S11: calcium metabolism & metabolic + endocrine control during special circumstances Flashcards
Explain the significance of maintaining serum calcium levels within set limits
Calcium plays a critical role is many cellular processes eg. hormone secretion, muscle contraction, nerve conduction etc
Free plasma calcium 1.0 – 1.3 mmol/L
Total concentration of all three forms of calcium 2.2 – 2.7 mmol/L
Describe the hormonal regulation of serum calcium
Parathyroid hormone – peptide hormone produced by the principal cells of the parathyroid gland
-increases plasma calcium levels
-decreases plasma phosphate levels
-acts on the bones, kidneys & GI tract indirectly via calcitriol
Calcitonin – peptide hormone produced by the parafollicular cells of the thyroid gland
-decreases plasma calcium levels
-decreases plasma phosphate levels
-minor role in humans (maybe important in childhood & during pregnancy)
Explain the regulation of parathyroid hormone and vitamin D
PTH promotes the formation of calcitriol (1,25-dihydroxycholecalciferol) = active form of vitamin D
Calcitriol increases the rate of Ca2+ & phosphate absorption from food in the GI tract into the blood
Explain the significance of renal function on calcium metabolism
Vitamin D biologically inactive when first enters blood Kidney enzymes (renal C-1 hydroxylase) covert in into active vitamin D (calcitriol) Calcitriol promotes intestinal absorption of Ca2+ & phosphate Not as important as PTH for rapid response – effects too slow
List the different effects of the three hormones on plasma calcium and phosphate levels
PTH – increases calcium, decreases phosphate
Calcitonin – decreases calcium, decreases phosphate
Calcitriol – increases calcium, increases phosphate
Describe hypercalcaemia
‘stones, moans, groans & bones’
Symptoms & signs: lethargy, depression, constipation, renal calculi, frequent urination, nausea & cardiac arrhythmias
Severe: > 3.0mmol/L -> polyuria leads to dehydration -> lethargy, weakness, confusion, coma & renal failure
Rehydration is main treatment
Describe hypocalcaemia
Usually seen in post total-thyroidectomy patients -> inadvertent removal/ischaemia of parathyroid glands
Hyper-excitability of NMJ -> pins & needles, tetany, paralysis, convulsions
Describe hyperparathyroidism
Primary – one of the 4 parathyroid glands develops an adenoma & secretes excessive PTH
Secondary – all 4 parathyroid glands become hyperplastic (seen in patients with vitamin D deficiency -> calcium absorption is low resulting in low serum calcium levels -> PTH levels rise)
How can malignancy cause hypercalcaemia?
1) Haematological malignancies & those that metastasise to the bone produce local factors that act in a paracrine manner to activate osteoclasts
2) Squamous tumours of lung, head and neck produce a hormone, PTHrp, that acts at parathyroid hormone receptors (mimics effects of PTH, except it doesn’t increase renal C-1 hydroxylase enzyme, which normal increases concentrations of 1, 25-dihydroxyvitamin D)
Describe the major metabolic fuels and their sources in the normal individual
Normally available – glucose & fatty acids
Available under special conditions – amino acids, ketone bodies & lactate
Describe the metabolic responses to feeding and fasting and explain how they are controlled
Feeding: increase in blood glucose stimulates pancreas to release INSULIN
-increases glucose uptake & utilisation by muscle and adipose (GLUT 4)
-promotes storage of glucose as glycogen in liver & muscle
Fasting: low blood glucose stimulates GLUCAGON
-glycogenolysis in the liver to maintain blood glucose for brain & other glucose dependent tissues
-lipolysis in adipose tissue to provide fatty acids for use by tissues
Describe the metabolic responses to starvation and explain how they are controlled
Low blood glucose levels = release of cortisol from adrenal cortex & glucagon from pancreas
Stimulate gluconeogenesis & breakdown of protein & fat
Liver starts to produce ketone bodies & brain stars to utilise these sparing glucose requirements from protein
Death usually related to loss of muscle mass (respiratory muscle: infection)
Describe the metabolic and hormonal response to pregnancy
Early pregnancy – mother is in an anabolic state
-nutrients are stored to meet future demands of rapid foetal growth in late gestation & lactation after birth
Late pregnancy – mother is in a catabolic state
-decreased insulin sensitivity
-increase in maternal glucose & free fatty acid concentration
-insulin/anti-insulin ration falls (transient hyperglycaemia after meals because of increased insulin resistance)
Explain the hormonal basis of gestational diabetes
Disease in which pancreatic B-cells do not produce sufficient insulin to meet increased requirement in late pregnancy
Clinical implications: increased incidence of miscarriage, fetal macrosomia -> disproportionate amount of adipose around shoulders & chest could lead to shoulder dystocia
Risk factors: maternal age > 25 years, BMI > 25kg/m2, race/ethnicity
Management: initially dietary modification & insulin inject if persistent hyperglycaemia present
Describe the metabolic and hormonal responses to various types of exercise
100m sprint – once high energy phosphate stores used must create ATP anaerobically -> lactate production, need muscle store of glycogen which helps to spare blood glucose for brain
1500m middle distance – can deliver some extra oxygen to muscles, but ~40% anaerobic metabolism, initial start uses creatine phosphate & anaerobic glycogen metabolism, long middle phase in which ATP is produced aerobically & final finishing sprint relies on anaerobic metabolism again
Marathon – 95% aerobic, utilisation of fatty acids steadily rises from 20-30 minutes
