Parathyroid Physiology Flashcards
Cells, Hormone synthesis and actions, Ca2+ homeostasis
What are the two types of cells in the parathyroid gland?
chief cells and oxyphils
What stimulates the release of PTH?
Low serum calcium
What indicates to the chief cells to synthesise and secrete PTH?
CaSR’s
If CaSR senses high serum Ca2= what kind of signal does it send the chief cells?
inhibitory
PTH is what class of hormone? And is it hydrophilic or hydrophobic?
Peptide, hydrophilic
What cells secrete calcitonin?
Parafollicular cells of the thyroid gland
What is the stimulus for calcitonin secretion?
High serum Ca2+
Describe the synthesis of PTH.
- CaSR on Cheif cells in PTG
- triggers transcription to mRNA
- mRNA translated into preprepetide form of PTH
- cleaved in the ER into propeptide form of PTH
- transported to golgi for enzyme modification and becomes peptide form of PTH and is pacjkaged into secretory vesicles.
Differentiate the roles of osteoclasts and osteoblasts.
Osteoclasts reabsorb bone and osteoblasts deposit bone
Through what mechanism does PTH stimulate osteoclast reabsorption of bone?
RANKL /RANK pathway
What chemicals are secreted by osteoclasts to break down and reabsorb bone components?
?? Cathepsins, ALP, acids
What is the primary regulator of Ca2+ levels?
PTH
What are the direct effects of PTH on the kidneys?
PTH acts on the DCT to promote reabsorption of Ca2+ from the filtrate and to excrete phosphate.
Describe the synthesis of vitamin D.
Sunlight on the skin converts 7-Dehydrocholesterol into cholecalciferol.
Cholecalciferal travels to the liver where the enzyme 25-hydroxylase converts it to 25 hydroxycholecalciferal. Because PTH causes the kindeys to express 1-alpha hydroxylase, 25-hydroxycholecalciferol is converted to the active form of vitamin D (calcitriol, 1,25- dihydroxycholecalciferol)
What is the role of vitamin D?
Vitamin D induces the synthesis of Ca2+ channels in the duodenum that allows absorption of Ca2+ from the GIT into the blood, therefor increasing serum calcium levels.
What is the target cell for calcitonin? and what is it’s effect? By what mechanism?
Osteoblasts.
Causes inhibition of Osteoclast activity.
Mechanism: - It tells the osteoblasts to make more RANK and to make less RANKL
So less preosteoclasts mature leading to less osteoclast activity.
Bone is the body’s primary storehouse of what compounds?
Ca2+
Phosphate
Carbonate
Magnesium
What is the most prevalent cation in the body?
Ca2+
99% of Ca2+ is stored as?
Hydroxyapatite
What is the the biologically active form of Ca2+?
Ionised Ca2+
What is the normal serum Ca2+ range?
8.5-10.5 mg/dL
41% of plasma Ca2+ is what
?
Bound to albumin
Name the 3 molecules involved in Ca2+ homeostasis.
PTH
Calcitonin
Vitamin D
Over-mineralisation of the bones results in which disorder?
Ostegenesis imperfecta
Briefly describe the mineralisation of bone.( making of hydroxyapitite)
alkaline phosphatase converts inorganic pyrophosphate into inorganic phosphate by joining to calcium to make hydroxyapatite
List the intracellular roles of Ca2+
o Muscle contraction.
o Hormone secretion.
o Glycogen metabolism.
o Cell division.
o Activation of enzymes.
o Transfer of the ions across the cell membrane.
List the extracellular roles of Ca2+
o Bone Mineralization.
o Blood coagulation factors.
o Plasma membrane potential.
o Maintenance of intracellular calcium.
o Calcium decreases neuromuscular excitability.
The organic matrix of the bone is made up of
- type 1 collagen
- ECF
- proteoglycans
- cell attachment factor
-osteonectin
osteopontin
What is the role of calcium in neurotransmission?
Ca2+ triggers synaptic vesicle exocytosis, thereby releasing the neurotransmitters contained in the vesicles and initiating synaptic transmission.
What are the 3 mechanisms that increase intracellular Ca2+ concentration?
- Voltage-gated Ca channels are activated by membrane depolarization, allowing Ca to enter the cytosol.
- Hormones or neurotransmitters can open ligand-gated channels on the cell membrane, allowing Ca to enter the cytosol.
- Hormones and neurotransmitters (such as norepinephrine and angiotensin II) can, via the phospholipase-C (PLC) pathway, cause an increase in intracellular inositol triphosphate (IP3).
What is calcium’s role in muscle contraction?
Calcium role is exposing myosin binding sites on actin to facilitate muscle contraction.
What are the name of the 2 receptors that form a complex linking the sarcoplasmic reticular membrane and the membrane of the t-tubules, that allows entry of Ca2+ for muscle contraction?
Ryanodine receptor and DHP receptor
Most Procoagulants and anti-coagulants are produced where?
the liver
What is required for anticoagulants and procoagulants ot bind to calcium in the clotting cascade?
vitamin-k-dependant gamma carboxylation of glutamic acid
What is required for calcium to promote conversion of factor X to Xa in the clotting cascade?
The exposure of tissue factor to factor VIIa and Ca2+
What is the role of Ca2+ in blood clotting?
IN summary, what is Ca2+’s role in the clotting cascade?
acceleration of the pathway.
The principle hormones involved in homeostasis are? And what are their 3 target organs?
Vitamin D
Calcitonin
PTH
Intestine
Bone
Kidney
What are the actions of PTH?
o Increases bone resorption by activating osteoclasts activity
o Increases renal Ca reabsorption by the distal renal tubules
o Increases renal phosphate excretion by decreasing tubule phosphate reabsorption
o Increases the formation of 1,25 dihydrocholecalciferol by increasing the activity of alpha-hydroxylase in the kidney
What are the actions of Vitamin D?
-decreases PTH production
- Increases bone growth and formation and sometimes calcium and phosphate relese from the bone inconjunction with PTH
- increases calcium reabsorption from the kidney
- inccreases calcium and phosphate ansorption fromthe intestines.
What are the actions of calcitonin?
o Inhibits bone resorption
o Increases renal Ca excretion
Calcium concentration in maintained via?
Maintained via absorption from the gut and excretion via the kidney with bone acting as a buffer with Ca2+ in reserve.
Maintaining a constant plasma [Ca2+] is important for:
o nerve transmission
o nerve conduction
o muscle contraction
o cardiac contractility
o blood clotting
o bone formation
o excitation–secretion coupling
o cell-to-cell adhesion
o cell-to-cell communication.
Hypocalcemia in general causes:
Neuromuscular excitability
In hypocalcemia, Neuromuscular excitability manifests as?
Pins and needles sensations
tetany
paralysis
convulsions
What is the most common cause of hypocalcemia?
Accidental damage or removal of parathyroid glands during a thyroid surgery.
Aside from removal or damage to the PTG’s, what are other possible causes of hypocalcemia?
Hypoparathyroidism
vitamin D deficiency nor disorder
What are the two clinical signs of hypocalcemia?
Trousseau’s sign (hand spasm)
Chvostek’s sign (face twitch)
Acute hypercalcemia causes what clinical manifestations?
Fits
vomiting
polyuria
Chronic hypercalcemia signs are?
Stones: (kidney stones/failure)
Bones: (pain, usually osteitis fibrosa cystica)
Groans: (abdominal Sc: nausea, comiting, constipation, indigestion)
Psychiatric Moans: (Nervous system sx: lethargy, fatigue, memory loss, psychosis, depression)
What are 5 causes of hypercalcemia?
- primary hyperparathyroidism
- extensive skeletal metastases
- PTHrH secretion from tumours
- Vitamin D excess
- granulomatous diseases
What is more dangerous, hypocalcemia or hypercalemia and why?
Hypocalcemia, can quickly lead to convulsions and death
