Physiology Flashcards
Describe Bone Resorption by Osteoclasts
Big Picture
Integrins bind to vitronectins on the bone surface to seal osteoclasts to the bone.
Osteoclast reabsorbs bone by secreting protons and acid pro teases into the lacuna (bone)
Acid secretion is mediated by a V-type proton pump and Cl- channel (ClC7) at the ruffled border.
Carbonic anhydride (CA) in the cytoplasm supplies the Protons in the H pump. Reacts with CO2 that diffused into the cell.
Biocarbonate/chloride exchangers located on the membrane opposite the ruffled border get the byproduct of CA (HCO3) out of the cell because it makes cell basic.
Clathrate mediates the formation of secretory vesicles.
TRAP is an enzyme that is present and used for staining to check for osteoclast activity. No TRAP is lowered or nonexistent osteoclast activity.
What is the purpose of bone remodeling?
Establish the optimum bone strength by replacing microscopic damage
Maintain calcium homeostasis.
What are the steps of Fracture repair?
Fracture Hematoma formation
Callus Formation
Spongy Bone formation
Compact Bone formation
Explain Osteoclast Signaling Inhibition
Big Picture
Calcitonin is released to decrease plasma Ca concentration in opposition to PTH
Binds to Osteoclast and triggers intracellular cAMP from ATP via adenylyl Cyclase.
Protein Kinase A (PKA) catalyzes transfer of terminal phosphate to inhibit bone resorption.
OPG (osteoprotegerin) is secreted by osteoblasts and osteopenia stromal stem cells to bind to RANKL and stop it from binding with RANK.
In additiion, WNT/B-catenin is created by osteoprogenitor cells that activate the production of OPG from osteoblasts.
Explain Osteoclast Signaling for activiation.
Big Picture
IL-6 is believed to play positive role by activating expression of RANKL. ***
PTH binds to osteoblast
This leads to the formation of RANKL and releases M-CSF to bind with Preosteoclasts. RANKL binds to RANK also on the Preosteoclasts.
PTH also inhibits the production of OPG which can bind to RANKL and inhibit preosteoclast maturation.
Mature osteoclasts develop ruffled border and release enzymes from lysosomes as well as acids to promote bone resorption.
*** Osteoprogenitor cells that make WNT/B-catenin to promote OPG can be inhibited by Sclerostin which is produced by osteocytes. Those Progenitor cells also make BMPs to bone osteoblasts and induce bone formation.
Explain the PTHs creation pathway
Starts at 115 AA in nucleus.
Drops to 90 AA in ER
Then 84 AA in Golgi.
By secretion it is broken into a large chunk and small chunk mostly. The small chunk of 1-34 AA is active and has 1/2 life of 30 seconds. The large chunk has 4 hr 1/2 life and is inactive. If it doesn’t break it has 1/2 life of 5 min and is active.
What increases plasma Ca and what decreases plasma Ca?
PTH will be released at low Ca levels to increase them.
Calcitonin is released at high levels of Ca to lower them. (From thyroid)
Which protein binds Ca? What percentage is bound?
Albumin
40%
The more acidemia there is in the blood, the more ionized Ca there can be because it isn’t stuck to albumin.
What effects does PTH have on the different systems of the body?
Bones: Mature osteoclasts break down bone and release Ca ions into plasma.
Kidneys: Make Calcitriol which stimulates Ca reabsorption in the kidneys. Less Ca lost in urine.
intestines: Calcitrol also enhances Ca absorption from food.
What are bodily effects of Cacitonin?
Bone: Osteoclast inhibited, letting osteoblasts continue to form bone.
Kidneys: Inhibits calcitriol and Ca reabsorption
Intestines: Ca absorption decreased with decreasing PTH and calcitirol.
Decreases Ca plasma levels.
What effect does FGF-23 have the body?
Made by Osteocytes and it is affected by the amount of Serum phosphorus. As phosphorus increases in the blood, FGF-23 is activated and inhibits the amount of PTH. The amount of PTH also stimulates FGF-23 to turn itself off. Both FGF-23 and PTH stimulate more urinary phosphorous as well.
What are the influencing factors of increasing osteoblasts activity?
Compressional load or exercise
Tension placed on bone
Testosterone
Adequate dietary intake of Ca, Vitamins C, D, and K
What decreases Osteoclast activity?
Estrogen
Calcitonin
Increase in blood Ca ion concentration.
What decreases Osteoblast activity?
Inadequate exercise
Inadequate Dietary intake of Ca and vitamins C, D, and K
What increases Osteoclast activity?
Continuous pressure placed on bone.
PTH
Decrease in blood Ca ion concentration.
Describe the two parts of Costameres and what they do
Costameres facilitate the lateral transmission of contraction force to stabilize the sarcolemma.
Dystrophin-glycoproteins complex (DGC)
Integrin-vinculin-talin complex
What are the two directions of muscle contraction?
Longitudinally to tendon by sarcolemma.
Laterally by Costameres.
Duchenne Muscular Dystrophy
X-linked recessive defect in the dystrophin gene.
Affects kids early 3-5.
Gives pseudohypertrophy of the calves, and overall muscle wasting.
What innervates the motor portion of skeletal muscle?
A-motor neurons.
The synaptic cleft between the muscle and neuron is also called the end plate.
Depolarization of the membrane
Hyperpolarization of the membrane?
Depolarization is making the potential less negative
Hyperpolarization is making it more negative.
How does the size of the motor neuron change the signal?
The bigger the cell the lower the conduction but higher the velocity for fast twitch fibers.
The smaller the cell the higher the conduction but lower velocity for slow twitch fibers.
Explain DHP and RyR
DHP is the voltage gated channel that physically connects to RYR or ryanodine receptors. The RYR is like a cap that lets Ca out from the SR.
What are the components and functions of troponin?
Troponin T: binds the complex to tropomyosin.
Troponin I: inhibits myosin binding to actin
Troponin C: Binds to Ca and is found only in striated muscle.
Explain the muscle cross-bridge cycle
Myosin binds to actin, Pi is released causing a Power stroke. ADP is released (Rigor myosin lower energy form). New ATP binds to myosin head unbinding myosin from actin. ATP is hydrolyzed to cock the myosin head in its high-energy form
What are the two things needed to stop an action potential?
Action potential has to stop, and then Ca ions are actively removed.
Ca is removed by Na/Ca channels into the extra cellular space, and by active transport moving Ca into the SR using ATP and swapping 2 H for 2 Ca.
What are the tree phases of twitch?
What is the Refractory period?
-What is special in these periods for smooth and cardiac muscle.
Latent period: time for AP to propagate across sarcolemma
Contraction period: crossbridging
Relaxation period: Ca reduced, tension diminishes.
Refractory period is the onset of the latent period to contraction
-Muscle fiber can’t respond to further stimuli. In the case of smooth muscle and cardiac muscle the refractory period is as long as their contractions.
Define Tetany
After a contraction, the muscle is stimulated before it relaxes completely giving an even stronger contraction
If no rest is given between twitches it is complete tetanus that causes large fatigue. Small rest between twitches gives unfused tetanus or sustained high power.
What changes as there are more sarcomeres (double) in parallel versus in series?
In parallel (hyperplasia or hypertrophy) doubles force
In series (lengthen) double velocity and shortening capacity.
What does the elastic element do during rest, isometric and isotonic contractions
At rest both the sarcomeres and the elastic components are at rest.
In isometric contractions the muscles contract, but only the elastic component of the muscle lengthens. There is no shortening of the muscle.
In isotonic contractions the entire muscle and elastic component shortens and lengthens respectively.
What factor is in charge of hypertrophy, more vascularization, an more mitochondria etc?
PGC-1a
Muscle adaptations
What is TFAM
It is a key activator for Citric acid cycle enzymes from exercise
What are the Transcription factors converting fast-twitch to slow-twitch muscle
NFAT and HDAC
