M2M Unit 4 Flashcards

Question

exocrine glands

Answer 1

secrete agent molecs onto epithelial surfaces - dev as simple invaginations of the epithelium - synthesize variety of sub's - have to cross the apical membrane to get to the "outside" of the epithelial cell -secretory units- invaginated pouches that function as exocrine glands these make secretions and transport them across the apical membrane and flow down the narrow part of invagination to reach the outside of the epithelium -don't always have invaginations; sometimes just single cells prod/secreting

Answer 2

mucus secretions | serous secretions- watery; sweat, saliva, etc.

Answer 3

always secrete agents into blood dev as invaginations of the epithelium that are pinched off from the epithelial surface surrounded by vessels in CT synthesize hormones generally cross basal membrane and get through CT and vessel surfaces to get to blood exception: thyroid endocrine hormones - secrete through apical membrane, mature in lumen, and transported across both membranes out again

Answer 4

most have self-renewing potential via specialized stem cells, stored in "crypts" or pouches at the bottom of epithelial sheets -tightly regulated; few of them, spread out, slowly dividing polarity of cell proliferation- new cells push up old cells and old migrate toward apical further differentiated as they migrate

Answer 5

Wnt proteins in the colon inhibit differentiation by dividing at the cell surface and setting off a signaling cascade; also promote cell division (more differentiation= less division) normally APC protein inhibits Wnt signaling pathway in colon (blocking APC activates cell proliferation) APC mutation--> colon cancer similar proteins in lung, but opposite pathways Wnt promotes differentiation and inhibits division

Answer 6

generally called carcinoma adenocarcinoma- cancers derived from glandular epithelia high levels of cadherin activity correlate w/ higher survival rates could be from: tighter connections between epithelial cells lead to less metastasis of epithelial cancer cells, or cadherins can act as signaling molecs to sense cancer and respond appropriately

Answer 7

tissue sample is cut out, put in saline buffer, and fixed (soln to preserve large cell structure) -carbs and lipids tend to leak out in process sample sliced thinly and stained to create 2-D image (general to specific) tip: find nuclei

Answer 8

methods of detecting presence of particular proteins in pathology slices- info about quantity and loc of protein use antibodies- have high affinity and specificity for certain proteins/antigens method: fix and stain apply primary antibody (sticks to pertinent protein); wash add secondary antibody (sticks to primary antibody) w/ a colored tag; wash look at color

Answer 9

most common lethal genetic disease in caucasians CF gene codes for CFTR protein- acts as apical ion channel controlling water and ions moving out large CF gene on Chr 7; multiple pathological mutations mutations cause: no protein synthesis misfolding, leading to degradation before reaching apical cell surface altered conductance so protein can't be conveyed to apical surface partial loss-of-func so CFTR proteins don't work normally

Answer 10

pseudomonas and staphyloccus aureus are the most common pathogens found in CF lungs CFTR normally excretes Cl- to move water into mucus layer overalying the lung epithelium defective CFTR- water doesn't move -also high levels of Na+ import, which further removes water from lumen/mucus chronic lung problems- chronic bronchitis and airway infection/inflammation -lead to loss of lung func

Answer 11

major diagnostic- test for Cl level in sweat -large levels of Cl- indicate homozygosity for CF (auto recessive) positive NBS ``` treat- lungs w/ airway clearance therapy antibiotics to keep lungs clear inhaled mucolytics (breakup mucus) bronchodilators ERT VitA, D, E, K replacement Azrithromycin used chronically ``` therapeutic- eventually need lung transplant "protein rescue" seems promising to fix misfolding/nonconduction problems

Answer 12

``` domains: centriole/basal body axoneme transition zone ciliary membrane intraflagellar transport (IFT) machinery ```

Answer 13

core anchors from which cilia are formed microtubule rich cylinder shaped structures form from 9 triplet microtubules polarized structure responsible for nucleating cilium

Answer 14

structural skeleton of cilium provide tracks for movement within cilila formed from doublet microtubules assembled from basal body polar lengths range from

Answer 15

links basal body to axoneme considered "gatekeeper" because it limits diffusion in/out of cilium ensures compartmentalization for signaling mutant transition zones associated with ciliopathies

Answer 16

continuous w/ cellular plasma membranes | compartmentalized by transition zone, so it's a distinct membrane with unique phospholipids and receptor molecs

Answer 17

transports cargo for assembly/maintenance of cilium and for movement of signaling components within cilium along the axoneme bidirectional transport w/ kinesin motors and the IFT-B protein complex directing movement to ciliary tip (anterograde transport) retrograde transport- cytoplasmic dynein 2 motor driven transport with the IFT-A protein complex both transport mech's are required for cilium formation and func

Answer 18

2 phases- centrioles/basal bodies assembly and formation of cilium centrioles interchange func at centrosomes and making basal bodies; upon cilogenesis, the older of the 2 centrioles in G1/S phase funcs as basal body/anchor ciliogenesis- normally in G1 (or G0) distal end of basal body is capped by ciliary vesicle; microbutuble doublets assemble into ciliary vesicles before structure fuses w/ plasma membrane terminally differentiated cells nucleate many cilia per cell; require more mech's (basal body assembly uncoupled from cell cycle; replication is amplified)

Answer 19

motile- most also possess sensory func's required for fluid movement in resp, neural, and repro tracts motility produced by axonemal dynein dependent sliding motion between the doublet microtubules of cilliary axoneme typically 9+2 microtubule arr; 9 doublets around central pair of singlet microtubules (not all have central) sensory- immotile/primary cilia 9+0 microtubule arr lack axonemal dynein arms normally perform signaling funcs

Answer 20

``` cilium concentrates the singal w/ a high receptor surface-to-vol ratio signal is localized and polarized within discrete domains receptors are positioned away from interfering cellular domains func as a mechanical detector of flow ``` can sense physical stimuli, light, chem stimuli; all produce range of downstream events: proliferation, motility, polarity, growth, differentiation, tissue maintenance

Answer 21

Hh signaling pathway well established to signal through cilia activation and repression of the target of the Hh paracrine signaling pathway (glioma tumor- Gli transcriptional activator) requires cilia Wnt, PDGF, FGF, and others

Answer 22

Hh signaling: limb formation, bone formation/homeostasis, neurogenesis ``` tissue and cellular polarity organogenesis tissue patterning (neuronal and limb) bone formation cell fate specification eye dev left-right-axis determination craniofacial dev neural tube formation tubule formation (kidney, liver, pancreas) renal cystic diseases and retinal degeneration (degenerative) ```

Answer 23

``` cystic kidneys nephronophthisis obesity polydactyly retinal degneration aminosa (loss in olfaction) cancer/tumorigenesis urinary tract malformation cognitive impairment diabetes mellitus infertility occipital meningoencephalocele microphthalmia lung hypoplasia renal hypodysplasia or displasia bile-duct dilatation situs inversus ```

Answer 24

autosomal recessive ciliopathy 19 genes mutated in BBS patients to date BBS proteins participate in a protein complex that is required for vesicle transport within the cilium ``` symptoms: photoreceptor degeneration anosmia mental retardation/developmental delay neural tube defects obesity hypogonadism kidney defects polydactyly diabetes ```

Answer 25

precursors to all CT family members primarily func in embryogenesis, but small numbers of them may persist through adulthood to fun as stem cells for generation of new CTs

Answer 26

the pre-eminent cells of most CT in body not really a single cell type look similar histologically but express different markers and proteins in dff tissues

Answer 27

derivatives of fibroblasts are capable of smooth muscle-like func found in CTs that require a contractile func often generated at sites of wounds where their contractile function contributes to retraction and shrinkage of scar tissue

Answer 28

CT- fibroblast derivatives and or primitive mesenchymal cells main types func to store fat as E for other cell types tissue w/ these cells called white fat brown fat- distinct tissue in newborns and children; contains many mitochondria that convert fatty acid to heat

Answer 29

make cartilage

Answer 30

some, particularly those in the walls of blood vessels, make some of the EC matrix components in which they are imbedded these (possibly not all) smooth muscle cells derive from the same types of precursors as other CT cells, which would explain ability to synthesize and secrete similar types of ECM components

Answer 31

EC fibers embedded in ground substance

Answer 32

collagens and elastins

Answer 33

EC fibers general unit is triple helix (formed outside cell); pack together to form fibrils (outside cell) N-telo cleaved ends can be detected in blood urine- indicator of metabolic activity in bone and other CTs fibrillar collagens- make long, thick composite fibers, or fibrils (primarily Type 1 collagen) -lots of tensile strength fibril-assoc collagens- make thin fibers connecting basal lamina to fibrillar collagens and fibrillar collagens to e/o networking collagens- form thin sheets that provide the scaffold for basal lamina (type 4)

Answer 34

from non-hydroxylated proline residues of collagens (caused by deficiency of Vit C)

Answer 35

EC fiber elastic, cross-linked to form "rubber bands" supported by fibrillin proteins (fibrillin mutation= Marfan's syndrome; susceptibility of cardiac problems from reduced elasticity of major vessels)

Answer 36

composed largely of proteoglycans- protein core w/ carb sidechains carb chains are negative- attract water to hydrate ground sub (solutes can move through)

Answer 37

stem cells that can differentiate into many kinds of basic cells; difference in func and ECM secretions of those differentiated cells more sketchy "we have working CT" and from one type of cell (mesenchymal stem cells) you can get wide variety of cells, depending on signaling and proteins

Answer 38

they can be remodeled at just about any point by protease and stem cells wound response: generally signaled by platelets from torn blood vessels inflammation phase: mast cells activated to secrete various molecs, among them histamines and chemoattractants (polypeps that attract migratory cells) - these go into blood vessels and cause influx of vascularly-located immune cells (leukocytes and macrophages) into the ECM at the site of the wound - macrophages, in addition to eating damaged tissue/bac, trigger angiogenesis in the wound (though doesn't transpire until tissue actually begins to heal) - cytokines are triggered; attract cells involved w/ next phase (proliferation/dev)

Answer 39

fibroblasts are attracted by cytokines and other signals these divide and increase ECM secretion rate fibroblasts in the area begin to repopulate damaged epithelium and CT (scar tissue if basal lamina is damaged extensively) fibroblasts also differentiate into myofibroblasts: exert pressure on area to restrict blood loss and close the wound generally die off after wound has healed

Answer 40

effectively a continuation of the dev phase, in which fibroblasts replace temporary collagen laid down to close the wound with more permanent collagen oriented for maximal tensile strength

Answer 41

CTs are always found next to the basal surfaces of epithelia CT surrounds muscle and nerves in distinct patterns CT surrounds all blood vessels, and surrounds and courses through all organs

Answer 42

serves as template for bone or as resilient/pliant support sys avascular mesenchymal stem cells form chondrocytes, which secrete cartilaginous ECM these chondrocytes become cocooned in "lacunae" of their own secretions (but can still divide and grow out the cartilage- interstitial growth) -chondrocytic matrix is covered in hard outer layer called "perichondrium", which contains the mesenchymal stem cells that give rise to the chondrocytes in the interior -cartilage can grow 2 ways- appositional and interstitial (bone can only grow appositionally)

Answer 43

chondrocytes arise from mesenchymal stem cells during fetal dev and conduct interstitial and appositional growth, with chondrocytes secreting cartilaginous ECM and becoming encased in lacunae from that point on

Answer 44

hyaline cartilage- full of hyaluronic acid (a GAG type that isn't bound to proteins) - fairly sparse and irregular fiber matrix - ossifies in long bones elastic cartilage- hyaline having a lot of elastic tissue (ex. earlobes) fibrocartilage- often found where tendons attach to bone or in joints -much more densely packed with fibrous collagen; tough

Answer 45

except for osteoclasts, bone cells form from mesenchymal stem cells, which form osteoprogenetor stem cells, which then self-renew and produce osteoblast secretory cells osteoblasts- assemble on surface of forming bone - secrete watery, loose ECM characteristic of bone called osteoid (contains collagen, but not dense) - become cocooned within their own secretions - fully enclosed, they transform into osteocytes osteocytes- vastly reduced secretory activity - send out processes that contact their osteocyte and osteoblast neighbors to form gap junctions (signaling) - these long processes form canaliculi through bone matrix - seem to be involved in sensing the current status of the bone matrix and regulating osteoblast activity, depending on the status d. Notice that osteoblasts also trigger the mineralization of the loose original bone ECM: they secrete Ca2+- and PO4-filled matrix vesicles, which break open in the ECM as their contents form crystallized calcium phosphate ("hydroxyapatite"). The released hydroxyapatite gives the bone ECM its extreme hardness; it also serves as the main storage site of calcium in the human body. e. As mentioned, due to this hardness, there is no interstitial growth in bone (matrix is too inflexible to allow it)-- bone only grows by appositional growth at the surface due to division and secretion of osteoblasts and osteoprogenitors. f. Completely different lineage of osteo- cells: osteoclasts, derived from monocytes in blood vessels (as are macrophages). i. Osteoclasts are effectively bone-matrix-specific macrophages: when directed, they 'chew up' and degrade bone matrix and release liberated calcium into newly loosened ECM, where it can get back into the bloodstream. ii. Functions of osteoclasts: 1. Degrade cartilage (for ossification of 'template' cartilage) as well as bone (for remodeling and calcium mobilization) 2. Stimulate angiogenesis (like macrophages). a. As these tunnel through bone, they bring blood vessels with them (note that bone is vascularized). 3. Innervation: Nerves follow osteoclast-formed channels in bone matrix.

Answer 46

Loose collagenous bone ECM is secreted from osteoblasts, which also secrete the matrix vesicles that contain the hydroxyapatite that will mineralize the original, soft ECM. Osteoclasts resorb the mineral matrix and excrete the inorganic ions inside into the reloosened ECM, from where they can get back to the bloodstream. Note that bone ECM is vascularized and innervated due to osteoclast action.

Answer 47

intramembranous ossification endochondral ossification

Answer 48

i. During development: mesenchymal stem cells condense (come together and proliferate) and form layers with surrounding connective tissue. Some of the stem cells differentiate into osteoprogenitors and then to osteoblasts, which secrete bone matrix that's vascularized/innervated/remodeled by osteoclasts and mineralized by osteoblasts. ii. Effectively this is the simple route of bone formation: direct formation of bone from mesenchymal stem cells without a cartilaginous intermediate. iii. Most of the flat bones form this way.

Answer 49

i. Initial, 'template' cartilaginous 'bones' are ossified and replaced with actual bone. ii. Recall that the perichondrium of cartilage contains mesenchymal stem cells which continue to create new chondrocytes. iii. At some point, a signal is received at around the middle of the diaphysis (center of long bone) which tells the mesenchymal cells to begin producing osteoprogenitors instead of chondrocytes. This begins a transitional wave that transforms the perichondrium to a periosteum. iv. Formation of periosteum induces two events: calcification of cartilage, and the destruction of chondrocytes embedded in the cartilaginous matrix. 1. Chondrocytes tend to get very large before they're killed off (apoptosed)-- this is called hypertrophy, which is an indicator that chondrocytes are becoming apoptotic prior to ossification. 2. Osteoprogenitors/osteoblasts send signals to bring osteoclasts to the cartilage-- the osteoclasts show up, see the calcified cartilage, and begin to degrade it and engulf the apoptosed chondrocytes. a. Note that osteoclasts bring blood vessels and nerves with them while this is going on. 3. After the osteoclasts have done their thing, the osteoblasts set in to lay down bone matrix and calcification around the vessels that have just invaded the nascent bone. 4. Notice that the cartilage is still growing (appositional and interstitially) wherever it can while this is going on. 5. The secondary ossification centers, one at each end (epiphysis) of the bone, form while the primary ossification center is still being vascularized and mineralized. These progress in the same manner as the primary. 6. Note that there's a layer of cartilage left behind (the epiphyseal or growth plate) between the diaphysis and epiphysis. a. This cartilage continues to grow interstitially in the direction of the epiphysis (towards the ends of the bone); the primary ossification center 'chases' this cartilaginous growth, ossifying the new growth as it occurs. i. If you're looking at a histology slide of ossifying cartilage, can always tell which layer is the cartilage by looking at 'lines' of proliferating chondrocytes pushing out in the direction of the end of the bone. b. Interstitial growth of cartilage is what drives the length of long bones; width of bone is driven by appositional growth of the periosteum (which completely replaces the perichondrium along the edge of the bone). v. Most of the skeleton (including all the long bones) are formed this way.

Answer 50

a. Periosteum forms on the surface of cartilage. b. Osteoblasts calcify the cartilage; chondrocytes undergo hypertrophy and apoptose. c. Osteoclasts degrade the cartilage, engulf chondrocytes, lay down new blood vessel and nerve pathways. d. Osteoblasts make bone matrix and mineralize it around vessels and nerves.

Answer 51

a. [Endosteum: inside surface of bone (inner surfaces of osteoclast-derived tunnels).] b. Bone remodeling (osteoclast activity and subsequent osteoblast secretions) occurs immediately upon formation of new bone, and also recurs almost continuously throughout life. i. Notice that the activation of osteoclasts is tightly linked to the activation (ie production and secretions) of osteoblasts. c. In early bone, the coordination of vessels/nerves with matrix is disorganized and random; over time, the constant remodeling leads to a particular division between compact and spongy bone. i. Compact bone: On the edge of the bone; dense, multi-layered, no trabeculae. ii. Spongy (or 'cancellous' or 'trabecular') bone: Deeper inside the bone, form honeycombed networks of endosteal surface, filled with bone marrow. iii. Notice that both flat and long bones show this pattern (spongy vs compact).

Answer 52

i. Short-range: Bone morphogenetic proteins (BMPs) released at bone site. 1. Don't travel through bloodstream. 2. Effectively instruct other cells to lay down and remodel bone. 3. Significant pathophysiologically due to FOP disease (Fibrodysplasia ossificans) that causes ossification to occur in loose connective tissue. Caused by the BMP4 gene being fused to an abnormal promoter; this causes it to be expressed in lymphocytes (from where it acts on fibroblasts/mesenchymal stem cells to form osteoprogenitors and bone). 4. Can also use Wnt and Notch proteins to do short-range signaling (no details needed). ii. Long-range: Endocrine hormones, particularly calcitonin (lay down more calcified matrix: Ca2+ out of bloodstream, build up bone) and parathyroid hormone (reabsorb more calcified matrix: Ca2+ into bloodstream, break down bone), as well as steroid hormones (no details). iii. Mechanical stress: as per anatomy, putting stress on bones leads to different cell activity in bone remodeling-- thickens bone (greater appositional growth) in particular directions. iv. Neuronal stimulation: CNS regulates bone remodeling. A "who knows" category.

Answer 53

a. Patients are tested for their molecular markers (EGFR activity, or ALK-EML4 activity).  You then give appropriate treatment to target the tumor specifically based on this information.

Answer 54

a. To design and develop targeted therapies, specifically designed to “attack” the molecular targets that are tumor specific. Find agents that work against specific biologic pathways. Ex: Non-small cell lung cancer: can choose bevacizumab or pemetrexed, blocks VEGF pathway or the formation of purine and pyridimine precursors.

Answer 55

a. Look at the patient’s cell type, molecular markers, histology. Clinical information is used as well. b. Use molecular profiling to determine the right therapy for the patient, leading to increased survival benefit and decreased toxicity. c. Certain tissue types will make the patient susceptible to toxicity or will confer specificity and effectiveness to a given treatment.

Answer 56

a. Prognostic: reflect natural history of disease independent of therapy- based on the tumor and the patient themselves b. Predictive: reflects the impact of a therapeutic intervention (predicts response to treatment).

Answer 57

a. Three layers surrounding lumen: i. Tunica intima: endothelial layer closest to the lumen of the vessel. ii. Tunica media: middle layer, composed of elastic tissue, smooth muscle, or collagen. iii. Tunica adventitia: outer layer, composed of collagen/collagenous tissue. 1. In large arteries, these often contain smaller vessels running through them; these are called vasa vasorum (vessels of vessels).

Answer 58

a. [In largest arterial vessels, like the aorta ("elastic arteries"):] i. Tunica intima: 1. endothelial cells (at the interface with the lumen) 2. Stuff just outside the endothelial layer but still in the intima: a. fibroblasts b. connective tissue c. myointimal cells (responsible for laying down fibrous plaque in atherosclerosis) ii. Tunica media: 1. Lots and lots of smooth muscle cells and, particularly, elastic fibers iii. Tunica adventitia: 1. Vasa vasorum (supplies blood and nutrients to outer parts of larger vessels) 2. Loose collagenous connective tissue, elastin a. This is loose so that leukocytes (white blood cells) can exit the blood vessels and get out into the connective tissue.

Answer 59

b. [In more distal but still large arteries ("muscular arteries"):] i. Less tunica intima volume ii. Shows characteristic "inner" and "outer" elastic laminae that form the boundary of the tunica media, containing smooth muscle cells (note less elasticity as you get farther from the aorta on account of there's less arterial pressure farther on). iii. Adventitia doesn't show vasa vasorum once you get to a sufficiently small size-- the blood from the lumen can diffuse well enough on its own. c. [In smaller muscular arteries:] i. Small (3-4 layers) tunica intima ii. In the tunica media, the outer elastic lamina disappears, but the inner remains. 1. Notice the smooth muscle remains thick-- dilation and constriction extremely important by this point. iii. Adventitia: quite thin, can blend into surrounding tissue.

Answer 60

d. [In smallest arteries immediately adjacent to capillaries ("arterioles"):] i. Tiny tunica intima, a few layers of smooth muscle, and a little collagenous tissue on the outide rim. ii. "Gatekeepers" for the capillaries (can constrict and shut off blood flow to them).

Answer 61

i. Still have a tunica intima, media and adventitia. Media is much, much smaller than those of similarly sized arteries. ii. Note that you can find valves or "flaps" in both veins and lymphatic vessels. iii. Occasionally a few smooth muscle cells in the media, but not many. iv. Notice that the shape of the lumen often looks "collapsed" (acircular).

Answer 62

i. Also have irregular lumen (acircular), but have extremely thin walls (just a thin endothelial layer, no media or adventitia) compared to veins. g. [Important note: the endothelial cells of the tunica intima are pretty much universally stratified squamous in shape (need to have things diffuse through them quickly, need to be thin). If it's cuboidal or columnar, odds are good it's not a vessel endothelium.]

Answer 63

a. All capillaries have relatively wide lumens and, thus, slower blood flow. i. This means that regulation of diameter is particularly important, since it's easier to close off or open up capillaries completely than larger vessels. b. Capillary structure: i. Small endothelial layer ii. Specialized layer wrapped around endothelium: pericytes. 1. If tissues are damaged, pericytes can generate smooth muscle cells; mechanism not clearly understood. c. Three different types of endothelial layers: i. Continuous (standard) endothelium: continuous wall of lumen; can have pinocytosis (vesicle-bound transport) across it, but no free flow. ii. Fenestrated endothelium: small windows in lumen, allows plasma to freely diffuse through endothelium. iii. In spleen and to some extent in the liver, can see discontinuous endothelium: large holes in lumen or between adjacent endothelial cells, allows entire red blood cells to diffuse out of endothelium.

Answer 64

a. Post-capillary venules: Where leukocytes interact with the endothelial walls (actually, they break them selectively down, a process called diapodesis) and leave the blood; also the action of histamines regulating permeabilities of blood vessels occurs at the post-capillary venules. Slow blood flow.

Answer 65

smooth muscle "gateways" in arterioles

Answer 66

connecting vascular passages between arterioles and post-capillary veins (controlled by smooth muscle sphincters).

Answer 67

System of vessels leading from arteriole through capillary beds to the post-capillary veins. Also controlled by smooth muscle sphincters.]

Answer 68

From a capillary bed to a capillary bed, ie. hepatic portal system. If that system is any indication, these probably aren't primarily used for oxygenation of the second capillary system in the chain.

Answer 69

Countercurrent heat exchange between arteries and veins. Say you're a scrotum. (did you say it?) You're hanging around, so to speak, outside the body and you're a little cold for a tissue system. What you don't want is for all that good warm blood coming out to you to get cold and carry that cold back into the body, cooling down the core. So you run your arteries right next to your veins on the following philosophy: if the veins coming in are cold, and the arteries going out are warm, then the incoming blood in the veins will be warmed up (thus preventing core cooling) and the outgoing blood will be cooled down (thus minimizing its heat loss). That arrangement is a pampiniform plexus.

Answer 70

: arteries that supply blood to a region that isn't supplied by any other artery-- eg. kidney/lung arteries.

Answer 71

. Draw two lines. These are Z lines. The actin (thin) fibers poke out from them. Draw a line in the middle. This is the M line. The myosin (thick) fibers poke out from it between the thin fibers (which don't extend all the way to the M line, but do extend enough to have some cross-over with the myosin). Ta-da, a sarcomere. Line up a whole bunch of them in a row. Now you have a myofibril. Repeat that a lot in an orderly fashion. Now you have a striated muscle.

Answer 72

a. Thin filaments are made up of actin chains with tropomyosin stuck to them and troponin stuck to the end of tropomyosin. Thick filaments are made up of myosin chains that have big globular loops ('heads') on them that interact with actin.

Answer 73

a. A myofilament is a polymerized strand made up of either myosin or actin/tropomyosin/troponin. b. A myofibril is a bunch of sarcomeres placed end to end. Each myofibril is covered with its own sarcoplasmic reticulum (see below).

Answer 74

a. Dystrophin connects actin to the surface membrane. Titin links myosin to the Z line (centering the thick filaments). Nebulin does something similar for the thin filaments. Alpha-actinin crosslinks actin fibers. b. The idea is that there's "passive" tension in a muscle fiber, presumably generated by attaching everything in its original configuration, that gives the cell something to return to after contraction. These proteins help maintain that configuration.

Answer 75

a. Motor nerve terminals (synapses) are located around the center of skeletal muscle fibers; the AP propagates in both directions from there. (note that the contraction of the muscle is not the same as the AP to the muscle-- the former depends on t-tubule-triggering of calcium release and occurs more or less at the same time throughout the muscle, as you'd like for maximum contraction.) b. The distribution of innervated cells varies greatly depending on the particular neuron and the particular muscle, but is generally called the motor unit whatever its size. i. Fine motor actions tend to have small-size motor units (you're triggering less muscle contractions with one AP); coarse motor actions tend to have larger motor units. ii. Notice that a single "muscle" (ie thigh muscle, triceps, etc) may have lots of different motor neurons innervating it, all attached to differently-sized motor units.

Answer 76

a. (1) Influx of calcium binds to troponin. b. (2) Bound troponin changes the configuration of tropomyosin. c. (3) The shifted tropomyosin exposes binding sites for myosin on the actin filament. d. (4) The actin filament binds to the myosin and the "spring" tension pre-loaded into the myosin releases, shortening the sarcomere by about 10 nm. e. (5) ATP binds to myosin, allowing actin to be released. f. (6) ATP is hydrolyzed to ADP + Pi, pre-loading the "spring" tension into the myosin fiber by shifting its configuration a little. g. (7) Repeat steps 4-7 as long as there's Ca2+ and ATP around. h. (8) Once the calcium supply runs out (Ca2+ is being pumped out while this is going on), troponin goes back to its original configuration, as does tropomyosin, causing actin to no longer be able to bind to myosin.

Answer 77

a. Regulatory proteins: means troponin and tropomyosin. b. As mentioned, troponin sits at the end of tropomyosin and binds calcium. c. Tropomyosin sits on actin and covers the myosin binding sites until troponin is triggered by Ca2+.

Answer 78

a. (1) AP in motor neuron travels down to the synaptic area. b. (2) AP causes a release of acetylcholine (neurotransmitter) at the synapse. c. (3) ACh binds to ACh receptors in the muscle fiber, opening ion channels in the muscle fiber and causing depolarization (muscular AP). d. (4) Muscle AP propagates down the fiber. e. (5) AP goes down into t-tubules on its way. f. (6) DHP receptors at ends of t-tubules sense voltage change and open the RyR channels in the SR, releasing calcium into the cytosol of the muscle. g. (7) Calcium binds to troponin, causing tropomyosin to shift and actin to bind to myosin and contract. h. (8) Calcium and ATP drive contraction as long as signal persists and calcium/ATP are present. i. (9) Calcium pumps (using ATP) move calcium back into the sarcoplasmic reticulum; troponin, released from calcium, relapses and causes tropomyosin to cover up the myosin binding sites on actin. The muscle relaxes.

Answer 79

a. Essentially you need a way to get the membrane surface signal (the AP) to get to the sarcoplasmic reticulum so it can trigger the release of calcium and cause contractions. Having the AP be transmitted throughout the SR would be too electrically laborious, so those wacky cells decided t-tubules were the way to do it. b. Ok. The AP's coming down the membrane, continuing down the t-tubule. When it gets down to the end of t-tubule (which sits down on the edge of the sarcoplasmic reticulum of the muscle cell), it runs into a particular kind of receptor system, consisting of two parts: i. DHP receptor: voltage-gated receptor ii. RyR (ryanodine receptor): Calcium channel in the sarcoplasmic reticulum. c. Current theory: voltage hits DHP receptor, causes it to shift in such a way as to cause the RyR channels to open and allow calcium to flow out into the muscle cell, causing contraction.

Answer 80

a. Skeletal muscle is tension-graded by the frequency of action potentials fired and the number of motor units recruited for the contraction. i. Note 'tetanic' tension at which the muscle can't contract any farther

Answer 81

involves four different parts of the contractile reaction: i. (1) K+ builds up and Na+ is reduced in the t-tubular network; this reduces its ability to propagate APs and trigger calcium release from the SR. This problem is corrected quickly (K-Na balance restores in seconds). ii. (2) - (4) Involves buildup of Pi (from ATP hydrolysis) and a drop in pH (6.5 from 7- pH drops due to lactate production after glycolysis under conditions of insufficient oxygenation). Notice that we don't really know why these happen, just how. 1. (2) Pi and H+ buildup inhibits calcium release from the sarcoplasmic reticulum. 2. (3) Likewise, Pi and H+ inhibit the binding of calcium to troponin. 3. (4) They also reduce the contractile force exerted by the myosin-actin binding.

Answer 82

a. Length of a sarcomere in resting muscle: around 2.4 µm. b. Length of a sarcomere in stretched muscle: around 3.6 µm. c. Length of a sarcomere in contracting muscle: unspecified. Less than 2.4 µm. d. Sarcomere is constantly stretching and contracting as it's used, thus length shifts.

Answer 83

a. Molecular basis: the different skeletal muscle types have different mixes of oxidative and glycolytic energy-producing frameworks. i. Fast-twitch muscles tend to be centered around glycolytic energy production (quick bursts of energy, less sustainable). Used for things you need quick bursts of energy for (ie. catching the last beer can after you knock it off the table). ii. Slow-twitch muscles tends to be red in color due to their high myoglobin content (high oxygen load); they have all that oxygen because they primarily use oxidative phosphorylation to generate ATP for contraction. Tend to be used for sustained or postural movements (ie. assuming a relaxed and attractive mien with that beer can). b. Usefulness: Well, obviously, if you can catch the beer can but not relax with it, you won't attract a mate on account of no one wants to date a spaz. If you're too slow to catch the beer can in the first place, you won't attract a mate because catching beer cans is just one of those intrinsic abilities that's very attractive. Only with the right mix do your slightly intoxicated genes get a chance to propagate.

Answer 84

a. Intercalated disks: only found in cardiac muscle. Two functions: hold adjacent muscle cells together and allow gap junctions (see next point). b. Mononucleated cells vs multinucleated in skeletal muscle. c. Actin-myosin contraction and relaxation is the same as skeletal muscle (though note (a) that smooth muscle contraction is quite different and (b) that cardiac AP excitation pathways are subtly different from their skeletal counterparts, see below). d. Cardiac cells cannot regenerate damaged tissue like skeletal muscle does (no satellite cells).

Answer 85

a. Smooth: because there's no striations (ie. the sarcomeres aren't nicely lined up like cardiac and skeletal muscle). b. Structural: smooth muscle cells are extremely thin-diameter, spindle-shaped cells. Classically these are the "involuntary" muscles of the body (ie. digestive muscles). c. Contractions: a little different from the other two: i. Instead of having calcium bind troponin as the catalytic step for actin to bind myosin, in smooth muscle calcium binds calmodulin (remember this one? With the EF hand domains?), which binds calmodulin kinase (CAMK), which phosphorylates the myosin chains, causing actin and myosin to bind and the ratchet action to begin. ii. This is a lot slower than skeletal/cardiac contractions. d. Notice that smooth muscle cells are mononucleated, like cardiac cells and unlike skeletal cells

Answer 86

a. You start out with individual myoblast cells (muscle precursors). These merge together into long chains during development. Predictably, the reason you get multinucleate cells from single cells is that the single cells decide to cohabitate.

Answer 87

a. Satellite cells: specialized stem cells that produce new skeletal muscle cells. These new cells, instead of replacing the muscle cell that's there, will fuse with it to form a larger muscle fiber. This is useful in both development of muscle during exercise and repair of damaged cells.

Answer 88

a. Exercise does not add more muscle fibers. What it does is increase the size of the muscle fibers you have. b. Atrophy, likewise, reduces the size of the fibers, not their numbers.

Answer 89

i. Similar to skeletal, but here the difference is that the voltage seems to release calcium before the RyR-equivalent channels will open-- the cardiac calcium release channels (to trigger contraction) open in response to a calcium signal. I think they're not entirely sure how this works.

Answer 90

i. Don't need t-tubules at all: calcium released at the cell surface can just go ahead and diffuse through the whole cell very quickly. The reason this works for smooth muscle (but not for the others) is that smooth muscle cells are so small and thin. If you tried this with skeletal muscle, you'd get weird asymmetrical contractions as the parts of the muscle that got calcium first would contract first and the other only later, as the calcium diffused. Obviously you don't want that, and you really don't want it in cardiac muscle-- thus t-tubules.

Answer 91

a. Gap junctions only occur in cardiac muscle fibers and some types of smooth muscle. Their role in cardiac muscle is to ensure that cardiac contractions occur rhythmically throughout the heart muscle by allowing selective passive of signaling molecules; they may also form the basis for synchronous contractions of gastroenteric smooth muscle (ie. peristalsis). Also link adjacent cells together, though this is usually associated less with gap junctions and more in the intercalated discs that they're found in.

Answer 92

a. Cardiac and smooth muscle: predominantly graded by cell length and neurotransmitter/hormone receptor activity. b. Skeletal muscle: Doesn't change length (anchored at both ends)-- thus its tension is graded differently

Answer 93

a. If the average size of a motor unit is small, that muscle is probably used largely for fine movement; if larger motor units, probably mainly gross movements.

Answer 94

a. Basis is a mutation in the calcium release channel proteins in the sarcoplasmic reticulum. b. This mutation causes inhaled anesthetic to trigger the release of calcium from the SR; this causes ATPases to pump calcium back out, and a vicious cycle is initiated in which the heat generated by the pump just keeps rising, causing hyperthermia. c. Patient's muscles also become rigid during this time (muscles firing at speed). d. It's not noticed until surgery because most of us don't jaunt around inhaling halothane all day. e. Dantrolene blocks calcium release from the SR; thus, administered as a prophylactic, it prevents malignant hyperthermia. f. Muscular paralysis (by which is meant blocking APs) would have nothing to do with this because this isn't AP-generated Ca2+ release-- it's triggered by inhaled anesthetic.

Answer 95

a. Familial hypertrophic cardiomyopathy (FHC) occurs as a result of mutations in cardiac muscle tissue. Usually the mutations are located in the cardiac myosin heavy chain, where it interacts with actin and ATP; occasionally a mutation will occur in troponin instead.

Answer 96

a. X-linked recessive inheritance b. Frequency: 1/3500 males c. “Climb up themselves” (“Gower” sign, showing early, ~1 year) d. Wheelchair bound by 12; die in 20s due to cardiorespiratory failure e. 1/3 from spontaneous (non-inherited) mutation f. 10 year old falls 30-40x/day g. Genetic defect in DMD: dystrophin protein (forms the “steelbelt” supporting the muscle cell membrane) is broken down due to a premature stop codon in its gene. i. Dystrophin is the largest gene known: on Xp21, 79 exons long, 2.4Mbases. ii. Dystrophin links t-acting component on one side, then to transmembrane complex on plasma membrane that enables force to be conveyed to outside matrix

Answer 97

a. Myostatin is normally made and secreted by muscles as a negative feedback for muscle growth b. Inhibiting myostatin could lead to less muscle atrophy

Answer 98

Genetic disorder (dominant): RYR1 mutations about 70% Environmental disorder- exposure to anesthesia (typically inhalation agents (halothane) and/or succinylcholine Phenotype: hypermetabolism, skeletal muscle damage, muscle rigidity, rhabdomyolysis, hyperthermia; death if untreated

Answer 99

Prolonged open state of RYR1; increased intracellular Ca2+ Sustained muscle contraction and increased metabolism Heat production Muscle cell hypoxia and death

Answer 100

``` Muscle rigidity (masseter spasm) Increased CO2 Rhabodmyolysis Hyperthermia Nonspecific- Tachycardia Tachypnea Acidosis (respiratory/metabolic) Hyperkalemia ``` Do halothane/caffeine test on muscle biopsy

Answer 101

Dantrolene 2.5 mg/kg

Answer 102

X-linked disease dystrophin (DMD) mutations ``` boys- onset 3-5 years toe-walking Gowers' sign calf pseudohypertrophy high creatine kinase (1000s) ``` death in 20s (cardiomyopathy 100% by 18 yrs)

M2M Unit 4 Flashcards

(127 cards)