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FSOM-Foundations
Exam 2
202
Medical
Graduate
09/25/2012

Additional Medical Flashcards

 


 

Cards

Term
H&E staining:
Definition
hematoxilyn: basic dye, dyes acids blue (nuclei) eosin: acidic dye, dyes bases red (structural proteins)
Term
Purpose of epithelium and general organization:
Definition
-Covers and acts as a barrier
-composed of: the epithelial cells, basement membrane, and the underlying connective tissue.
Term
Describe the make up of microvilli.
Definition
-They are made up of actin filaments, they extend the surface area, and are extensions of the cytoplasm. -The actin filaments terminate at the terminal web
Term
Describe Cilia and their make up.
Definition
Cilia are feathery extensions made of microtubules (a 9+2 arrangement). -They terminate in terminal bodies
Term
What are stereocilia composed of?
Definition
They are composed of actin and are more similar to microvilli.
Term
Zonula Occludens
Definition
-Tight junctions: seals cells together, acts as a barrier to prevent material from moving in between cells
-They form bead like structures that are used to zipper the cells together.
Term
Zonula adherens
Definition
-Intermediate junctions: seals cells together, tissue morphogenesis, and cell communication
-Membranes aren't as closely associated -Have a large plaque that anchors to actin in the cytoplasm.
Term
macula adherens
Definition
-Desmosomes: adhesion and signaling -Have keratin filaments
Term
Hemidesmosome
Definition
-Anchor the cell to the basement membrane
-Not really a half desmosome because it has a different protein make-up distinct from desmosomes.
Term
Dense CT
-Types and examples
Definition
-Dense regular: ligaments/tendons, parallel collagen, flattened nuclei
-Dense irregular: mammary gland/dermis, organ capsules, random arrangement of fibers
Term
Loose CT
-major composition
Definition
-Packing material throughout the body -Mostly type I Collagen and elastin -ground substance is made of GAGs (the strong negative GAGs hydrate the CT)
Term
Embryonic CT
Definition
-Mesenchyme: pretty much loose CT with lots of reticular fibers -Mucouse CT: found in umbilical cord, know Wharton's Jelly
Term
CT Fibers
Definition
-Collagen, elastic, or reticular fibers -Secreted by fibroblasts or smooth muscle cells
-Fibers formed from fibrils
Term
Collagen
Definition
-Forms a triple helix -α chains are assembled into procollagen in the ER -Vitamin C is required for hydroxylation (makes H bonds for) -Collagen synthesis is finished in extracellular grooves
Term
Elastic Fibers
-What holds elastic fibers to each other?
Definition
-Composed of random coils of elastin -Fibrillin is a key component and without it the fibers form sheets -Marfan's Syndrome results dysfunctional elastic tissue -Desmosine holds fibers to each other
Term
Reticular Fibers
Definition
-Meshwork, branched network
-Important for wound healing -Made up of collagen fibrils
Term
Resident CT Cells Transient CT Cells
Definition
-Fibroblast: the main player that secretes most of the fiber and matrix
-Macrophages: come from monocytes
-Mast cells: similar to basophils, release histamine and heparin, good for allergic rxns and inflammation
-Adipocytes and adult stem cells
-Transient: white blood cells that come in
Term
Hyaline cartilage basics
-Where's it found, what's in it?
Definition
-Found in the ribs, larynx, and trachea.
-Most of it is water
-Mostly type II collagen
-Can grow by deposition or interstitially.
-No blood vessels in cartilage layer
Term
What's the largest GAG?
Definition
Hyaluronic acid
Term
What type of hyaline cartilage does not have a perichondrium?
Definition
-Articular cartilage in joints
Term
Elastic Cartilage
Definition
-Basically hyaline cartilage but with a network of elastic fibers.
-Pretty rare. examples include the ear and the epiglottis
Term
Distinguishing features of hyaline cartilage (histologically)
- physical matrices
Definition
-Chondrocytes: secrete the matrix
-Perichondrium: surrounds cartilage, where chondroblasts come from
-Isogenous groups: clusters of chondrocytes
-Capsular matrix: dark rim around each chondrocyte
-Territorial matrix: dark shadow around isogenous groups.
-Interterritorial matrix: old matrix in between chondrocytes
Term
Fibrocartilage
-What are you going to look for?
Definition
-Has Type I cartilage to withstand shearing and compression forces.
-May look like DRCT, but LOOK FOR round chondrocytes in lacunae.
-Examples: intervertebral discs, pubic symphysis, and meniscus.
-No perichondrium on this one
Term
How does most of the diaphysis get its nutrients?
Definition
-A single nutrient artery
Term
4 main components of a synovial joint:
Definition
-Synovial cavity
-Synovial membrane
-Articular cartilage
-Periosteum
Term
3 Types of bone cells
Definition
-Osteoblast: on bone surface, secrete osteoid(organic), and leave vesicles that cause mineralization
-Osteocyte: in lacunae
-Osteoclast: bone breakdown, monocyte
Term
What is bone composed of?
Definition
-Mostly matrix
-30% organic (Type I collagen), 70% mineral (hydroxyapatite)
-too little collagen=brittle; too little mineral=soft
Term
How osteons are remodeled
Definition
-A cutting cone of osteoclasts carves out an osteon and osteoblasts follow close behind in the closing cone and fill it back in.
Term
Area carved out by an osteoclast:
Definition
-It's called a Howship's lacuna.
-The ruffled border is the part of the osteoclast working on bone.
Term
Effects of Calcitonin and Parathyroid hormone -Vitamins necessary for bone growth
Definition
-Calcitonin puts calcium in the bone
-PTH results in bone breakdown and increases serum Ca
-Vit D needed for Ca absorption from intestine
-Vit C needed for collagen synthesis
-Too much Vit A results in fragile bones, too little halts bone growth
Term
3 Places bone comes from
Definition
-Somite scleratome
-Lateral plate mesoderm (somatopleure)
-NC
Term
4 Steps of forming bone endochondrally
Definition
1) Mesoderm condenses into hyaline cartilage model
2) Periosteal bone collar forms in the diaphysis
3) Cartilage gets calcified, dies, and is replaced. A primary center of ossification is formed.
4) Secondary centers of ossification appear
Term
Where does bone length growth occur?
Definition
-Only at the epiphysis due to the epiphyseal plate
Term
Bone growth zones
Definition
1) Zone of reserve: cartilage backup
2) Zone of proliferation: cartilage cells divide
3) Zone of hypertrophy: cartilage cells expand
4) Zone of calcification: cartilage matrix calcifies and cells die
5) Zone of resorption: where ossification happens.
Term
Woven vs. lamellar bone
Definition
-All bone starts out as woven (fetal)
-All compact bone is lamellar
-Spongy can be woven or lamellar
Term
Harris lines
Definition
-Due to childhood illness or trauma
-Cells don't divide, zone of proliferation is affected and no growth occurs
-Zone of resorption is not as affected and mineralization continues
Term
Ossification timeline
Definition
-At birth the diaphysis are ossified. The epiphysis, tarsal, and carpal bones are mostly cartilage
-Secondary and primary ossification in childhood. Fusion of epiphy-diaphy in adolescence.
Term
What is a motor unit?
Definition
-number of muscle cells innervated by one neuron
-
Term
Skeletal Muscle -Characteristics & hierarchy
Definition
-Striated w/peripheral nuclei -myofilaments-->myofibril-->fiber(cell)-->fascicle-->skeletal muscle
Term
Skeletal muscle CT layers
Definition
-Endomysium: around each muscle cell(fiber)
-Perimysium: around fascicles and forms septa
-Epimysium: surround an entire muscle
Term
[image]
Definition
a) Z-line
b) H-zone
c) I-band
d) A-band
*=sarcomere
1-myosin
2-actin
Term
How muscles contract and how the strength is determined.
Definition
-All about actin and myosin ratchet system.
-Need Ca for myosin to bind to tropomyosin on actin
-Z-lines get closer and H-zone disappears.
-Strength of contraction depends on the number of myosin heads that are bound.
Term
Role of dystrophin
Definition
-Dystrophin is a protein that connects the sarcomere to extra-cellular components
-Without it fibers break down and get replaced by CT
Term
T-tubules and triads
Definition
-T-tubules bring the membrane depolarization to the sarcomeres
-A triad is a t-tubule with 2 ER cisterns
Term
T-Tubules in skeletal vs cardiac muscle
Definition
Skeletal: all about the depolarization, the mechanical connection for Ca is not as important.Triad.
Cardiac: extra cellular Ca is crucial, depolarization doesn't matter at all. Diad.
Term
muscle contraction cycle
Definition
1) Ca-->myosin binds to actin
2) ATP attaches to myosin--> head is released from actin
3) ATP hydrolyzed to ADP & Pi-->myosin head cocks
4) Pi is released--> tight reattachment and power stroke
Term
Things that make smooth muscle contract:
Definition
Lots of stimuli including hormones, nerves, stretch.
Term
How smooth muscle contracts
Definition
-Uses actin and myosin, but different mechanism.
-Myosin gets phosphorylated, but calcium is still important.
Term
3 Functions of the lymph system
Definition
1-remove excess fluids
2-absorb and transport fat
3-produce immune cells
Term
B-Lymphocyte vs C-Lymphocyte
Definition
B-Lymphocyte: Matures in bone marrow, secretes antibodies
T-Lymphocyte: Matures in thymus, involved in cell-mediated immunity to foreign invasion.
Term
Defining characteristics of lymphatic vessels.
Definition
-No smooth muscle, covered in endothelium, basement membrane is scant if present at all.
-Valves to prevent back flow.
Term
MALT
Definition
Mucosa-associated lymphatic tissue
Also BALT- bronchi
-Lymphatic nodules are not enclosed by a capsule with plasma cells and lymphocytes
-Secondary nodules also exist: germinal center and mantle zone
Term
Lymph node characteristics
-Where are the T and B Cells?
Definition
-Have a capsule, lymphatic nodules (B-Cell rich), diffuse/deep cortical zone (T-Cell rich), medulla, hilus
Term
Thymus
Definition
lobulated, where T-cells proliferate.
-Distinguishing feature is Hassall's corpuscle in the medulla has large lymphocytes
Term
Defining characteristics of splenic tissue
-PALS
Definition
-Encapsulated with deep CT trabeculae
-White(B-lymphocytes) and Red(filter for/stores RBCs) pulp
-PALS: periarteriolar lymphatic sheath: similar to lymphatic nodule, follows central artery.
Term
Functions of the spleen (7)
Definition
-Proliferation of lymphocytes
-Production of abs
-Removal of macromolecular antigens
-Formation of blood cells
-Removal of damaged/old red blood cells and platelets
-Retrieval of iron from red cell hemoglobin
-Storage of blood
Term
What 3 layers make up the chorion?
Definition
-Cytotrophoblast, syncitiotrophoblast, and extraembryonic mesoderm
Term
Important weeks in development of the embryo:
Definition
1-fertilization/travel to the uterus/morula and blastocyst
2-implantation/week of 2s
3-gastrulation, 3 layer disc
4-somites, neural tube, folding
Term
Where does a cell body in the CNS come from? PNS?
Definition
CNS: neural tube
PNS: Neural Crest Cell
Term
Describe a typical spinal nerve
Definition
-Has ventral and dorsal rami
-Has a has dorsal, lateral, and anterior cutaneous branches
Term
What do ventral horns contain? Dorsal horns? Dorsal root ganglion?
Definition
-Ventral: cell bodies of the somatomotor neurons
-Dorsal horn: relay neurons
-Dorsal Root Ganglion: cell bodies of sensory neurons
Term
What is the structure that separates the dorsal and ventral roots?
Definition
-The denticulate ligaments
-The dorsal root is superior to the denticulate ligaments and the ventral root is deep.
Term
Where does the spinal cord end?
What's the structure called where it ends?
What anchors the spinal cord?
Definition
-L1/L2
-Conus medularis
-Filum terminale (pia mater)
Term
Where do sympathetic nerves exit the spinal cord?
-Then where do they go?
Definition
-Only between T1 and L2 out of the lateral horns
-They have two options: synapse in the sympathetic trunk or in the collateral ganglia (pelvic viscera)
-If they synapse in the sympathetic trunk they can then either go straight to their target (thoracic viscera) or come back into the spinal nerve to the body wall.
Term
Parasympathetics
-Where do they come from?
Definition
-Cholinergic
-Only leave the brain or sacral region
-Very long pre-synaptic nerves
Term
Unique aspects of perineurium
Definition
-Secretes collagen like a fibroblast
-tight junctions like epithelium
-can contract like smooth muscle
Term
Elements of the TBS
Definition
"Typical Body Segment"
-spinal cord/vertebrae
-epaxial/hypaxial muscle
-spinal nerves (dorsal/ventral rami)
-blood vessels, gut, lining
Term
The 3 muscle layers of the abdomen converge into what?
Definition
-The aponeurosis, form the linea alba, and cover the rectus abdominis
-also continuous down to the inguinal ring
Term
[image]
Definition
1. Anterior Longitudinal Ligament
2. Posterior Longitudinal Ligament
3. Ligamentum Flava
4. Interspinous Ligament
5. Supraspinous ligament
6. Intertransverse ligament
Term
What are the 3 main future divisions of the intraembryonic celom?
Definition
1) Pericardial cavity
2) Pleural cavity
3) Peritoneal Cavity
These three are continuous in early development
Term
Describe the layers of the pericardium.
Definition
There are 3: A fibrous parietal layer, a serous parietal layer, and a serous visceral layer.
-The serous parietal layer is the inner surface of the fibrous parietal layer
-The visceral serous layer is the same as epicardium.
Term
What is contained in the pleural cavity?
Definition
-Normally nothing except serous fluid
-It is the space between the parietal/visceral pleura in the deflated balloon analogy.
Term
Summary of muscles involved in breathing
Definition
-Inspiration: diaphragm/ext. intercostals
-Expiration: passive-relaxation of diaphragm/ex.intercostals
-Forced inspiration: add on scalenes, SCM, pecs
-Forced expiration: abs, internal intercostals
Term
Describe the contents of the mediastinum.
Definition
-Heart, great vessels, trachea, esophagus.
Term
Where does lymph re-enter the blood stream?
Definition
Via the jugular trunk, subclavian trunk, and the bronchomedastinal trunk.
-Only on the left side of the body
Term
Left-right lymph drainage
Definition
-Drainage into the neck veins is bi-lateral above the umbilicus
-Below the umbilicus all lymph dumps into the thoracic duct and then into the left side veins
-Deep thoracic body wall dumps into the thoracic duct
Term
Superficial vs deep lymph flow
Definition
-Superficial body wall lymph goes to the axillary or superficial inguinal nodes before penetrating the deep fascia
-Deep body wall lymph goes directly to the deep ascending pathway
Term
Lymph flow in the leg
Definition
-All superficial lymph goes to the superficial inguinal nodes
-Deep lymph goes to the deep inguinal nodes
-Exception is the lateral foot drains into the popliteal nodes and joins up with the deep path.
Term
Breast lymph drainage
Definition
-upper lateral breast drains to the axillary nodes
-part of the mammary gland drains deep (this is an exception to the stratification rule), this joins up with the liver and sometimes the superficial inguinal nodes
Term
What is the ALARA principle?
Definition
As low as reasonably achievable
Term
5 x-ray densities from lowest to highest
Definition
Air(black)
Fat
Soft tissue/water (gray)
Calcium
Metal (white)
Term
4 Imaging modalities
Definition
1) x-ray
2) ultrasound
3) Magnetic resonance
4) Nuclear Medicine
Term
X-ray modalities: (7)
Definition
-Plain radiographs
-mammography
-fluoroscopy (oral/rectal contrast of barium or iodine)
-Angiography (iodine injected into an artery or vein)
-Myelography (iodine into the epidural space)
-Arthography (air or contrast injected into a joint)
-CT (can use contrast to enhance)
Term
Nuclear medicine
Definition
-Tagging a tissue specific molecule
-Physiologic imaging rather than anatomic
-Includes PET-positron emission tomography
Term
4 types of drug receptors
Definition
-Enzymes
-Cell surface/intracellular proteins
-Structural proteins
-Nucleic acids
Term
Classes of drugs based on action
Definition
1) Agonists: typically mimic the natural ligands
2) Antagonists: devoid of activity on their own, but block the action of agonists
3) Partial agonist: don't produce the max effect, can act as antagonists
4) Inverse agonists: really antagonist, lower activity below basal level
Term
Orthosteric vs allosteric
Definition
Orthosteric is the normal agonist binding site
Allosteric is a site separate from the active site and can be positive or negative.
Term
Uncompetitive vs. noncompetitive
Definition
-Both are allosteric
Uncompetitive: agonist must bind first in order for the site to be accessible
Noncompetitive: accessible even if the agonist isn't
Term
What would the EC50 be for a partial agonist that has a 60% maximal effect?
Definition
It would be the concentration of drug that gives 30% of the max.
Term

How do you calculate the

drug effect of a drug?

Definition

Effectmax·[A]

EC50 + [A]

Term

What is the relationship between A and B? A and C?

[image]

Definition
A is more potent than B.
A is equipotent with C.
Potency is a comparative measure of the conc/dose of drugs that produces a relative effect.
Term
What is the efficacy of a drug?
Definition
-The effectiveness of a drug to produce a response.
-The max effect is 100% efficacy.
-Antagonists have 0 efficacy
Term
Quantal dose curve
Definition
-Measures all or none drug responses. Dead or alive, pregnant or not.
-ED50: effective dose where 50% of the individuals exhibit a response.
Term
What is the therapeutic index?
Definition
-A measure of drug safety.
=(Toxic ED50)/(ED50)
Term
Competitive antagonist curves
-How are efficacy and potency affected?
Definition
-The effect of the antagonist can be overcome with higher concentration, curves get pushed to the right
-Efficacy is not affected, but potency is.
Term
Noncompetitve antagonist curves
-How are efficacy and potency affected?
Definition
-Efficacy is reduced
-Potency is unaffected
-Can bind at the agonist site or an allosteric site, doesn't matter if agonist is present or not
Term
What is IC50?
Definition
Related to inhibition response curves
-Keep a constant [antagonist] and vary [agonist].
-IC50 will depend on [agonist] and is not constant
Term
What is a Schild analysis?
Definition
-A good measure of antagonist activity
-Gives a constant independent of agonist and experimental conditions.
Term
Spare receptors
Definition
-The maximal response can be reached without all of the receptors binding
Term
Monod-Wyman-Changeux
vs.
Kosland-Nemethy-Filmer
Definition
MWC: receptors are only in two conformations
KNF: receptors undergo sequential changes to many possible conformations.
Term
5 Types of receptor families
Definition
1) Cytoplasmic/nuclear receptors
2) Receptor Tyrosine Kinase
3) TK-Associated
4) Ligand and voltage gated channels
5) GPCR
Term
Intracellular Receptors
-types of ligands, what they do, examples
Definition
-Ligand must be lipophilic
-Usually enter the nucleus at some point and act as a TF
-examples: Thyroid and estrogen
Term
RTK and TK associated receptors
-general characteristics
-Types of ligands for each
Definition
-Ligands are extracellular
-Slow pathway
-Dimerization of receptor is necessary
-Many RTK ligands are growth factors
-Tk-associated ligands are cytokines
Term
3 ways to activate RTKs and how cancer is associated w/RTKs
Definition
1) ligand that is a dimer
2) Transmembrane protein with GAGs that force dimerization
3) Receptors on another cell membrane
that force dimerization
-Cancer: cancer cells can mutate the receptor against drugs
Term
Ligand and voltage gated ion channels
-Ways to activate
-Types of ligand based
Definition
-3 ways to activate: ligands(NTs), membrane voltage, mechanical deformation
-Fast signaling
-3 Types of ligand based: Cys-looped, glutamate, ATP
-Most are excitatory, except the GABA family of cys looped
Term
What is a channelopathy?
Definition
-When good ion/voltage gated channels go bad
-Examples include Cystic Fibrosis and Long QT syndrome
Term
GPCRs
-What are the ligands?
-Classes
Definition
-Speed: faster than RTK, but slower than ion channels
-ligands can be small molecules, peptides, or proteins
-4 classes that differ greatly in their structure (Rhodopsin, Secretin, Metabotropic, & Frizzled)
Term
Another name for drug desensitization and the two types
Definition
Tachyphylaxis-in the constant presence of a drug many receptors have diminished responsiveness.
1) Receptor-mediated: only the activated receptor desensitizes, leads to loss of function and fewer functional receptors.
2) Non-receptor-mediated: downstream elements are affected
Term
Functions of membrane potential
Definition
All cells: Influx of Ca2+, ATP synthesis
Excitable cells: influx of Na+
Term
What is responsible for the resting membrane potential of a cell?
Definition
-It's the imbalance of Na+ and K+ due to the Na-K-ATPast pump
-More Na+ on the outside, more K+ on the inside
-K+ is leaky
Term
Ion permeability model
Definition
-Due to leaky K+, it leaks out and leaves a net neg charge on the inside of a cell
-Opposing electrostatic and chemical forces prevent further leakage
Term
Nernst Equations for permeability
-How to account for permeabilties
Definition
At room temp:Ei=58mV*Log(Ci-out/Ci-in)
Goldman-Hodgkin-Katz accounts for individual permeabilities
Term
Equivalent Circuit model for membrane potential
-basic description
-advantages
Definition
-plasma membrane is essentially a simple electric circuit
-lipid bilayer is a capacitor, ion channels are conductors
-parameters are easily measured
-explains response times
Term
Stimuli that can change membrane potential
-Natural and Artificial
Definition
Natural: Neurotransmitters, hormones, toxins
Artificial: increased extracellular K+, injected Na+, drugs
Term
[image]
Definition
A: Na channels open
B: More Na channels open
C: Na channels close
D: K channels open
E: K channels close
Term
Two types of transport proteins
Definition
1) Carrier protein: slow, solute binds, requires conformational change
2) Channel protein: fast, filters by size and charge, allows ions and H20 to slip through
Term
How the Na/K ATPase pump works
Definition
-Enzyme is open to the inside of the cell, 3 Na+ bind, ATP binds, one Phosph group is hydrolyzed, enzyme changes and opens up to the outside of the cell, Na+ leave and 2 K+ bind, P is released and enzyme switches back to the inside to release the 2 K+.
Term
SERCA Pump
Definition
-Ca pump in the ER
-Has a negatively charged cage to hold Ca2+
Term
4 ways to activate a gated ion channel
Definition
1) Voltage
2) Ligand outside
3) Ligand inside
4) Mechanically
Term
Categories of cells based on replication
Definition
-Continuous: skin, bone
-Conditional: can replicate if needed, liver, pancreas, kidney
-Non-dividing: heart, brain, get replaced with collagen if damaged
Term
Stem Cells
-Potency
-How quick do they divide?
Definition
-Totipotent or pluripotent
-Used to think that stem cells divided slowly, but now think that they divide very quickly
-Asymmetric division and retention of maternal DNA
Term
Vocab: mitogen, motogen, morphogen
Definition
Mitogen: cause cell division
Motogen: cause cells to migrate/scatter
Morphogen: induce differentiation
Term
Metaplasia
-def
-examples
Definition
-Change of one differentiated cell type to another differentiated cell type
-Reversible
-Examples are Barrett's esophagus(intestine like esophageal tissue) or myositis ossificans (calcification in muscle), also smokers lung
Term
Dysplasia
-what do the cells look like?
Definition
-abnormal cell growth
-sometimes reversible
-always linked to DNA damage
-cells have an increasing nucleus:cytoplasm ratio.
Term
What can a cell do in response to injury?
Definition
-Ignore it
-Adapt
-Divide
-Die
Term
Necrosis
-Types
Definition
-Death of groups of cells
-5 types: coagulative, liquefaction, caseous, fat, and tumor
Term
Coagulative necrosis
-What causes it?
-Physical descriptions?
-Responses?
Definition
-Caused by ischemia or toxic agents
-Commonly seen in heart, kidney, spleen, brain
-pale, opaque, dry, no nuclei
-early response is inflammation, late response is scarring by fibroblasts
Term
Liquefaction necrosis
Definition
-Necrotic area is liquefied
-Mostly seen in brain
-necrotic tissue is digested and a cyst is formed
Term
Liquefaction necrosis
Definition
-Necrotic area is liquefied
-Mostly seen in brain
-necrotic tissue is digested and a cyst is formed
Term
Caseous necrosis
Definition
-A mix of coagulation/liquefaction
-Hallmark is a Granuloma
-Looks like cheese
Term
Fat necrosis
Tumor Necrosis
Definition
Fat:Almost exclusively in adipose, leads to saponification
Tumor: it exists
Term
Mechanisms of injury that lead to necrosis
Definition
1) ATP Depletion-ie from hypoxia, can lead to membrane damage, leakiness, and swelling
2) Free radicals: can damage proteins, nucleic acids, fats.
3) Loss of membrane permeability: leads to Ca influx, critical event in irreversible cell damage
4) Loss of calcium homeostasis: Ca comes in and activates degrading enzymes
Term
Apoptosis
-Def and what is the main player?
Definition
-Individual cell death, can be physiological or pathological
-Caspases are the ultimate executioners
Term
Two pathways of apoptosis
Definition
1) Intrinsic: Cell can't repair its DNA, so p53 gets activated, activated in chemo, signals work through mitochondria, Cytochrome C is released.
2) Extrinsic: initiated by extracellular receptors, can be activated by T-Cells or macrophages,
Term
Apoptosis vs. Necrosis
Definition
Apoptosis: Cell shrinkage, specific DNA cleavage, no inflammatory response,
Necrosis: cell swelling, organelles disrupted, plasma membrane disrupted, inflammatory response is common
Term
Fatty Liver
Definition
-Can be reversible
-End stage steatosis is cirrhosis
Term
What does ERAD do?
Definition
It's a protein (pore) in the ER that recognizes bad protein and moves it into the cytosol to be tagged and degraded.
Term
Pigments that can accumulate in cells
Definition
-Lipofuscin: wear and tear aging pigment, brownish, not toxic as far as we know
-Melanin: macrophages can pick it up
-Hemosiderin: Blackish iron storing from Hb, colors from bruises
Term
Pathological Calcification
-2 types and distinguishing feature of one of them
Definition
1) Dystrophic: happens in dying tissues, normal Ca level
2) Metastatic: happens in normal tissue, elevateed Ca level
Dystrophic leads to Psammoma bodies which are calcified entombed tumor cells
Term
Pathological Ossifications
Definition
-If due to trauma is called myositis ossificans
-Due to the release of BMPs
Term
What is the Hayflick Limit?
Definition
-Cells stop dividing after about 50 cycles or so
-Related to telomeres and telomerase activity
Term
7 Hallmarks of Cancer
Definition
1) Self sufficiency in growth signals
2) Insensitivity to growth inhibition signals
3) Evasion of apoptosis
4) Defects in DNA repair
5) Limitless replicative potential
6) Sustained angiogenesis
7) Ability to invade and metastasize
Term
How does EBV relate to cancer?
Definition
-Ebstein Bar Virus leads lymphomas
Term
4 Types of pro to-oncogenes+definition
Definition
Def: normal gene that has the potential to change and act as an oncogene
1) Growth Factors
2) Growth Factor Receptors
3) Signal Transducers
4) Transcription Factors
Term
3 general targets of oncogenes
Definition
1) Cell proliferation
2) Cell differentiation
3) Cell survival
Term
Key players in the apoptosis cascade:
Definition
Pro-apoptosis: p53, BAX, BAK, Cytochrome C, Caspases
Anti-apoptosis: BCL2, MCL1, IAP
Term
What does it mean that a neoplasm is clonal?
Definition
-Clonal means all the cells come from one abnormal progenitor cell
Term
Malignant vs. benign
Definition
Malignant are not well defined in the tissue and mix with the normal tissue, fast growth
Benign are well defined and may have a capsule
-Benign almost never change to malignant, slow growth
Term
4 Categories of malignant neoplasms
Definition
1) Carcinoma: epithelial derived
2) Sarcoma: mesenchymal derived
3) Lymphoma: lymphocytic derived
4) Melanoma: Melanocytic derived
Term
More tumor nomenclature:
Adeno, squamous, leio, rhabdo, chondro, osteo
Definition
Adeno: glandular
Squamous: squamous tumor
Leio: smooth muscle
Rhabdo: skeletal muscle
Chondro: cartilage
Osteo: bone
Term
Pleomorphism
Anaplasia
Definition
Pleomorphism: difference in cell shape/size
Anaplasia: lack of differentiation
Term
3 Factors that affect tumor growth rate
Definition
1) What proportion of cells are dividing?
2) How often do they divide?
3) How many are dying?
Term
4 Steps of tumor invasion
Definition
1) Loosening cell-cell adhesions
2) Degrade ECM (including BM and interstitial CT)
3) Changes in attachment to ECM proteins (these normally keep epithelial cells in a resting state)
4) Locomotion/migration-tumor cells have to contract the actin cytoskeleton to move forward
Term
7 Steps of metastasis
Definition
1) subclone of original tumor cells invades BM
2) Migrate through ECM
3) Penetrate a vessel
4) Survive/transport in the vessel
5) Arrest-stop in an organ
6) Extravasation-get out of the vessel
7) Survive and grow, set up shop in the new tissue
Term
Routes of metastasis
Definition
1) Lymph-most comon for carcinomas
2) Hematogenous
3) Seeding in body cavities: common for ovarian carcinomas
Term
Grading tumors
Definition
-Grading is for the level of differentiation
-Lower level is better
-Grade 1 (75% resemblance to original tissue)
-Grate 2 (50-75%)
-Grade 3 (25-50%)
-Grade 4 (almost completely anaplastic)
Term
Staging tumors
Definition
-Staging is only for metastatic tumors
-TNM
-T: Size/tissues involved (T1-T4)
-N: how many/number of lymph nodes involved (N0-N3)
-M: Metastasis: Y/N
Term
How cancers actually affect the host
Definition
1) Direct effects: i.e. bowel obstruction
2) Cachexia: wasting/lethargy
3) Paraneoplastic: ie extra hormones
4) Hematologic: immunity, bleeding, anemia
Term
What's the most common dominant oncogene?
Definition
-RAS mutations
Term
What's the key cyclin?
Definition
-Cyclin D-CDK4
-It's the on/off switch for the cell cycle
-It phosphorylates Rb
Term
What is the two hit hypothesis?
Definition
-Described by Knudson as a genetic change as the first hit and an environmental factor as the second hit in cancer
Term
What are 4 regulators of the cell cycle that are dysregulated in most human tumors?
Definition
-Cyclin D
-CDK4
-Rb
-p16: inhibits CDK4
Term
What happens if you have a mutated APC/β-catenin pathway?
Definition
You get 1000's of colon polyps at an early age
Term
Angiogenesis in tumors
Definition
-The angiogenic switch is essential for tumor growth
-vessels are usually tortuous and leaky
Term
How do BRCA1 and BRCA2 lead to cancer?
Definition
-Both are involved in DNA repair, specifically recombination repair
Term
What are the 3 necessary factors in chemical carcinogenesis?
Definition
1) Initiation: Irreversible DNA damage in a critical gene
2) Promotion: Cell proliferation, reversible
3) Progression: genetic mutations accumulate and invasion
Term
Electrophilic Theory of chemical carcinogenesis
Definition
-Direct acting carcinogens: seek out nucleophilic DNA and bind to it, creating DNA adducts. Not as common
-Indirect acting carcinogens: must be metabolized first, most carcinogens
Term
Relevance of UV as a carcinogen
Definition
-UVA and UVB are the perps
-They cause pyrimidine dimers and can mutate p53
-nonmelanoma skin cancer is the most common and most preventable cancer
Term
What's the underlying cause of cancer in H. Pylori?
Definition
-Chronic inflammation/infection leads to reactive oxygen species.
Term
How does HPV lead to cancer?
Definition
-The HPV protein E6 & E7 promote the degradation of p53, block p21 and inhibits Rb
Term
What is the major target of radiation in a cell?
-How does the radiation have its effect?
Definition
-DNA
-If enough DNA is damaged a cell will die
-Effect through direct or indirect action
-Indirect is when radiation hits water and creates radical hydroxyl groups that then act on DNA
Term
What is the first event that takes place after ionizing radiation?
Definition
-ATM is activated, which induces downstream effects including activating p53
Term
What can a survival curve tell us about a radiation effect?
Definition
-We can know the D0, the slope of the curve.
-A low D0 means the cell is sensitive to radiation
-A high D0 means the cell is resistant to radiation
Term
What are the most radiosensitive parts of the cell cycle?
Most resistant?
Definition
-Sensitive: M and G2
-Resistant: late S Phase, G1/2 checkpoints
-G0 is especially resistant to radiation
Term
Typically, the more a cell divides the more sensitive it is to radiation. What is the exception?
Definition
-lymphocytes are the most radiosensitive, even though they are reverting postmitotic cells
Term
Four Rs of Radiobiology
Definition
-Repair: waiting lets normal systems repair
-Reassortment: late S cells will be left, if you let them turnover, then they can become a target
-Repopuation: tumor repopulates, giving small low doses allows the tumor to grow back
-Reoxygenation: enhances therapy, hypoxic cells become poxic and radiosensitive
Term
When do early and late reactions show up after radiation exposure?
Definition
-Early: within 90 days things like skin, intestine, and testis
-Late: from 6 months to 5 years, things like spinal cord, kidney, lung, and bladder.
Term
The effects of acute total body radiation exposure
Definition
1) Cerebral syndrome: 50 Gy, death in 30-50 hours
2) GI syndrome: 10Gy, death in 9 days
3) Hematopoietic syndrome: 2.5-10 Gy, possibly survivable
Term
Stochastic vs. Deterministic radiation events
Definition
-Stochastic: no threshold, DNA damage can happen at any level
-Deterministic: some threshold must be passed. For stuff like hematopoietic syndrome,
Term
External Beam Radiation Therapy
Definition
Many different types: photon, electron, proton, neutron
Photon is very common and includes:
-High energy x-ray beam
-Level in the megavolt range
Term
Typical breast cancer treatment dose
Definition
Total dose: 50 Gy
2 Gy per day
so 25 treatments
Term
IMRT radiation
-Dose for throat cancer
Definition
Intensity modulated radiation therapy
-uses input from a bunch of computers
-Dose 7o Gy
-60-70% of patients are treated with this right now
Term
Brachytherapy
Definition
-Used in prostate cancer, place radioactive material directly into the cancer
-Low dose is permanent, dose given in days to weeks
-High dose is temporary, dose given in minutes
Term
Radiosurgery
Definition
-Short course, high dose
-Use a gamma knife: head is fixed
or cyberknife: can track a moving target (lung cancer)
-
Term
Intra-operative radiotherapy
Definition
-Delivered at the time of surgery
-Single treatment
-Good for breast cancer
-Novel tech is the TARGIT machine that uses various spherical applicators
Term
What are interferons and interleukins?
-toxicities?
-what recurrence do they prevent?
Definition
-They are secreted molecules that effect cell proliferation
-They are glycoproteins that are antiviral and antiproliferative
-Can activate T and NK cells
-Toxicity includes cytopenias and elevated liver function
-Good against melanoma recurrence
Term
Monoclonal antibodies
-What's the best one?
Definition
-Have many targets for many malignancies
-Best one is Rituximab
Term
What is Adoptive Immunotherapy?
Definition
-Using NK cells, T-cells, macrophages, etc. to fight cancer
-Common for is stem cell transplant
Term
What is the area on a lymph node where the afferent duct dumps lymph?
Definition
-Subcapsular sinus
-usually a white space on a sample
Term
What is Nissl substance?
Definition
-Ribosomes in neurons
Term
What is the feature of a myelinated nerve with continuous cytoplasm?
Definition
-Schmidt-Lanterman clefts
-SL cleft
Term
Dorsal Root ganglion histological features
Definition
-Round cell bodies
-Central nuclei
Term
Distinguishing features of sympathetic ganglion
Definition
-Multipolar bodies
-irregular cell body
-eccentric nuclei
Term
What is Myelin Basic Protein?
Definition
MBP is the protein targeted by the autoimmune response in MS that is responsible for keeping myelin compacted
Term
What are the 3 classes of synapses?
Definition
-Axosomatic/axodentritic
-Asospinous
-Axoaxonic
Term
Layers of the thoracic body wall
Definition
-Skin(epidermis (epithelial) and dermis (CT))-->superficial fascia-->deep fascia-->muscle/bone-->endothoracic fascia-->parietal pleura
Term
Intrinsic muscles of the back
Definition
1) Splenius
2) Erector spinae (longissimus, spinalis, ilocostalis
3) Transversospinalis
Term
Calculating odds ratio:
Definition
-Use when you have small numbers
Odds ratio=(A/C)/(B/D)
Term
How does estrogen affect bone deposition?
Definition
-Estrogen inhibits osteoclasts.
Term
4 functions of tumor suppressor genes
Definition
block oncogenes, repress TF, regulate cell cycle, initiate apoptosis
Term
4 classes of proto-oncogenes
Definition
growth factors, growth factor receptors, signal transducers, transcription factors
Term
1) Where does the dural sac end?
2) What's the Stellate trunk?
Definition
1) S2
2) sympathetic trunk for heart and lungs
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