Calcium/phosphate balance Flashcards

1
Q

functions of calcium (6)

A
  1. formation of bone and teeth
  2. muscle contraction
  3. enzyme function
  4. blood clotting
  5. cellular functions - eg apoptosis, role as secondary messenger, metabolic regulator eg for the krebs
  6. normal heart rhythm
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2
Q

dietary requirement for Ca

A

around 500

1000 for pregnant and lactating women (bcos of milk production)

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3
Q

FORMS OF CALCIUM IN THE BODY

A

intake = diet

  1. plasma: present as protein bound, chelated and ionised
  2. ECF (<1%)
  3. bones (85%)
  4. kidneys

output = faeces from colon, sweat and urine from kidneys

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4
Q

describe the 3 types of calcium present in plasma

A

40% protein boud (albumin) - cant be utilised by tissues

50% ionised Ca2+ which is used by tissues (exchangeable)

10% chelated Ca (ie bound to anion complexes like phosphate and bicarbonate) which IS exchangeable

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5
Q

how do pH changes affect serum calcium

A

AFFECTS THE 40% OF CALCIUM THAT IS PROTEIN BOUND:

in acidosis –> albumin releases more Ca (bcos there are more protons competing for albumin binding sites) so you have an increase in ionised Ca2+

in alkalosis –> the opposite, decrease in ionised Ca2+

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6
Q

what would be the effect of a liver disorder on the calcium in the serum

A

LIVER DISORDER - would mean less albumin synthesised

hence a decrease in protei bound calcium of serum, and a big increase in ionised Ca2+

RESULT: hyperalcemia (and hence all its consequences)

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7
Q

how is calcium UPTAKEN into cells

A

Either through transporters (high to low conc gradient) in the membrane OR via electroporation (the membrane becoming more permeable for calcium)

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8
Q

what is needed for Ca to enter the cells via transporters

A

to set up a conc gradient - this is done by keeping Ca2+ cytosolic conc low so that there is a movement from high to low conc from outside to inside the cell
IN 3 WAYS:
1. Ca2+ associating with storage proteins in the cytosol like calmodulin
2. SERCA pump moving Ca into the SER
3. uptake into mitochondria (MCU) for krebs

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9
Q

how is calcium RELEASED from cells (4 ways)

A
  1. PMCA - plasma membrane calcium ATPase
  2. NCX channels (sodium calcium exchangers)
  3. NCKX (sodium calcium potassium exchangers)
  4. electroporation (permeabilising the membrane)
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10
Q

ways that Ca2+ cna be absorbed at intestine (2)

A
  1. transcellular (active transport)
  2. paracellular (passive transport)

!! 2 mechanisms exist for the sake of redundancy

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11
Q

describe transcellular Ca absorption at intestine (3 steps)

A

ACTIVE PROCESS

  1. Ca2+ enters across brush border through voltage gated channels
  2. internalised calcium moves to the basolateral membrane and associates with CALBINDINS (proteins with high affinity for Ca)
  3. Ca2+ extrusion at basal membrane into blood via: PMCA, NCX
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12
Q

describe paracellular Ca absorption at intestine

A

Movement of Ca2+ between the cells, passing through the tigh junctions of adjacent enterocytes. (mainly composed of occludin and claudins)

PASSIVE PROCESS

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13
Q

calcium reabsorption at the kidney

A

90% of the calcium is reabsorbed in the PCT/TAL

the other 10% is reabsorbed at the level of the DCT/CD with VARIABILITY depending on the Ca2+ level od the body at that moment.
HENCE these are the regions where PTH/ aldosterone have an effect on the reabsorption

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14
Q

differences in the mechanism of calcium reabsorption in the diff regions of the kidney tubular system

A

PCT - mainly paracellular

TAL –> presence of CASR

DCT –> mainly transcellular

CD –> specific AQP2 for water transport also affected by ADH

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15
Q

structure and function of CASR

A

CASR = calcium sensing receptor

-G protein C receptor that senses levels of ionised calcium (active form)
-expressed in TAL, parathyroid gland and brain

IN KIDNEY: INHIBITS THE REABSORPTION OF CA, K, Na AND H2O. Hence allows -ve feedback when Ca is sensed.
MECHANISM: binding of a factor on CASR induces PKC response to increase IP3 and DAG hence increasing intracellular Ca2+ (and its associated responses)

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16
Q

OVERVIEW OF CALCIUM REGULATION FACTORS AND THEIR ROLE

A

PTH: released by chief cells in parathyroid gland when calcium is too low to increase it again

CALCITRIOL (VD3): released in C cells of thyroid when calcium is too low to increase it again

CALCITONIN: produced (in skin, liver and kidney) when calcium is too high to decrease it again

(FGF23 plays role in Ca conservation in the kidneys)

17
Q

phosphorys functions (2)

A
  1. structural (hydroxyapatite crystals, DNA and RNA, phospholipids)
  2. buffering
18
Q

phosphorus distribution in the body

A

INPUT = DIET

  1. serum phosphorus (HPO42- and H2PO4-)
  2. ECF (<1%)
  3. bones (85%)
  4. kidneys

OUTPUT = faeces + urine

19
Q

dietary requirement for phosphorus

A

baby =100-300
child = 400 - 500
teen= 1250
adult = 900

20
Q

general statement connecting calcium and phosphate control

A

INVERSE CONTROL: increasing calcium levels decreases phosphate levels and vice versa

21
Q

intestinal absorption of phosphate

A

TRANSCELLULAR: Na+ dependent, secondary active transport using the conc gradient set up by Na/K ATPase

passage into the enterocyte occurs through NaPi transporters

22
Q

how does serum phosphate change with changes in pH

A

NORMALLY: the majority of ions are in the form of HPO42- and the minority as H2PO4-

in acidic conditions: there is a relative increase in H2PO4- for acid base balance (ie buffering) and hence a decrease in HPO4-

23
Q

PTH mechanism of action for Ca and Pi

A

INTESTINE: increases both Ca and Pi absorption

BONE: increases Ca and Pi by stimulating osteoclasts and causing bone reabsorption and osteolysis

KIDNEY: increases reabsorption of Ca but decreases reabsorption of Pi (hence less Ca and more Pi is excreted)

OTHER: Stimulates VitD3 and FGF23 - both for Ca conservation

24
Q

CALCITONIN mechanism of action

A

!! action through cAMP/PLC cascades

INTESTINE: inhibits Ca absorption

BONE: inhibits osteoclasts to reduce bone resorbtion and stimulates osteoblasts to increase mineralisation (hence decrease Ca)

KIDNEY: decreases reabsorption of Ca and increases its excretion

25
VITD3 overall effect on Ca and Pi
INTESTINE: increases absorption of both Ca and Pi OTHER: inhibtis PTH (-ve feedbakc bcos they have the same function) and stimulates FGF23
26
synthesis of active version of vitamin D
SKIN: 7-hydrocholesterol using UV radiation LIVER: this is hydroxylated and becomes calcidiol KIDNEY: transformed into CALCITRIOL (active form) in tubular cells) via 2nd hydroxylation
27
how is vitD carried in the blood
BOUND TO: 1. vitD binding protein 2. albumin (enters cells via vesicle mediated mechanism)
28
Describe the receptor of VD3:
VDR - cytoplasm and nucleus of target cells. upon binding in the cytosol the complex translocates to the nucleus VDR upregulates some genes and downregulates others
29
ROLE OF CASR on PTH and VD3
CASR -- detects a high calcium concentration and elicits the IP3/DAG response to increase intracellular Ca2+ 2 EFFECTS: 1. increases VDR expression 2. decreases PTH expression (which is also further decreased by the activation of VDR)
30
FGF23-KLOTHO AXIS explanaiton
FGF23 --> fibroblast GF secreted by osteoclasts, osteoblasts and bone marrow. -stimulated by PTH and by VitD3 ACTS ON THE KIDNEY: -decreases the reabsorption of Pi in PCT (hence more is excreted and leads to hypophosphatemia) -conserves Ca and Na by increasing reabsorption in DCT !! BINDING OF THE FGF23 TO ITS RECEPTOR IN THE PCT/DCT IS alpha KLOTHO DEPENDENT
31
hypercalcemia effects
CALCIUM TOO HIGH: -arrythmias -muscle weakness
32
hypocalcemia effects
CALCIUM TOO LOW: -seizures -muscle cramps -heart failures -spasms of SM
33
RICKETS (2 types)
1. calcipenic - calcium deficiency or VitD3 deficiency 2. phosphopenic - renal phosphate wasting causing deficiency SYMPTOMS: frontal swelling of the head, bowing of legs, swelling in joints.