What are the function of bones?
- Serve as reservoir for calcium and phosphate
- Provide mechanical support to soft tissues
- Act as levers for muscle action
- House and protect the brain and spinal cord
What cells are used for bone remodeling?
Osteoblasts - deposit bone
Osteocytes - maintain bone
Osteoclasts - digest bone by secreting acid into Howship's lacunae (require lots of H pumps --> ATP --> and mitochondria)
What embryonal layer does the thyroid develop from?
--> It originates in the foramen cecum and mirates down the thyroglossal duct system
--> can lead to ectopic thyroid hormone
What is the histological structure of the thyroid gland?
It is an endocrine gland made up of follicles lined with follicular epithelium as the functional unit
--> consists of parenchyma and stroma
--> does NOT contain ducts
--> Divided into lobes and lobules
How is thyroid hormone synthesized?
- Thyroglobulin is synthesized and modified before being packaged into vesicles
- It is then secreted by exocytosis into the follicle lumen to wait until needed
- Iodide is transported into the cell and oxidized ito iodine, then also released into the follicle
- Thyroid peroxidase iodinates thyroglobulin into monoiodotyrosine (MIT) and diiodotyrosine (DIT) making T4 and T3
- Stimulation of thyroid cells by TSH leads to release of thyroid hormones
What is the difference between Thyroxine (T4) and Triiodothyronine (T3)?
T4 = DIT+DIT
- less active
T3 = MIT+DIT
- more active
What are C cells?
Thyroid parafollicular cells
- They secrete calcinotin
- Calcitonin reduces blood [Ca2+]
What is the embryological development pattern of the parathyroid glands?
Early 5th week:
- Inferior parathyroid glands form in dorsal portion of 3rd pharyngeal pouch
- Superior parathyroid glands form in the 4th pharyngeal pouch
- Detach and migrate inferiorly and medially
- Come to rest in final location
What are the cells of the parathyroid?
- Produce PTH and release it in response to low serum Ca levels
- Eosinophilic due to large amounts of mitochondria
- Function unknown
What are the hormones that regulate calcium homeostasis?
- Vitamin D: increases intestinal reabsorption
- PTH: Causes bone resorption
Increases activation of Vit. D
Increases renal Ca reabsorption
How are serum Ca levels detected?
By Calcium-sensing Receptors (CaSR) on the chief cells of the parathyroid gland
Where is PTH active?
How does the system of osteoclast activation/inhibition work?
Osteoclasts and osteoclast precurors express RANK (receptor activator of nuclear factor kappa-beta)
As PTH increases (along with growth factors, hormones, and cytokines), it activates osteoblast lineage cells to produce RANKL
In the absence of PTH, osteoprotegerin (OPG) is expressed by osteoblast lineage cells and inactivates RANKL, preventing it from binding to RANK and activating osteoclasts
What is Denosumab?
Pharmalogical Antibody against RANKL
--> acts like OPG
--> Leads to increased bone mineral density in lumbar spine, total hip, distal third radius
How does PTH and Estrogen expression affect RANKL and OPG?
Where does calcitonin come from and what is its MOA?
Produced in parafollicular cells of the thyroid
It inhibits absorptive activity of osteoclasts and decreases formation of new osteoclasts
Works to decrease serum [Ca2+]
What stimulates bone formation?
- Increased blood Ca levels
(increased calcitonin levels)
- Increased mechanical loads
- Estrogen (decreases number of osteoclasts by reducing RANKL synthesis)
What are the target tissues of PTH?
Increases expression of RANKL --> indirectly increases differentiation and activation of osteoclasts
Kidney: Late distal tubule
Decreases Ca2+ excretion
Increases phosphate excretion
Increases absorption of Ca2+ and Phosphate
What stimulates bone resorption?
- Decreased serum Ca2+ levels
- Immobilization of bones
--> bedrest, austronauts
- Estrogen deficiency