Normal Cells and Matrix Flashcards

1
Q

What are cells?

A
  • Organizational unit of an animal
    • Building blocks of tissues and organs
  • Provide focal point for learning pathology
  • All cells originate from a single primordial cell
    • Differentiates into a diverse population of different cells
  • Cell functions are highly interrelated
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2
Q

What is the plasma membrane?

A
  • A lipid bilayer interspersed with membrane proteins
  • Membrane proteins are critical for cell function and communication
  • The membrane is fluid and constantly changing
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3
Q

What is Cytosol?

A
  • Fluid that bathes all intracytoplasmic organelles
  • Site of most intermediary metabolism
  • Accounts for 50 - 60% of the total cell volume
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4
Q

What is mitochondria?

A
  • Responsible for energy production
  • Oxidative phosphorylation
    • 18x more efficient than anaerobic glycolysis
  • Energy is released as electrons move down the electron transport chain
    • ATP
  • May have originated as intracellular prokaryote
    • Rickettsia prowazekii
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5
Q

What is the Endoplasmic Reticulum?

A
  • Membrane-bound space where proteins, lipids, and carbohydrates are produced
    • These can be incorporated into organelles or are secreted
  • Rough ER produces proteins
    • contains ribosomes
  • Smooth ER produces lipids
    • Detoxification reactions also occur here
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6
Q

What is golgi apparatus?

A
  • Membrane-bound sacs that are closely associated with the ER
    • it modifies, sorts and exports products of the ER
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7
Q

What are Lysosomes?

A
  • Membrane-bound sacs of enzymes
    • primary lysosomes bud from the golgi apparatus
    • Secondary lysosomes are primary lysosomes that fuse with other organelles or cytoplasmic vacuoles
  • They degrade macromolecules d extracellular material taken up by the cell
    • Contents are predominately hydrolases
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8
Q

What are peroxisomes?

A
  • Small enzyme-containing vesicles
  • Mainly a site of oxidative reactions
    • Catalase accounts for 40% of protein content
    • Catalase converts H2O2 to H2O
  • Detoxification and fatty acid breakdown also occur here
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9
Q

What are the functions of the Cytoskeleton?

A
  • Provides properties of shape, organization and movement to a cell
  • Cytoskeletal assembly and disassembly is regulated by calcium
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10
Q

What proteins made up the cytoskeleton?

A
  • Microfilaments
  • Microtubules
  • Intermediate Filaments
  • Regulatory proteins
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11
Q

What is the Nucleus?

A
  • The location of chromatin
    • Chromatin consists of cellular DNA and associated proteins
    • Chromatin is organized into chromosomes
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12
Q

What is the nuclear evelope?

A
  • 2 layered membrane
  • separates the nucleus from the cytoplasm
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13
Q

What is the origin of a cell?

A
  • All cells are derived from a single primordial cell ; the zygote
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14
Q

What are the types of embryogenic cells?

A
  • Ectoderm
  • Mesoderm
  • Endoderm
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15
Q

What is made from Ectoderm?

A
  • Forms a cephalic disc and a neural tube
  • Cells and tissues derived from ectoderm include:
    • Central and peripheral nervous systems
    • Sensory epithelium
    • Epidermis
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16
Q

What is made from the Mesoderm?

A
  • Somites located adjacent to the neural tube
  • Cells and tissues derived from mesoderm include:
    • Connective tissue (mesenchyme)
      • Fibroblasts, osteoblasts, chondroblasts
    • Muscle
    • Kidney
    • Heart and blood vessels
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17
Q

What is the Entoderm?

A
  • Originates as a flat disc by the ectoderm
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18
Q

What is made from the Entoderm?

A
  • Gastrointestinal epithelium
  • Respiratory epithelium
  • Parenchymal organs
    • Liver
    • Pancreas
    • Endocrine glands
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19
Q

What is Cell Replication?

A
  • “The cell cycle”
  • Complex and critical to normal cell development and homeostasis
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20
Q

What is cell differentiation?

A
  • Most cells are adapted to perform a specific function
    • Neurons
    • Osteoblasts
    • Hepatocytes
    • Many more
  • Functions of cells are highly interrelated
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21
Q

How do cells grow and differentiate?

A
  • Depends on its microenvironment
    • Growth factors and other cytokines
      • regulate many cell activities within an organism from embryogenesis to aging
    • Features of the extracellular matrix
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22
Q

What are developmental anomalies?

A
  • Growth and differentiation of each cell line needs to occur in a well orchestrated and coordinated manner or sad things happen
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23
Q

Why do cells interact?

A
  • A cell must be able to interact with it’s environment and other cells
    • Exchange nutrients/wastes, secretion of products, responding to stimuli, communication
      • For Homeostasis
      • For Coordination of activity
24
Q

What are the mechanisms of Cell interactions?

A
  • Membrane pumps and enzyme systems
  • Receptors
    • Hormone and cytokines
  • Cell-to-cell connections
    • Membrane interactions (antigen presentation)
    • Channels between adjacent cells (connexins)
  • Exocytosis
  • Endocytosis
    • Pinocytosis
    • Phagocytosis
25
Q

What are the mechanisms of intercellular interactions?

A
  • Autocrine
    • self stimulation
  • Paracrine
    • Stimulate local cells
  • Endocrine
    • Stimulate cells throughout body
26
Q

What is the Extracellular matrix?

A
  • Structural framework in which cells organize, move, and interact
  • Has structural, adhesive, and absorptive components
  • Provides sites for cell adhesion and a conduit for exchange of cell nutrients and wastess
27
Q

What are the functions of the ECM?

A
  • Dictates tissue architecture and organization
    • Has specific features for each tissue/organs
  • Regulates or modifies many cell activities
  • Serves as a reservoir of growth factors and bioactive molecules
  • Constantly remodeling and changing
28
Q

What are the components of the ECM?

A
  • “matrisome” consists of over 300 different proteins
    • Fall into 3 categories:
      • Structural
      • Absorptive
      • Adhesive
29
Q

What is the function of the structural components of the ECM?

A
  • Build the framework for cells to exist upon and within
30
Q

What are the Structural components of the ECM?

A
  • Collagen
    • many types exist
  • Elastin
    • most prominent were elasticity is needed
31
Q

What are the types of Collagen?

A
  • 28 different types of collagen
  • I - Structural collagen of most tissues
    • fibrous tissue, bone
  • II - Major component of cartilage
  • IV - Basement membranes
32
Q

What is the function of the Absorptive components of the ECM?

A
  • Absorb water and other soluble substances which bathe surrounding cells
  • Exert important osmotic pressures to help maintain water balance
33
Q

What are the major absorptive components of the ECM?

A
  • Glycosaminoglycans
  • Proteoglycans
    • Proteins with GAG side-chains
34
Q

What are glycsaminoglycans (GAG)?

A
  • Polysaccharides
  • 4 main groups:
    • Hyaluronic acid
    • Heparan sulfate
    • Chondroitin/dermatan sulfate
    • Keratan sulfate
35
Q

What is the function of the Adhesive components of the ECM?

A
  • Sites of attachment for structural ECM components and cells
  • Mediate interactions of fixed or mobile cells with the ECM
36
Q

What are the adhesive components of the ECM?

A
  • Fibronectin
  • Laminin
  • Many others
37
Q

What is Fibronectin?

A
  • A cell adhesin
  • Links cell membrane integrins to ECM components
    • such s collagen and proteoglycans)
38
Q

What is Laminin?

A
  • Major component of basement membranes
    • along with Type IV collagen
  • Binds cell membrane integrins
39
Q

What are some ECM abnormalites?

A
  • ECM impacts all organs and tissues in the body
  • Defects of any component can result in a wide variety of conditions
    • Skin, Bone, and joint disease (collagen dysplasia’s)
    • Muscle disease
    • Fibrosis
    • Neoplasia
    • Cardiovascular disease
    • Inflammation
40
Q

What are the connections between cells?

A
  • Various types of junctions link cells together to provide functional attributes to populations of cells
    • Adhering junctions
    • Tight Junctions
    • Gab Junctions
    • Desmosomes / Hemidesmosomes
41
Q

What are cardiac myocytes?

A

intercalated disks connect cardiac myocytes to each other

  • Includes:
    • Desmosomes - mechanical coupling
    • Fascia adherens (anchoring junctions) - mechanical coupling
    • Gap Junctions - electrical transmission between (depolarization cue) - electrical couplimg
42
Q

What is the result of Intercalated disc abnormalities?

A
  • Damage (often ischemia / inflammation) to any component of the intercalated discs can lead to heath disease
    • Arrhythmia
    • Ventricular hypertrophy
    • Cardiomyopathy
  • Any of these can result in either acute or chronic heart failure
43
Q

How are Enterocytes connected?

A
  • Desmosomes
    • linking of cytoskeletons via cadherin molecules
  • Adherens junctions - (Zonula adherens)
    • Linking of cells via actin molecules
  • Gap Junctions
    • Connexins that allow small molecule exchange
  • Tight Junctions - (Zonula occludens)
    • Tight binding to form a seal between cells with selective permeability
44
Q

What are enterocyte tight junction abnormalities?

A
  • Over 40 different macromolecules are identified as contributing to tight junction
    • Major families of molecules include occludins, claudins, Junction Adhesion Molecules (JAMs), and tricellulins
  • Pathogenic enteric bacteria toxins, inflammation or non-inflammatory stimuli can disrupt the tight junction
    • Leaky intestine can expose the body to intralumenal components that can cause disease
      • Loss of fluid and electrolytes (diarrhea)
      • Systemic bacterial invasion (bacteremia and endotoxemia)
      • Antigen exposure and hypersensitivity or autoimmunity
        • Food or respiratory alergies (due to activation of mucosal immunity)
        • Immune-mediated islet cell destruction and type I diabetes mellitus
      • Metabolic disorders
        • Type II diabetes mellitus
        • Obesity
        • Chronic inflammatory bowel disease
45
Q

How does aging affect cells?

A
  • Functions of all cells and tissues progressively decline with age
  • Mechanisms:
    • Altered gene expression
    • Telomere shortening
    • Progressive metabolic injury
46
Q

What does an aging cell look like?

A
  • Irregular nuclei
  • Vacuolated mitochondria
  • Reduced endoplasmic reticulum
  • Lipofuscin
  • Accumulation of metabolic products
47
Q

What is Apoptosis?

A
  • Physiological cell death
    • This is the mechanism to remove damaged or unneeded cells in the least disruptive way possible
  • Maintains homeostasis, but can also be involved in pathological states
  • Active process that requires energy from the cell
48
Q

What are the physiologic causes of Apoptosis?

A
  • Patterned death during embryogenesis
  • Hormone/cytokine-induced death
    • Tissue involution
  • Maintain balance in proliferating populations
  • Removal of cells following completion of their purpose
    • Inflammatory cells following the end of the stimulus
  • Removal of self-reactive lymphocytes
49
Q

What is the mechanism of Apoptosis?

A
  • Initiation phase
    • Extrinsic pathway
    • Intrinsic pathway
  • Execution phase
  • Considerable overlap between the pathways and multiple areas where these can be modified to influence the outcome of the process
50
Q

What is the Extrinsic Pathway for Apoptosis?

A
  • Death receptor pathway
  • Membrane receptors are activated that contain a cytoplasmic death domain
    • TNF receptor family - activated by TNF
    • Fas (CD 95) - activated by Fas-ligand
  • Activation leads to autocatalytic activation of procaspase 8
51
Q

What is the Intrinsic Pathway?

A
  • Mitochondrial Pathway
  • Survival factors/growth factors stimulate production of anti-apoptotic Bcl-2 and Bcl-x
    • Maintain mitochondrial membrane integrity
    • Inhibit activation of Apoptosis activating factor-1 (Apaf-1)
  • Loss of survival factor stimulation or injury stimulates production of pro-apoptotic Bax, Bak, Bim
    • Loss of Bcl-2/Bcl-x increases mitochondrial permeability
    • Mitochondrial proteins (cytochrome C) leak into the cytosol
    • Cytochrome C activates Apaf-1, which then activates procaspase 9
52
Q

What is the execution phase of apoptosis

A
  • Various stimuli can initiate apoptosis, but they all converge to one final pathway
    • Caspases mediate this pathway
      • Caspases 3, 6, 7 are the main “executioner” caspases
  • End result is cleavage of structural and functional cell proteins
53
Q

What are the Modifications present with Apoptosis?

A
  • Many pro- and anti- apoptotic factors that can modify an initial signal for apoptosis, including:
    • Pro-apoptotic
      • Bak, Bax, Bim
      • Smac/DIABLO
        • Second mitochondria-derived activator of caspases
    • Anti-apoptotic
      • Bcl-2 and Bcl-x
      • IAP (Inhibitor of Apoptosis Protein)
54
Q

What is the morphology of a cell going through apoptosis?

A
  • Cell shrinkage
  • Condensation of cytoplasmic and nuclear components
  • Formation of membrane-bound vesicles
    • Apoptotic bodies
  • No inflammation or host response to the dead cell
55
Q

What are the pathologic causes of apoptosis?

A
  • Unrepaired DNA damage
    • Damaged transformed cells
  • Heat
  • Hypoxia
    • Mitochondrial injury
  • Viral infection
  • Physical pressure
    • ureteral or secretory duct obstruction
56
Q

What are the diseases caused by abnormal apoptoss?

A
  • Autoimmunity
  • Developmental anomalies
  • Neoplasia
  • Inflammatory disease
  • Neurodegeneration
  • Cardiovascular disease
  • Hepatic disease
  • Among others