lecture 8 (renal) Flashcards
(55 cards)
1
Q
what are the physiological actions of calcium in intracellular fluid?
A
- normal functioning
- muscle contraction
- neurotransmitter release
- enzyme activation
2
Q
what does the presence of calcium salts in bone provide?
A
- structural integrity of skeleton
3
Q
what occurs when extracellular Ca2+ ion conc falls below normal?
A
- nervous system becomes progressively more excitable
- increased permeability of neuronal membranes to Na+
4
Q
what are the consequences of hyperexcitability?
A
- titanic contractions (occurs at neuromuscular junction)
5
Q
what is hypocalcaemic tetany?
A
- tetanic muscle contractions
- occurs in hands
- almost a muscle spasm
- painful
6
Q
what is the extracellular Ca2+ conc?
A
- milimolar range
- 2.3 to 2.6 x10-3
7
Q
what is the intracellular Ca2+ conc?
A
- nano and micro molar range
- 0.1 to 10 x10-6
8
Q
what forms does extracellular calcium exist as?
A
- 50% free ionised Ca2+
- 10% bound to anions (bicarbonate, citrate, phosphate)
- 40% protein bound calcium (albumin, globulins)
9
Q
what makes up filterable calcium?
A
- free Ca2+ ions
- anion bound Ca2+
10
Q
what tissues and organs are used in calcium homeostasis?
A
- GI tract
- intestine
- kidney
- liver
11
Q
how does calcium balance occur?
A
- 35% absorb Ca2+ from GI tract into extracellular calcium (dietary)
- 15% excreted in feoces
- 20% through urinary excretion
12
Q
how much of the excreted Ca2+ is reabsorbed into the blood?
A
- 98%
13
Q
what is the rapidly exchangeable pool?
A
- calcium ions on surface of bones
- can be moving from extracellular fluid into the bone or reversed
14
Q
what is this process called?
A
- bone remodelling (bone formation and bone resorption)
15
Q
what are the major target organs for calcium homeostasis?
A
- intestine (absorption/secretion)
- kidney (filtration/reabsorption)
- bone (formation/resoprtion)
16
Q
what is the indirect effect of the kidney?
A
- kidney produces vitamin D metabolite 1,25 DCC
- responsible for calcium reabsorption in intestine
17
Q
how much calcium does the PCT reabsorb?
A
- around 60%
- by active transport mechanism
18
Q
what is the passive calcium reabsorption?
A
- in ascending loop
- calcium ions move between the cells (paracellular transport)
19
Q
what is the active reabsorption of calcium ?
A
- calcium ions move into cell form lumen
- move out across opposite membrane
- traverse the cell
- in proximal and distal tubules
20
Q
why are both methods needed?
A
- ensure can absorb calcium ions no matter the binding/form
21
Q
what is passive reabsorption driven by?
A
- concentration gradient of calcium between lumen and the blood (needed higher in lumen to move down conc gradient into blood)
22
Q
what is the advantage of passive?
A
- no rate limiting step
- the larger the conc gradient, the more calcium moving down paracellular transport pathway
23
Q
what is the disadvantage of passive?
A
- if no conc gradient, no movement of calcium
24
Q
what is the disadvantange of active?
A
- can trigger calcium dependent physiological responses
- has a rate limiting step (PMCA pump can only pump so much)
25
what occurs in active reabsorption?
- calcium binds to calcium binding proteins to buffer so no rising calcium in cell
- over time, ca2+ ions pumped out cell into blood by PMCA
26
why is this an active mechanism?
- PMCA pump as pumps calcium against conc gradient so energy is required
27
what is the advantage of active?
- always a sufficient gradient of calcium so occurs all the time
- can be regulated
28
what does the parathyroid hormone do?
- opens calcium channels so allows more movement into cell in trans cellular pathway
29
what are the 3 principal hormones that regulate Ca2+?
- parathyroid hormone
- 1,25 DHCC (calcitriol)
- calcitonin
30
where does parathyroid hormone come from?
- chief cells in parathyroid gland
31
what is the main effect of parathyroid?
- to increase plasma calcium levels
- known as hypercalcaemic hormone
32
when is parathyroid hormone stimulated?
- through decrease in plasma calcium concentration
33
what is the mechanism of action of parathyroid hormone in the kidney?
- stimulates Ca2+ reabsorption in the distal tubule
- stimulates activity of 1-alpha-hydroxylase which catalyses formation of 1,25 DHCC
34
what is the mechanism of PTH and calcium in kidneys?
- PTH secreted when Ca2+ drops
- stimulates distal tubule mechanism
- increased calcium reabsorption
- decreased urinary excretion
- increases plasma calcium
35
what is the mechanism of PTH and 1,25 DHCC in kidneys?
- PTH in kidney stimulates formation of 1,25 DHCC
- released from kidney circulating to GI tract
- stimulates calcium absorption from GI tract
36
what is 1,25 DHCC?
- metabolite of vitamin D
- natural form in humans is vitamin D3
- steroid hormone
37
where do humans get vitamin D3 from?
- ingested in diet and skin
- ultraviolet radiation
38
what is the base molecule of vitamin D3?
- cholesterol
39
what is vitamin d3 when administered?
- inactive
- needs to undergo activation process to be converted to 1,25 DHCC
40
how does vitamin d3 convert to 1,25 DHCC?
- vita circulates to hepatic circulation
- converted to 25 hydroxy vitamin d3
- circulates in blood
- enters renal circulation in kidney
- 1 alpha hydroxyls causes 1,25 DHCC formation
- form of vitamin d3 that stimulates calcium absorption
41
what stimulates release of 1-alpha hydroxylase?
- parathyroid hormone
42
what is the main mechanism of action of 1,25 DHCC?
- stimulate absorption of Ca2+ from intestine
43
what is the overall effect of 1,25 DHCC?
- elevate plasma calcium conc
- hypercalcaemic hormone
44
what is the purpose of calcitonin?
- decrease plasma Ca2+ levels
- hypocalcaemic hormone
45
what is hypocalcaemia?
- deficiency in vitamin D activity
46
what does hypocalcaemia cause?
- neuromuscular excitability
- numbness, tingling, hyperventilation, tetany
- prolonged Q-T interval in ECG (Ca2+ in heart)
- metabolic bone disease
47
what two phases does bone have?
- organic matrix (oestoid)
- mineralisation
48
what happens in mineralisation?
- becomes mineralised
- forms hydroxyapatite
- made of collagen
49
what occurs in metabolic bone disease?
- inadequate mineralisation of new bone matrix
- ratio of mineral to organic is lower than normal
50
what are the examples of metabolic bone disease?
- rickets (issue in bone development)
- osteomalacia (bone softening)
51
why does these occur?
- too flexible bone as too much collagen (organic form)
- not enough mineralised form
52
what are the causes of rickets and osteomalacia?
- vitamin D deficiency
- insufficient exposure to sunlight
- insufficient in diet
- malabsorption of vitamin D in GI tract
- inability to convert vitamin D to 1,25 DHCC
- inability of 1,25 DHCC to act on target tissue
53
what is vitamin D dependent rickets type II?
- inability of 1,25 DHCC to act on target tissue
- due to mutation on 1,25 DHCC receptor on surface of GI tract
54
what is vitamin D dependent rickets type II characterised by?
- impaired intestinal Ca2+ absorption
55
what is the treatment for rickets and osteomalacia?
- vitamin D analogs (calcitriol)
- dietary calcium increased
- malabsorption treated with dietary Ca2+ and high doses of vitamin D
