ENDOCRINE-PARATHYROID (cell)

Question 1

PARATHYROID GLAND - ANATOMY

Most species have 2 pairs (4 total)
 Pigs and rats have only ? pair

Location varies between ?
 Usually at the poles of the 2 lobes of the ? glands

CHEMICAL STRUCTURE OF HORMONES (RECALL)
1. PROTEIN OR PEPTIDE HORMONES * Makes up the ? of hormones
o Ex: Insulin, ACTH, ** ? **, CCK
o LH, FSH and TSH (glycoproteins)

• Are ** ? ** as a larger molecule
  (PRE-PROHORMONE->PROHORMONE) inside of the ER and Golgi apparatus
  o Packaged into secretory ? awaiting for secretion

Answer 1

PARATHYROID GLAND - ANATOMY

Most species have 2 pairs (4 total)
 Pigs and rats have only 1 pair (2 total)

Location varies between species
 Usually at the poles of the 2 lobes of the thyroid glands

CHEMICAL STRUCTURE OF HORMONES (RECALL)
1. PROTEIN OR PEPTIDE HORMONES * Make up the majority of hormones
o Ex: Insulin, ACTH, ** PTH **, CCK
o LH, FSH and TSH (glycoproteins)

• Are ** made ** as a larger molecule
  (PRE-PROHORMONE->PROHORMONE) inside of the ER and Golgi apparatus
  o Packaged into secretory granules awaiting secretion

Question 2

PARATHYROID GLAND

There are 2 types of parathyroid cells in the glandular tissue:

1. CHIEF CELLS (darker colored ones)
    Produce ? (Parathormone or Parathyroid hormone)
2. OXYPHIL CELLS
    ? function, larger than chief cells, present ? and ? enzyme activity

Answer 2

PARATHYROID GLAND

There are 2 types of parathyroid cells in the glandular tissue:

1. CHIEF CELLS
    Produce PTH (Parathormone or Parathyroid hormone)
2. OXYPHIL CELLS
    unknown function, larger than chief cells, present oxidative and hydrolytic enzyme activity

Question 3

PTH SYNTHESIS

Parathyroid cells are ** very ? ** to a decline in blood ionic calcium [iCa]
 ?-sensing receptors on gland membrane surface
 e.g. of ? coupled receptors (cAMP-PKA-gene transcription)

 ** Decrease in blood [iCa] (hypocalcemia) stimulates ? release **
 Normal or increased [iCa] in blood (hypercalcemia) – inhibition of ? release

PTH synthesis is similar to other ? hormones
o ?-PTH is synthesized in rER and then cleaved to pro-PTH
o The “pro” portion is removed (in the Golgi) and the resulting ? is secreted by exocytosis
 Metabolized by ? and the ?
 Half-life of ? min

Answer 3

PTH SYNTHESIS

Parathyroid cells are ** very sensitive ** to a decline in blood ionic calcium [iCa]
 calcium-sensing receptors on gland membrane surface
 e.g. of g-protein coupled receptors (cAMP-PKA-gene transcription)

 ** Decrease in blood [iCa] (hypocalcemia) stimulates PTH release **
 Normal or increased [iCa] in blood (hypercalcemia) – inhibition of PTH release

PTH synthesis is similar to other protein hormones
o Prepro-PTH is synthesized in rER and then cleaved to pro-PTH
o The “pro” portion from the pro-PTH is removed (in the Golgi) and the resulting PTH is secreted by exocytosis
 Metabolized by the liver and the kidneys
 Half-life of 5-10 min

(the previous trigger for this receptor is Ca+
so once there is low level of calcium then triggers cAMP .. then creb in preproPTH)

Question 4

Where is parathyroid hormone (PTH) produced?

PARATHYROID GLAND – Calcium and Phosphate

Main gland involved in the Calcium (Ca2+) & Phosphate (PO4) metabolism
o These ions play a major role in physiological ?

PHOSPHATE PO4
* ? system
* Composition of cell membrane and
intracellular components
* ? acid
* ? Triphosphate (ATP)
* Adenosine Monophosphate (AMP)
* ** 85% in ? **; 14% Intracellular; 1% ECF

CALCIUM
* ? contraction
* ? cell activity
* Release of ? by exocytosis
* Activation of several ?
* Blood coagulation
* Maintenance of membrane stability
* Structural integrity of ? and teeth
** 99% in ? (when not enough calcium - take it from bones) **; <1% Intracellular; 0.1% ECF

Answer 4

Where is parathyroid hormone (PTH) produced? CHIEF CELLS

PHOSPHATE PO4
* buffer system
* Composition of cell membrane and
intracellular components
* nucleic acid
* Adenosine triphosphate (ATP)
* Adenosine Monophosphate (AMP)
* ** 85% in bones **; 14% Intracellular; 1% ECF

CALCIUM
* muscle contraction
* nerve cell activity
* Release of hormones by exocytosis
* Activation of several enzymes
* Blood coagulation
* Maintenance of membrane stability
* Structural integrity of bones and teeth
** 99% in bones!! ** (when not enough calcium - take it from bones) **; <1% Intracellular; 0.1% ECF

Question 5

POOL OF CALCIUM

 99% in ?
-> (in the form of hydroxyapatite crystals, which contain calcium, phosphate, and water)
 <1% ?
-> Bound to ?, within ER or ?
-> Increased intracellular ? concentrations are indicative of increased cell activity

0.1% ECF (insterstitial fluid and blood)
 50% is ? (iCa)
-> ** Biologically ? form
-> ? regulated **
 40% bound to proteins
-> Mainly albumin
 10% is combined with other anions

iCa is the most important pool for physiological control of ? concentrations in the blood

Answer 5

POOL OF CALCIUM

 99% in bones
-> (in the form of hydroxyapatite crystals, which contain calcium, phosphate, and water)
 <1% intracellular
-> Bound to proteins, within ER or mitochondria
-> Increased intracellular calcium concentrations are indicative of increased cell activity

0.1% ECF (insterstitial fluid and blood)
 50% is ionized (iCa)
-> ** Biologically active form
-> precisely regulated **
 40% bound to proteins
-> Mainly albumin
 10% is combined with other anions

iCa is the most important pool for physiological control of calcium concentrations in the blood

Question 6

CALCIUM-PHOSPHATE METABOLISM

The regulation of calcium levels involves control of the movement of calcium between the ECF and 3 organs:
o ?
o ?
o ? tract

 3 hormones are involved in this process o ? (parathyroid hormone)
o Active ? (Calcitriol – steroidlike molecule)
o ? (thyroid hormone – parafollicular cells/C-cells)

Answer 6

CALCIUM-PHOSPHATE METABOLISM

The regulation of calcium levels involves control of the movement of calcium between the ECF and 3 organs:
o bones
o kidneys
o GI tract

 3 hormones are involved in this process
o PTH (parathyroid hormone)
o Active form of vit D (Calcitriol – steroidlike molecule)
o Calcitonin (thyroid hormone – parafollicular cells/C-cells)

Question 7

PTH actions

The net effect of PTH is to:
- increase ?
- decrease ?
concentrations in ECFs

 Direct effect on ? and ? metabolism of calcium
 ? effect on GI metabolism of calcium * Via calcitriol

Answer 7

PTH actions

The net effect of PTH is to:
- increase calcium
- decrease phosphate
concentrations in ECFs

 Direct effect on bone and kidney metabolism of calcium
 indirect effect on GI metabolism of calcium * Via calcitriol

(calcium phosphate ratio (they both go together - are inversely proportional to each other so PTH will have a direct effect on bones and kidneys and an indirect effect on GI metabolism of calcium - that works with calcitriol)

Question 8

BONES

Osteoblasts - responsible for the formation of ? ? tissue (bone developing and remodeling)
(osteogenic cell: ? cell)

Osteocytes - ? (local mineral deposition at the bone matrix), differentiated from osteoblasts (mesenchymal stem cells)

Osteoclasts - ? bone tissue (remodeling or pathological processes). Differentiated from ? which are big multinucleated cells (hematopoietic stem cell)

Answer 8

BONES

Osteoblasts - responsible for the formation of new bone tissue (bone developing and remodeling)

(osteogenic cell: stem cell)

Osteocytes - biomineralization (local mineral deposition at the bone matrix), differentiated from osteoblasts (mesenchymal stem cells)

Osteoclasts - degrade bone tissue (remodeling or pathological processes). Differentiated from monocytes which are big multinucleated cells (hematopoietic stem cell)

Question 9

PTH ACTIONS – TWO DIRECT EFFECTS ON BONE

PTH:
1. Promotes the transfer of ? across the osteoblast-osteocyte membrane

 Osteocytes pump iCa from the fluids within bone canaliculi → into the ? fluid → blood vessels

2.Binds to receptors on bone ? cells and stimulates the production of ?-activating factor

Causes activation of nearby ?
 Moves toward the bone and begin to digest the organic matrix – called bone ?
 ** Releases ? and ? into the blood **

Answer 9

PTH ACTIONS – TWO DIRECT EFFECTS ON BONE

PTH:
1. Promotes the transfer of iCa across the osteoblast-osteoc”y”te (b”io”=sounds like “yo” mineralization) membrane

 Osteocytes pump iCa from the fluids within bone canaliculi → into the ECF → blood vessels

2. Binds to receptors on bone osteoblast cells and stimulates the production of osteoclast-activating factor

Causes activation of nearby osteoclasts
 Moves toward the bone and begin to digest the organic matrix – called bone resorption
 ** Releases iCa and PO4 (phosphate) into the blood **

(2 diff steps, 1 is acting on osteoblast - pumping only calcium in blood and then action osteoclasts that will be eating bone as a whole
OVERALL - better increase in calcium in blood plasma)

Question 10

PTH ACTIONS - DIRECT EFFECTS ON KIDNEYS

1. Acts on the ? convoluted tubules increasing reabsorption of ? (taking calcium back into blood plasma)
2. Acts on the proximal convoluted tubules decreasing renal reabsorption of ?

(let more phosphate go into urine as we want to raise calcium and let go of phosphate so the ratio is more calcium and less phosphate

so if low calcium then need to get rid of phosphate as well to maintain the calcium and phosphate ratio)

3. Acts on VIT ? activation by the kidneys

 Vit D must be transformed by ? and ? to become biologically activated
 ** PTH stimulates the kidney enzyme 1-alfa-? which converts ** calcidiol 25(OH)D → ? 1,25(OH)2D

 Calcitriol increases the absorption of calcium by the ? tract
 Also enhances the effects of PTH on bone metabolism of ?

Answer 10

PTH ACTIONS - DIRECT EFFECTS ON KIDNEYS

1. Acts on the distal convoluted tubules increasing reabsorption of calcium (taking calcium back into blood plasma)
2. Acts on the proximal convoluted tubules decreasing renal reabsorption of phosphate

(so as to let more phosphate go into urine as we want to raise calcium and let go of phosphate so the ratio is more calcium and less phosphate

so if low calcium then need to get rid of phosphate as well to maintain the calcium and phosphate ratio)

3. Acts on VIT D activation by the kidneys

 Vit D must be transformed by kidney and liver to become biologically activated
 ** PTH stimulates the kidney enzyme 1-alfa-hydroxylase which converts ** calcidiol 25(OH)D → calcitrol 1,25(OH)2D

 Calcitriol increases the absorption of calcium by the GI tract
 Also enhances the effects of PTH on bone metabolism of calcium

Question 11

VITAMIN D METABOLISM

UV (sun) -> vitamin D3 cholecalciferol
- made in the ?
- found in oily ?, egg yolks,and ? food

** VIT D BECOMES AN ? HORMONE UNDER ? ACTION ON RENAL (kidney) CELLS ** (recall: PTH secretes 1-alfa-?)

Because of its lipid nature, calcitriol is carried in plasma by ? (produced in the liver)

Answer 11

VITAMIN D METABOLISM

UV (sun) -> vitamin D3 cholecalciferol
- made in the skin
- found in oily fish, egg yolks,and fortified food

** VIT D BECOMES AN ACTIVE HORMONE UNDER PTH ACTION ON RENAL (kidney) CELLS ** (recall: PTH secretes 1-alfa-hydroxylase)

Because of its lipid nature, calcitriol is carried in plasma by transcalciferin (produced in the liver)

Question 12

PTH ACTIONS - INDIRECT EFFECT ON GI

Calcitriol stimulates the active transport of dietary ? across the intestinal epithelium

 Without calcitriol, most animals are unable to acquire enough calcium from the diet to support normal ? structure
 By regulating [calcitriol] the animal can regulate ? entering the blood from ?

 EXCEPT for ? (cecum) fermenters (i.e., horse and rabbits)
*? mechanisms to absorb calcium all the time
* Regulate blood Ca2+ by increasing/decreasing ? loss
* ** Chalky ?-colored ? **

What are the 3 main organs participating in the regulation of calcium
blood levels?

Answer 12

PTH ACTIONS - INDIRECT EFFECT ON GI

Calcitriol stimulates the active transport of dietary calcium across the intestinal epithelium

 Without calcitriol, most animals are unable to acquire enough calcium from the diet to support normal bone structure
 By regulating [calcitriol] the animal can regulate ionized Calcium (iCa) entering the blood from diet

 EXCEPT for hingut (cecum) fermenters (i.e., horse and rabbits)
*intestinal mechanisms to absorb calcium all the time
* Regulate blood Ca2+ by increasing/decreasing urinary loss
* ** Chalky white-colored urine **

What are the 3 main organs participating in the regulation of calcium
blood levels? -> kidney, liver and intestines

Question 13

PTH secretion is mainly controlled by:

 Free (ionized) ? concentration in the blood
 Decrease in [iCa] stimulates ? secretion
 Increase in [iCa] inhibits ? secretion

Answer 13

PTH secretion is mainly controlled by:

 Free (ionized) calcium concentration in the blood
 Decrease in [iCa] stimulates PTH secretion
 Increase in [iCa] inhibits PTH secretion

Question 14

CALCITONIN

• Calcitonin is produced by ? cells or C-cells in the THYROID gland

o They are scattered throughout the body of the ? gland (among the follicles)

• Synthesized as ? hormones (Preprohormones – prohormones – hormones)

** Increase in blood [ ? ] stimulates calcitonin release
* It ? the effects of PTH **

Answer 14

CALCITONIN

• Calcitonin is produced by parafollicular cells or C-cells in the THYROID gland

o They are scattered throughout the body of the thyroid gland (among the follicles)

• Synthesized as protein hormones (Preprohormones – prohormones – hormones)

** Increase in blood [ iCa ] stimulates calcitonin release
* It counterbalances the effects of PTH **

Question 15

CALCITONIN ACTIONS

? the movement of calcium from the bone
 from bone ? pool (behind the osteoblast-osteocyte barrier) to the ECF
 bone resorption through an inhibitory effect on osteoclasts

Increases
 movement of ? from ECF into bone
 renal ** excretion of ? and ? **

Calcitonin secretion is regulated by ? concentration in the blood
-> Increased [iCa] stimulates calcitonin secretion

? hormones also stimulate the secretion of calcitonin
EX: Gastrin, ?, ?

Answer 15

CALCITONIN ACTIONS

decreases the movement of calcium from the bone

 from bone calcium pool (behind the osteoblast-osteocyte barrier) to the ECF
 bone resorption through an inhibitory effect on osteoclasts

Increases
 movement of PHOSPHATE from ECF into bone
 renal ** excretion of CALCIUM and PHOSPHATE **

Calcitonin secretion is regulated by calcium concentration in the blood
-> Increased [iCa] stimulates calcitonin secretion

GI hormones also stimulate the secretion of calcitonin
EX: Gastrin, secretin, CCK

Question 16

Calcium metabolism

pic:

a decrease in calcium leads to the secretion of ? which in turn increases reabsorption of calcium in the kidneys, GI tract & increases ? in bones (increases storage)

and this in turn leads to an increase in calcium which causes a release in ? which in turn increases excretion of calcium in the kidneys

Calcitriol also increases absorption of calcium in ? tract (same effect as PTH)

Answer 16

Calcium metabolism

pic:

a decrease in calcium leads to the secretion of PTH which in turn increases reabsorption of calcium in the kidneys, GI tract & increases mobilization in bones (increases storage)

and this in turn leads to an increase in calcium which causes a release in calcitonin which in turn increases the excretion of calcium in the kidneys

Calcitriol also increases the absorption of calcium in GI tract (same effect as PTH)

Question 17

Choose the main factor regulating production and secretion of PTH and calcitonin

1. Free (ionized) calcium levels in the blood 2. Calcium (mineralized) levels in the bones 3. Phosphates levels in the blood 4. Phosphates levels in the bone

Answer 17

Free (ionized) calcium levels in the blood

Question 18

Which are the net effects of calcitonin and PTH on blood calcium levels, respectively:

Answer 18

decrease and icnreaase

Question 19

HYPERPARATHYROIDISM

Primary Hyperparathyroidism: excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal ? cells of the parathyroid gland (parathyroid adenoma)
 Lead to persistent ?
 ? feedback control is lost (secretion of PTH is not suppressed by high calcium levels)

Symptoms related to hypercalcemia, affect mainly ?, ? and ? system
 Polydipsia and Polyuria - decreases ability of the kidneys to respond to ?
hormone (ADH)
 ? that can lead to urolithiasis and secondary urinary tract infection (UTI)
 Depresses the excitability of the ? and peripheral nervous systems; decreases GI ? muscle excitability; and decreases cell membrane ? of muscles
 Cardiac ? (bradycardia) can be caused by hypercalcemia

Diagnosis:
 ? (crystalluria)
 ? biochemistry (both total and ionized calcium levels are elevated)

Answer 19

HYPERPARATHYROIDISM

Primary Hyperparathyroidism: excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal chief cells of the parathyroid gland (parathyroid adenoma)
 Lead to persistent hypercalcemia
 negative feedback control is lost (secretion of PTH is not suppressed by high calcium levels)

Symptoms related to hypercalcemia, affect mainly kidney, GI and neuromuscular system
 Polydipsia and Polyuria - decreases ability of the kidneys to respond to ADH hormone (ADH)
 calciuria that can lead to urolithiasis and secondary urinary tract infection (UTI)
 Depresses the excitability of the central and peripheral nervous systems; decreases GI smooth muscle excitability; and decreases cell membrane permeability of muscles
 Cardiac arrhythmias (bradycardia) can be caused by hypercalcemia

Diagnosis:
 urinalysis (crystalluria)
 serum biochemistry (both total and ionized calcium levels are elevated)

Question 20

HYPOPARATHYROIDISM

FYI
Hypoparathyroidism is an absolute or relative deficiency of parathyroid hormone (PTH).
 Can be idiopathic (most common), caused by autoimmune destruction of parathyroid or other causes (trauma, agenesis, surgical destruction of PT gland…)
 Inappropriately low levels of PTH classically result in hypocalcemia, hyperphosphatemia, and decreased calcitriol FYI

IMP. below

Symptoms mild to severe, related to calcium ?
 ?, pain,
 muscle ?,
 ?, seizures,
 ? and neurologic signs,
 ? manifestations,
 skeletal deformities and bone effects

Diagnosis: serum biochemistry
 ? total and ionized calcium
 Undetectable ? PTH concentrations
 ? is also common

Answer 20

IMP. below

Symptoms mild to severe, related to calcium deficiency
 fever, pain,
 muscle weakness (troponin - contraction - calcium needed)
 cramps, seizures,
 neuromuscular and neurologic signs,
 cardiac manifestations,
 skeletal deformities and bone effects

Diagnosis: serum biochemistry
 low total and ionized calcium
 Undetectable intact PTH concentrations
 hyperphosphatemia is also common