Calcium Homeostasis Wk 3 Flashcards
Explain the importance of calcium regulation
Ca2+ is a signalling ion; influx into the cell results in changes to cellular function.
Activity of muscles (contraction), nerve cells, enzyme activation, exocytosis (hormone release), blood coagulation, cell membrane stability and cell linkage, bone and teeth structural integrity.
List the three main tissues involved in calcium homeostasis
- Gut for absorption
- Bone for exchange
- Kidney for losses via urine, faeces (+ lactation)
NB. 98% of Calcium filtered and reabsorbed by kidneys/day.
Describe how Parathyroid Hormone hormone involved in calcium regulation is produced and has its effect on target tissues.
Parathyroid Hormone:
- Peptide hormone produced in Parathyroid gland, released when low Ca2+ in blood.
- Major effect on uptake in Kidneys, some on the brain [Ca2+ bone release], and indirect effect on absorption of calcium in the intestines.
- PTH protein stored in secretory granules of chief cells of parathyroid gland.
- Secretion regulated by circulating calcium levels. HIGH calcium INHIBITS secretion and LOW calcium ALLOWS section.
- Minute to minute regulation and prevents hypocalcemia.
Explain how clinical abnormalities arise from incorrect hormone activity (Active Vit D)
A. Active Vitamin D deficiency (nutritional hyperparathyroidism):
- Young animals diet deficient in Vit D AND housed indoors.
- Also rare genetic disease renal 1α-hydroxylase deficiency.
- Hypocalcemia -> increased PTH -> Breakdown hydroxyapatite crystals by osteoclast activity.
- Cartilage not properly mineralised, weak and malformed bones.
What are the biological actions of parathyroid hormone on bone?
Bone:
- Ca2+ salts in bone ECF (fast). PTH activate osteoblasts to release Ca2+ from labile pool, releasing Ca2+ back into circulation fast. Nb. As bone is constantly remodeling due to mechanical stress, thus labile pool is available.
- Breakdown hydroxyapatite crystals (slow). Dissolution of bone through osteoclast activity.
What are the biological actions of active vitamin D?
- Longer-term regulation of Ca2+ homeostasis
- Increase absorption of Ca2+ from intestine (protects bones). Vit D instructs cellular DNA to produce various proteins to absorb calcium from intestinal lumen:
a. Ca2+ channels
b. Ca2+ binding proteins
c. Ca2+ pumps
d. Ca2+ exchanger proteins
What are the biological actions of parathyroid hormone on the kidney?
Kidney: Increase tubular Ca2+ absorption (decreasing loss in urine).
What are the biological actions of parathyroid hormone on the small intestine?
Small intestine: Promotes formation of active Vitamin D which enhances absorption of Ca2+ in the intestine.
Explain how clinical abnormalities arise from incorrect hormone activity: horses with nutritional hyperparathyroidism?
Horses with Nutritional hyperparathyroidism
- Grasses high in oxalate (insoluble complex with Ca2+)
- Vit D present, no Ca2+ in gut to absorb
- Increase PTH
- Breakdown hydroxyapatite crystals by osteoclast activity.
Explain how clinical abnormalities arise from incorrect hormone activity: Primary hyperparathyroidism?
Primary hyperparathyroidism
- Parathyroid cells secrete PTH unregulated by Ca2+
- Caused by adenomas of chief cells
Explain how clinical abnormalities arise from incorrect hormone activity: Secondary hyperparathyroidism?
Secondary hyperparathyroidism
- Chronic renal failure
- Kidney not able to retain Ca2+
- Active Vit D production lowered
- Ca2+ gut absorption decreased
- Hypocalcemia
- Excessive PTH secretion
- Increased breakdown hydroxyapatite crystals and dissolution of bone through osteoclast activity.
- Bone deformation and fractures.
Explain how clinical abnormalities arise from incorrect hormone activity: paturient hypocalemia (milk fever) and prevention?
Paturient hypocalemia (milk fever)
- Soon after birth (few hours).
- Ca2+ lost to fetus in late pregnancy and lactation.
- Untreated results in paresis (partial paralysis).
- Ca2+ required for muscle contraction and release of neurotransmitters at neuromuscular junctions, thus excitation-contraction coupling is lost.
- Prevention: Supplementing diet with calcium during risk period (prior and post parturition). Calcium intake during dry period 50g/day (dry / transition period = 3 weeks pre/post parturition). Long fibre feed to transition cows. Avoid diets high in strong cations (potassium and sodium).
Explain how clinical abnormalities arise from incorrect hormone activity: puerperal hypocalcemia in bitches?
Puerperal hypocalcemia in bitches:
- Ca2+ lost in lactation
- excitation-contraction coupling maintained by NMJ
- Low Ca2+ concentration in ECF has excitatory effect on nerve and muscle cells, triggering tetany where nerve fibres become high excited and muscles are over excited.
Describe how Calcitonin hormone involved in calcium regulation is produced and has its effect on target tissues.
Calcitonin:
- Peptide hormone produced in Thyroid Gland, released from C-Cells when rising Ca2+ blood levels, returning Ca2+ to set point, preventing hypercalcemia.
- Reduces Ca2+ uptake in Kidneys, increasing calcium release in urine.
- Stimulates Ca2+ deposition (laying down) in bones by binding directly to and inhibiting osteoclast activity (causing them to shrink and detach).
- C-cells found between follicular cells containing colloid of the thyroid gland (which produce thyroid hormone). C-cells are nestled between the follicles, and are round and dark nuclei, which produce calcitonin.
- Emergency hormone prevents hypercalcemia after postprandial absorption of Ca2+, and, protect against excessive loss of Ca2+ from maternal skeleton during pregnancy whereby Ca2+ must be sourced elsewhere (gut and diet) to protect the maternal skeleton.
Describe how Active Vitamin D hormone involved in calcium regulation is produced and has its effect on target tissues.
Active Vitamin D:
- Steroid hormone produced by cholesterol, and also diet. Falling Ca2+ increases uptake in intestines.
- Reliant on PTH indirectly as Vit D is activated by renal 1α-hydroxylase in the Kidney; stimulated by PTH.
