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
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
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
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
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
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
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
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
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
10
Q
What proteins made up the cytoskeleton?
A
- Microfilaments
- Microtubules
- Intermediate Filaments
- Regulatory proteins
11
Q
What is the Nucleus?
A
- The location of chromatin
- Chromatin consists of cellular DNA and associated proteins
- Chromatin is organized into chromosomes
12
Q
What is the nuclear evelope?
A
- 2 layered membrane
- separates the nucleus from the cytoplasm
13
Q
What is the origin of a cell?
A
- All cells are derived from a single primordial cell ; the zygote
14
Q
What are the types of embryogenic cells?
A
- Ectoderm
- Mesoderm
- Endoderm
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
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
- Connective tissue (mesenchyme)
17
Q
What is the Entoderm?
A
- Originates as a flat disc by the ectoderm
18
Q
What is made from the Entoderm?
A
- Gastrointestinal epithelium
- Respiratory epithelium
- Parenchymal organs
- Liver
- Pancreas
- Endocrine glands
19
Q
What is Cell Replication?
A
- “The cell cycle”
- Complex and critical to normal cell development and homeostasis
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
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
- Growth factors and other cytokines
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
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
- Exchange nutrients/wastes, secretion of products, responding to stimuli, communication
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
What are the mechanisms of intercellular interactions?
* Autocrine
* self stimulation
* Paracrine
* Stimulate local cells
* Endocrine
* Stimulate cells throughout body
26
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
27
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
28
What are the components of the ECM?
* “matrisome” consists of over 300 different proteins
* Fall into 3 categories:
* Structural
* Absorptive
* Adhesive
29
What is the function of the structural components of the ECM?
* Build the framework for cells to exist upon and within
30
What are the Structural components of the ECM?
* Collagen
* many types exist
* Elastin
* most prominent were elasticity is needed
31
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
32
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
33
What are the major absorptive components of the ECM?
* Glycosaminoglycans
* Proteoglycans
* Proteins with GAG side-chains
34
What are glycsaminoglycans (GAG)?
* Polysaccharides
* 4 main groups:
* Hyaluronic acid
* Heparan sulfate
* Chondroitin/dermatan sulfate
* Keratan sulfate
35
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
36
What are the adhesive components of the ECM?
* Fibronectin
* Laminin
* Many others
37
What is Fibronectin?
* A cell adhesin
* Links cell membrane integrins to ECM components
* such s collagen and proteoglycans)
38
What is Laminin?
* Major component of basement membranes
* along with Type IV collagen
* Binds cell membrane integrins
39
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
40
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
41
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
42
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
43
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
44
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
45
How does aging affect cells?
* Functions of all cells and tissues progressively decline with age
* Mechanisms:
* Altered gene expression
* Telomere shortening
* Progressive metabolic injury
46
What does an aging cell look like?
* Irregular nuclei
* Vacuolated mitochondria
* Reduced endoplasmic reticulum
* Lipofuscin
* Accumulation of metabolic products
47
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
48
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**
49
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
50
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**
51
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
52
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**
* End result is **cleavage of structural and functional cell proteins**
53
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)
54
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
55
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
56
What are the diseases caused by abnormal apoptoss?
* Autoimmunity
* Developmental anomalies
* Neoplasia
* Inflammatory disease
* Neurodegeneration
* Cardiovascular disease
* Hepatic disease
* Among others
