Normal Cells and Matrix Flashcards
What are cells?
- 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
What is the plasma membrane?
- A lipid bilayer interspersed with membrane proteins
- Membrane proteins are critical for cell function and communication
- The membrane is fluid and constantly changing
What is Cytosol?
- Fluid that bathes all intracytoplasmic organelles
- Site of most intermediary metabolism
- Accounts for 50 - 60% of the total cell volume
What is mitochondria?
- 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
What is the Endoplasmic Reticulum?
- 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
What is golgi apparatus?
- Membrane-bound sacs that are closely associated with the ER
- it modifies, sorts and exports products of the ER
What are Lysosomes?
- 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
What are peroxisomes?
- 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
What are the functions of the Cytoskeleton?
- Provides properties of shape, organization and movement to a cell
- Cytoskeletal assembly and disassembly is regulated by calcium
What proteins made up the cytoskeleton?
- Microfilaments
- Microtubules
- Intermediate Filaments
- Regulatory proteins
What is the Nucleus?
- The location of chromatin
- Chromatin consists of cellular DNA and associated proteins
- Chromatin is organized into chromosomes
What is the nuclear evelope?
- 2 layered membrane
- separates the nucleus from the cytoplasm
What is the origin of a cell?
- All cells are derived from a single primordial cell ; the zygote
What are the types of embryogenic cells?
- Ectoderm
- Mesoderm
- Endoderm
What is made from Ectoderm?
- Forms a cephalic disc and a neural tube
- Cells and tissues derived from ectoderm include:
- Central and peripheral nervous systems
- Sensory epithelium
- Epidermis
What is made from the Mesoderm?
- 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
- Connective tissue (mesenchyme)
What is the Entoderm?
- Originates as a flat disc by the ectoderm
What is made from the Entoderm?
- Gastrointestinal epithelium
- Respiratory epithelium
- Parenchymal organs
- Liver
- Pancreas
- Endocrine glands
What is Cell Replication?
- “The cell cycle”
- Complex and critical to normal cell development and homeostasis
What is cell differentiation?
- Most cells are adapted to perform a specific function
- Neurons
- Osteoblasts
- Hepatocytes
- Many more
- Functions of cells are highly interrelated
How do cells grow and differentiate?
- 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
- Growth factors and other cytokines
What are developmental anomalies?
- Growth and differentiation of each cell line needs to occur in a well orchestrated and coordinated manner or sad things happen
Why do cells interact?
- 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
- Exchange nutrients/wastes, secretion of products, responding to stimuli, communication
What are the mechanisms of Cell interactions?
- 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
What are the mechanisms of intercellular interactions?
- Autocrine
- self stimulation
- Paracrine
- Stimulate local cells
- Endocrine
- Stimulate cells throughout body
What is the Extracellular matrix?
- 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
What are the functions of the ECM?
- 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
What are the components of the ECM?
- “matrisome” consists of over 300 different proteins
- Fall into 3 categories:
- Structural
- Absorptive
- Adhesive
- Fall into 3 categories:
What is the function of the structural components of the ECM?
- Build the framework for cells to exist upon and within
What are the Structural components of the ECM?
- Collagen
- many types exist
- Elastin
- most prominent were elasticity is needed
What are the types of Collagen?
- 28 different types of collagen
- I - Structural collagen of most tissues
- fibrous tissue, bone
- II - Major component of cartilage
- IV - Basement membranes
What is the function of the Absorptive components of the ECM?
- Absorb water and other soluble substances which bathe surrounding cells
- Exert important osmotic pressures to help maintain water balance
What are the major absorptive components of the ECM?
- Glycosaminoglycans
- Proteoglycans
- Proteins with GAG side-chains
What are glycsaminoglycans (GAG)?
- Polysaccharides
- 4 main groups:
- Hyaluronic acid
- Heparan sulfate
- Chondroitin/dermatan sulfate
- Keratan sulfate
What is the function of the Adhesive components of the ECM?
- Sites of attachment for structural ECM components and cells
- Mediate interactions of fixed or mobile cells with the ECM
What are the adhesive components of the ECM?
- Fibronectin
- Laminin
- Many others
What is Fibronectin?
- A cell adhesin
- Links cell membrane integrins to ECM components
- such s collagen and proteoglycans)
What is Laminin?
- Major component of basement membranes
- along with Type IV collagen
- Binds cell membrane integrins
What are some ECM abnormalites?
- 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
What are the connections between cells?
- Various types of junctions link cells together to provide functional attributes to populations of cells
- Adhering junctions
- Tight Junctions
- Gab Junctions
- Desmosomes / Hemidesmosomes
What are cardiac myocytes?
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
What is the result of Intercalated disc abnormalities?
- 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
How are Enterocytes connected?
- 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
What are enterocyte tight junction abnormalities?
- 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
- Leaky intestine can expose the body to intralumenal components that can cause disease
How does aging affect cells?
- Functions of all cells and tissues progressively decline with age
- Mechanisms:
- Altered gene expression
- Telomere shortening
- Progressive metabolic injury
What does an aging cell look like?
- Irregular nuclei
- Vacuolated mitochondria
- Reduced endoplasmic reticulum
- Lipofuscin
- Accumulation of metabolic products
What is Apoptosis?
- 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
What are the physiologic causes of Apoptosis?
- 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
What is the mechanism of Apoptosis?
- 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
What is the Extrinsic Pathway for Apoptosis?
- 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
What is the Intrinsic Pathway?
- 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
What is the execution phase of apoptosis
- 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
- Caspases mediate this pathway
- End result is cleavage of structural and functional cell proteins
What are the Modifications present with Apoptosis?
- 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)
-
Pro-apoptotic
What is the morphology of a cell going through apoptosis?
- Cell shrinkage
- Condensation of cytoplasmic and nuclear components
- Formation of membrane-bound vesicles
- Apoptotic bodies
- No inflammation or host response to the dead cell
What are the pathologic causes of apoptosis?
-
Unrepaired DNA damage
- Damaged transformed cells
- Heat
-
Hypoxia
- Mitochondrial injury
- Viral infection
-
Physical pressure
- ureteral or secretory duct obstruction
What are the diseases caused by abnormal apoptoss?
- Autoimmunity
- Developmental anomalies
- Neoplasia
- Inflammatory disease
- Neurodegeneration
- Cardiovascular disease
- Hepatic disease
- Among others