Calcium Metabolism + Exercise Flashcards
1
Q
What is normal serum calcium level
A
2.2-2.6 mmol/L
2
Q
What are some roles of calcium in the body
A
Hormone secretion, muscle contraction, nerve conduction, exocytosis, activation/inactivation of enzymes
3
Q
What are some roles of phosphate in the body
A
ATP production, membrane formation, genetic information (RNA/DNA)
4
Q
What hormones regulate serum calcium
A
Parathyroid hormone
Vitamin D (calcitriol)
Calcitonin
5
Q
What are the actions of parathyroid hormone
A
- Elevates calcium concentration and lowers serum phosphate
- Stimulates bone reabsorption and calcium release into circulation
- Stimulates calcium reabsorption in kidney and excretion of phosphate
- Stimulates activation of vitamin D (calcitriol)
- Shorter term regulation
6
Q
Where are parathyroid hormones produced
A
- Produced in chief cells in parathyroid gland
- Preprohormone cleaved to form PTH
- Water soluble
- Short half life (4.5 min)
7
Q
What are the actions of vitamin D
A
- Elevate serum calcium and serum phosphate
- Increase intestinal absorption and renal reabsorption of calcium and phosphate
- Increase bone reabsorption
- Longer term regulation
8
Q
How is vitamin D obtained and activated
A
- Obtained from sun exposure, food and supplements
- Active form known as calcitriol - produced in liver and kidney
- D3 - cholecalciferol requires sunlight - formed in skin and from diet
- D2 - ergocalciferol from yeast and fungi added to margarines
9
Q
What are the actions of calcitonin
A
- Lowers serum calcium and serum phosphate
- Counteracts PTH effects
10
Q
Where is calcitonin produced
A
Produced in C cells (parafollicular cells) in thyroid
11
Q
What cells are in the parathyroid hormone
A
- Parathyroid gland discrete glandular structures at the back of the thyroid gland
- Chief cells - pink, not much cytoplasm
- Produce parathyroid hormones
- Oxyphil cells - paler pink, lots of cytoplasm
12
Q
What is the role of bone for calcium control
A
- Structural support and maintenance of serum calcium concentration
- Control release and uptake of calcium phosphate
- Calcium phosphate crystals found within collagen fibrils (hydroxyapatite crystals)
- Bone deposition - osteoblasts produce collagen matrix which is mineralised hydroxyapatite
- Bone reabsorption - osteoclasts dissolve hydroxyapatite crystals
- PTH increase osteoclasts
13
Q
What is the role of kidney in calcium control
A
- PTH and calcitriol affect reuptake of calcium in distal convoluted tubule and ascending limb
- Increase reabsorption to blood
- PTH increase phosphate loss in kidney - inhibit reabsorption
- Prevents calcium stone formation
14
Q
What is the role of gut in calcium control
A
- Normally, only 30% of dietary calcium is absorbed
- PTH stimulates conversion of vitamin D to calcitriol in gut to increase calcium absorption
15
Q
Explain the regulation of parathyroid hormone and vitamin D
A
- High serum calcium binds to calcium G protein receptor
- Slow down release and production (transcription) of PTH
- PTH continually synthesised but Chief cells degrade hormone when in excess
- Released PTH cleaved in liver
- PTH stimulates activation of vitamin D to calcitriol
- Both regulated through negative feedback
- High serum calcium causes release of calcitriol which lowers calcium concentration
- Leads to release of PTH to increase calcium concentration back to normal
- High serum calcium causes release of calcitriol which lowers calcium concentration
16
Q
How is calcium used in EDTA
A
- Calcium is factor IV in the clotting cascade
- EDTA is a calcium chelator - binds to calcium to prevent blood clotting in blood samples and transfusions
- IV calcium given after patient gives blood calcium is chelated
17
Q
How can cancer cause hypercalcaemia
A
- Malignant osteolytic bone metastases - breaking up bone into circulation
- Multiple myeloma - cancer spreading through bone
- Common cancers that metastasise to bone causing lytic lesion and hypercalcaemia - breast, lung, renal, thyroid
- Prostate gland common cause of bone metastases - doesn’t break down bone - osteoblastic
- Common sites for metastases are the vertebrae, pelvis, femur, ribs, proximal part of humerus, skull
- Sites are active, produce many red blood cells, good blood supply
- Osteoblastic does not increase calcium concentration
18
Q
What are the effects of Parathyroid hormone related peptide (PTHrP)
A
- Peptide produced by cancer cells leading to humeral hypercalcaemia of malignancy (HNM)
- Produced in squamous cell tumours on head, neck and lung
- Produced commonly in patients with breast or prostate cancer, occasionally in myeloma
- PTHrP shares many actions with PTH leading to increased calcium release from bone, reduced renal calcium excretion and reduced renal phosphate reabsorption
- Does not increase activation of vitamin D to calcitriol
19
Q
Differentiate between primary and secondary hyperparathyroidism
A
- Primary - one of parathyroid glands develops adenoma and secretes excessive parathyroid hormones
- Increases serum calcium and decreases serum phosphate
- Secondary -all 4 parathyroid glands become hyperplastic
- Vitamin D deficiency - not enough sunlight, diet insufficiency, chronic renal failure
- Low calcium absorption resulting in low serum calcium levels, causing PTH levels to rise (parathyroid hyperplasia)
- Raised PTH activates osteoclasts to mobilise calcium from bone
- Symptoms - bone pain due to osteomalacia in vitamin D deficiency
- Renal osteodystrophy in renal failure
20
Q
How can you differentiate between primary and secondary hyperparathyroidism and malignant hypercalcaemia through blood components
A
Primary - high serum calcium, medium/low serum phosphate, normal alkaline phosphatase, high serum PTH
Secondary - low serum calcium, high serum phosphate,, high serum alkaline phosphatase, high serum PTH
Malignant hypercalcaemia - high serum calcium, normal serum phosphate, high serum alkaline phosphatase, lower serum PTH
21
Q
What is alkaline phosphatase
A
- Alkaline phosphatase high in secondary hyperparathyroidism
- Enzyme present on osteoblasts and in plasma
- Marker of bone turnover - increase bone formation
22
Q
What are symptoms of primary hyperparathyroidism
A
- Moans - tired, exhausted, depressed
- Groans - constipation, pancreatitis
- Stones - kidney stones, polyuria
- Bones - bone and muscle aches
23
Q
How does calcium affect neuronal activity
A
- Hypercalcaemia suppresses neuronal activity - raises threshold of depolarisation
- Coma, confusion, lethargy
- Hypocalcaemia leads to excitable nerves - tingling, muscle tetany, epilepsy
24
Q
What are symptoms of severe hypercalcaemia
A
- Symptoms of severe hypercalcaemia > 3.0 mmol/L
- Polyuria can lead to dehydration which further increases hypercalcaemia
- Lethargy, weakness, confusion, coma, renal failure
- Rehydration main treatment
- Polyuria can lead to dehydration which further increases hypercalcaemia
25
What are signs of hypocalcaemia
- < 2.1 mmol/L
- Seen mostly in patients after removal of thyroid gland (inadvertent removal of parathyroid gland)
- Tingling around mouth and in fingers, tetany of muscles
- Carpopedal spasms - flexor strongest at elbow, wrist, fingers
- Can result in death due to laryngeal muscle spasm
26
Differentiate between osteoporosis and osteomalacia
- Osteoporosis - decreased bone density with normal mineral
- Degeneration of already constructed bone leads to brittle bones prone to fracture
- Osteomalacia - not enough mineral content
- Affect bone building in children (rickets) or bone mineralisation in adults
- Leads to soft bones prone to bending
27
Describe the metabolic responses to starvation and explain how they are controlled
- Reduction in blood glucose stimulates release of cortisol from adrenal cortex and glucagon from pancreas
- Stimulate gluconeogenesis and breakdown of protein and fat
- Reduction in insulin and anti-insulin effects of cortisol, prevent most cells from using glucose and fatty acids are preferentially metabolised
- Glycerol from fat provides important substrate for gluconeogenesis, reducing the need for breakdown of proteins
- Liver starts to produce ketone bodies and brain starts to utilise these sparing glucose requirement from protein
- Kidneys begin to contribute to gluconeogenesis
- Once fat stores depleted, system must revert to use protein as fuel
- Death related to loss of muscle mass
28
Describe the metabolic and hormonal responses to various types of exercise
- ATP stores in muscle are limited to ~2 seconds during a sprint
- Needs to be rapidly resynthesised to meet metabolic demand
- Muscle creatine phosphate stores can rapidly replenish ATP for ~5 seconds during a sprint
- Further ATP supplied by glycolysis (ineffective) and oxidative phosphorylation (needs oxygen)
- In intensive exercise (anaerobic) - muscle glycogen can sustain for ~2 minutes
- In low intensity exercise, if enough oxygen can be supplied for oxidation of glucose and glycogen stores, could last for ~60 minutes
- In aerobic conditions, triacylglycerol stores in adipose tissues can slowly be released
- Capacity limited by carnitine shuttle
29
Explain the benefits of exercise
- Body composition changes - decrease adipose, increase muscle
- Glucose tolerance improves - increase muscle glycogenesis
- Insulin sensitivity of tissue increases
- Blood triglycerides decrease - decrease in VLDL and LDL, increase HDL
- Blood pressure falls
- Psychological effects - feeling of well-being
