MECH 430 Lecture Notes - Lecture 12: Parathyroid Gland, G Protein–Coupled Receptor, Calcitriol Receptor
9 Jun 2018
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Lecture 11
➢ Regulation of Calcium (PTH/calcitonin/D3)
o Physiological role of calcitonin in humans in uncertain
o If we have rising levels of Ca, it will increase the release of calcitonin from our thyroid gland
that will decrease reabsorption of Ca from the urine filtrate → pee it away
o There seems to be no need for calcitonin in the human body although it is there
o If you have too high levels, you will automatically release Ca through the urine whether
calcitonin is there to regulate it or not
▪ However this is not true in other animals where calcitonin is very important in the control
of Ca levels in the body
➢ History
o 17th century:
▪ rickets is described in children
▪ softening and bending of the bones
o Remedies:
▪ Fish liver oil
▪ Sun exposure
▪ UV-irradiation of certain foods
▪ As a result of this, vitamin D was isolated and characterized and came to the recognition
that this hormone was promoting the absorption of Ca
o Active ingredient:
▪ Vitamin D → collective term of a series of related
compounds
▪ Promotes absorption of calcium from the gut
• Present in fish liver oil
• Inactive precursors can be activated by UV
o Later parathyroid hormone and calcitonin were discovered
o bound Ca in the body is always bound to proteins and tied
up in a lot of anions like lactate
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➢ Calcium has many roles in the body
o Major structural component of the skeleton
o Required for blood clotting → cross-linking of fibrin
o Regulation of enzyme activities → induction of conformational changes of co-factor
o Membrane excitability
▪ Action of neurotransmitter → hypocalcemia
• Epilepsy, tetany (spastic paralysis)
• Exocytosis of various substances
o “second messenger” of hormones signals
▪ release from endoplasmic reticulum (smooth)
o Muscle contraction
▪ Triggered by the release of Ca++ from the sarcoplasmic reticulum
o **extracellular and intracellular Ca++ levels are tightly regulated
▪ intracellular levels are about 1/1000 fold lower than extracellular
• levels are lower in the intraceullular
• roughly half of all Ca in the blood is complexed to albumin & the rest is
complexed to citrate
• free ioned that is not complexed is the portion of Ca that we are regulated &
bound forms are not regulated
• we are constantly regulating as we are taking in from our diet or excreting from
our systems
▪ there is a limited range in which they are regulated
➢ Distribution of Ca++ in normal human plasma
o The non-complex Ca++ is readily available and hence is the most important
o Protein bound and complexed Ca and metabolically inert and are not regulated by hormones
only ionized Ca levels are regulated by PTH and vitamin D
o i.e. Ca homeostasis maintains constant level of Ca in extracellular
fluid while providing enough Ca to cells, to bones, and renal excretion
▪ while compensating on a constant basis for changes in dietary
absorption, bone metabolism and renal function
o The equilibria between bound and unbound
Ca++ is important as indicated by the
induction of tetany by overbreathing →
hyperventilation
▪ The equilibrium is always changing
▪ Hyperventilation reduces the partial pressure of CO2
• If you hyperventilate, you might go into a tetany
• Overbreathing → less CO2, you produce less
biocarbonate that results in this dissociation where
hydrogen ions are released to counter the alkalosis
you are experiencing
▪ Less H2CO3 is produced and H+ falls → alkalosis
▪ To compensate H+ is released from serum proteins
• The negatively charged protein binds Ca++
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▪ Reduction in free serum Ca++ → tetany (extensive spasm of skeletal muscle) + other
complications
• Similarly, blood transfusions in which citrate is the anti-coagulant can cause
tetany
• Ca is now binding to proteins to counter those charges from the hydrogen ion that
have been released that is causing alkalosis to occur
• We have disturbed our Ca balance and cause tetany → muscles spasm&tighten up
➢ Concentration differential of Ca++ drives many biological processes
o Note the 1000 fold difference between the inside & outside of cells
o Additional compartmentalization in the cytoplasm
▪ Higher concentrations in the endoplasmic reticulum and mitochondria than in the rest of
the cytoplasm
▪ We maintain all these levels with ATP dependent Ca pumps
o ATP dependent Ca Pumps embedded in the membrane maintain the Ca++ gradient
o Intracellular → 0.1-1 uM
o Interstitial → 1.5 mM
o Serum → 2.5 mM
➢ Parathyroid glands
o 4 glands located adjacent to thyroid
▪ about 40 mg each
▪ about 15% of people have a 5th
▪ but most people only have 4 parathyroid glands
▪ the 5 would produce the equivalent of an individual to 4 because they respond to Ca
levels accordingly
o chief cells and oxyphil cells produce produce parathyroid hormone (PTH) in response to low
levels of ionized Ca in ECF
➢ Parafollicular of C-cells produce calcitonin
o Reduces serum Ca++
o C cells do not have a discrete location in the parathyroid gland, they are located randomly
o Calcium sensing receptor (CaR) located on cell membrane of chief cells detect ECF Ca++
o In the face of high levels of Ca, low levels of PTH are produced, thus high levels of Ca are
inhibitory & conversely, low levels of Ca in their ionized form, it is stimulatory for the release of
PTH granules from these parathyroid cells
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Inactive precursors can be activated by uv: later parathyroid hormone and calcitonin were discovered, bound ca in the body is always bound to proteins and tied up in a lot of anions like lactate. Ca++ is important as indicated by the induction of tetany by overbreathing hyperventilation: the equilibrium is always changing, hyperventilation reduces the partial pressure of co2. Calcium regulation of pth release: parathyroid gland chief cell calcium receptor has two signal transduction systems. Composition of bone: mineral content, 99% of total ca2+ acts as a structural matrix, 90% of total po4. Ca2+ pumps located in the osteocytic- osteoblastic bone membrane: in a slow exchange, ca2+ is moved from the stable pool in the mineralized bone into the plasma by means of. Compact bone and trabecular bone: compact bone: adult long bones, regularly arrayed columns of osteons, trabecular bone (woven bone): epiphysis, fractures, juvenile bone, bone disorders.
