Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FHB IV- Endocrinology > Endocrinology 8 > Flashcards

Endocrinology 8 Flashcards

1
Q

Explain the importance of Ca2+ and PO4 for normal physiological processes, and describe the normal range of dietary Ca2+ and PO4- intake, distribution in the body, and excretion.

What is the range of Ca in the plasma?
Functions Ca participates in?
Which involved in blood coagulation? Bone structure? Muscle function?

A 
Calcium: 
Most abundant cation
Tightly regulated range in plasma (2.2 - 2.6 mM)
Membrane stability and cell function
Neuronal transmission
Bone structure/formation
Blood coagulation
Muscle function
Hormone secretion
Phosphate:
Cellular energy metabolism (ATP)
Intracellular signaling pathways
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What will occur in hypocalcemia? Hypercalcemia?

A

Hypocalcemia = muscle failure, tetany, convulsions, death

Hypercalcemia = renal dysfunction, calcification of soft tissues, muscle weakness, coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When might hyperphosphatemia occur?

A

Hyperphosphatemia = result of severe tissue injury “crush”

10-fold more Pi than Ca2+ in soft tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which is the more abundant in tissue? Pi or Ca2+?

Which is most abundant cation?

A

10-fold more Pi than Ca2+ in soft tissue

Ca- most abundant cation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does calcium travel in plasma?

A

Ca in body is mostly in the bone
in plasma it is usually complexed… ionized 50 percent free, 45 percent bound to albumin, 5 percent complexed to other things (Ca-Phos. Ca-citrate)

Calcium bound to albumin - albumin levels good indicator of free calcium availability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the two primary regulators of calcium? (and third)

A

Two primary regulators of calcium :

Parathyroid hormone (PTH)

Vitamin D = Calcitriol (skin,diet)

(3rd)
Calcitonin (thyroid) *potentially not important for humans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the daily calcium turnover.

A

Diet 1000mg
350mg absorbed, 150mg secreted

(rapidly exchangeable pool- 4000mg)

Urinary excretion-200 mg
Fetal excretion - 800mg

slide 8

Daily calcium turnover in humans.
Typical dietary intake of calcium is
1000mg. The intestines absorb about half
of dietary intake, but also secrete
removal from the body making net
uptake only ~ 200mg. Urinary excretion
is about the same as GI absorption. Bone
is third major organ governing calcium
homeostasis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List the primary cell types and their products in the parathyroid glands.

A

PARATHYROID GLAND – located on anterior surface of thyroid gland

Paired glands (4 total) located at posterior borders on lateral lobes of thyroid gland (usually embedded in capsule)

Chief Cells (also called Principal cells) – synthesize PTH

Oxyphil Cells – no known function, increase with age and chronic kidney disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the biosynthesis and receptors for PTH and explain the clinical importance of measuring the 1-84 fragment and the importance of PTHrP.

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe Parathyroid hormone (PTH) synthesis.

Describe N and C terminal fragments

Half life?

A

Signal peptide directs processing to the ER.

Parathyroid hormone-related peptide (PTHrP) is highly homologous to PTH 1-34 AA

N-terminal fragment 1-34 biologically active – binds to PTH receptor

C-terminal fragment 35-84 has longer half-life than other fragments – inactive

Intact 1-84 fragment: half-life of 4 min. Clinically important measurement

Slide 12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the action of parathyroid hormone – related peptide (PTHrP).

Where does it act? What kind of action?

Concentration?

What is clinical relevance?

A

Mimics action of PTH in bone and kidney

Normally at very low concentrations; not a regulator of plasma Ca2+

Many tumors produce PTHrP (renal, bladder, lymphoma, head/neck) resulting in hypercalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the PTH receptors.

A 
PTH 1R – primary receptor
Located in osteoblasts and kidney
G-protein coupled receptor
Gαs ---- adenylyl cyclase/cAMP pathway
Gαq ---- PLC/IP3/DAG
Binds 1-34 fragment, 1-84, PTHrP

PTH 2R
physiological importance in humans unclear
Binds 1-34
Does not bind PTHrP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the main PTH targets and net effects?

A

PTH Targets – Bone and Kidney

Net Effects: Increase plasma Ca2+, decrease plasma Pi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the function of osteoblasts and osteoclasts in bone remodeling.

Which are involved in bone resorption/bone reabsorption? Which express PTH receptors? What type of stem cell are each derived from?

Describe role of osteocytes.

A

99% body Ca2+ content is in bone

Osteoblasts –

  • Bone formation and mineralization
  • High expression of PTH receptors
  • Derived from mesenchymal stem cells

Osteoclasts –

  • Bone reabsorption
  • Derived from hematopoietic stem cells
  • Do not express PTH receptors

Osteocytes –

  • Make up most of the bone matrix
  • Terminally differentiated from osteoblasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the effect of PTH on the bone.

What does PTH stimulate in osteoblasts, osteoclasts?

How does it affect bone reabsorption?

What effect will bone degradation have?

A

PTH Target – Bone Remodeling

PTH stimulates macrophage colony-stimulating factor (M-CSF) in osteoblasts

M-CSF stimulates differentiation of osteoclast precursors

Key Concept
PTH stimulation of osteoclasts is indirect

PTH stimulates RANK ligand – leads to maturation of osteoclast and bone reabsorption

Bone degradation releases Ca2+ and Pi to systemic circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the role of osteoblasts in maintaining plasma calcium homeostasis.

A

Osteoblasts export Ca2+ and Pi into the extracellular space for bone mineralization

Major factor in maintaining plasma calcium homeostasis.

17
Q

What is osteoprotegerin (OPG)?

What effect do estrogens and cortisol have on OPG?

A

*Osteoprotegerin (OPG) antagonist of RANK ligand.

Estrogens stimulate and Cortisol inhibits OPG

18
Q

Describe PTH effect on the kidney.

A

Stimulates CYP1alpha – encodes 1alpha-hydroxylase which converts active form of Vitamin D

Stimulates Ca2+ channel insertion in apical membrane of distal tubule

19
Q

Describe the regulation PTH and the role of the calcium-sensing receptor.

Where is the Calcium sensing receptor located?

What does it inhibit? What does it stimulate?

A

Graph slide 26

Calcium-sensing receptor (CaSR)

Located in chief cells, kidney tubules, C cells

Binds ionized Ca2+

Inhibits PTH synthesis at promoter level

Stimulates degradation of preformed PTH

20
Q

Describe PTH regulation as it relates to Vitamin D.

A

Vitamin D

Binds nuclear receptor - VDR

Inhibits PTH synthesis at promoter level

Stimulates CaSR gene transcription – indirect regulation of PTH

21
Q

Identify the sources of Vitamin D and diagram its biosynthetic pathway.

A

Slide 32-33

22
Q

Describe the following (Vitamin D nomenclature)

Calciferol

Cholecaciferol

Calcidiol

Calcitriol

Ergocaliferol

A

Calciferol = general term for vitamin D and other natural structural analogs.

Cholecaciferol = specifically refers to vitamin D3 (from animal tissues).

Calcidiol = calcifidiol = 25-hydroxy-vitamin D (25-D) = 25-hydroxy-cholecalciferol (immediate precursor)

*Calcitriol = calcifitriol = 1,25-dihydroxy-vitamin D (1,25-D) = 1,25-dihydroxy-cholecalciferol (this is the active form)

Ergocaliferol = Vitamin D2 – dietary from vegetables

23
Q

Describe Vitamin D synthesis.

From what is it derived?

Receptor?

Active form?

How does it travel in the plasma?

A

Derived from cholesterol – steroid hormone

Nuclear Receptor = VDR

Active form = 1,25-dihydroxycholecalciferol

Bound in plasma to vitamin D-binding protein

24
Q

Describe factors regulating conversion of 25-D to 1,25(OH)2-D by CYP1α or inactive 24,25(OH)2-D by CYP24.

A

Slide 33

25
Q

Explain how Ca2+ and PO4 is regulated by PTH and vitamin D.

A

…

26
Q

Describe the pleiotropic effects of Vitamin D.

A

Deficiency linked to:

Multiple Sclerosis
Asthma
Cardiovascular disease
Type II Diabetes mellitus
Colorectal/breast cancer
27
Q

Describe Vitamin D targets (direct and indirect if applicable).

A

Slide 36

Bone:
Direct:
-Mobilize Ca2+ from bone
-Osteoblasts and osteoclasts have VDRs
-Vitamin D stimulates osteoclast proliferation/differentiation

Indirect:
-Increases plasma Ca2+ which promotes bone mineralization

Intestine:

  • Increases transcellular Ca2+ absorption in duodenum
  • Stimulates Pi reabsorption from small intestine
28
Q

Describe how calcium is transported across the cell.

A

Slide 39

29
Q

Draw a flow chart for calcium homeostasis.

A

Slide 40

30
Q

Describe osteoporosis.

What happens?
Causes?
Treatment?

A

Osteoporosis
Reduced bone density – mainly trabecular bone

Causes: genetic, menopause (low estrogen), glucocorticoid therapy/chronic stress, low dietary Ca2+

Treatment: estrogens, calcitonin, biphosphonates (inhibit bone resorption), Vitamin D

31
Q

Describe hyperparathyroidism.

Primary and Secondary.

A

Hyperparathyroidism

Primary: hyperplasia, carcinoma of parathyroid gland
Hypercalcemia, kidney stones

Secondary: due to chronic renal failure
Reduced Vitamin D leads to excess PTH synthesis

32
Q

Describe the consequences of under production of PTH and vitamin D.

Give 2 examples.

A

Hypoparathyroidism
Hypocalcemic tetany
Chvostek sign: twitching of facial muscles in response to tapping of facial nerve

Rickets (children)/Osteomalacia (adults)
Unmineralized bone due to Vitamin D deficiency
“bowing” of long bones (children)
Decreased bone strength

33
Q

Describe Pseudohypoparathyroidism. What is it?

What are clinical signs?

A

Pseudohypoparathyroidism
Congenital defect in G protein that associates with PTHR1
Generalized resistance to PTH, TSH, LH, and FSH
Clinical signs: low Ca++, high phosphate, elevated PTH, short stature

34
Q

How does PTH infusion affect low serum Ca and high serum phosphate?

How does tubular reabsorption of phosphate change as phosphate excretion increases?

What does urinary hydroxyproline indicate?

A

Low serum calcium and high serum phosphate are normalized by the PTH infusion

Tubular reabsorption of phosphate (TRP) falls as phosphate excretion increases.

Urinary hydroxyproline = enhanced bone resorption

35
Q

Describe the source and role of calcitonin in calcium regulation.

How many aa?
Physiological purpose?

A

32-amino acid peptide produced in the C-cells of thyroid gland.

Inhibits calcium reabsorption in bone?

Normal physiological importance is unclear –
Complete thyroidectomy (with parathyroids left intact) does not alter normal physiological range of Ca2+.
C-cell tumors – extremely high calcitonin – does not affect Ca2+ levels.
36
Q

Describe therapeutic use of calcitonin.

What can calcitonin be used to treat?

What is the “escape” phenomenon?

A

Therapeutic use: inhibits osteoclast reabsorption of and slows bone turnover (net effect = hypocalcemic action).

Used to treat Paget disease:
Excessive localized regions of bone resorption and reactive sclerosis.
Very high bone turnover
Cause is unknown.

“Escape” phenomenon – rapid downregulation of calcitonin receptors cause the antiosteoclastic actions of calcitonin to diminish within a few hours making this a less effective treatment option.

FHB IV- Endocrinology (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions