Normal Cells and Matrix Flashcards
Cells
Cell are the organizational unit of an animal
Building blocks of tissues and organs
Provide a focal point for learning pathology
All cells originate form a singel primordial cells
This single cell differentiates into a diverse population of different cells
Cell functions are highly interrelated
Cell components:
Plasma Membrane
- Lipid bilayer interspersed with membrane proteins
- Membrane proteins are critical for cell function and communication
- The membrane is fliud and constantly changing
Cell Component:
Cytosol
Cytosol is fluid that bathes all intracytoplasmic organelles
site of most intermediary metabolism
Accounts for 50-60% of the total cell volume
Cell Component:
Mitochondria
Responsible for energy production
Oxidative phosphorylation - 18x more effectient than anaerobic glycolysis
Energy is released as electrons move down the electron transport chain - ATP
May have originated as an intracellular prokaryote
Down side - reactive oxygen molecules, oxudative damage to the cells
Cell Component:
Endoplasmic Reticulum
Membrane-bound spave 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
Cell Component:
Golgi Apparatus
Membrane-bound sacs that are closely associated with the ER
Modifies, sorts and exports products of the ER
Cell Component:
Lysosomes
- Membrane-Bound sace of enzymes
- Primary lysosomes bud from the golgi apparatus
- Secondary lysosmes are primary lysosomes that fuse with other organelles or cytoplasmic vacuoles
- They degrade macromolecules and extracellular material taken up by the cell
- Contents are predominately hydrolases
Cell Component:
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
Cell Component:
Cytoskeleton
The cytoskeleton provides properties of shape, organization, and movement to a cell
Consists of a variety of proteins
Microfilaments - actin / myosin
Microtubules
Intermediate filaments
Regulatory proteins
Cytoskeleton assebly and disassembly is regulated by calcium
Cell Component:
Nucleus
The nucleus is the location of chromatin
Chromatin consists of cellular DNA and associated proteins
Chromatin is organized into chromosomes
Separated from the cytoplasm by a two-layered membrane - Nuclear Envelope
Life History of a cell:
Origins
All cells are derived from a single primordial cell; the zygote
There are 3 main embryogenic cell types:
Ectoderm
Mesoderm
Endoderm
Ectoderm
Forms a cephalic disc and the neural tube
Cells and tissues derived from ectoderm include:
Central and peripheral nervous systems
Sensory epithelium
Epidermis
Mesoderm
Somites located adjacent to the neural tube
Cells and tissues derived form mesoderm include:
Connective tissues (mesenchyme)
Fibroblasts, osteoblasts, chondroblasts
Muscle
Kidney
Heart and Blood vessels
Endoderm
Originates as a flat disc by the ectoderm
Cells and tissues derived from endoderm include:
Gastrointestinal Epithelium
Respiratory Epithelium
Parenchymal Organs:
Liver
Pancreas
Endocrine Glands
Life History of a cell:
Replication
The Cell Cycle
The cell cycle is complex adn critical to normal cell development and homeostasis
Cell Differentiation
Most cells are adapted to perform a specific Function
Neurons
Osteoblasts
Hepatocytes
Functions of cells are highly interrelated.
Developmental Anomalies
Growth and differentiation of each cell line needs to occur in a well orchestrated and corrdinatied manner of sad things can happen
How cells talk to eachother
A cell must be able to interact with it’s environment as well as other cells
Exchange nutrients and wastes, secretions of products, responding to stimuli, communication
Homeostasis
Coordination of activity
Cell Interactions
- Mechanisms of interaction
- Membrane pumps and enzyme systems
- Receptors
- hormones and cytokines
- Cell-to-cell connections
- Membrane interactions
- Channels between adjacent cells
- Exocytosis
- Endocytosis
- Pinocytosis
- Phagocytosis
Cell Function
Of critical importance is the interaction of a cell with other cells
This is essential for homeostasis
Mechanisms:
- Autocrine
- Self stimulation of a cell
- Paracrine:
- Stimulation of local cells only
- Endocrine:
- Stimulation of cells throughout the body
Extracellular Matrix
This is the structural framework in which cells organize, move and interact
It provides sites for cell adhesion and a conduit for exchange of cell nutrients, and waste
It has structural, adhesive and absorptive components
Properties of the ECM
Dictates tissue architecture and organizations
It has specific features for each tissue/organ
It regulates or modifies many cell activities
Serves as a reservoir of growth factors and bioactive molecules
It is constantly remodeling and changing
Components of the ECM
the “Matrisome” consists of over 300 different protiens
These components fall into 3 categories:
- Structural
- Absorptive
- Adhesive
Extracellular Matrix:
Structural
Structural components of the ECM build the framework for cells to exist upon and within
Structural Components Include:
- Collagen
- Many different types exist for different situations
- Elastin
- most prominent where elasticity is needed
Collagen Types
There are at least 28 different types of collagen
- Type 1
- Structural collagen of most tissues
- fibrous tissue, bone
- Structural collagen of most tissues
- Type 2
- Major component of cartilage
- Type 4
- Basement membranes
Extracellular Matrix:
Absorptive
These absorb water and other soluble sunstances which bath surrounding cells
Major absorptive components:
- Glycosaminoglycans (GAG)
- polysaccharides consisting of 4 main groups:
- Hyaluronic Acid
- Heparan Sulfate
- Chondroitin / Dermatan sulfate
- Keratan Sulfate
- Proteoglycans
- There are proteins with a GAG side chain
- These exert impotant osmotic pressures to help maintain water balance
- polysaccharides consisting of 4 main groups:
Extracellular Matrix:
Adhesive
Sites of attachment for structural ECM components and cells
Adhesive Components: Fibronectin, Laminin, and many others
Mediate interactions of fixed or mobile cells with the ECM
Fibronectin
Cement
A cell adhesion that links cell membrane integrins to ECM components.
Collagen and Proteoglycans
Laminin
Major component of basement membranes that binds cell membrane integrins
ECM Abnormalities
The extracellular matrix impacts all organs and tissues in the body
Has recently been studied as a unique organ/system
Defects of any component can result in a wide variety of conditions
- Skin, bone and joint disease
- Muscles Disease
- Fibrosis
- Neoplasia
- Cardiovascular Disease
- Inflammation
Connections Between Cells
Various Types of junctions link cells together to provide functional attributes to populations of cells
- Adhering Junctions
- Tight Junctions
- Gap Junctions
- Desmosomes and hemidesmosomes
Tissue function dictates the most appropriate Junction
Cardiac Myocytes
Intercalated disks connect cardiac myocytes to each other
Components include:
Desmosomes - mechanical coupling
Fascia Adherens - Mechanical Coupling
Gap Junctions - Electrical transmission between cells - electrical coupling
Intercalated Disc Abnormalities
Damage (often ischemia or inflammation) to any component of the intercalated discs can lead to heart disease
- arrythmia
- ventricular hypertrophy
- Cardiomyopathy
Any of these can result in either acute or chronic heart failure
Intestinal Epithelium
Enterocytes are connected by:
- 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 Occuldens):
- Tight binding to form a ceal between celsl with selective permeability
Enterocyte Tight Junction Abnormalities
Over 40 different macromolecules are identified as contributing to tight junctions
Major families of molecules include occludins, claudins, Junctional Adhesion Molecules (JAMs), and tricellulins
Pathogenic Enteric bacteria Toxins, Inflammation, or Non-inflammatory stimuli can disrupt the tight junctions
“Leaky” intestine can expose the body to intralumenal components that can cause disease
- Loss of fluid and electrolytes
- Systemic Bacterial invasion
- Antigen exposure and hypersensitivities or autoimmunity
- Metabolic disorders
Life History of a Cell:
Aging
Functions of all celsl and tissues progressively decline with age
Mechanisms
- Altered gene expression
- Telomere shortening
- Progressive metabolic injury
Morphology of Aging Cells
Irregular Nuclei
Vacuolated mitochondria
Reduced endoplasmic reticulum
Lipofuscin
Accumulations of metabolic products
Life History of a Cell:
Death
Apoptosis: Physiological Cell Death
Maintaines homeostatis in response to physiologucal and protective processes
Apoptosis
- Physiological Cell Death
- this is the mechanism to remove damaged ot 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
Apoptosis:
Causes
Patterned death during embryogenesis
Hormone/cytokine-induced death
Maintain balance in proliferating populations
Removal of cells following completion of their purpose
Removal of self-reactive lymphocytes
Apoptosis:
Mechanisms
Initiation phase:
- extrinsic pathway
- intrinsic pathway
Execution phase
There is considerable overlap between the pathways and multiple areas where these can be modified to influence the outcomes of the process
Apoptosis:
Extrinsic Pathway
Death Receptor
Membrane receptors are activated that contain a cytoplasmic death domain
- TNF receptor family
Fas (CD95)
Death domain activation leads to autocatalytic activation of procaspase 8
Apoptosis:
Intrinsic Pathway
Mitochondrial
- Survival factors/grwoth factors stimulate production of anti-apoptotic Bcl-2 and Bcl-x
- maintain mitochondrial memebrane intergrity
- Inhibit activation of apoptosis activating factor - 1
- Loss of survival factor stimulation or injury stimulates production of pro-apoptotic Bax, Bak, and Bim
- Loss of Bcl-2/Bcl-x increases mitochondrial permeability
- Mitochondrial protiens leak into the cytosol
- Cytochrome C activates Apaf-1, which then activates procaspase 9
Apoptosis:
Morphology
Cell shrinkage
Condensation of cytoplasmic and nuclear components
Formation of membrane-bound vesicles
No inflammation or host response to the dead cell
Apoptosis:
Causes
Pathologic Causes:
Unrepaired DNA damage
Heat
Hypoxia
Viral infection
Physical Pressure
