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SGUL - Physiology 2 > MSS: The Skeleton And Metabolism > Flashcards

MSS: The Skeleton And Metabolism Flashcards

1
Q

What are the functions of our bones?

A
  • Support and movement: attachment site for muscles
  • Protection for internal organs
  • provide home for bone marrow
  • Acts as mineral reservoir
  • Endocrine: Source of some ‘non classical’ hormones
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2
Q

Describe the bone structure

A
  • Cortical (compact) bone
  • Trabecular (spongy, cancellous) bone
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3
Q

Describe the composition of the bone

A
  • Protein: Organic osteoid matrix (25%)
  • Mineral (75%)
  • Cells
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4
Q

Describe the organic osteoid protein matrix in more detail

A
  • Mainly type 1 collagen
  • Gives both flexibility and tensile strength
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5
Q

Describe the bone minerals in more detail

A
  • Has a hydroxy apatite
  • Calcium and phosphate
  • Rigid, brittle: Gives a higher compressive strength
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6
Q

Describe the cells part of the bone composition

A

Consists of:
- Osteoblasts
- Osteocytes
- Osteoclasts
- Bone marrow cells such as
- Mesenchymal (stromal) stem cells
- Haematopoietic stem cells

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7
Q

How can the bone be seen as a metabolic organ?

A

Bone turnover serves homeostasis of Serum, Calcium, Phosphates in conjugation with:
- Parathyroid hormone (PTH)
- Vitamin D (1,25 dihydroxy D3)
- FGF-23

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8
Q

What is the daily calcium turnover?
List the Daily intake and Extracellulae plasma conc

A
  • Daily intake recommended: 1000-1200mg (25-30 mmol)
  • Extracellular plasma [Ca]:2.2-2.6 mmol L-1
  • About half is free [Ca2+] (physiologically active)
  • And the other half is protein bound (mainly albumin)
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9
Q

Name some hormones that have skeletal effects

A
  • Oestrogen
  • Androgens
  • Cortisol
  • Parathyroid hormone (PTH)
  • Vitamin D (calcitriol)
  • Calcitonin
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10
Q

What hormone is secreted from the skeleton?

A

FGF-23 (Fibroblast growth factor 23)

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11
Q

Where are Parathyroid glands synthesised from?

A
  • Parathyroid hormone (PTH) synthesised by parathyroid chief cells
  • Function is to increase Serum [Ca]
  • Secreted as 84 AA polypeptide
  • Short half life in circulation (<5 min)
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12
Q

What is the function of the parathyroid hormone?

A

To increase Serum [Ca]

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13
Q

How is the Parathyroid hormone related to Calcium?

A
  • Major hormone in calcium homeostasis
  • Plasma Ca is maintained 2.2 - 2.6 mM (total Ca; ionised Ca2+ is approximately half)
  • Free (ionised) Ca2+ sensed by GPCR on chief cells
  • Ca binding suppresses PTH release
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14
Q

Name one type of Vitamin D

A

Calcitriol (The most active form)

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15
Q

Where is it synthesised?

A

Synthesised in the skin in response to exposure to UV (Sunshine vitamin)

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16
Q

How is Calcitriol activated?

A

Activated by 2 metabolic steps:
- 25 hydroxyl action in liver to form 25 OH D3, major circulating metabolite
- 1â hydroxylation of 25 OH D3 in kidney produces 1,25 (OH)2 D3 or calcitriol, the active hormone
- Needed for Ca absorption of the gut

17
Q

Where are the Parathyroid hormones regulated?

A
  • Regulated at the chief cells of the PT gland
  • Secretion increases as plasma [Ca2+] decreases
18
Q

What activity does PTH carry out?

A
  • Promotes release of Ca from bone
  • Increases renal Ca reabsorption
  • Increases renal phosphate excretion
  • Upregulates 1α hydroxylase activity
19
Q

Where is Calcitriol regulated?

A
  • Regulated by the control of 1ã hydroxyl in the kidney
  • Increased by: PTH, Low phosphate
20
Q

What are the actions of Calcitriol?

A
  • Increase absorption of Ca and Pi from GI tract
    Little absorption in absence
  • Inhibits PTH secretion (transcription)
  • Complex effects on bone, generally in synergy with PTH
21
Q

Describe the calcium homeostasis

A
  • 99% of body calcium is in the bones
  • Remaining 1% is mainly intracellular
  • Hormonal control of the tiny (0.1%)
  • Extracellular fraction is what maintains Ca balance
22
Q

What are the actions of PTH on the bone?

A
  • PTH receptors on osteoblasts and osteocytes
  • Activates osteoclasts via RANKL
  • Promotes bone remodelling
23
Q

What are the effects dependent on?

A

Depends on concentration dynamics
- Intermittent low doses are anabolic (bone formation)
- Persistent high concentration are catabolic (excess resorption over formation – bone loss)

24
Q

What are osteocytes also known as?

A
  • as Endocrine cells
  • Lacunocanalicular network permits communication between osteocytes and from osteocytes to surface cells and systemic circulation
25
Q

Where does communications take place in the Structure of lacunocanalicular network?

A

Communications via osteocytes between systemic circulation and bone

26
Q

Describe the FGF 23 hormone

A
  • secreted by osteocytes
  • Hypophosphatemic rickets: rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)
  • Consortium investigating autosomal-dominant HR (ADHR) traced mutation in gene that turned out to be FGF-23
27
Q

What is the role of FGF-23?

A

Has a central role in phosphate homeostasis

28
Q

What are the actions of FGF-23?

A
  • Expressed and secreted by osteocytes
  • Increases renal Pi excretion (by reducing Na-Pi reabsorption from proximal tubule)
  • Increased by calcitriol and Pi
  • Inhibits calcitriol synthesis
29
Q

What is Osteoporosis?

A

A loss of bone mass (Mineral and organic matrix)

30
Q

What are the causes of osteoporosis?

A
  • Endocrine
  • Malignancy
  • Drug-induced
  • Renal disease
  • Nutritional
  • Age
31
Q

What is Osteomalacia?
What are some signs and symptoms?

A
  • Loss of bone mineralisation (termed rickets in children)

Signs and symptoms:
- Permanent deformities in bone growth (rickets)
- Diffuse aches and pains
- Chronic fatigue
- Weak bones

32
Q

What is Osteomalacia characterised by?

A
  • Low Ca, and / or Pi
  • Elevated alkaline phosphatase
  • PTH may be elevated
    Causes
  • Vit D deficiency (most common)
  • Vit D metabolism defect (rare)
  • Phosphate wasting (rare)
33
Q

State some endocrine causes of osteoporosis

A
  • Hypogonadism – notably any cause of oestrogen deficiency
  • Excess glucocorticoids – endogenous or exogenous
  • Hyperparathyroidism
  • Hyperthyroidism
34
Q

What is the normal level of Calcium?
- State some Calcium disorders

A

Normal range 2.2 – 2.6 mM
- Hypocalcaemia
- Hypercalcaemia

35
Q

State some clinical features of hypercalcemia

A
  • Depression, fatigue, anorexia, nausea, vomiting
  • Abdominal pain, constipation
  • Renal calcification (kidney stones)
  • Bone pain
  • Severe: cardiac arrhythmias, cardiac arrest
36
Q

List the most common causes of hypercalcaemia

A
  • In ambulatory patients: primary hyperparathyroidism
  • In hospitalized patients: malignancy
37
Q

List the least common causes of hypercalcaemia

A
  • Hyperthyroidism
  • Excessive intake of vitamin D
38
Q

What is Primary hyperparathyroidism?

A
  • Usually due to a benign adenoma in one or more PT glands
  • Often detected on screening – many patients asymptomatic
    -~10% of patients present with clinical evidence of bone disease
  • 10 - 20% of patients present with kidney stones
  • Resolved by surgical removal of affected gland(s)
39
Q

Describe the Hypercalcaemia of malignancy

A
  • Common problem of advanced malignancy
  • Tumour may secrete PTH-related peptide, binds and activates PTH receptor

SGUL - Physiology 2 (37 decks)

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