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FSOM Foundations 2
Exam 2
255
Medical
Graduate
10/09/2012

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Term
Stellate ganglion
Definition
Ganglion in the sympathetic trunk (inferior cervical/T1) for heart and lungs.
Term
Splanchnic nerves
Definition
These nerves head to the splanchnic compartment (viscera)
Term
Collateral (prevertebral) ganglia
Definition
These ganglia contain cell bodies for sympathetic nerves going to the abdominal and pelvic viscera. The pre-synaptic nerves pass through the sympathetic trunk without synapsing.
Term
Adrenergic
Definition
Sympathetic nerves
Term
Cholinergic
Definition
Parasympathetic nerves
Term
Parasympathetic nerves come from:
Definition
Parasympathetics have "craniosacral outflow." They come from the vagus nerve and pelvic splanchnic nerves (spinal ventral rami S2,3,4)
Term
At what levels do sympathetic nerves leave the spinal cord?
At what levels do they return?
Definition
Leave: T1-L2
Return: All levels. Through the communicating rami and the dorsal root.
Term
The somatic nervous system invades:
The autonomic invades:
The exception is:
Definition
Somatic - somatopleure (body wall)
Autonomic - splanchnopleure (viscera)
Exception - Sympathetics. They're everywhere (arteries)
Term
Nissl bodies
Definition
Ribosomes in a neuron. Look like black sprinkles in the cell body.
Term
Ependymal cells
Definition
Support cells in the CNS. Line ventricles and central canal.
Term
Astrocytes
Definition
A scaffolding in brain tissue. Processes surround small vessels, neurons and CSF spaces. Most common source of brain tumors.
Term
Microglia
Definition
Phagocytotic. Proliferate as needed. From the monocyte cell line, not the neural crest.
Term
Multiple sclerosis targets which part of the nervous system?
Definition
It is an autoimmune disorder affecting myelination.
Term
Schmidt-Lanterman Cleft
Definition
Areas of cytoplasm that allow for cytoplasmic continuity from the outside to the inside of the schwann cell.
Term
How is a nerve signal sent?
Definition
Depolarization causes Calcium channels to open. The influx causes synaptic vesicles to fuse to the cell wall and release their neurotransmitter. This attaches to postsynaptic receptors, causing a change in conformation that opens ion channels. Depolarization and propagation or hyperpolarization are both possible.
Term
Why is perinerium different from perimyseum?
Definition
It has tight junctions (blood nerve barrier), dense bodies (actin), can act like smooth muscle and produce collagen like fibroblasts.
Term
Internal Vertebral Plexus
Definition
Veins lining the epidural space. How prostate cancer metastasizes to the brain.
Term
Adrenal Medula Cells
Definition
These are like post-synaptic sympathetic cells for the whole body. They are innervated by pre-synaptic sympathetic neurons.
Term
Neurilemma
Definition
AKA Sheath of Schwann. The outermost layer of Schwann cell that surrounds the axon.
Term
Initial segment
Definition
Thin part between the axon hillock and the myelin sheath. Where an axon potential is generated.
Term
Slow transport (in a neuron)
Definition
Only anterograde (body to terminal). For structural elements.
Term
Fast transport (in a neuron)
Definition
Both directions. Anterograde is for many cell organelles and elements (including small molecules like AAs, sugars, etc). Retrograde is for the same, plus things endocytosed at the terminal.
Term
Bouton
Definition
Button like dilation at the terminal of the axon. Filled w/ synaptic vesicles.
Term
Presynaptic density
Definition
conical dense inward projections of the neural membrane at the axon terminal.
Term
Myelin Basic Protein (MBP)
Definition
Protein that is part of the myelin sheath that aids in compaction. MS is an autoimmune attack on MBP.
Term
Protein O
Definition
A transmembrane glycoprotein that connects adjacent layers of myelin sheath. A major structural component of myelin.
Term
Neurofilaments
Definition
Intermediate filaments that, along with microtubules, are important components of axons and dendrites.
Term
Where does the phrenic nerve come from?
Definition
C3,4,5 keeps the diaphragm alive. It comes from the ventral rami of these 3 vertebrae.
Term
Gastroschisis
Definition
When the abdominal wall doesn't entirely form and the intestines are outside the body.
Term
Follow the developmental chain of paraxial mesoderm
Definition
Turns into somites. These divide into deramyotome, and sclerotome. Deramyotome divides into dermatome and myotome. Myotome divides into hypo mere and epimere.
Term
Intermediate mesoderm develops into:
Definition
The Urogenital system.
Term
Lateral plate mesoderm turns into:
Definition
Splanchnic mesoderm and somatic mesoderm. These along with endoderm and ectoderm respectively form splanchnopleure and somatopleure.
Term
Melanocytes
Definition
Non-nervous tissue that comes from the neural crest.
Term
Rectus Sheath
Definition
The aponeuroses that cover the rectus abdominous.
Term
In the lower 1/4 of the abdomen what are the layers and their order?
Definition
X Oblique, I Oblique, Transversus abdominous, rectus abdominous, transversalis fascia, parietal peritoneum.
Term
Suspensory Ligaments
Definition
AKA Cooper's ligaments. Attach the breast to deep fascia.
Term
Intercostal nerves run between which two layers?
Definition
It runs between the internal innercostal muscles and the innermost intercostal muscles.
Term
Kyphosis
Definition
Bowed outward. Thoracic region of the spine.
Term
Lordosis
Definition
Inward curvature. As in the cervical and lumbar regions of the spine.
Term
[image]
Definition
Term
What are the 3 intrinsic muscle layers of the back?
Definition
Splenius, Erector spinae, and Transversospinalis.
Term
Endothoracic fascia
Definition
The facia right above the parietal pleura in the thorax.
Term
Transversalis fascia
Definition
The layer right above the parietal peritoneum in the abdomen.
Term
Exudate
Definition
Protein rich fluid (from thoracentesis or pericardiocentesis).
Term
Transudate
Definition
Water fluid from thoracentesis or pericardiocentesis.
Term
Septum Transversum
Definition
Embryologic precursor for the central tendon of the diaphragm.
Term
Pleuropericardial folds
Definition
Embryonic precursors that eventually combine to separate the pleural and pericaridal cavities. It turns into the fibrous pericardium.
Term
Layers of the pericardium
Definition
Fibrous (connective tissue anchoring the heart), then two serous layers: parietal pericardium (fused to the fibrous pericardium) and the visceral pericardium (aka epicardium on the heart muscle itself).
Term
Derivatives of the celom
Definition
Plural space, pericardial space, peritoneal space.
Term
Boyle's Law
Definition
For respiration. Increased volume leads to decreased pressure.
Term
Inspiration muscles
Definition
Diaphragm, External Intercostals, Pectoralis Maj. and min., Serratus anterior.
Term
Forced Expiration Muscles
Definition
Internal intercostals, rectus abdominous.
Term
Carina
Definition
Where the trachea splits.
Term
Lymphatic Functions (4)
Definition
1. Drain fluids 2. Absorb emulsified fat 3. Immune system 4. Re-circulate proteins from blood capillaries.
Term
What are the 3 main lymphatic trunks?
Definition
1. Jugular trunk (drains head/neck) 2. Subclavian trunk (drains axillary nodes) 3. Bronchomediastinal trunk (drains heart and lungs). All dump in at the junction of the internal jugular vein and the left subclavian vein.
Term
What part of the body's lymph empties in the right side?
Definition
Above the umbilicus and right of center. The only exception being the deep body wall which drains into the thoracic duct.
Term
Where does lymph cross the superficial fascia from the superficial body wall to go to deeper lymphatic vessels?
Definition
The axillary or superficial inguinal nodes.
Term
Femoral Sheath
Definition
Where the lymph drains from the superficial inguinal nodes to the deeper lymphatics. LVAN - nerve is outside the sheath.
Term
Pectinate line
Definition
The line separating the gut from the body wall. (anus) Lymph will not penetrate this.
Term
Aortic lymphatics
Definition
Receive lymph in the abdomen. Dumps into the cisterna chyli. Collects everything from lower half of the body (superficial and deep - including the abdominal organs)
Term
Where does deep lymph in the arm go?
Definition
The axillary lymph nodes.
Term
Where does lymph from the heart and lungs drain?
Definition
To the bronchomediastinal trunk. (lymph can pass to opposite sides here).
Term
Where does lymph from the breast drain?
Definition
Upper lateral - axillary nodes. Medial - can drain to the parasternal nodes. Some can drain to the opposite breast. Possibly the superficial inguinal nodes as well (rare).
Term
What and to where do the deep parasternal lymph nodes drain?
Definition
They drain anterior intercostal lymph, upper liver lymph, and some breast lymph to the bronchomediastinal trunk.
Term
Where does esophageal lymph go?
Definition
To the thoracic trunk and/or the bronchomediastinal trunk.
Term
What are the 6 imaging modalities?
Definition
X-ray, Ultrasound, MRI, CT Scan, Nuclear medicine, PET scan
Term
What does effective radiation does account for?
Definition
Dose, harm, sensitivity of organs.
Term
What is the ALARA principle?
Definition
For radiation exposure: As Low As Reasonably Achievable. Think: is there an alternative?
Term
5 X-ray densities
Definition
1. Air 2. Fat 3. Soft tissue or water 4. Bone 5. Metal/contrast
Term
Types of X-ray imaging (7)
Definition
X-ray, Mamography, Fluoroscopy (GI contrast studies), Angiography (blood vessel studies), Myelography (spinal subarachnoid space), Arthrography (joint space), CT
Term
What material can ultrasound not penetrate?
Definition
Air. Therefore it can only be used on certain structures. (Black you see is fluid)
Term
What is duplex dopler used for?
Definition
Echocardiography. To see blood flow.
Term
What is nuclear medicine?
Definition
Imaging where an image is generated by a radioactive agent tagged to a specific tissue. Tests for function rather than anatomy. Eg: bone scan
Term
What allows for specificity in pharmacology (and biology)?
Definition
Receptors. The body has many unique chemical receptors that are incredibly specific.
Term
What is a receptor (pharmacology)?
Definition
Anything that can be a drug target, including: 1. Cell surface or intracellular regulatory proteins 2. Enzymes 3. Structural Proteins 4. Nucleic Acids (ATP)
Term
What two features does a receptor need?
Definition
A recognition site and a transduction mechanism.
Term
What determines the quantitative relationship between a drug and its pharmacological effects?
Definition
Receptors.
Term
What does an antagonist do?
Definition
It inhibits an agonist.
Term
Inverse agonist
Definition
Binds and eliminates the constitutive activity of a receptor, something an antagonist cannot do. Has negative efficacy.
Term
Chemical antagonism
Definition
Inactivation of one drug by the direct binding of another drug. Bind the drug before it can act.
Term
Physiological antagonism
Definition
Using a drug targeting a physiological response that will counteract the actions of another drug. Eg: Insulin
Term
Pharmacological antagonism
Definition
Ligands that bind to, but do not activate, receptors. What you normally think of.
Term
Orthosteric site
Definition
The active site.
Term
Why are some antagonists irreversible?
Definition
They form covalent bonds with the receptor.
Term
What is an uncompetitive allosteric site?
Definition
A site that requires receptor activation before it becomes accessible.
Term
What is a noncompetitive allosteric site?
Definition
An allosteric site where the antagonist can bind regardless of the presence or absence of agonist.
Term
Agonist independent negative allosterism
Definition
Inverse agonist. Reduces activity regardless of the presence of the agonist.
Term
Partial Agonist vs. Full agonist
Definition
Full agonist can elicit a maximum effect. Partial can't no matter how much you use.
Term
Do competitive antagonists have to look like their agonist?
Definition
No. They may resemble the agonist, or they may be quite different.
Term
What is pharmacokinetics?
Definition
Quantitative relationship between drug concentration and response. Looking at drugs in vivo. What is its effect? Will it metabolize? Are the metabolites active? What is their effect?
Term
Drug Effect =
Definition
[image]
Term
EC50/ED50
Definition
The concentration/dose that yields 50% of the maximum response that drug can elicit.
Term
Drug Activity
Definition
This is a measure of the drug effect. Seen by the equation.
Term
[image]
Definition
A & B are equally effective. A & C are equipotent. They are more potent then B.
Term
What has an efficacy of 0? (Pharm)
Definition
Antagonists. They never produce a response by themselves.
Term
Quantal Dose Response Curve
Definition
This is used when the response is binary (death or not, pregnant or not, etc.) ED50 is the dose where half of the people had the effect.
Term
Therapeutic Index
Definition
Toxic ED50/Beneficial ED50. Measures the relative toxicity vs the therapeutic utility of a drug. The farther apart the two curves are the better. You want the Index to be a high number.
Term
LD50
Definition
Lethal Dose 50. The Toxic ED50 when death is the measure of toxicity.
Term
Pharmacogenomics
Definition
The study of how genetics affects variation in drug response. Often an enzyme variant can greatly affect drug response (metabolized faster or slower than normal).
Term
Dose Response Curves
Definition
The important graph you see in pharmacology.
Term
How do competitive antagonists affect the DR curve?
Definition
Parallel shift to the right. Requires a higher concentration of agonist to have the same effect, but it can overcome it completely. Decreases potency, no effect on efficacy.
Term
How does a non-competitive antagonist affect the DR curve?
Definition
[image]
Term
Noncompetitive antagonist
Definition
An antagonist that binds covalently to the orthosteric site or an allosteric site. It takes certain receptors out of play. This decreases the efficacy of a drug, but doesn't affect its potency.
Term
What is an inhibition-response relationship?
Definition
Agonist dependent. Determines the potency of the antagonist at a given agonist concentration.
Term
Schild Analysis
Definition
Agonist independent. Determines the antagonist equilibrium constant.
Term
Inhibition Response Curves
Definition
These measure response at various antagonist concentrations.
Term
IC50s
Definition
These measure antagonist concentration at which 50% of the effect is inhibited. This will change depending on the agonist concentration.
Term
Dose Ratio
Definition
The fold increase in agonist concentration needed to give the same % response in the presence of a given concentration of antagonist.
Term
Coupling
Definition
The name for the transduction process between receptor binding and biological effect
Term
Spare receptors
Definition
Not all receptors need to be bound to achieve 100% effect. This can make low doses of non-competitive antagonist seem like competitive antagonists.
Term
Monod-Wyman-Changeux model
Definition
Receptors are in two states, active or inactive. Agonists and antagonists shift the eqbm toward one or the other.
Term
Koshland-Nemethy-Filmer model
Definition
Receptors undergo sequential non-concerted changes to a multitude of possible conformations.
Term
Name the 5 major receptor families.
Definition
1. Intracellular receptors 2. Receptors that act as an enzyme 3.Enzyme-Linked Receptors 4. Ligand/Voltage Gated Ion Channels 5. G Protein-coupled receptors
Term
List 3 characteristics of Intracellular receptors
Definition
1. Ligands must be lipophilic (to cross the plasma membrane - often these are steroids) 2. Receptors often enter the nucleus after binding to alter gene transcription 3. This action usually takes time.
Term
List characteristics of Enzyme-Linked Receptors
Definition
Signaling response is slow (hours). Start a cascade that leads to changes in transcription. Kinases and kinase associated.
Term
Receptor Tyrosine Kinases (RTKs)
Definition
These are Enzymatic receptors (type 2).
Term
Tyrosine-Kinase associated receptors (type 3)
Definition
These kinases can float away and trigger other mechanisms in the cell once activated. Cytokine receptors are the largest family of these.
Term
Ion channels have 3 gating mechanisms. What are they?
Definition
1. Voltage gated 2. Ligand gated 3. Mechanically gated
Term
Name 3 types of ligand gated ion channels.
Definition
1. Cys-loop receptors (pentameric) 2. Ionotropic Glutamate Receptors (tetrameric) 3. Ionotropic ATP receptors (trimeric)
Term
What are two examples of channelopathies?
Definition
Cystic fibrosis, long QT syndrome
Term
What are 4 families of G protein coupled receptors?
Definition
A. Rhodopsin-like B. Secretin-like C. metabotropic 4. Frizzled family
Term
What are the relative time frames of the receptors?
Definition
Fastest to slowest - ion channels, GPCRs, Enzyme linked, Intracellular
Term
What is Tachyphylaxis?
Definition
Drug desensitization.
Term
What are the two types of tachyphylaxis?
Definition
Receptor Mediated: only the activated receptor desensitizes (loss of receptor function or decrease in receptor number)
Non-receptor mediated: Decoupling of downstream elements required for signaling.
Term
What is Beta-arrestin an example of?
Definition
Receptor mediated tachyphlaxis. It prevents interaction between the receptor and the G-protein. It also promotes internalization of receptors (decreasing receptor #).
Term
What is the resting potential of a cell?
Definition
-70mV
Term
What is the Vm (membrane potential) of cells used for?
Definition
1. Potential Energy. It acts as a battery to power many cellular processes. 2. Communication (in excitable cells only).
Term
What is the ion permeability model?
Definition
The conceptual explanation for membrane potentials and how they work. They key is K+ is leaked out of the cell until the chemical force equals the electrical force (occurs w/ a net - inside the cell).
Term
Nernst Equation
Definition
[image]
Term
Goldman-Hodgkin-Katz Equation
Definition
This equation is used to find the membrane potential. It does this by evaluating the equilibrium potentials of all of the ions and adjusting for their permeability. Sort of a weighted average.
Term
Equivalent Circuit Model
Definition
Uses Ohm's Law to understand membrane potentials. Can be used experimentally.
Term
How does the cell compare to a circuit?
Definition
Ion channels are conductors, the membrane is a capacitor, the nernst potentials are batteries. Helps explain the time delay.
Term
What is G in the Equivalent Circuit model?
Definition
Conductance. You use that and their potentials to calculate the membrane potential. They are capacitors and conductors in series.
Term
Na-K ATPase does what?
Definition
It moves 3 Na out and 2 K in. Balances when the pump equals the flux due to leakage. This one complex uses ~30% of your energy.
Term
Name two types of action potentials that differ from each other.
Definition
1. Cardiac 2. Neurons
Term
Why can't you have multiple action potentials in a row?
Definition
Absolute Refractory period. The Na and K channels are inactivated after they open. Afterward the hyper-polarization causes the relative refractory period.
Term
How does the NaKATPase work?
Definition
Exposed Na+ sites inside the cell. ATP driven mech. (phophorylates the pump). The change in conformation
lowers the binding affinity for Na+. Potassium binding sites are exposed. Then the phosphate is hydrolyzed, which make it change conformation again. This lowers binding affinity for K+ and we start over.
Term
Ion transporters
Definition
Have a binding site like an enzyme. Have conformational change. Slow flux rates.
Term
Ion Channels
Definition
Discriminate based on size and charge. Open channels allow ions and H20 to pass. Fast flux.
Term
Voltage gated Na channels have many pores all part of the same polypeptide.
Definition
They are repeats of 6 subunits 4 repeats form the channel.
Term
How does a voltage sensor work?
Definition
It has to be packed with charges opposite the charge you want to sense. It will attract or repel. This tugging motion opens the gate.
Term
How many types of K+ channels are there?
Definition
Many. 6 TM and 2TM versions. Each repeat is its own peptide. Products of different genes form the pore. Functional heterogeneity.
Term
How do channels have ion selectivity?
Definition
They have built in hydrogen bonding that only works for the ion of the right size.
Term
List some unique characteristics of stem cells.
Definition
They retain DNA markers due to asymmetric DNA division, they replicate as needed, they are able to pump out drugs quickly (a protective mechanism).
Term
How does a stem cell know what to become?
Definition
The stroma! The microenvironment around the cell.
Term
Why does scar tissue form rather than replacement of healthy tissue by stem cells?
Definition
If the stroma/microenvironment is destroyed, stem cell formation is blocked, so scar tissue forms.
Term
Describe the difference between endocrine, paracrine, and autocrine signaling.
Definition
Endocrine - releases hormone into the bloodstream. Widespread affect. Paracrine - affects nearby cells. Autocrine - affects itself.
Term
Hypertrophy
Definition
Increase in the size of cells. Proliferation of organelles. Eg: muscle growth after weight lifting.
Term
Hyperplasia
Definition
Increase in the number of cells. Eg: a callus.
Term
Atrophy
Definition
Decrease in the size of cells
Term
Hypoplasia
Definition
Decrease in the number of cells. Eg: Post menopausal endometrium
Term
Metaplasia
Definition
Change in differentiation from one cell type to another. Reversible. Eg: Barret's esophagus, Myositis ossificans, smokers lung (simple squamous). Can serve as a nidus for dysplasia.
Term
Dysplasia
Definition
Abnormal hyperplasia with a propensity to malignant change. Sometimes reversible. Linked to DNA damage. Eg: HPV - 1/3 will go away, 1/3 won't do anything, 1/3 will cause cancer.
Term
Neoplasia
Definition
Cellular autonomy and uncontrolled growth. Benign and malignant tumors. Irreversible.
Term
Mitogen
Definition
Causes cell division. Activates a receptor and starts a cascade that initiates the cell cycle.
Term
Motogens
Definition
Causes cells to migrate or scatter.
Term
Morphogens
Definition
Differentiation-inducing factors (cause morphology to change)
Term
Intracrine
Definition
Cell releases signaling molecules intracellularly (within itself). Never leave the cell like autocrine signals.
Term
List the 4 ways a cell can respond to a stimulus or injury.
Definition
1. Ignore (quiescence) 2. Adapt 3. Divide and differentiate 4. Die (Apoptosis or Necrosis)
Term
Necrosis
Definition
Death of groups of cells. Plasma membrane damage and activation of degradation enzymes in an uncontrolled manner. Leads to inflammatory response, and random breaks in DNA. Ghost like appearance - due to degradation of proteins/organelles.
Term
List the 5 types of necrosis
Definition
1. Caseous 2. Coagulative 3. Liquefactive 4. Fat 5. Tumor
Term
Pathology: Pink means... Blue means...
Definition
Pink - Cell death. Blue - WBCs are infiltrating, or it's malignant.
Term
Coagulative necrosis
Definition
Cell death caused by ishemia (aka infarction) or by exposure to toxic agents. Early acute inflammation, later scar formation.
Term
Liquefactive Necrosis
Definition
A form of coagulative necrosis. Tissue dissolves and a cyst forms. No immune response is triggered. Eg: Brain after ischemic injury.
Term
Granuloma
Definition
A group of macrophages that are turned on and become large. Trying to wall off things the immune system can't remove. May be caseous in the center. If they are that's a sign of infection rather than genetic or foreign body disease.
Term
Caseous Necrosis
Definition
Occurs in a granuloma. Looks like cheese. Has characteristics of both coagulative and liquefaction necrosis (center slowly liquefies).
Term
Fat necrosis
Definition
Term
Fat necrosis
Definition
Occurs w/ the pancreas. Damage causes it to auto digest. Yellowish to white. Accumulates calcium (saponification) which can cause physiologic problems.
Term
Gangrenous Necrosis
Definition
A term used for a type of coagulation necrosis in the soft tissues of the lower limbs.
Term
Tumor necrosis
Definition
Cell death that occurs when a tumor's growth outstrips its blood supply. Therapy leads to necrosis of tumors.
Term
What are the 5 mechanisms that lead to necrosis?
Definition
1. ATP Depletion 2. Loss of calcium homeostasis 3. Free radicals (as in re-perfusion injury) 4. Loss of membrane permeability 5. Damage to DNA and proteins.
Term
Can necrosis be genetic?
Definition
Yes. Certain storage diseases can cause necrosis. Once the cell accumulates too much of something it will die.
Term
How do you measure the degree of necrosis?
Definition
Serum enzymes. They're released into the blood when the cells die.
Term
What are two key differences between apoptosis and necrosis?
Definition
Apoptosis is the death of a single cell (not groups of cells). Also apoptosis does not trigger an immune response.
Term
What is the ultimate cell executioner in apoptosis? What activates it in intrinsic apoptosis?
Definition
Caspases (through proteolytic cleavage). Activated by cytochrome c.
Term
How does extrinsic apoptosis work?
Definition
Apoptotic receptors are activated.
Term
What are 5 uses for apoptosis?
Definition
1. Tissue remodeling in embryo 2. Removal of activated T cells at the end of immune response 3. Removal of DNA damaged cells 4. Killing of inflammatory cells at immune privileged sites (eye) 5. Elimination of virus infected cells
Term
Hepatic Steatosis
Definition
Fatty liver. Reversible. Eventually over accumulation leads to cell death which triggers an inflammatory response which leads to fibrosis (cirrhosis) which is not reversible.
Term
Mallory Bodies
Definition
Liver accumulations. Tangled intermediate filaments. Reversible.
Term
What is ERAD?
Definition
Basically a pore that brings bad proteins back into the cell where they can be targeted by the ubiquitin-proteosome system.
Term
List 4 things that accumulate in the cell.
Definition
1. Lipofuscin - The "sludge" of cells. Accumulates of the cell's life. Non-toxic to the cell. Clears when cells divide. 2. Melanin 3. Hemosiderin - accumulation of ferritin. 4. Uric acid - leads to gout
Term
Hematoma
Definition
Bruise. The body wants to recover the iron.
Term
Dystrophic Calcification
Definition
Calcium deposition in damaged tissue due to negative charge in dead tissue. Also Psammoma bodies - tomb for cancer cell.
Term
Metastatic Calcification
Definition
Due to hypercalcemia.
Term
Hayflick Limit
Definition
Limited replication of cells. They can only divide about 50 times.
Term
What are the 7 Hallmarks of cancer?
Definition
1. Self-sufficiency in growth signals 2. Insensitivity to growth-inhibitory signals 3. Evasion of apoptosis 4. Limitless replicative potential 5. Sustained angiogenesis 6. Tissue invasion and metastasis 7. Defects in DNA repair
Term
Anaplasia
Definition
Extreme disorganization. Lack of differentiation. As in neoplasia.
Term
What are the two factors needed to cause cancer?
Definition
Initiation and promotion.
Term
What are some pro to-oncogene products?
Definition
Growth Factors, Growth Factor Receptors, Signal transducers, Transcription factors.
Term
What are the 4 ways a Proto-oncogene can become an oncogene?
Definition
1. Mutation 2. Abnormal activity (removal of the regulatory domain) 3. Gene translocation (anything to chrome 14) 4. Amplification (additional repeats).
Term
What do oncogenes affect?
Definition
1. Cell proliferation or 2. Cell differentiation (keeps a cell in it's active proliferative state) 3. Cell survival (no apoptosis)
Term
What are the 4 functions of tumor suppressor genes?
Definition
1. Antagonize an oncogene. 2. Transcription factors 3. Regulate the cell cycle (RB, p53) 4. Induce apoptosis.
Term
Do malignancies come from dysplasia?
Definition
Yes, but more commonly they arise de novo.
Term
What are the 4 main categories for cancer?
Definition
Carcinoma (epithelial), Lymphoma (lymphocytic), Melanoma (melanocytic), and Sarcomas (most everything else - mesoderm)
Term
Adeno-
Definition
Glandular tumor
Term
Leio-
Definition
Smooth muscle tumor
Term
Rhabdo-
Definition
Skeletal muscle tumor
Term
Chondro-
Definition
Cartilage tumor
Term
Pleomorphism
Definition
Variation in cell size and shape.
Term
Malignant cells have what characteristics?
Definition
Ugliness. Pleomorphism and Anaplasia. Loss of architecture.
Term
What 3 factors determine tumor growth rate?
Definition
What proportion of the cells divide, how fast they divide, and the ratio of cell division to cell death (turnover).
Term
What are the 3 pathways of metastatic spread?
Definition
1. Lymphatic 2. Hematogenous (usually through small veins to other sites) 3. Seeding of body cavities (tumors in the peritoneum)
Term
TNM what are the ranges?
Definition
T1-4 N0-3 M0-1 The combined measure is used to determine the stage of the cancer.
Term
Why are people w/ cancer sick?
Definition
Direct effect of the tumor, Cachexia, Paraneoplastic syndromes, infection, bleeding/thrombosis
Term
Cachexia
Definition
Wasting, lethargy, loss of appetite. Due to increased caloric consumption (some due to tumor, mostly metabolic). Etiology linked to cytokines.
Term
Paraneoplastic Syndromes
Definition
Remote effects of the tumor. Eg: Ectopic hormone production (parathyroid leads to hypercalcemia), Autoimmune (body trying to attack the tumor accidentally self attacks).
Term
Hematologic effects of cancer
Definition
Infection/immunosuppression, Thrombosis/bleeding, anemia. This is usually what actually kills people w/ cancer.
Term
Are geographic risk factors for cancer environmental, or racial/cultural?
Definition
Environmental.
Term
Cancer grade vs stage
Definition
Stage - extent of the tumor spread (0-IV) Grade - degree of differentiation.
Term
PCNA stain
Definition
Used to measure DNA synthesis and thus see tumor growth.
Term
What are the 4 steps of tumor invasion?
Definition
1. Changes of tumor cell-cell interactions (cadherins) 2. Degradation of the ECM (using MMPs) 3. Changes in the attachment of tumor cells to ECM proteins (prepare for migration) 4. Locomotion - directed by tumor cell-derived cytokines.
Term
What are the 7 steps of metastasis?
Definition
1 Invasion of the basement membrane 2 migration through the ECM 3 Penetration of the vessel wall 4 Survival and transport in vessels 5 Arrest in target organ 6 Extravasation in secondary sites (leave vessel) 7 Survival and growth at metastatic site
Term
Dominant or Recessive? Tumor suppressor genes vs oncogenes.
Definition
Oncogenes are dominant. Tumor suppressors are recessive.
Term
HER-2
Definition
An oncogene in breast cancer.
Term
What is the most commonly mutated oncogene?
Definition
The RAS oncogene. RAS is a signal transducer used in a lot of pathways in the cell. A mutation here causes lots of problems.
Term
What is MYC?
Definition
A commonly mutated oncogene, involved in apoptosis.
Term
What does Cyclin D-CDK4 do? Why is it important?
Definition
It phosphorylates RB. The on-off switch for the cell cycle.
Term
Which checkpoints in the cell cycle check for DNA damage?
Definition
The G1-S checkpoint (mediated by p21 and p53) and the G2-M checkpoint (mediated by p53).
Term
What is the "guardian of the genome"?
Definition
The P53 gene. It acts as a molecular policeman looking for DNA damage. It can arrest the cell cycle or initiate apoptosis if it finds problems.
Term
What are the pro-apoptotic genes?
Definition
Intrinsic: p53, cytochrome-c, BAK, BAX, Caspases.
Extrinsic: TNFr and FAS are the receptors. They induce the assembly of DISC and recruitment of caspases through the FADD.
Term
What are the anti-apoptotic genes?
Definition
BCL2 (if this gets translocated to an active site it will suppress apoptosis and can lead to tumor formation), MCL1, IAP.
Term
What is the APC/B-Catenin pathway?
Definition
Two genes whose mutation leads to colon cancer.
Term
BRCA-1,2 are what kind of genes?
Definition
DNA recombination repair genes.
Term
What are the 3 types of DNA repair that can be defective in cancer?
Definition
1. Mismatch repair 2. Nucleotide excision repair 3. Recombination repair.
Term
What are "caretaker" genes?
Definition
DNA repair genes. Defects here lead to a higher risk of malignancy vs defects in the "gatekeeper" genes (i.e. oncogenes and tumor suppressor genes).
Term
Why are carcinogens electrophilic?
Definition
They bind to nucleophilic DNA to form a carcinogen-DNA adduct. Direct acting are naturally electrophilic, indirect acting must first be activated by the body to become electrophilic.
Term
Ames Test
Definition
A test for carcinogenicity.
Term
Nitrogen mustards
Definition
Direct-acting carcinogens. Used as chemotherapy agents.
Term
Aflotoxin is a fungus that tends to mutate what gene?
Definition
P53. This is correlated w/ a specific mutation that is involved with hepatocellular carcinomas.
Term
Physical Carcinogens
Definition
UV light, radiation, asbestos
Term
Mesothelium
Definition
The epithelium that lines the body cavities.
Term
What is an infectious carcinogen?
Definition
HPV. This has proteins that when they insert into the genome they block p53 and bind RB not allowing either to prevent proliferation. Also H. Pylori
Term
Why may inflammation cause cancer?
Definition
Reactive oxygen species.
Term
Isogenous groups
Definition
Groups of cells in lacunae of cartilage.
Term
Epithelial reticular cells
Definition
Make up Hassal's (thymic) corpuscle
Term
ATM
Definition
A molecule activated by DNA damage. Involves p53 in it's cascade.
Term
What does a high D0 indicate?
Definition
Radiation resistance. Low D0 indicates radiation sensitivity.
Term
When in the cell cycle are cells most radiosensitive?
Definition
M>G2>G1>early S>late S G0 most resistant of all. Also all are more resistant in hypoxic conditions.
Term
Differentiated and non dividing cells are radio resistant or radio susceptible?
Definition
Radio resistant. Undifferentiated and dividing are the most radio susceptible.
Term
What is the effect of hypoxia on cells?
Definition
Make them more susceptible to mutation, but more resistant to radiation damage.
Term
What are the 4 effects of fractionation of radiotherapy?
Definition
1. Repair/recovery (benefits normal cells) 2. Reassortment in the cell cycle (aids in killing tumor cells) 3. Repopulation of cells (benefits the tumor) 4. Reoxygenation (aids in killing tumor cells)
Term
Acute effects of Total body radiation exposure (3)
Definition
From highest does to lowest 1. Cerebrovascular syndrome 2. GI syndrome 3. Hematopoietic syndrome - Bone marrow transplant can be utilized.
Term
Stochastic vs Deterministic events w/ radiation
Definition
Stochastic - can happen at any level. All radiation is bad.
Deterministic - there is a threshold that causes damage (usually to whole systems)
Term
Late response vs early to radiation
Definition
Early <90 days. Commonly dividing tissues (skin, jejunum, colon, testis). Late - .5-5yrs. (affects spinal cord, kidney lung bladder). Alpha-beta ratios tell about late effects. It is easier to effect division than function. That's why you see late effects.
Term
List 3 types of Electron Beam Radiation Therapy (EBRT).
Definition
1. 3D Conformal (plan based on CT scan) 2. Conventional (based on body landmarks) 3. Intensity Modulated Radiation Therapy (planned w/ a computer)
Term
Brachytherapy
Definition
Close therapy. Inserting radiation emitting seeds into the target area. Used for prostate, Head and neck, Gynecologic, Intraoperative.
Term
Radiosurgery
Definition
High dose, very focused external beam RT. Gama knife (great for the brain - must completely immobilize the pt), linear accelerator, cyperknife (on robot arm - good for moving targets (lungs).
Term
TARGIT Procedure
Definition
Intraoperative RT.
Term
Radiation considerations you should look at
Definition
Time, Distance (1/R2) - 2 times the distance is 4 times less dose, shielding.
Term
1 Gray =
Definition
1 J/Kg
Term
Biologic Response Modifiers
Definition
Using the immune system to fight cancer.
Term
Epitope
Definition
The part of an antigen that is recognized by the immune system.
Term
What are the 8 ways Biotherapy can be used (cancer)?
Definition
1. Promotion of apoptosis 2. Augmentation of the immune response 3. Differential/cellular maturation 4. Interfere w/ growth promoting factors 5. Inhibition of metastases 6. Amelioration of chemo/radiation toxicity 7. Targeting of cytotoxic molecules to tumors 8. Inhibition of angiogenesis.
Term
What are 5 biotherapy treatments?
Definition
1. Interferons/Interleukin - Used for renal and melanoma malignancies. 2. Monoclonal Antibodies - _umab's, Creating antibodies specifically tailored to the disease. 3. Vaccines - Only vaccine like is where you ship white cells out 4. Recombinant Toxins - Targeted toxins 5. Adoptive Immunotherapy - Bone marrow transplant. Relied on donor cells to do the work. Getting better. For leukemias.
Term
TGF - Beta
Definition
A potent immunosuppressor. Used by tumors.
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