The Peripheral Endocrine Glands Lecture 9

Question 1

Calcium

Answer 1

50% of ECF Ca2+ is bound to plasma protein or is complexed to PO43-
Other 50% is free and can freely pass from plasma to ISF - regulated

Question 2

Role of free ECF Ca2+

Answer 2

Conversion of receptor potential into action potentials.
(a) Specialized afferent ending as sensory receptor. Local current flow between a depolarized receptor ending undergoing a receptor potential and the adjacent region initiates an action potential in the afferent fiber by opening voltage-gated Na+ channels. (b) Separate receptor cell as sensory receptor. The depolarized receptor cell undergoing a receptor potential releases a neurotransmitter that binds with chemically gated channels in the afferent fiber ending. This binding leads to a depolarization that opens voltage-gated Na+ channels, initiating an action potential in the afferent fiber.

Question 3

Decrease in free ECF Ca2+

Answer 3

Increases Na+ permeability – influx of Na+, moving resting potential closer to threshold

Question 4

Hypocalcaemia?

Answer 4

excitable tissue brought to threshold by normally ineffective stimuli, skeletal muscle contract spontaneously, spastic contraction of respiratory muscles – asphyxiation

Question 5

Hypercalcaemia?

Answer 5

cardiac arrhythmias, depression of neuromuscular excitability

Question 6

Excitation-contraction coupling in cardiac and smooth muscle

Answer 6

• Action potential: increases Ca2+ permeability, ECF Ca2+ entry into cardiac- and smooth muscle –> triggers contractile mechanism.

Skeletal muscle: Ca2+ is released from intracellular stores in response to action potential.

Cardiac muscle: calcium-induced calcium release – also from intracellular stores.

NB: increased cytosolic Ca2+ within muscle cells cause contraction, whereas increase in free ECF Ca2+ decreased neuro-muscular excitability and decrease likelihood of contraction.

Question 7

Excitation–contraction coupling in cardiac contractile cells.

Answer 7

Question 8

Excitation-secretion coupling

Answer 8

Pancreatic beta cells Ca2+ entry from ECF in response to membrane depolarization, leads to insulin secretion

Question 9

Other functions of Ca2+

Answer 9

Maintenance of tight junctions between cells
Clotting of blood, second messengers, cell motility and cilia action

Question 10

Maintaining proper free [Ca2+] differ from Na+ and K+ regulation in 2 ways:

Answer 10

1. Na+ and K+ homeostasis is maintained by regulating the urinary excretion of these electrolytes so that output matches input. Not all ingested Ca2+ is absorbed from the GIT, the extent of absorption is hormonally controlled and depends on Ca2+ status of the body, urinary excretion of Ca2+ is also hormonally controlled.
2. Bone serves as Ca2+ reservoir – exchange of Ca2+ between ECF and bone is also hormonally controlled; no similar stores for Na+ and K+ .

Question 11

Ca2+ homeostasis VS Ca2+ balance

Answer 11

• Ca2+ homeostasis: Immediate adjustment
• Ca2+ balance: Slowly responding adjustments

Question 12

Ca2+ homeostasis:

Answer 12

Immediate adjustment
Rapid exchange between bone and ECF
Modifications in urinary excretion of Ca2+

Question 13

Ca2+ balance:

Answer 13

Slowly responding adjustments
Required to maintain a constant total amount of Ca2+ in the body
Ensures that Ca2+ intake is equal to Ca2+ excretion over the long term (weeks to months).
Is maintained by adjusting of intestinal Ca2+ absorption and urinary excretion

Question 14

Calcium Balance in the Body

Answer 14

Question 15

Endocrine Control of Calcium Metabolism
Three hormones regulate plasma concentration of Ca2+ (and PO43-)

Answer 15

Parathyroid hormone (PTH)
Calcitonin
Vitamin D (calcitriol)

Question 16

Bone remodelling

Answer 16

Through bone remodelling (deposition/formation) and resorption/removal), the adult skeleton is completely regenerated every 10 years.
Bone contains calcified extracellular matrix – forms when calcium phosphate crystals precipitate & attach to collagenous lattice support
Most common form of calcium phosphate – hydroxyapatite, Ca10(PO4)6(OH)2.
Living cells – well supplied with oxygen & nutrients by blood vessels

Question 17

Question 18

Osteoblasts

Answer 18

control deposition of Ca2+ in bone

Question 19

Osteoclasts

Answer 19

are responsible for bone resorption
Secretes acid (with aid of H+-ATPase) and protease enzymes (low pH) - freeing Ca2+ which can enter blood

Question 20

Osteocytes

Answer 20

are retired osteoblasts imprisoned within lakunae

Question 21

Osteocytic-osteoblastic bone membrane

• osteoclasts are activated by parathyroid hormone
  = Ca2+ released via Lamellae (slow mechanism)- homeostasis

Question 22

Fast and slow exchanges of Ca2+ across the osteocytic-osteoblastic bone membrane.
(b) Schematic representation of fast and slow exchange of Ca2+ between the bone and plasma.

Question 23

Endocrine Control of Calcium Metabolism
- PTH (parathyroid hormone)

Answer 23

• Secreted by parathyroid glands
• Primary regulator of Ca2+
  Raises free plasma Ca2+ levels by its effects on bone kidneys, and intestines
• Essential for life
  Prevents fatal consequences of hypocalcemia
• Facilitates activation of Vitamin D

Question 24

3 hormones control Calcium Balance
Parathyroid hormone (parathyroid gland - essential for life)

Answer 24

• Peptide hormone
• increases plasma [Ca2+]
• Stimulus: decreases plasma [Ca2+]
• Sensor: chief cells of parathyroid gland, cell membrane Ca2+ -sensing receptor (CaSR) – G protein-coupled receptor [ligand: ion, rather than organic molecule]
  Mobilizes calcium from bone
  Enhances renal reabsorption
  Indirectly increases intestinal absorption

Question 25

PTH mobilizes calcium from bone & intestine

Answer 25

Bone: 12 hour to become measurable (slow exchange)
Although osteoclasts dissolve bone, they DO NOT have PTH receptors
PTH effects are mediated by paracrines:
Osteoblasts secretes:
Osteoprotegerin (OPG)
RANK Ligand (RANK=receptor activator of NF-Weird K looking sign)B)

Intestine: indirectly increases intestinal absorption of calcium through influence of vitamin D3

Question 26

Role of osteoblasts in governing osteoclast development and activity.

Question 27

PTH enhances renal reabsorption of calcium

Answer 27

• Reabsorption in distal nephron
• PTH simultaneously increases renal excretion of phosphate – reducing its reabsorption
• Opposing effects of PTH on calcium & phosphate necessary to keep combined [ ] below critical level
  > [ ] exceed critical level – calcium phosphate crystals form and precipitate out of solution – kidney stones

Question 28

Question 29

Calcitriol

Answer 29

1,25-dihydroxycholecalciferol (1,25(OH)2D3) or Vitamin D3
Vitamin D obtained form diet or made in skin by action of sunlight on precursors (7-dehydrocholesterol)–> modified in liver & kidney –> calcitriol (1,25-(OH)2-vitamin D3)
- increases intestinal absorption of Ca2+
- Facilitates renal reabsorption of Ca2+
- Mobilize Ca2+ from bone
Production of calcitriol is regulated at kidney by action of PTH
decreases plasma [Ca2+] - + PTH secretion - + calcitriol synthesis
increases plasma [Ca2+] – turning off PTH in negative feedback loop - decreases calcitriol synthesis
Prolactin – milk producing hormone - increases calcitriol synthesis
- Ensure maximal absorption of Ca2+ from diet when metabolic demands for Ca2+ are high

Question 30

Difference between hormones and vitamins?

Question 31

Calcitonin

Answer 31

• Peptide produced by C-cells of thyroid gland
• Released when plasma [Ca2+] increases
  > Decreases bone resorption
  > Increases renal calcium excretion
• Minor role in daily calcium balance
  > Removal of thyroid gland - no disturbances in calcium balance
  > Thyroid tumours – large secreted amounts of calcitonin – no ill effects
• Therapeutic: Calcitonin – treat patients with Paget’s disease – genetic-linked condition where osteoclasts are overactive – bone weakened by resorption – stabilizes abnormal bone loss
  > Functions of Calcitonin
  important in childhood growth when bone deposition is needed
  during pregnancy & lactation when mother’s body must supply calcium for herself & child

Question 32

Question 33

Question 34

Negative-feedback Loops Controlling Parathyroid Hormone (PTH) and Calcitonin Secretion

Question 35

Question 36

Question 37

https://www.youtube.com/watch?v=sD9st1ZPFrQ

Question 38

Calcium Disorders

Answer 38

• PTH hypersecretion (hyperparathyroidism)
• PTH hyposecretion (hypoparathyroidism)
• Vitamin D deficiency

Question 39

PTH hypersecretion (hyperparathyroidism)

Answer 39

Characterized by hypercalcemia and hypophosphatemia
- decreased excitability of muscle and nerve tissue –> muscle weakness, neurologic disorders including decrease alertness, poor memory, depression.
- Cardiac disturbances, high blood pressure
- Excessive mobilization of Ca2+ and PO43- from skeletal stores leads to thinning of bone – increased incidences of fractures
- Ca2+ containing kidney stones
- Serum calcium is filtered in urine, osmotic diuretic at high levels (nocturia)
- Peptic ulcers, nausea and constipation

Disease of “stones, moans (depression) and groans (abdominal pains)”

Question 40

PTH hyposecretion (hypoparathyroidism)

Answer 40

Characterized by hypocalcemia and hyperphosphatemia
- increased neuromuscular excitability
- Milder symptoms: muscle cramps and twitches – spontaneous activity in motor nerves; tingling and pins-and-needles sensation – spontaneous activity of sensory nerves; mental changes – irritability & paranoia.
- Complete absence of PTH - death

Question 41

Vitamin D deficiency

Answer 41

• Impaired intestinal absorption of calcium – PTH maintain plasma Ca2+ levels at expense of bones – soft and deformed bones.
  > Children – rickets (ragitis)
  > Adults – osteomalacia

Question 42

A 36 year old professional bodybuilder required emergency care for chest pain and is admitted to hospital. After thorough consultation and tests the following information about the patient is known: He lost 40 kg in 12 months; he admitted using anabolic steroids as well as artificial growth hormone for the past 15 years. He also started to inject insulin a year after commencing growth hormone intake. Clinical tests revealed the following: inflammation in the liver, enlarged kidneys, very high blood sugar and dehydration.

a.) Name the metabolic effects of growth hormone which is not growth related. (3x1/2=11/2)
b.) What was the reason for the body builder also to take insulin? (1/2)
c.) Thyroid hormone is permissive to growth hormone. Define the term “permissive” and also indicate which symptoms will be present in hypothyroid adults, children and babies? (6x1/2=3)

Answer 42

a.)
Increases fatty acid levels in blood by enhancing breakdown of triglyceride fat stored in adipose tissue
Increases blood glucose levels by decreasing glucose uptake by muscles
THUS: mobilize fat stores as major energy source while conserving glucose for glucose dependent tissue such as the brain, eg. fasting or when body’s energy needs exceed glucose stores

b.)
to decrease the high blood glucose levels

c.)
Permissiveness: One hormone must be present in adequate amounts for full exertion of another hormone’s effect.

In adults:
Slow metabolic rate and oxygen consumption
Patients intolerant to cold
Decreased protein synthesis - brittle nails, thinning hair, dry thin skin
Accumulation of mucopolysaccharides under skin – puffy appearance of myxedema
Bradycardia – slow heart rate

Children:
slow bone & tissue growth – shorter than normal for their age
Slowed reflexes, slow speech and thought processes, and feelings of fatigue

Infants:
Cretinism – decreased mental capacity