Muscle contraction and bone diseases

Question 1

Describe muscle contraction

Answer 1

1. AP depolarization opens voltage-gated Ca channels in the presynaptic nerve
2. The presynaptic nerve releases neurotransmitter. ligand binding to postynaptic muscle leads to muscle cell depolarization
3. Depol travels along muscle and down the T tubule
4. Depol of voltage-sensitive dihydropyridine receptor is mechanically coupled to the ryandoine receptor on the sarcoplasmic reticulum. This induces a conformation change, and Ca is released from the sarcoplasmic reticulum.
5. Ca floods the cytosol. Ca binds C-troponin. C-troponin can then move tropomysin, which had been blocking the myosing binding sites on the actin.
6. Myosin releases bound ADP. Inorganic P cuases displasement of myosin on the actin filament (Power stroke).

Question 2

Describe the bands of muscle contraction

Answer 2

A band: length of myosin. always constant
H band: amount of myosin in the middle that isn’t overlaping with actin. shortens with contraction
I band: amount of actin on either end of z band that doesn’t overlap with myosin. shortens with contraction.

Question 3

type 1 muscle fibers: speed, amt of mitochondria/myoglobin, color, vascularization, source of energy type of contraction. weight training effects

Answer 3

slow twich. slow twitch muscles are red because they have lots of mitochondria and myoglobin, and do lots of oxidative phosphorylation. good for sustained contraction. no change with weight training.
(dark meat of chicken legs)

Question 4

type 2 muscle fibers: speed, amt of mitochondria/myoglobin, color, vascularization, source of energy, type of contraction, effect of weight training

Answer 4

fast twich, little mitochondria/myoglobin, white, not as vascular- anaearobic glycolysis. fast contraction. weight training results in hypertrophy of fast twich molecs.

Question 5

Describe smooth muscle contraction

Answer 5

1. action potential causes an L-type voltage gated channel to open.
2. calcium floods the cell and forms a calcium calmodulin complex.
3. calcium calmodulin complex activates myosin light chain kinase
4. MLCK phosphorylates myosin, allowing it to interact with actin

Question 6

Describe smooth muscle relaxation

Answer 6

1. NO enters cell
2. NO activates guanylate cyclase, which converts GTP to cGMP
3. cGMP activates myosin light chain phosphorylase
4. myosin-P is converted to mysoin, which can’t interact with actin. causes relaxation

Question 7

endochondrial ossification vs. membranous ossification

Answer 7

endochondrial: axial and appendicular skeleton. cartilaginous model of bone is made by chondrocytes, then replaced by woven bone, then lamellar bone. Woven bone is seen in adults in Paget’s disease and post-fracture
membranous ossification: calvarium and face. woven bone is made without caritlage, then remodeled to lamellar bone

Question 8

What effect does estrogen have on bones?

Answer 8

inhibits apoptosis in bone forming osteblasts and promotes apoptosis in osteoclasts.

Question 9

Achondroplasia

Answer 9

endochondrial ossification is inhibited, while membranous ossification occurs normally. This leads to short limbs and relatively large heads. constitutive activation of FGFR3 actually inhibits chondrocyte proliferation. usually sporatic mutations related to advanced paternal age, though is autosomal dominant.

Question 10

What is osteoporosis? Dx? What is one iatrogenic cause?

Answer 10

spongy bone loses mass and interconnection despite normal lab values and normal bone mineralization. Dx with DEXA scan T scorle less than -2.5. may be caused by long-tern steroid use. no abnormal labs.

Question 11

Complication of ostoeporosis

Answer 11

vertebral crush fractures: acute back pain, loss of height, kyphosis

Question 12

type I osteoporosis: cause and complications

Answer 12

post-menopausal. increased bone resorption d/t decr. estrogen levels. see femoral neck fracture and distal radius fracture.

Question 13

type II osteoporosis and treatments

Answer 13

men and women > than 70. treatment with bisphosphonates (get into bone, are eaten by osteoclasts, and induce osteoclast apoptosis), low dose PTH, SERMs, (calcitonin), denosumab (monoclonal ab against RANKL, which acts as a signal for bone removal)

Question 14

What is osteopetrosis? Symptoms?

Answer 14

failure of normal bone resorption d/t defective osteoclasts. causes thickened, dense bones that are prone to fracture. bone fills the marrow space, so you see pancytopenia and extramedullary hematopoeisis. can cause cranial nerve impingement and palsies from narrow foramina (visual and hearing impairment). hydrocephauls, and renal tubular acidosis.
(alk phos is high b/c osteoblasts are working more than osteoclasts)

Question 15

Defects responsible for osteopetrosis. treatment

Answer 15

mutations that impair the ability of osteoclasts to generate acid for bone resorption. think of carbonic anhydrase: H20 + CO2 converted to H2CO3 by carbonic anhydrase. you get acid and bicarb. Acid leaves the cell. in this disease, carbonic anhydrase is mutated, so they can’t make acid.
tx: bone marrow transplant.

Question 16

What is osteomalacia? biochemical findings (calcium, phosphate, alk phos, PTH)

Answer 16

seen in adults (is rickets in kids. deposition of osteoid). from vitamin D deficiency. defective mineralization/calcification means bones that bow out. decr. vitamin d = decr. serum calcium = increased PTH = decr. serum PO4. osteoblasts are hyperactive, so alk phos goes up (osteoblasts require alkaline environment)

Question 17

osteogenesis imperfect

Answer 17

congenital defect in bone formation resulting in weak bone. AD defect in collagen synthesis type I. multiple fractures, blue sclera, and hearing loss bones of the ear fracture). sclera are blue b/c of exposure of the coroidal veins.