a cell dies (Na, K, Ca, protein)
What is necrosis?
form of accidental cell death marked by cellular swelling, cell rupture, and lack of ATP-dependence
caused by non-physiological pathways: heat, trauma, toxins
direct, acute damage to the cell
What are the three types of regulated cell death?
- Necroptosis: similar to necrosis but activated through regulated pathways
- Ferroptosis: mediated by iron; characterized by glutathione depletion and ROS damage to cell membranes
- Apoptosis: cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies; activation of caspases; highly regulated; intrinsic and extrinsic pathway
What is autolysis?
spontaneous disintegration of tissues or cells post-mortem from proteases
What is the point of no return?
specific even/moment after which the adaptive mechanisms are exhausted + cell is destined to die
What causes cells to die?
- Assault: acute trauma, ischemia, toxins, poison
- Design: activation of death receptors
- Neglect: deprivation, unrepaired injury
- Aging: replicative senescence (signaling, accumulation of unrepaired injury)
What is released from the cell during necrosis?
DAMP’s: Damage Associated Molecular Patterns = proinflammatory molecules that activate innate immunity activates Toll Like Receptors (TLR)
ex) HMGB1, HSP
PAMPS: pathogen-associated molecular patterns
What are the 4 cellular responses from necrotic injury?
- Mitochondrial Damage: reduced ATP and enhanced ROS
- Entry of Ca2+ into the cytoplasm leading to membrane damage and inappropriate activation of lipases, proteases, nucleases, etc.
- Widespread membrane damage
- Protein misfolding and DNA damage
What are the morphological changes during apoptosis?
- loss of contact from neighboring cells and specialized surface features
- shrinkage, distortion
- conservation of organelle integrity
- chromatin condensation and fragmentation
- phagocytosis by healthy cells or macrophages
Where is apoptosis prominent?
- Nervous system: excess neurons, refinement of neural networks
- Embryonic development: interdigital webs
- Immune system: termination of inflammatory response by deletion of neutrophils
- Endocrine and reproductive system: cell turnover and cyclic tissues (endometrium)
- All epithelia
What is the extrinsic pathway of apoptosis?
“Death by design”
1. TNF receptor- FAS ligand interactions
2. initiator caspases or adaptor proteins with death domains
3. execution caspases: catabolism of cytoskeleton
4. endonuclease activation (DNA fragmentation)
5. Phagocytosis
What is the intrinsic pathway of apoptosis?
“Death by neglect” activated from DNA damage, metabolic stress, hormone withdrawal
1. withdrawal of GF or hormones
2. changes in the permeability of mitochondria: BCL closes with BH3 and Bax/Bak opens (pro-apoptotic)
3. releases Cyt C and ROS
What is the pathway of necroptosis?
- TNF binds to TNFR1
- RIPK1&3 inactivate caspase 8 and form necrosome
- activates MLKL which punch holes in the membrane after oligomerization –> then like necrosis
salvage pathway for apoptosis
