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463 Cards in this Set
- Front
- Back
What are the four types of tissue?
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- Muscle
- Connective Tissue - Epithelium - Nerve |
|
What are the three types of muscle?
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- Skeletal
- Cardiac - Smooth |
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What types of cells are found in skeletal muscle?
|
- Skeletal myocytes (muscle cells)
- Endothelial cells (blood vessel epithelium - vascular system for nourishment) - Connective tissue (fibroblasts) |
|
What is the hierarchy of skeletal muscle? What units is it measured in?
|
- Gross anatomical muscle (cm)
- Fascicles (mm) - Skeletal myocytes aka fibers/cells (10-100 µm) - Myofibrils (1-2 µm) - Myofilaments (nm) |
|
How does the number of nuclei per myocyte (muscle cell) differ for skeletal and cardiac muscle?
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- Skeletal muscle - hundreds of nuclei
- Cardiac muscle - 1-3 nuclei |
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Where are nuclei located in a healthy myocyte (muscle cell)?
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Periphery (side) of cell (as opposed to in the middle of the cell)
|
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What are the three layers of connective tissue that surround muscular tissue?
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- Epimysium (aka deep fascia) - surrounds whole gross muscles
- Perimysium - surrounds fascicles (bundles of myocytes) - Endomysium - surrounds individual myocytes |
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What connective tissue is the basal lamina continous with?
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Endomysium (which surrounds the individual myocyte; therefore there is a basal lamina for every muscle cell)
|
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What is the structure at the end of the muscle where the connective tissue invests the skeletal myocytes called?
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Myotendon junction
|
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The connective tissue at the myotendon junction (CT that invests skeletal muscle) is continous with what?
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Dense regular connective tissue of tendons that attach the muscle to the bone
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What tool can be used to visualize the striations of skeletal and cardiac muscle
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Light micrograph
|
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What does it mean if the nuclei of skeletal myocytes are centrally located (as opposed to on the periphery)?
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Pathology or injury
|
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What causes the striations in skeletal muscle?
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- Light bands (I-bands)
- Dark bands (A-bands) |
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What breaks up the light band (I-band)?
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Z-line (contains α-actinin)
|
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What is the space between successive Z-lines called?
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Sarcomere - fundamental unit of muscle contraction
|
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What is the fundamental unit of muscle contraction? Where is it located?
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Sarcomere - between successive Z-lines
|
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What is the light structure that bisects the dark band (A-band)?
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H-zone - which is bisected by a dark line, the M-line
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What is found on the M-line (which is in the middle of the H-zone, in the middle of the A-band)?
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- Skeletal: MM-creatinine kinase (MM-CK)
- Cardiac: MB-CK |
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What are the two types of myofilaments in a myofibril?
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- Thick filaments (myosin)
- Thin filaments (actin, troponin, tropomyosin) |
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Why are I-bands light?
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They contain ONLY thin myofilaments (actin, troponin, and tropomyosin)
|
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Why are A-bands dark?
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They contain both thin and thick myofilaments (thick - myosin; thin - actin, troponin, and tropomyosin)
|
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What two membrane systems are found at the A-I junction in each myofibril?
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- Transverse Tubules (T-tubules)
- Sarcoplasmic Reticululm (SR) |
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T-tubules are invaginations of what structure? What is their purpose?
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- Invaginations of sarcolemma
- Carry depolarization deep into cell to stimulate SR to release Ca2+ |
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What structures form the 'triad' at the A-I Junction?
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- T-tubule in middle
- Two SR membranes surround T-tubule |
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What steps happen in the excitation phase of the excitation-contraction copuling?
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1. ACh binds the ACh-Receptor
2. Wave of depolarization runs down sarcolemma 3. Wave travels deep into muscle via T-tubule 4. At triad, the T-tubule depolarizes the SR 5. SR releases stored Ca2+, increasing Ca2+ conc. in myofibrils |
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What steps happen in the contraction phase of the excitation-contraction coupling?
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1. In the thin filament, Ca2+ binds troponin-C (TnC)
2. Troponin-I (TnI) moves, opening up the myosin-binding-sites on actin 3. Actin binds to myosin 'head', which contains ATP that is then hydrolyzed 4. ATP hydrolysis provides energy for 'power-stroke' (thin filaments are pulled into A-band) 5. Sarcomeres shorten; multiple cycles of attachment and release results in contraction |
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How does striated muscle relax?
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- Specialized ion-channel Ca2+ pump in SR pumps Ca2+ back into SR
- When Ca2+ levels decrease, fresh ATP binds myosin head, actin and myosin are dissociated, and myocyte relaxes |
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What gene is affected in malignant hyperthermia?
|
RYR (Ryanodine Receptor) gene
|
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What happens in malignant hyperthermia?
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- Inherited autosomal dominant mutation of RYR (ryanodine receptor) gene in SR membrane
- Dysregulated Ca2+ transport |
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Why is malignant hyperthermia significant for patients undergoing anesthesia?
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- Dysregulated Ca2+ transport in Ryanodine Receptor (RYR)
- Sustained skeletal muscle contraction - Increase in body temperature |
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What is a preventative intervention for dealing with patients with malignant hyperthermia?
|
Administer dantrolene - muscle relaxant that inhibits Ca2+ release through the RYR (ryanodine receptor) channel
|
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What causes Rigor Mortis?
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Absence of fresh ATP prevents acto-myosin dissociation, preventing relaxation thereby resulting in stiffening
|
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Can you see striations of skeletal muscle in cross-section?
|
No
|
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How many thin filaments surround each thick filament (can be viewed in cross-section with EM)?
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Six thin filaments surround each thick filament
|
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How does skeletal muscle store energy?
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- ATP
- Creatine Phopshate - Glycogen - Fatty acids |
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Sprinters rely more on what type of energy?
|
Glycogen
|
|
Marathoners rely more on what type of energy?
|
Fatty Acids
|
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What are the two types of muscle fibers?
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Type I = red = slow-twitch
Type II = white = fast-twitch |
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What characteristics define Type I muscle fibers?
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- Red / slow-twitch
- Enriched in mitochondria and myoglobin - Use FA oxidation and oxidative metabolism to support continuous contraction |
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What characteristics define Type II muscle fibers?
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- White / fast-twitch
- Less myoglobin - Modified for rapid, discontinuous contraction - Glycolytic or mixed oxidative / glycolytic |
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How can skeletal muscle be regenerated?
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Resident Adult Stem Cells (Satellite Cells / Myoblasts)
|
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Describe the resident adult stem cells (aka satellite cells / myoblasts)?
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- Regenerate skeletal muscle cells
- Mononuclear, residing between sarcolemma and basal lamina of myocyte (niche) - Rest in Go phase of cell-cycle in normal tissue - Enter cell cycle at G1 when basal lamina is damaged |
|
What phase of the cell cycle do satellite cells / myoblasts (adult stem cells of muscle tissue) stay in when resting? What stimulates them to leave that phase?
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- Rest: stay in Go phase
- Enter G1 phase when basal lamina damaged |
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What factor limits the growth of satellite cells / myoblasts (adult stem cells in muscle tissue)?
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The growth factor myostatin - released by mature myocytes
|
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What are myotubes? When are they formed? What happens to them?
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- Multinuclear muscle cells
- Form when cells irreversibly withdraw from cell-cycle and fuse together - Undergo robuts muscle differentiation |
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What are two clinical cases in which satellite cells/myoblasts can be used as a part of the treatment?
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- Cardiac Insufficiency
- Duchenne Muscular Dystrophy (DMD) |
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What were the implications of studies that tried to utilize satellite cells/myoblasts for treatment of cardiac insufficiency?
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- Modest improvement of ejection fraction
- Several patients exhibited arrhythmia however |
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What was discovered to be the cause of Duchenne Muscular Dystrophy (DMD)?
|
- Mutations in genes encoding dystrophin (sub-sarcolemmal protein that participates in stabilization of myocyte cytoskeleton)
- Without dystrophin, sarcolemma breaks down leading to muscle cell death |
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What is the function of the Dystrophin gene?
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Sub-sarcolemmal protein that participates in stabilization of myocyte cytoskeleton
|
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Describe the gene for Dystrophin and how it can be mutated.
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- Enormous (2.6 million bp with 97 exons) - takes 16 hrs to transcribe
- Mutations usually introduce premature stop signals for transcription - X-linked mutation (so affects males only) |
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What is the best available treatment for Duchenne Muscular Dystrophy (DMD)?
|
- Prednisone, or gentamicin, which enable transcription read-through of stop codons
- Also new interventions are being studied including cellular therapy, gene therapy, orally administered drugs, and inhibition of myostatin |
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How would cellular therapy be targetted towards Duchenne Muscular Dystrophy (DMD)?
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Use myo-satellite or bone marrow-derived adult stem cells
|
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How would gene therapy be targetted towards Duchenne Muscular Dystrophy (DMD)?
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Via adenovector-mediated introduction of normal dystrophin genes into skeletal myocytes
|
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What orally-administered drug can be used to treat Duchenne Muscular Dystrophy (DMD)?
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PTC124 - circumvents unscheduled stop signals in mutated Dystrophin gene
|
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How are cardiac muscle and skeletal muscle similar?
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- Basal lamina
- Striated - Contractile proteins - Mechanism of contraction |
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How is cardiac muscle different from skeletal muscle?
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- Involuntary
- Smaller myocytes - Only 1-3 central nuclei - Myocytes branch - More vascular, more mitochondria, more myoglobin, and more lipid droplets - MB-Creatinine Kinase (MB-CK) - Intercalated discs (enables synchronous contraction) |
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What is the objective of the vascular system?
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To maintain quality and volume (10-15L in adults) of ECF
|
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How far can a cell be from a nurturing capillary?
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200 μm
|
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The vascular system is covered by what three 'tunics'?
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- Tunica adventitia
- Tunica media - Tunica intima |
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What kind of tissue makes up the tunica adventitia? What layer is this?
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Mostly Connective Tissue (CT) - outermost
|
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What kind of tissue makes up the tunica media? What layer is this?
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Smooth muscle cells (SMCs) and CT - middle layer
|
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What kind of tissues make up the tunica intima? What layer is this?
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Endothelium with basal lamina and CT - innermost layer
|
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What is the 'vasa vasorum'? Where is it located?
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- 'Vessels of the vessels' - the blood vessels have their own blood supply
- Found in tunica adventitia (outermost layer) |
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What is the 'nervi vascularis'? Where is it located?
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- Nerve supply of blood vessels
- Found in tunica adventitia (outermost layer) |
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Which layer of the three tunics of the vascular system is the most variable?
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Tunica media
|
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What kind of cells form the endothelium of the tunica intima (aka epithelium) of the vascular structures?
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Single flat (i.e., squamous) cells
|
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What connects the endothelial cells of blood vessels?
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Tight junctions
|
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What is the name of the three tunics when applied to the heart?
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- Epicardium (~ tunica adventitia = outer)
- Myocardium (~ tunica media = middle) - Endocardium (~ tunica intima = inner) |
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What kind of cells are found in the epicardium (~ tunica adventitia)?
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- Simple squamous mesothelium
- CT - Blood vessels and nerves (vasa vasorum and nervi vascularis) enter heart here |
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What kind of cells are found in the myocardium (~tunica media)?
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- Cardiac myocytes
- Cardiac fibroblasts |
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At what tunic do the coronary arteries and veins enter the heart?
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Myocardium (~tunica media)
|
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What kind of cells are found in the endocardium (~ tunica intima)?
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- Simple squamous endothelium with basal lamina
- Connective Tissue (CT) |
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Where are the cardiac conduction system (Purkinje fibers) located?
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'Sub'-endocardium
|
|
How do arteries compare to veins?
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- Arteries have relatively thick, highly developed wall, with small lumen
- Veins have a relatively thin, under-developed wall with a large lumen |
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Which tunic is highly developed in arteries? What is significant about this layer?
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Tunica media - with elastin and smooth muscle cells (SMCs)
|
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Which tunic is the most developed in veins? Which layer is almost non-existant?
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- Tunica adventitia - thickest covering (outer)
- Tunica media - relatively nondescript (middle) |
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What defines the tunica intima of large (elastic) arteries?
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- Tight junctions
- Pinocytotic vesicles that transport nutrients from lumen to tissue and endothelial cells that secrete Factor VIII, which functions in blood coagulation |
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What is the function of large elastic arteries?
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Maintain blood pressure during diastole
|
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In what layer of the vessel tunic does an aneurysm occur?
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Outpocketing of tunica media of large arteries
|
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What characterizes the medium (muscular) arteries?
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- Prominent external elastic lamina in tunic adventitia
- Prominent layer of ~40 smooth muscle cells (SMCs) in tunica media (less elastin) - Prominent elastic lamina in tunica intima |
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What is the function of the medium (muscular) arteries?
|
Maintain blood pressure via Smooth Muscle Cell (SMC) contraction in tunica media
|
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In what vessels do atherosclerotic plaques form?
|
Medium (muscular) arteries
|
|
What cells can form atherosclerotic plaques?
|
- Macrophages
- Smooth muscle cells (SMCs) |
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How do macrophages contribute to atherosclerotic plaque formation in medium arteries?
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Macrophages migrate to sites of endothelial wall damage (caused by hypertension, microbes, etc) where they ingest lipid (LDL and cholesterol)
|
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How do Smooth Muscle Cells (SMCs) contribute to atherosclerotic plaque formation in medium arteries?
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SMCs migrate to tunica intima where they proliferate and take-up LDL (bad cholesterol)
|
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What does the term 'foam cells' refer to?
|
The combination of lipid-laden macrophages and smooth muscle cells (SMCs) which form artery-blocking plaques
|
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Which type of venules have valves?
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Medium veins and small veins
|
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What are the valves in the medium and small veins made from?
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Folds of tunica intima
|
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What is 'phlebitis'?
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Inflammation of a vein, usually in the leg, which can be a prelude to thrombosis
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What are 'varicosities'?
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Stretching of veins (medium and small); exacerbated by a sedentary lifestyle
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How large is the diameter of the small arteries and arterioles? How does this compare to the size of an RBC?
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- 50 μm in diameter
- 6-7 RBCs can pass at once |
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How many layers of smooth muscle cells (SMCs) are found in small arteries and arterioles?
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- Small arteries = 8 layers
- Arterioles = 2 layers - Found in tunica media |
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What is a clinical problem associated with the small arteries and arterioles?
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- Narrowing of lumen due to uptake of lipid by SMCs in tunica media
- Leads to hypertension |
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What regulates the bloodflow to the vascular bed?
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Smooth muscle cells (SMCs) in the arteriolar wall
|
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How large is the diameter of the venules?
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~ 50 μm (same as the small artery diameter)
|
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How do leukocytes enter the tissue space?
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- Via diapedesis
- Enter into post-capillary venules |
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How large is the diameter of the capillaries?
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~10 μm (1/5 the size of the small arteries/arterioles/venules)
|
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What tunics are found in the capillary wall?
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Only a single layer of endothelium with basal lamina (no tunica adventitia or tunica media)
|
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The diameter of the capillary allows how many RBCs to pass?
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~10 μm allows 1 RBC to pass at a time
- 1 RBC = 7.5 μm |
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What is the size of a RBC (diameter)?
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~7.5 μm
|
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What are the three morphological types of capillaries?
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- Continuous capillaries (Type I)
- Fenestrated capillaries (Type II) - Sinusoidal (discontinuous) capillaries (Type III) |
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What kind of tissues contain continuous capillaries (Type I)?
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Heart, skeletal muscle, CNS, lung
|
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What kind of tissues contain fenestrated capillaries (Type II)?
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Endocrine organs, GI tract, kidney
|
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What kind of tissues contain sinusoidal (discontinuous) capillaries (Type III)?
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Bone marrow, liver, spleen
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What can continuous capillaries transport?
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O2
|
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What can fenestrated capillaries transport?
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Hormones, nutrients, ions
|
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What can sinusoidal (discontinuous) capillaries transport?
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Whole cells
|
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What characterizes the continuous capillaries (Type I)?
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- Endothelial cells with tight junctions
- Pinocytotic vesicles (except in CNS) transport stuff from blood vessel to adjacent connective tissue |
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What characterizes the fenestrated capillaries (Type II)?
|
- Fenestrations are ~100 nm
- Windows may represent permanent pinocytotic vesicles - Fenestrations admit passage of molecules >10 kDa |
|
What characterizes the sinusoidal (discontinuous) capillaries (Type III)?
|
- Large structures, including whole cells can pass between them
- Basal lamina is also discontinuous - ~30 μm diameter - Filter out whole RBCs |
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What is the function of the capillary endothelial cells? How do molecules pass across membrane?
|
- Exchange gases and nutrients
- Gases go directly through cell membrane - Nutrients pass via pincoytotic vesicles, fenestrations, and discontinuities - Small molecules (<10 kDa) pass between adjacent endothelial cells - Larger molecules (>10 kDa) transported directly through cell via pinocytosis or fenestrae |
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What are the vasoactive factors secreted by endothelial cells?
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- Endothelin - potent vasoconstrictor
- NO (nitric oxide) - vasorelaxant |
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What are the growth factors / cytokines secreted by endothelial cells?
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- Fibroblast Growth Factor (FGFs)
- Platelet-Derived Growth Factor (PDGF) - Interleukins |
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Lymphatics are found in all tissues except for what?
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- Bone marrow
- CNS |
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What is the function of lymphatics?
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- One-way drainage from extracellular space to venules/veins
- Very leaky vessels |
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Lymphatic fluid contains what components?
|
WBCs and lipid
|
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What is the difference between angiogenesis and vasculogenesis?
|
- Angiogenesis - regeneration of blood vessels in adults
- Vasculogenesis - generation of blood vessels in embryo |
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What are the various vascular endothelial cell membrane ligands/receptors involved in angiogenesis?
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- Vascular endothelium growth factor / receptor (VEGF/R)
- Fibroblast growth factor / receptor (FGF/R) - TIE-2 receptor for angiopoietin |
|
What are some inhibitors of blood vessel formation?
|
- Angiostatin (derivative of plasminogen)
- Endostatin (derivative of collagen isoform XVIII) |
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In what kind of diseases would pro-angiogenic therapy be beneficial?
|
- Ischemic heart disease
- Diabetes |
|
What hormones are used for pro-angiogenic therapy?
|
- VEGF (vascular endothelium growth factor)
- FGF (fibroblast growth factor) |
|
In what kind of diseases would anti-angiogenic therapy be beneficial?
|
Cancerous tumors - starve tumors to death by preventing formation of vascular supply
|
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What drug can be used to inhibit angiogenesis to a tumor? How results have been shown with this drug in mice with cancer?
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Endostatin --> decreases tumor volume in mice
|
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What is the purpose of the drug 'Avastin' aka Bevacizumab?
|
- Anti-angiogenic molecule
- Inhibits VEGF (vascular endothelium growth factor) - Used to treat colo-rectal, breast, and non-small cell lung tumors that have metastacized |
|
What other drug can be used in combination with Avastin?
|
- Thalidomide - synthetic anti-angiogenic
- Avastin - inhibits VEGF |
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Where are the nuclei of skeletal muscle fibers located?
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Peripherally
|
|
What are the pink, wispy material found in the endomysium of skeletal muscles?
|
Collagen fibers
|
|
What structures can be seen within the endomysium of skeletal muscles?
|
- Collagen fibers (light pink wispy material)
- RBCs in capillaries (refractile/shiny, eosinophilic) |
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Groups of myofibers (muscle cells) are called what? What surrounds them?
|
Fascicles - surrounded by perimysium
|
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What structures can be seen within the perimysium of skeletal muscles?
|
- Arterioles
- Venules - Nerves |
|
What shape are the myofibers (muscle cells)?
|
Cylindrical
|
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How many nuclei are associated with each skeletal muscle myofiber?
|
Many
|
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Do skeletal muscle myofibers normally branch?
|
No
|
|
Dark patches on the muscle fibers mark location of what?
|
Motor end plates
|
|
What is located at the motor end plate?
|
Region where a motor neuron contacts a skeletal muscle myofiber
|
|
A motor neuron releases what hormone at the motor end plate?
|
Acetylcholine (ACh)
|
|
What enzyme deactivates ACh?
|
Acetylcholinesterase
|
|
Where is acetylcholinesterase located?
|
In the synaptic cleft (at the motor end plate)
|
|
What happens to a muscle with disuse?
|
- Muscle atrophy
- Muscle fatigues more readily - Structurally weaker sarcomeres and myotendinous junctions - Microscopic tears occur when weight is put on the muscle - this further weakens the muscle |
|
What is located between the basal lamina and plasma membrane of muscle cells?
|
Satellite cells - distinct class of myogenic cells
|
|
What is the source of myoblasts?
|
Satellite cells
|
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What would the clinical significance of finding or engineering satellite cells for cardiac muscle?
|
Possibility of cardiac mucle regeneration
|
|
What is the function of the neuromuscular spindle?
|
Stretch receptor that regulates muscle tone
|
|
Which structure is surrounded by a capsule in the perimysium?
|
Neuromuscular spindle (inside capsule are intrafusal fibers)
|
|
What layer is found on the proximal 1/3 of the esophagus (outer-most layer)? What is found in this layer?
|
Muscularis externa - skeletal muscle
|
|
What is found in the distal 1/3 of the esophagus (inner-most layer)?
|
Smooth muscle
|
|
What is found in the middle 1/3 of the esophagus?
|
Combination of skeletal and smooth muscle
|
|
What is the shape of smooth muscle cells? How does this affect the diameter of the cells in cross-section?
|
Spindle-shaped (as opposed to cylindrical) --> this causes a variable diameter size
|
|
Do cross-sections of smooth muscle cells often show nuclei?
|
No, because of their spindle shape
|
|
How many nuclei are in a smooth muscle cell?
|
1
|
|
Where is the smooth muscle cell nucleus located?
|
Centrally
|
|
How can the ductus deferens be identified in a spermatic cord cross-section?
|
Lumen surrounded by a thick muscular wall; elongated nuclei in smooth muscle cells ('cigar-shaped')
|
|
How are smooth muscle cells arranged around the lumen of a blood vessel?
|
Circular (not longitudinal)
|
|
Why is it functionally advantageous for smooth muscle cells to be arranged circularly around the lumen of a blood vessel?
|
Enables regulation of blood vessel diameter thereby affecting blood pressure and flow
|
|
What mucle is located around the periphery of the spermatic cord?
|
Cremaster
|
|
Do cardiac muscle cells normally branch?
|
Yes
|
|
Where are cardiac muscle cell nuclei located?
|
Centrally
|
|
Why are the cross-sectional diameters of cardiac myofibers variable?
|
Branching of myofibers
|
|
What are the two components of the circulatory system?
|
- Cardiovascular system
- Lymphatic system |
|
What are the functions of the cardiovascular system?
|
- Transportation of O2, nutrients, waste products, body fluid, solutes, and immune system components
- Facilitates body heat homeostasis |
|
What separates the tunica intima from the tunica media?
|
Internal elastic lamina
|
|
What kind of vessels have external elastic lamina? What is it between?
|
Large arteries - found between tunica media and tunica adventitia
|
|
What are the three elastic laminae levels?
|
- Internal elastic lamina (between tunica intima and tunica media)
- Fenestrated elastic laminae (within tunica media) - External elastic lamina (between tunica media and tunica adventitia) |
|
What does 'fenestra' mean?
|
Windows
|
|
What do the fenestrated elastic laminae in the tunica media look like on a slide?
|
Dark pink wavy lines
|
|
What is the function of the fenestrated elastic laminae?
|
Maintain constant arterial pressure by stretching during ventricular contraction (systole) and recoiling during ventricular relaxation (diastole)
|
|
The nuclei within the tunica media of elastic arteries belong to what cell type?
|
Smooth muscle cells
|
|
What can be said about the tunica adventitia in elastic arteries?
|
Unremarkable
|
|
How do the fenestrated elastic laminae compare in the elastic arteries vs muscular arteries?
|
Less prominent in the muscular arteries
|
|
What is the function of the vasa vasorum? Where is it located?
|
- Provide nutrients to smooth muscle of artery
- Found in tunica adventitia |
|
What procedure can enlarge the coronary artery lumen?
|
Angioplasty
|
|
What can prevent restenosis after an angioplasty?
|
Endothelialization - promoted by local administration of endothelial cell growth factor (e.g. VEGF) or estrogen-loaded stents (which promote healing and reduce SMC migration and proliferation as well as attract circulating endothelial cells)
|
|
What kind of cells line the uterine tube?
|
Simple columnar epithelium
|
|
What characterizes an arteriole?
|
- External diameter <100 μm (~15 RBC)
- Wall thickness approximately equals lumen diameter - Little or no subendothlial connective tissue - 2-5 SMC layers in tunica media - No external elastic lamina - Very thin tunica adventitia |
|
What regulates blood flow from arterioles to capillaries?
|
Metarterioles with precapillary sphincters
|
|
What is the lumen diameter of the capillaries?
|
~ 7 μm (~1 RBC)
|
|
What forms the wall of the capillary?
|
Single endothelial cell
|
|
What tool is needed to distinguish between capillary type?
|
Electron Microscopy (EM)
|
|
How do tumor cells signal the need for angiogenesis?
|
- Secrete vascular permeability factor (VPF) aka vascular endothelial growth factor (VEGF)
- VEGF binds endothelial cells of nearby blood vessels and induces a microvascular hyperpermeability - Leakiness leads to extravasation of plasma proteins and stromal changes which promote angiogenesis |
|
What happens in the in situ hybridization technique?
|
- Radioactive nucleotide used to synthesize a nucleic acid 'probe' that contains a sequence complementary to the mRNA of interest
- Probe is applied to a tissue section that is mounted on a microscope slide - Probe hybridizes with mRNA of interest in tissue - Site of probe and the mRNA is detected by autoradiography |
|
What is the purpose of the in situ hybridization technique?
|
To localize specific mRNAs within cells
|
|
How is epithelial tissue (ET) distinguished from connective tissue (CT)?
|
- ET is entirely cellular with the only CT being from the basement membrane
- CT has very few cells with abundant extracellular matrix (ECM) |
|
What are the functions of the epithelial tissue?
|
- Protection
- Diffusion - Absorption - Secretion - Excretion - Sensation |
|
What does epithelial tissue (ET) protect the body from? What kind of ET's main function is protection?
|
- Mechanical injury
- Chemical injury - Pathogenic invasion - Water loss - E.g., epidermal layers of skin |
|
What does epithelial tissue (ET) promote diffusion of? What kind of ET's main function is diffusion?
|
- Gases
- Liquids - Nutrients - E.g., lung epithelium |
|
How does epithelial tissue (ET) function in absorption? What is an example of this?
|
- Uptake of materials from a lumen
- E.g., digestive tract |
|
What kind of substances do epithelial tissues (ET) secrete? What kind of ET secretes?
|
- Mucus
- Hormones - Enzymes - E.g., glands (pancreas) |
|
What kind of epithelial tissues excrete waste products from the body?
|
Renal epithelium
|
|
What are some examples of epithelial tissue that detect sensory stimuli?
|
- Inner ear cells
- Eye (retina) cells |
|
What are the three characteristics of epithelial tissues (ET)?
|
- Polarized (basal vs apical vs lateral surfaces)
- Avascular (no direct blood supply; receives nutrients by diffusion) - Basement membrane (ECM that basal layer lies upon) |
|
What are the three surfaces of an epithelial cell?
|
- Apical (towards lumen)
- Basal (against basement membrane) - Lateral (sides) |
|
How do epithelial cells receive nutrients/hormones/etc. and remove waste products?
|
In and out of cell via diffusion; there is no blood supply directly to cells ('avascular')
|
|
What are the ways in which epithelial cells can be organized?
|
- Number of cellular layers (simple/stratified/pseudostratified)
- Shape of cells (squamous/cuboid/columnar) - Presence of cell-surface modifications |
|
What is the difference between simple, stratified, transitional, and pseudostratified epithelia?
|
- Simple = single layer of cells
- Stratified = 2+ layers of cells (only basal cell layer contacts basement membrane) - Transitional = stratified but number of apparent layers differs when it is relaxed vs stretched - Pseudostratified = appears to have more than one layer but really all cells contact basement membrane making it really a 'simple' epithelia |
|
What kind of epithelium is found in the urinary tract? Why does this make sense?
|
- Transitional epithelium
- When bladder is full, epithelium stretches causing appearance of fewer layers than when relaxed |
|
Where is a location where pseudostratified epithelium is found?
|
Respiratory epithelium
|
|
What is a quick way to distinguish between pseudostratified and a truly stratified epithelium?
|
Stratified epithelium are NEVER ciliated; so if you see cilia it is pseudostratified
|
|
What does a squamous cell look like? What function does this serve?
|
Flat (Scale-like) - ideally suited for diffusion (simple squamous)
|
|
What does a cuboid cell look like? What function do they typically serve?
|
Cube-shaped (intermediate between squamous and columnar); small ducts and tubules (simple cuboidal)
|
|
What does a columnar cell look like? What function does it commonly serve?
|
Rectangular in shape - ideally suited for high metabolic function; also for absorptive tissues and secretory tissues
|
|
What are the types of epithelium?
|
- Simple squamous
- Simple cuboidal - Simple columnar - Stratified squamous - Stratified cuboidal (NO stratified columnar!) - Pseudostratified columnar - Transitional |
|
What are examples of cell surface specializations for epithelial cells?
|
- Keratinized epithelium
- Glycocalyx |
|
What happens to epithelial cells that are keratinized?
|
- Outermost surface of stratified epithelium becomes covered by intermediate filament protein keratin
- During maturation, cells accumulate protein keratin and lose their nuclei - Keratin protein is wrapped in residual plasma membrane - Keratinization provides a tough, water-resistant, non-living surface to protect from abrasion and dehydration |
|
What is the function of keratinization of epithelium?
|
- Provide a tough, water-resistant, non-living surface on outside
- Protects from abrasion and dehydration |
|
What is another name for a keratinized epithelium?
|
'Cornified epithelium' = (epithelium of skin)
|
|
What kind of cells typically become keratinized?
|
Stratified epithelium; skin cells
|
|
What happens to epithelial cells that have the glycocalyx modification?
|
- Carbohydrate-rich complex formed on extracellular surface
- Functions in cellular protection and recognition |
|
What is an example of a type of epithelium that has the glycocalyx modification?
|
Intestinal epithelium
|
|
Where are cilia commonly found?
|
- Respiratory tract
- Oviduct - Single, highly elaborated cilium (aka flagellum) used by sperm - Cells that have a need to propel material through a tube |
|
What are the mechanical-structural components of cilia?
|
- Basal body / centriole anchors cilia at surface (contains 9 triplets of microtubules)
- 9 doublets of peripheral microtubules with dynein (ATPase motor) arms + 2 central microtubules project outward forming the fingerlike extension - 9+2 arrangement = axoneme |
|
What is the function of microvilli? Where are they commonly found?
|
Increase surface area for absorption (commonly found in intestinal tract and proximal renal tubule)
|
|
What are the mechanical-structural components of microvilli?
|
- Each microvillus contains actin microfilaments cross-linked by villin
- Actin and villin connect to a 'terminal web' consisting of actin and spectrin molecules and intermediate filaments - Actin bundles attach to lateral plasma membrane via myosin and calmodulin |
|
What is another name for microvilli when they are on the apical surface?
|
Brush border
|
|
What are some lateral cell membrane specializations?
|
- Zonula occludens (aka tight junctions or occluding junctions)
- Zonula adherens (aka adherens junctions) - Macula adherens (aka desmosome) - Gap junctions |
|
What are examples of apical cell membrane specializations?
|
- Cilia
- Microvilli |
|
What kind of microscope must be used to detect cilia?
|
Light microscope
|
|
What kind of microscope must be used to detect microvilli?
|
Electron microscope
|
|
What are some of the general functions of lateral cell membrane specializations?
|
- Coherence
- Communication - Distribute stress |
|
What kind of microscope must be used to detect lateral cell membrane specializations?
|
Electron microscope
|
|
Where are zonula occludens (or tight junctions) located?
|
- Lateral cell membrane near apical cell surface
- Completely surrounds cell |
|
What can pass through a zonula occludens (tight junction)?
|
- Water
- Small solutes |
|
What special purpose do zonula occludens (tight junctions) provide?
|
Coerce transcellular transport across polarized cells instead of paracellularly
|
|
What feature can be viewed on an EM to classify a zonula occludens (tight junction)?
|
Pentalaminar (five-layered) appearance = dark-light-dark-light-dark
|
|
What causes the pentalaminar appearance of the zonula occludens (tight junction)?
|
Fusion of outer members of lipid bilayers of two adjacent cells
|
|
What proteins are involved in zonula occludens (tight junction)?
|
- Occludin
- Claudin - Junctional adhesion molecule (JAM) |
|
What do the tight junction proteins (occludin, claudin, and JAM) interact with in the sub-plasmalemmal plaque?
|
Interact with actin cytoskeleton via Zonula Occludens proteins (ZOs)
|
|
Where are the zonula adherens (adherens junction) modifications located?
|
- Lateral cell surface just beneath the Zonula Occludens (which is found closest to apical surface)
- Completely surround cell like a belt |
|
What are the three components of the zonula adherens (or adherens junctions)?
|
- Cadherin - transmembrane linker proteins
- Sub-plasmalemmal plaque proteins (catenins, α-actinin, vinculin, and others) - Actin microfilaments - cytoskeletal filaments |
|
What is cadherin? What is it a part of?
|
- Ca2+ dependent protein in the CAM (Cell Adhesion Molecule) family
- Important for transmembrane linkage for zonula adherens (adherens junctions) |
|
What proteins are found in the sub-plasmalemmal plaques of zonula adherens?
|
- Catenins
- α-actinin - Vinculin |
|
What are the prominent members of the cadherin family found in adherens junctions? Where are they commonly found?
|
- E-cadherin - many epithelia
- N-cadherin - neurons, heart, skeletal muscle, lens, and fibroblasts - P-cadherin - placenta, epidermis, breast epithelium - VE-cadherin - endothelial cells |
|
Where is the macula adherens (aka desmosome) located?
|
Lateral surface of epithelial cells; do not encircle cell like a belt, rather aka 'spot welds'; common in epidermis
|
|
What are the components of the macula adherens (desmosomes)?
|
- Transmembrane linker protein: non-classical cadherin (aka desmogleins and desmocollins)
- Sub-plasmalemmal plaque proteins: desmoplakin, plakoglobin, and plakophilin - Cytoskeletal filaments: keratin (intermediate filament) |
|
What are the functions of macula adherens (desmosomes)?
|
Provide mechanical strength (hence why they are common in the epidermis)
|
|
What do macula adherens (desmosomes) look like on an EM?
|
Train tracks
|
|
What is the function of gap junctions?
|
To provide electrical and metabolic communication channels on lateral membrane of epithlial cells
|
|
What is the structure of a gap junction?
|
- 2 Connexons join two adjacent cells
- Each connexon is made of 6 subunits called connexins - Total of 12 Connexins - Channel is ~1.5 nm |
|
What is the size of the gap junction? What size molecules can fit through this?
|
~1.5 nm
Small molecules <1500 Daltons can fit through (Ions, sugars, AAs, nucleotides, vitamins, cAMP, IP3) NOT: proteins, nucleic acids, polysaccharides, etc. |
|
What are some basal membrane specializations of epithelial cells?
|
- Hemidesmosomes
- Adhesion plaques |
|
In general, what is the function of basal membrane specializations of epithelial cells?
|
Mechanical attachment to ECM of basement membrane - anchoring junctions
|
|
What is the structure of hemidesmosomes?
|
Transmembrane linker proteins: integrins - attach to major ECM components (laminin, collagen, and fibronectin)
|
|
What do hemidesmosomes attach to?
|
Major ECM components: laminin, collagen, fibronectin) rather than to the cell
|
|
What do adhesion plaques attach to?
|
ECM components via integrins rather than directly to the cell
|
|
What are adhesion plaques similar to? How?
|
Zonula adherens (type of lateral epithelial cell modification) because the plaque contains α-actinin and vinculin which attach to the actin microfilaments
|
|
What kind of junctions utilize actin microfilaments?
|
- Zonula occludens
- Zonula adherens - Adhesion plaques |
|
What kind of junctions utilize intermediate filaments?
|
- Macula adherens (desmosomes)
- Hemidesmosomes |
|
What kind of junctions utilize integrin as their transmembrane linker protein?
|
- Hemidesmosomes
- Adhesion plaques (Both basal membrane specializations) |
|
What are the junction(s) that function for occlusion?
|
Zonula occludens
|
|
What are the junction(s) that function for anchoring?
|
- Zonula adherens
- Macula adherens (desmosomes) - Hemidesmosomes - Adhesion plaques |
|
What are the junction(s) that function for communication?
|
Gap junctions
|
|
What is a junctional complex?
|
Group of cell membrane specializations along the lateral surface of epithelial cells including the zonula occludens, zonula adherens, and macula adherens
|
|
Can epithelial cells replace themselves?
|
Yes; turnover rate depends upon location and function (although some do not renew at all)
- Ex: skin - 28 days; small intestine - 5 days |
|
What is metaplasia?
|
Changes in epithelial cells to a biochemically different type
|
|
What are carcinomas?
|
Malignant tumors of epithelial cells
|
|
What are adenocarcinomas?
|
Malignant tumors of epithelial glandular cells
|
|
How common are carcinomas and adenocarcinomas relative to all cancers?
|
Comprise 85% of all cancers
|
|
What is the explanation for why carcinomas and adenocarcinomas are so common among cancers?
|
- Mitotic activity of epithelial cells
- And/or the position of epithelial cells as barriers to an environment from which they receive insults |
|
What is important for preventing the metastatic spread of carcinomas and adenocarcinomas?
|
Mechanisms that prevent loss of epithelial adhesiveness
|
|
What can be done to detect the type of intermediate filament proteins present in tumor cells? Why would this be important?
|
- Immunohistochemical staining
- Determine origin of tumor so that you can use appropriate anti-tumor therapies |
|
What are some markers of different cell types that make them identifiable by immunohistochemical staining?
|
- Keratin - epithelial tumors
- Glial fibrillary acidic protein - glia tumors - Desmin - muscle tumors - Vimentin - connective tissue tumors |
|
What are the functions of connective tissue?
|
- Mechanical support / structure
- Exchange of metabolites - Storage of energy reserves - Protection from infection - Repair following injury |
|
What are the components of connective tissue?
|
- Fixed cells
- Free (or wandering) cells - Extracellular matrix (ECM) |
|
How do fixed cells and free cells differ in connective tissue?
|
- Fixed cells - stable, long-lived (wks-months), develop from mesenchyme
- Free cells - changing, short-lived (days), enter CT from blood vessels |
|
What is a unique capability of fixed cells of connective tissue? What does this mean?
|
Regenerate in mature tissue - indicates population of stem cells persist
|
|
What are the two types of fixed cells in connective tissue?
|
- Fibroblasts - form ECM
- Adipocytes - store lipids |
|
What is the general function of free (wandering) cells of connective tissue?
|
Specific defense cells (WBCs)
|
|
What are the types of free (wandering) cells of connective tissue?
|
WBC:
- Eosinophils - Macrophages - Lymphocytes - Plasma cells - Mast cells - Neutrophils |
|
What does extracellular matrix consist of?
|
- Fibers and fluid matrix (ground substance)
- Determines physical properties of each type of supporting tissue |
|
How does connective tissue function in mechanical support?
|
- Bundles cells of the same tissue type together
- Anchors tissues to each other to form organs - Binds organs together |
|
How does connective tissue function in the exchange of metabolites between blood and tissues?
|
Ground substance of ECM provides hydrated medium for diffusion of metabolites
|
|
How does connective tissue function in the storage of energy reserves?
|
- Storage of lipids in fat cells
- Storage of proteins (albumin, immunoglobulin) in the ECM and the blood |
|
How does connective tissue function in protection against infection?
|
- Phagocytosis by macrophages, neutrophils and eosinophils
- Mast cell degranulation during inflammation |
|
How does connective tissue function in repair following injury?
|
Fibroblasts proliferate and secrete during wound healing
|
|
What is the non-cellular component of connective tissue?
|
Extracellular matrix (ECM)
|
|
What is the extracellular matrix (ECM)?
|
- Non-cellular component of connective tissue
- Non-living macromolecules that are manufactured by the cells that make up the tissue - Exported by them into the extracellular space |
|
What is the function of the extracellular matrix (ECM)?
|
- Structural stability
- Determine properties of tissues |
|
How does the matrix:cell ratio differ for various tissues?
|
- High (lots of matrix, not a lot of cells) in connective tissue
- Low (lots of cells, not a lot of matrix) in nervous tissue |
|
What happens to extracellular matrix (ECM) in bones?
|
Becomes calcified to form rock-hard substances
|
|
What are some variations in extracellular matrix that are suited for the needs of the tissue?
|
- Calcified to become rock-hard for bone and teeth
- Transparent for cornea - Rope-like organization to give tendons tensile strength |
|
What is the function of the ground substance in the extracellular matrix (ECM)? of the fibers?
|
- Ground substance resists forces of compression
- Fibers withstand tensile forces |
|
What is the ground substance of ECM composed of?
|
- Glycosaminoglycans (GAGs) - unbranched polysaccharide chains consisting of repeating disaccharide units
- Proteoglycans - core protein linked to GAGs |
|
What are the fibrous components of ECM?
|
- Collagen - triple helix of α chains
- Cross-linked Elastin - coated with fibrillin - capable of stretch and recoil |
|
What binds the extracellular matrix (ECM) to the cell?
|
Adhesive glycoproteins such as laminin and fibronectin by binding to integrins located in cell membrane
|
|
What is found at the interface between epithelium and connective tissue?
|
Felt-like cell rug called the basal lamina
|
|
What is the purpose of the basal lamina?
|
- Provides stability
- Interfaces with the ECM - Important in controlling cell behavior |
|
What is the 'beginning' of the ECM?
|
Basal lamina
|
|
What are the two repeating sugars in Glycosaminoglycans (GAGs)?
|
- One is always an amino sugar (N-acetylglucosamine or N-acetylgalactosamine)
- Other is typically a uronic acid (glucuronic or iduronic) |
|
What charge are glycosaminoglycans (GAGs)? What makes them that way?
|
- Highly negatively charged
- Amino sugar is usually sulfated - Carboxyl groups projecting from them |
|
What is the impact of glycosaminoglycans (GAGs) being negatively charged?
|
- Negative charges bind Na+
- Osmotically attracts water into matrix - Matrix swells and occupies a lot of space/mass - Resulting porous, hydrated, gel serves as a cushion to absorb and disperse compressive loads |
|
What are the four main types of glycosaminoglycans (GAGs)?
|
1. Hyaluronate (not sulfated)
2. Chondroitin sulfate and dermatan sulfate 3. Heparan sulfate and heparin 4. Keratan sulfate |
|
What is the predominant glycosaminoglycan (GAG) in loose supporting tissues?
|
Hyaluronate (hyaluronic acid, hyaluronan)
|
|
What is the structure of the glycosaminoglycan (GAG) hyaluronate?
|
- Non-sulfated
- Single disaccharide unit - Long chains, >300 units up to 25,000 units - Does not form covalent links to protein molecules |
|
What are proteoglycans formed from?
|
- Sulfated glycosaminoglycan (GAG) chains (other than hyaluronate) form covalent links with a protein core
- GAGs are attached to protein core in golgi |
|
What kind of proteoglycans are found in cartilage and connective tissue?
|
- Large multimeric complexes
- Aggregan proteoglycans are bound by 'link proteins' to a hyaluronate backbone |
|
What are the functions of proteoglycans?
|
- Form molecular filters of variable pore size and charge density (screen and retard macromolecules)
- Contain binding sites for secreted growth factors (FGF and TGFα), proteases, and protease inhibitors (can impede function by preventing molecules from reaching destination or enhance function by concentrating them in specific location) |
|
What is an example of proteoglycan function in filtering?
|
In kidney, heparan sulfate proteoglycan in glomerular basal lamina
|
|
What is an example of a proteoglycan that remains attached to the cell membrane?
|
Syndecan - core proteins act as transmembrane proteins and are attached to actin filaments of cytoskeleton and to collagen and fibronectin in ECM
|
|
What is the function of syndecans (proteoglycan that is attached to the cell membrane) in fibroblasts?
|
In fibroblasts, they bind FGF and present it to cell membrane FGF receptors in their vicinity
|
|
What protein constitutes the largest percentage of protein mass in mammals? What percentage?
|
Collagen (25%)
|
|
What synthesizes and secretes collagen?
|
Connective tissue fibroblasts
|
|
What is the structure of collagen?
|
- Triple helix of three α chains
- α chain sequence is usually a repeat of Gly-X-Y, where X and Y can be any AA (proline is most common X and hydroxyprolineis most common Y) - Polymerizes to form collagen fibrils typical of Types I, II, III, and IV - Covalent bonds formed between lysine and hydroxylysine - Further aggregated into collagen fibers |
|
Collagen is secreted into ECM as what?
|
Tropcollagen
|
|
Why is vitamin C important for formation of collagen?
|
- Vit. C is required for hydroxylation of proline residues
- Without it get scurvy - α chains are unable to form stable helices and tropocollagen fibers incapable of aggregating into fibrils |
|
What are the symptoms of scurvy? (Vit. C deficiency)
|
- Collagen not made properly
- Fragile blood vessels - Poor wound healing - Teeth loosen in sockets |
|
What happens if there is excessive accumulation of collagen during wound healing?
|
Elevated scar - aka keloid
|
|
What is osteogenesis imperfecta?
|
- Defect in type I collagen (fibril-forming)
- Leads to easily fractured bones |
|
What is chondrodysplasia?
|
- Defect in type II collagen (fibril-forming)
- Results in cartilage joint deformities (and Dwarfism) |
|
What is Ehlers-Danlos syndrome?
|
- Defect in type III collagen (fibril-forming)
- Characterized by weak skin, fragile blood vessels, and hypermobile joints - Wide-gaping wounds |
|
Where are elastic fibers found?
|
ECM of skin, lung, and blood vessels
|
|
What are elastic fibers composed of?
|
- Elastin - rich in glycine, lysine, and proline; covalently linked by lysine residues
- Fibrillin - elastic glycoprotein |
|
How are elastic fibers synthesized?
|
Elastin synthesized by fibroblasts, assembled in ECM into elastic fibers consisting of an elastin core and surrounded by sheath of microfibrils composed of fibrillin
|
|
What is Marfan syndrome?
|
Mutations in fibrillin gene; patients may have ruptured aneurysms of root of aorta
- Fibrillin is important for elastic fibers in connective tissue |
|
How is the basal lamina linked to a cell?
|
- Fibronectin and laminin are adhesive proteins that link basal lamina to integrins
- Integrins are linked intracellularly to cytoskeleton |
|
What are integrins important for?
|
- Transmembrane proteins similar to cell receptors
- Linked to actin filaments by carboxyl ends in cytoskeleton and ECM proteins by amino ends - Important for linking the basal lamina to the cells |
|
What is the structure of integrins?
|
- Heterodimers composed of α and β subunits
- Carboxyl ends of α/β chains link to actin filaments (cytoskeleton) - Amino ends bind proteins in ECM - Different isoforms determine specificity |
|
How can the attachment of cells to matrix components be modulated?
|
Down-regulation of the number of integrin molecules on the cell surface
|
|
What is the structure of laminin?
|
- Large glycoprotein (950,000 daltons)
- Three large polypeptide chains (α, β1, and β2) - β chains wrap around the α chain, forming a cross like pattern of one long and three short chains - Held together by disulfide bonds |
|
Where are laminins found?
|
Basal lamina - forms links between cell membranes and other constituents of basal lamina
|
|
What is the structure of fibronectin?
|
- Large glycoprotein heterodimer
- Disulfide-linked - Contains collagen, heparin, and cell (integrin) binding domains separated by flexible hinge peptides |
|
What is fibronectin's role in binding the basal lamina to the cell?
|
- Contains cell binding site (for integrin) is an RGD (Arg-Gly-Asp) tripeptide sequence
- Fibronectin receptors on integrin within cell membrane bind to actin filaments within cytoskeleton and to fibronectin in ECM - Fibronectin binds collagen and heparin sulfate in ECM to establish continuity |
|
What is the basal lamina?
|
- AKA basement membrane
- Sheet-like network of ECM proteins which acts as an interface between epithelia and connective tissue - Composed of Type IV collagen, proteoglycan perlecan heparan sulfate, and adhesive glycoproteins laminin and entactin |
|
What are the functions of the basal lamina?
|
- Molecular filter
- Selective barrier to cells - Scaffolding for regeneration |
|
What about the structure of the basal lamina makes it a good molecular filter?
|
- Anionic charge of heparan sulfate proteoglycan glycosaminoglycan (GAG) chains
- Regulates movement based on charge (negatively charged molecules are repelled) |
|
What kind of cells does the basal lamina form a barrier to?
|
Fibroblasts and endothelial cells - normally do not penetrate basal membrane and migrate among the skin epithelial cells
|
|
How does the basal lamina influence regeneration of cells?
|
Skeletal muscle fiber regeneration is orchestrated by myoblasts migrating along the inside of the basement membrane
|
|
How is the extracellular matrix (ECM) degraded?
|
- By extracellular proteases (matrix metaloproteinases and serine proteases)
- Degrade collagen, laminin, and fibronectin |
|
What is able to penetrate the basal lamina when it is being degraded?
|
Macrophages, lymphocytes, and nerve fibers
|
|
How does proteolysis of matrix proteins contribute to cell migration?
|
- Clears a path through matrix
- Exposes cryptic sites on cleaved proteins for cell binding and/or migration - Promotes cell detachment so cell can move - Releases extracellular signal proteins to stimulate migration |
|
How is matrix degradation regulated?
|
- Peptide tissue inhibitors of metalloproteaes (TIMPs)
- Serine protease inhibitors (serpins) - Diffusion of these peptides and others in ECM is limited by binding to proteoglycans - Secreted by cells in margins of areas of active protein degradation to protect uninvolved matrix - Also protect cell-surface proteins required for cell adhesion and migration |
|
How does WBC movement relate to basal lamina?
|
- WBC migrate across basal lamina of a blood vessel into a tissue
- In response to infection or injury |
|
How does metastasis of malignant melanoma skin epithelial cells relate to the basal lamina?
|
- Usually skin epithelial cells remain attached to basal lamina (except during cell division)
- Proteolytic breaking through basal lamina allows metastases of cancer cells into blood stream |
|
How does angiogenesis relate to the basal lamina?
|
- During angiogenesis, sprouting endothelial cells penetrate ECM by secreting hyaluronidase and plasminogen activator
- These enzymes break down basal lamina allowing new blood vessels to penetrate matrix |
|
What are the cellular components of connective tissue?
|
- Fibroblasts (myofibroblasts)
- Adipose cells - Leukocytes (monocytes, neutrophils, eosinophils, lymphocytes, mast cells) |
|
What is the most abundant and widely distributed cell in connective tissue?
|
Fibroblasts
|
|
What is the function of fibroblasts?
|
Synthesis of almost all of ECM of connective tissue
|
|
Where are fibroblasts located?
|
- Close association with collagen fibers
- Lie parallel to axis of collagen fibers |
|
What is the structure of fibroblasts?
|
- Large ovoid fibroblast nucleus
- Contains patches of marginal heterochromatin and 1 or 2 well defined nucleoli - Prominent golgi apparatus - Slender mitochondria - Abundant rough ER - for manufacture and secretion of collagens and ground substance (especially during wound healing) - No basal lamina |
|
How do you know that fibroblasts are active in synthesis of protein (collagen and ground substance)?
|
Lots of rough ER
|
|
What are myofibroblasts?
|
- Modified fibroblasts
- Characteristics of both fibroblasts and smooth muscle cells - Result from transdifferentiation of fibroblasts and SMCs |
|
How are myofibroblasts similar to fibroblasts?
|
- Little or no basal lamina
- Abundant in areas of wound healing (for synthesis of collagen and ground substance) |
|
How are myofibroblasts similar to smooth muscle cells?
|
- Contain bundles of actin filaments and dense bodies
- Allows for contraction of and shrinkage of scar tissue |
|
Besides from areas surrounding wound healing, where are myofibroblasts found?
|
Periodontal ligament - assist in tooth eruption
|
|
Lipids found in adipose cells are derived from what sources?
|
- Dietary fat circulating in bloodstream as chylomicrons
- TGs synthesized in liver and transported in blood - TGs synthesized from glucose within adipose cells themselves |
|
What kind of receptors do adipose cells have? Why are these important?
|
- Insulin, glucocorticoids, growth hormone, and NE receptors
- Modulate uptake and release of fat |
|
What hormone is released by adipocytes? What does it do?
|
Leptin - involved in regulation of appetite
|
|
What influences fat metabolism?
|
- Dietary uptake
- Energy expenditure - Insulin (increases conversion of glucose to TG) - NE (stimulates lipase activity) |
|
What are the two main types of adipose tissue?
|
- White adipose tissue
- Brown adipose tissue |
|
What percentage of a normal male and female is from white adipose tissue?
|
- Males: 20%
- Females: 25% |
|
What is the structure of a white adipose cell?
|
- Single, large lipid droplet (unilocular)
- Thin rim of cytoplasm - Thin basal membrane - Heavily supplied with blood vessels (type III collagen) |
|
What is the structure of a brown adipose cell?
|
- Multiple, small lipid droplets (multilocular)
- Abundant capillaries and mitochondria |
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What are the two types of obesity?
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- Hypertrophic obesity - accumulation and storage of fat in white adipose cells (increase in size by as much as 4x)
- Hypercellular obesity - more severe, overabundance of adipocytes |
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What regulates adipose mass?
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Leptin - hormone secreted by adipocytes that is involved in regulation of appetite
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How does leptin function?
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- Leptin secreted by adipocytes
- Binds to leptin receptors in appetite center of hypothalamus - Activates SNS to release NE - NE shifts adipose tissue from storage to mobilization and oxidation |
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What happens to someone who does not produce enough leptin or an inactive form of leptin?
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- Voracious appetite
- Uncontrollable weight gain |
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Where do monocytes come from and what do they mature to form?
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- Enter the connective tissue from the blood
- Mature into free (mobile) or fixed resident macrophages |
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How long do macrophages live for?
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2 months
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What are the two types of macrophages?
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- Phagocytes
- Antigen presenting cells |
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What are the more location specific names for macrophages?
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- Histiocytes in CT, lymphoid organs, and bone marrow
- Alveolar phagocytes in lungs - Kupffer cells in liver - Microglia in CNS - Osteoclasts in bone |
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What are the functions of macrophages?
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- Phagocytosis and degradation of dead cells and cellular debris
- First-line cellular defense against bacteria - Process and present antigens to lymphocytes for antibody generation |
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What are the structural characteristics of macrophages?
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- Kidney-shaped indented nucleus
- Abundant lysosomes (cytoplasm contains primary and actively digesting secondary lysosomes) - Large juxtanuclear golgi - Cell surface receptors for Fc portions of antibodies - Complement peptides (bind immunoglobulins to bacteria) |
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What is the purpose of complement peptides?
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- Bind immunoglobulins to surface of bacteria
- Makes bacteria susceptible to phagocytosis (aka opsinization) |
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What is opsinization?
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Phagocytosis of bacteria
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When/where are neutrophils located?
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- Rare in normal CT
- Attracted to injured tissue |
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What attracts neutrophils?
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Injured tissues:
- Cleavage products of complement - Cytokines - Bacterial lipopolysaccharide liberated during the inflammation process |
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What is the function of neutrophils?
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- Phagocytosis and digestion of bacteria in areas of acute inflammation
- Form pus |
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What are the structural characteristics of neutrophils?
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- Multilobulated nucleus
- Non-specific cytoplasmic granules (primary lysosomes) |
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What attracts eosinophils?
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- Areas of inflammation by leukocyte chemotactic factors
- Sites of allergic inflammation |
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What is the function of eosinophils?
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- Attack parasitic organisms by releasing cytotoxins to degrade membranes
- Phagocytose antibody-antigen complexes and degrade histamines to moderate the allergic reaction |
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What are the structural characteristics of eosinophils?
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- Multilobulated nucleus
- Cell type-defining eosinophilic specific granules |
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Where are eosinophils in high numbers?
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Regions associated with allergic reactions (nasal mucosa, lung, skin, and lamina propria of gut)
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What are the structural characteristics of lymphocytes?
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- Small dark cells
- Contain a dark round nucleus - Thin rim of cytoplasm |
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What are the principal cells of the immune system?
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Lymphocytes
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Where are lymphocytes in high numbers?
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- Lymphoid tissue
- Lamina propria of gut - Sites of chronic inflammation |
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What are plasma cells derived from?
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B Lymphocytes that have interacted with antigen and secrete antibodies
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What are the structural characteristics of plasma cells?
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- Large cells
- Round nucleus - 'Clock face' pattern of heterochromatin - Extensive basophilic cytoplasm of RER |
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Where do mast cells come from? How long do they live?
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- Bone marrow
- Weeks to months |
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What are the functions of mast cells?
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Involved in mediating inflammatory process and immediate hypersensitivity reactions
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What are the structural characteristics of mast cells?
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- Large cells
- Basophilic granules (contain heparin, histamine, neutral proteases, neutrophil and eosinophil chemotactic factors, and leukotrienes) - Small round nucleus - Surface receptors for immunoglobulins |
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Where are mast cells prevalent?
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Connective tissue surrounding small blood vessels
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What chain of events occurs when IgE molecules bind to the Fc receptors on mast cells?
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- IgE molecules bind and are cross-linked by antigen to activate degranulation
- Histamine release increases capillary and postcapillary venule permeability - Mucosal edema results |
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What happens to patients with hay fever?
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- Suffer from effects of histamine released by mast cells of nasal mucosa
- Causes localized edema from increased permeability of small blood vessels - Leads to feeling 'stuffed up' and hinders breathing |
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What happens to patients with asthma?
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- Release of leukotrienes from mast cells in lungs
- Initiates bronchial smooth muscle contractions - Causes difficulty breathing |
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What are the types of connective tissue?
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- Mesenchymal CT
- Loose (areolar) CT - Dense CT (Regular and Irregular) - Reticular CT |
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Where is mesenchymal CT present?
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Only in the embryo
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Which type of connective tissue is also known as embryonic CT?
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Mesenchymal CT
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What are the structural characteristics of mesenchymal CT?
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- Mesenchymal cells
- Gel-like ground substance - Reticular fibers - Hyaluronic acid and some fibrillar collagens |
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What does mesenchymal CT give rise to?
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Loose connective tissue
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What are the structural characteristics of loose (areolar) connective tissue?
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- Loose arrangement of fibers and dispersed cells
- Cells: fibroblasts, macrophages, mast cells, and some WBCs - Gel-like ground substance |
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Where is loose (areolar) connective tissue found?
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- Under epithelia of body
- Packages organs and surrounds capillaries |
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What are the functions of loose (areolar) connective tissue?
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- Wraps and cushions organs
- Holds tissues together - Macrophages phagocytose bacteria |
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How does dense connective tissue compare to loose CT?
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- Dense has a greater abundance of fibers
- Also has fewer cells |
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What are the structural characteristics of Irregular Dense CT?
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- Irregularly arranged collagen fibers
- Few cells |
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Where is irregular dense CT found?
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- Reticular layer of dermis of skin
- Submucosa of digestive tract - Fibrous capsule of visceral organs and joints |
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What are the functions of irregular dense CT?
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- Withstands tension in multiple directions
- Provides structural strength |
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What are the structural characteristics of Regular Dense CT?
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- Coarse collagen bundles densely packed and oriented in parallel cylinders or sheets
- Few cells |
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What are the functions of Regular Dense CT?
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- Withstands great tensile strength in one direction
- Attach muscles to bones or muscle, and bones to bones |
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Where is regular dense CT found?
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- Tendons, most ligaments, and aponeurosis
- Cornea |
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Why is the cornea transparent (normally)?
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- Contains overlapping Type I collagen fibers stacked at nearly right angles and embedded in proteoglycans (regular dense CT)
- Orderly packing makes it transparent |
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Why does cornea surgery temporarily generate hazy vision?
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- Normally the collagen fibers are organized neatly and embedded in proteoglycans (regular dense CT)
- After surgery the orderliness is temporarily disrupted |
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What are the structural characteristics of reticular CT?
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Network of reticular fibers (composed from collagen type III) in loose ground substance
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What is the location and function of reticular CT?
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- Supports the parenchyma of organs
- Liver, lymph nodes, spleen, and pancreas |
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What is a big difference between epithelial cells and connective tissue re: intercellular space?
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- Epithelial cells have little intercellular space
- Connective tissues have lots of intercellular space |
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Where are simple squamous epithelia found?
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- Lining of blood vessels (endothelium)
- Lining of body cavities (mesothelium) - Lining of renal corpuscle |
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Where are simple cuboidal epithelia found?
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- Lining of kidney tubules
- Lining of ducts of some glands - Covering of the free surface of ovary |
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Where are simple columnar epithelia found?
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- Lining of stomach, intestines, and rectum,
- Lining of uterus and oviducts - Lining of ducts of some glands |
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The oval nuclei in columnar cells are located closer to which surface of the cell?
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Basal
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Where are pseudostratified epithelia found?
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- Male reproductive tract
- Respiratory epithelium (in ciliated form) |
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What are the two types of stratified squamous epithelia? How are they distinguished? Where are they found?
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- Keratinized - surface layer of dead, anucleated cells filled with keratin (skin)
- Non-keratinized - surface layer of nucleated cells, aka mucous membrane (oral cavity, esophagus, vagina, anal canal, and vocal folds |
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How can the layers of the skin be distinguished on a slide?
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- Surface - dark pink - epidermis (keratinized, stratified squamous epithelium)
- Underlying connective tissue - light pink - dermis - Separated by a jagged line |
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Do non-keratinized stratified squamous cells have nuclei?
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Yes
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What is the functional advantage of having multiple cell layers in the epithelia of the skin, oral cavity, esophagus, vagina, anal canal, and vocal folds?
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Surface cells are sloughed, thereby protecting underlying tissues from friction, abrasion, and infection
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What is the functional advantage of having a keratinized (cornified) vs. nonkeratinized (non-cornified) epithelium in a given region?
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Non-keratinized epithelia are less resistant to water loss
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Where are stratified cuboidal and stratified columnar epithelia located?
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Rare but in parts of pharynx, larynx, urethra, conjunctiva, ducts of salivary, sweat, and mammary glands, and anorectal junction
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Where is transitional epithelia located?
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- Bladder
- Renal pelvis - Ureters - Proximal urethra |
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When the bladder is distended the transitional epithelia appear as what?
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Squamous cells
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What are three examples of tissues in the body in which zonula occludens between adjacent cells is necessary for proper functioning?
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1. Intestinal epithelium - restricts food to lumen and only allows access of nutrients to bloodstream through cells
2. Vasculature of brain and spinal cord - make up blood-brain barrier 3. Urinary bladder and kidney |
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What layer of skin cells are located just superficial to the basal cells at the epidermal/dermal junction?
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Stratum spinosum
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What specialization is found on the stratum spinosum?
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Spiny projections apparent as fine lines between cells that represent etensions of cytoplasm from adjacent cells linked by desmosomes
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How do desmosomes and hemidesmosomes differ functionally?
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- Desmosomes - link adjacent cells
- Hemidesmosomes - link cells to basal lamina (via intermediate filaments to transmembrane proteins) |
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What proteins are involved in hemidesmosomes?
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- Transmembrane proteins - BP180 and α6β4 integrin - receptors
Basal Lamina proteins - laminin 5 - Anchoring fibrils of collagen type VII (extra linkage to ECM) |
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What type of cytoskeletal proteins insert into a zonula adherens?
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Actin microfilaments
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What type of cytoskeletal proteins insert into a desmosome?
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Intermediate filaments
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In which tissues of the body would you expect to find numerous adhering junctions? Why?
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Tissues subject to mechanical stress (e.g. skin, cardiac muscle and skeletal muscle) have numerous adhering junctions to prevent tissue tearing by shear forces
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What are the implications of pemphigus vulgaris (PV) and vullous pemphigus (BP)?
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- Autoimmune disease in which patient develops antibodies against proteins of desmosome or hemidesmosome
- Patients experience blisters in response to mechanical trauma |
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What is the advantage of having cells electrically coupled (e.g. cardiac muscle cells)?
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Act in synchrony
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What is the main component of the basal lamina? What is its function?
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Extracellular molecules secreted by epithelial cells to provide structural support and to serve as a barrier to materials that might pass between the epithelium and connective tissue
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What does a Periodic Acid-Schiff stain do to cells?
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Makes the acellular basement membrane appear magenta by reacting with proteoglycan-rich macromolecules concentrated in this structure
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What is the light microscope term for the layer between the basal surface of epithelial cells and their underlying CT?
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Basement membrane
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What is the electron microscope term for the layer between the basal surface of epithelial cells and their underlying CT?
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Basal lamina
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Epithelial cells on surfaces are always polarized; the side adjacent to the basement membrane is what side?
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Basal
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What is the function of cilia in the trachea?
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Remove particles in air passageways towards the oropharynx for removal by swallowing
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What is the name of cancers that come from epithelial cells?
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Carcinomas
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What are some changes that are noted in carcinomas (cancers of epithelial cells)?
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- Anaplasia - loss of polarity of nuclei
- Loss of orderly maturation of cells (esp. in squamous cells) - Variation in size and shape of cells - Hyperchromatism of nuclei (w/ clumping of chromatin) - Increase in nuclear-cytoplasmic ratio |
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What are the characteristics of dense regular connective tissue?
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- Purple stained, elongated nuclei are scattered among the thick pink collagen fibers
- Cytoplasm is difficult to distinguish - Normally fibers are packed but tissue prep makes separations appear between parallel fibers |
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What type of collagen predominates in dense regular CT?
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Type I
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The nuclei in dense regular CT are from what cells?
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Fibroblasts
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What are the layers of the skin?
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- Epidermis
- Papillary layer of dermis (pale pink) - Reticular layer of dermis (dark pink, containing thick fibers) |
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Why is the reticular layer of the dermis called that?
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Because the thick collagen fibers are oriented in all directions, forming a reticulum (network) although it is classified as 'dense, irregular CT' NOT reticular CT
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What type of CT encapsulates most organs?
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Dense irregular CT
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What is the advantage of having collagen fibers oriented in all directions in dense irregular CT?
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Protects from mechanical stress in multiple directions
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What is the function of the fibroblasts in dense regular and dense irregular CT?
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Synthesize, secrete, and maintain ECM
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Is epithelium or CT more cellular?
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Epithelium
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Does epithelium or CT have more ECM?
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Connective tissue
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What is found at the core of a villus? What is it called?
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Lamina propria - filled with loose connective tissue
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What is the function of the loose connective tissue in the villus?
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- Physical support for epithelium
- Metabolic support for avascular epithelium - Support for lymphoid tissues dealing with foreign antigens from gut |
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What cells are found in the loose connective tissue? Which two are identifiable and how?
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- Fibroblasts (not identifiable)
- Macrophages (not identifiable) - Mast cells (not identifiable) - Smooth muscle cells (not identifiable) - Eosinophils (bright pink granules with bi-lobed nuclei) - Lymphocytes (small intensely basophilic cells w/ little cytoplasm) |
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What are the characteristics of plasma cells?
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- Mature B lymphocyte
- Eccentric nucleus (displaced to one side) - Clock-faced arrangement (large clumps of heterochromatin regularly spaced arund inner nuclear membrane) - Cytoplasm is basophilic and more pale in region near nucleus where Golgi is located |
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Where does some of the connective tissue found in the lamina propria of the GI tract villi originate?
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Bone marrow and gets to lamina propria via the circulatory system
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Where is loose connective tissue often found?
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- Lamina propria in villi of GI tract
- Epithelia and mesothelia of pleural, pericardial, and abdominal cavities - Supports blood vessels and nerves - Fills spaces between other tissues |
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What is the collective function of the cells in the loose connective tissue that underly epithelia of the GI tract, respiratory tract, and skin?
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First line of defense against invasion of the body by microorganisms or foreign antigenic substances
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What structure appears as thin black branching lines in loose connective tissue? as thick green lines?
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- Thin branching black lines - elastic fibers
- Thick green lines - type I collagen fibers |
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What is the function of the elastic fibers in loose connective tissue?
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Distensibility and flexibility
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What two vital organs require elastic fibers for proper funtionality?
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- Blood vessels (especially elastic arteries for modifying BP)
- Lungs |
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What are the empty spaces called in loose connective tissue? What is found here?
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Intersitial spaces - filled with non-fibrous ECM material (glycosaminoglycans, proteoglycans, and glycoproteins)
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What are the three components of the non-fibrous ECM material?
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- Glycosaminoglycans
- Proteoglycans - Glycoproteins |
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What is it called when there is excess watery fluid in interstitial spaces?
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Edema
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What are the two types of cells in an organ? What are they specialized for?
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- Parenchyma - functional units of organ
- Stroma - suppertive connective tissue framework |
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What are the thin, black lines in reticular connective tissue? What is its function?
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- Reticular fibers
- Form supportive scaffolding for parenchyma; confer resilience to the tissues |
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What type of collagen makes up reticular fibers?
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Type III
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How do Type I and Type III collagen fibers compare?
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- Reticular fibers (type III) are thinner and shorter than Type-I fibers
- Reticular fibers (type III) also branch whereas Type-I do not |
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What is the major function of adipose tissue?
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Energy storage
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During conventional tissue preparation, what happens to lipid droplets?
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The lipid is extracted leaving an empty space
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Where are the nuclei and cytoplasmic organelles located in unilocular adipocytes?
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Peripherally around droplet
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