Week 3 Flashcards
Anatomy of parathyroids
The parathyroids consist of 4
glands located adjacent to the
thyroid gland
Each gland weighs
approximately 40 mg
The two superior glands are
usually found near the
posterior aspect of the capsule
The inferior glands are most
often located near the inferior
thyroid margin
Parathyroid
hormone
(PTH)
PTH gene is in chromosome 11
PTH is synthesized as a 110 amino acid polypeptide called pre-pro-PTH
It is cleaved to pro-PTH (90 amino acids) and then PTH (84 amino acids)
PTH is the major storage, secreted and biologically active form of the hormone. Ca regulates synthesis, release and degradation of PTH
Most important endocrine regulator of calcium and phosphorus
Parathyroid hormone is the
most important endocrine
regulator of calcium and
phosphorus concentration in
extracellular fluid.
is secreted from cells of the
parathyroid glands and finds its
major target cells in bone and
kidney.
primary hormone that is stored,
secreted and functions in the
body.
PTH receptors
Type 1 parathyroid
hormone receptor:
Binds both parathyroid
hormone and amino-
terminal peptides of PTHrP.
Type 2 parathyroid
hormone receptor:
Binds parathyroid hormone
but shows very low affinity
for PTHrP.
Function of PTH receptor 1
The PTH1R also mediates the
paracrine actions of PTHrP,
which play a particularly vital
role in the process of
endochondral bone formation.
These important functions, the
likely involvement of the
PTH1R in certain genetic
diseases affecting skeletal
development and calcium
homeostasis,
Function of PTH receptor 2
The PTH2R suggest
involvement in regulation of
fear, anxiety, reproductive
behaviours.
PTH Function-recap
Directly involved in the bones,
kidneys, and the small
intestine
Effects of PTH in the Bones
-Stimulates the release of calcium in an indirect process through osteoclasts which ultimately lead to resorption of the bones
Effects of PTH on the Kidneys
-Targets the distal convoluted
tubule and collecting duct,
directly increasing calcium
reabsorption.
-Parathyroid hormone decreases
phosphate reabsorption at the
proximal convoluted tubule
Activates vitamin D
•Plays a role in calcium
reabsorption in the distal
convoluted tubule via
calbindin-D, a cytosolic
vitamin D dependent calcium
binding protein. In the small
intestine, vitamin D allows
the absorption of calcium
Calcium sensing receptors
The CaSR allows regulation of parathyroid hormone (PTH) secretion and renal tubular calcium re-absorption in response to alterations in extracellular calcium concentrations.
CaSR and CAMP
Activation of phospholipase C :
Leads to generation of the second
messenger’s diacylglycerol and
inositol trisphosphate.
Inhibition of adenylate cyclase:- which
suppresses intracellular concentration
of cyclic AMP.
PTH and calcitriol function
PTH and calcitriol are the major hormones modulating calcium and phosphate homeostasis
Parathyroid hormone (PTH) Regulation
When blood calcium is high the Thyroid gland releases Calcitonin to drop the calcium blood levels
When blood calcium is low the Parathyroid gland releases PTH to increase the calcium blood levels
RANKL and IL expression
Bone metabolism is a dynamic process
that balances bone formation and bone
resorption
Central to this process is
the RANK/RANKL/OPG pathway
Bone formation
Performed by stimulating
osteoblasts and inhibiting
osteoclasts
Bone resorption
-Performed by active osteoclast
Stimulated by RANKL in
normal process
Stimulated by PTH in
pathologic
process (metastatic disease)
Interleukin 1 (IL-1)stimulates
osteoclast differentiation and
thus bone resorption
Three types of hyperparathyroidism + signs
A clinical syndrome causing
signs and symptoms that result
from ↑ PTH, PTH induced bone
resorption and hypercalcemia
- Primary
- Secondary
- Tertiary
Primary Hyperparathyroidism
Generalized disorder resulting
from excessive secretion of
parathyroid hormone (PTH) by
one or more parathyroid glands.
It probably is the most common
cause of hypercalcemia
Epidemiology Primary Hyperparathyroidism
Overall incidence is
42 in 100,000
Incidence increases
with age
Prevalence is 1:1000
Female to male ratio
is 2-3:1
Pathogenesis Primary Hyperparathyroidism
Overproduction of PTH by parathyroid chief cells
Effect of PTH on bone → increased bone resorption → ↑
release of calcium phosphate → ↑ calcium levels
Induces RANKL expression in osteoblasts → binding
of RANKL to RANK on osteoclasts → activation of
osteoclasts
Induces IL-1 expression in osteoblasts → activation
of osteoclasts
Effect of PTH on the kidneys → ↑ phosphate
excretion (phosphaturia)
Secondary hyperparathyroidism
Occurs most commonly in advanced
chronic kidney disease when decreased formation of
active vitamin D in the kidneys and other factors lead
to hypocalcemia and chronic stimulation of PTH
secretion.
Secondary hyperparathyroidism Pathogenesis
↓calcium and/or ↑ phosphate blood levels leads
to → reactive hyperplasia of the parathyroid glands → ↑ PTH
secretion
Chronic kidney disease → impaired renal phosphate excretion
→ ↑ phosphate blood levels→ ↑ PTH secretion
In addition, CKD → ↓ biosynthesis of active vitamin D → ↓
intestinal calcium resorption + ↓
renal calcium reabsorption → hypocalcemia → ↑ PTH secretion
Tertiary Hyperparathyroidism Pathogenesis
Chronic renal disease → refractory and
autonomous secretion of PTH → hypercalcemia
Renal disease → secondary or
tertiary hyperparathyroidism →
renal osteodystrophy → bone lesions
Familial hypocalciuric hypercalcemia benign
condition that causes chronically elevated
serum calcium and reduced calcium excretion.
Hypoparathyroidism 3 types
Deficient parathyroid hormone
secretion
Inability to Make Active Parathyroid
Hormone.
Resistance to Parathyroid Hormone
(pseudo-hypoparathyroidism).
Deficient Parathyroid Hormone Secretion
Lack of PTH leads to decreased
blood levels of calcium
(hypocalcemia) and increased
levels of blood phosphorus
(hyperphosphatemia).
There are no symptoms of too
little parathyroid hormone other
than the symptoms due to
having a blood calcium that is
too low.
Inability to Make Active Parathyroid Hormone.
Deficient PTH secretion without
a defined cause (e.g. surgical
injury) is termed Idiopathic
hypoparathyroidism.
This disease is rare and can be
congenital or acquired later in
life.
Congenital: Patients in this
category are born without
parathyroid tissues.
Acquired: Arises because the
immune system has
developed antibodies against
parathyroid tissues
Resistance to Parathyroid Hormone (pseudo-hypoparathyroidism)
Characterised by hypocalcemia
(too low blood calcium levels)
and hyperphosphatemia (too
high blood phosphorus levels)
But they are distinguished by
the fact that they DO produce
NORMAL parathyroid hormone.
The problem is that their bones
and kidneys do not respond to
the parathyroid hormone
