calcium regulation Flashcards
1
Q
Ionised calcium level
A
1.3-1.5mmol/L (4.5-5.6mg/dL)
physiologically active
2
Q
Total plasma calcium level:
A
2.1 – 2.6 mmol/L (9-
11mg/dL)
3
Q
Exists in 2 forms
A
55% Diffusible (ionized ~active & non-ionized ~inactive)
- 45% protein bound
4
Q
Function of calcium in the body
A
extracellular matrix compartmentt, ecf, icf
5
Q
Extracellular matrix
compartment (1)
A
99% total body Ca
6
Q
Extracellular matrix
compartment (2)
A
Formation of
bone & teeth
7
Q
ECF (1)
A
0.1% total body Ca
8
Q
ECF (2)
A
Hormonal excitationsecretin (i.e gastrin)
9
Q
ECF (3)
A
Cardiac & smooth muscle contraction Neuron excitation Coagulation cascade
10
Q
Icf (1)
A
0.9% total body Ca
11
Q
icf (2)
A
• Skeletal muscle
contraction
12
Q
icf (3)
A
Membrane
excitation by
regulating Ca2+
influx
13
Q
Calcium Homeostasis
A
3 organs and 3 hormones
14
Q
3 organs:
A
Bone
Kidney
Small intestine
15
Q
3 hormones:
A
PTH
Vit D (calcitriol)
Calcitonin
16
Q
Factors Affecting Ca2+ absorption (1) high ca absorption
A
pH (presence of H+) in intestine Bile salts PTH & calcitriol hormones Calbindin -carrier protein in intestine
17
Q
Factors Affecting Ca2+ absorption (1) low ca absorption
A
Calcitonin hormone -Diet (nuts, spinach) -malabsorption (celiac disease) Phosphates
18
Q
Calcium absorption: pH
A
H+ and Ca2+ compete for binding sites on the albumin molecule
19
Q
Metabolic acidosis
A
↑ available H+ more H+ binds to albumin low Ca2+ binding to albumin ↑ ionised calcium
20
Q
Metabolic alkalosis
A
low available H+ less H+ binds to albumin ↑Ca2+ binding to albumin lowionised calcium
21
Q
Calcium absorption: Ca2+ level
A
Absorption site: Small intestine (90%) (10 site: duodenum), Large intestine (10%)
22
Q
Two distinct mechanisms of absorption:
A
Active transcellular absorption (when calcium intake low*)
Passive paracellular absorption
(when calcium intake is
moderate or high)
23
Q
Calcium absorption: Calbindin level
1) Transcellular entry
A
Lumen to Passive entry to transport across cell via calbindin to Active
transport exit to Blood
24
Q
entry of transcellular entry
A
passive entry via Ca2+
channels
25
how transcellular entry is exported out
• Active transport Ca2+ -ATPase pump
26
Calcium absorption: Calbindin level
| 1) paracellular entry
Tight junctions:
Vit D regulates tight
junction permeability
for Ca2+ absorption
27
Influence of Ca2+ on neuronal excitability
↑ free Ca 2+ to ↓ permeability to Na+ to less
influx of Na+ to resting potential farther
from threshold to ↓ generation of action
potential to ↓ n e r v e excitability
28
Hormonal Regulation of Calcium Level
pth, active vt d (calcitriol), calcitonin
29
Hormonal Regulation of Calcium Level : pth
* Increase Ca2+ level by acting on bone, kidney & GIT
* ↑ bone resorption (Ca2+ release from bone)
* ↑ conversion of 25-HCC to 1,25-DHCC (active Vit. D)
* ↓ Ca2+ secreted in milk to conserve Ca2+
30
Regulation of Parathyroid Hormones
Direct Calcium Feedback Loop
| Indirect Calcium Feedback Loop
31
Regulation of Parathyroid Hormones :
| Direct Calcium Feedback Loop
↓ Serum Ca2+ → stimulate PTH secretion
→ mobilization of Ca2+ from bone
(resorption)
32
Regulation of Parathyroid Hormones :
| Indirect Calcium Feedback Loop
↑ Serum PO4- →stimulate PTH secretion
and influence Ca2+ absorption in intestine
via Calbindin
33
Abnormalities in PTH secretion
hyperparathyroidism and hypoparathyroidism
34
Hyperparathyroidism
```
• Consequences: hypercalcaemia,
hypercalciuria, hypophosphataemia
• 1°: Parathyroid gland adenoma or
hyperplasia
• 2°: Low calcium e.g. vitamin D deficiency
```
35
Hypoparathyroidism
```
• Consequences: hypocalcaemia
• Thyroidectomy
• Autoimmune disease
• Absence or dysfunction of parathyroid
glands
```
36
Main actions of PTH on target organs
bone, kidney, small intestine
37
Main actions of PTH on target organs : bone
```
Stimulates calcium release from bones
↑ bone resorption (↑ dissolution of CaPO4 crystal)
rapidcalcium mobilisation from bone
↑ serum Ca2+ ↑phosphate (PO4
3-)
```
38
Main actions of PTH on target organs : kidney
- ↑ Ca2+ reabsorption from DCT
- ↑ PO43- urinary excretion (inhibit reabsorption)
- Activates Vit. D
(Stimulates renal 1α-hydroxylase activity to convert 25-hydroxy vitamin D3 to 1,25-dihydroxy vitamin D3)
Fast-acting: decreasing urinary Ca2+ levels within minutes
39
Main actions of PTH on target organs : small intestine
Indirectly↑ intestinal absorption of Ca2+
through its influence on vitamin D3
-PTH stimulates renal 1α-hydroxylase
activities to activate Vit D3
-Active Vit D3↑ intestinal absorption of Ca2+
by inducing calbindin-D synthesis to
mediates Ca2+ transport
40
Calcitriol (Vitamin D)
```
Two forms (Vit D2+ D3) are activated to form
calcitriol from 1,25 -DHCC
```
41
source of vitamin D
• Vit D3 (cholecalciferol) – generated in the skin
(UV light), dietary source (dairy produce, fish)
• Vit D2 (ergocalciferol)- derived from fungi, yeast
42
Activation of Vitamin D
* Vit D is obtained either from the skin through the action of sunlight, or from diet
* Vit D2, D3: biologically inactive
* Product of these hydroxylation reactions: 1,25- dihydroxyvitamin D3 i.e. calcitriol (metabolically active)
43
↓ [ Ca2+ ] in ECF → ↑ PTH secretion → ↑ 1α-hydroxylase activity
↑ Calcitriol
44
Causes of vitamin D
| deficiency
```
-Severe liver or kidney
diseases - interfere with
the generation of active
vitamin D3
-Drugs e.g. anti-epileptic drugs, which interfere with vitamin D metabolism in the liver
-Genetic defects in the
vitamin D receptor
-Insufficient exposure
to sunlight
-Decreased dietary
intake of vitamin D
```
45
Vitamin D toxicity
Ingestion of excess vitamin D – supplementation
| >100ng/mL
46
symptoms of vit d toxicity
```
– Hypercalcaemia
– Hypercalciuria - calcium excreted in urine resulting in
osmotic diuresis & polyuria
– Kidney stones - deposition of calcium
– Calcification of blood vessels
```
47
Calcitonin
```
• Counteracts PTH effect by ↓ serum Ca2+
• Stimulated when Ca2+ serum levels
>2.2mmol/L
• Target organs: bones & kidneys
• Negative loop on Ca2+ serum levels
```
48
Other hormones affecting Ca2+ homeostasis
1. Sex hormones (estrogens & androgens)
2. Growth hormones
3. • Insulin
4. Glucocorticoids
5. • Thyroid Hormones
6. Prostaglandins
49
```
Sex hormones (estrogens &
androgens)
```
- bone resorption (inhibit
osteoclast; stimulate
osteoblast)
- ↑ osteoprotegerin synthesis
50
Growth hormones
- ↑ serum Ca2+ & Ca2+ excretion
| in urine
51
• Insulin
- ↑ bone formation
52
Glucocorticoids
- inhibits osteoblast &
osteoclast activity →
osteoporosis
- ↓ Ca2+ absorption in GIT & ↑ Ca2+ excretion in kidney
53
• Thyroid Hormones
stimulates hypercalcemia &
| hypercalciuria
54
Prostaglandins
- ↑ plasma Ca2+
- action inhibited by
glucocorticoids
55
ABNORMALITIES IN PLASMA CALCIUM LEVEL Hypocalcemia
cns, cvs, muscle
56
hypocalcemia affects cns
```
Irritability & Anxiety
Paresthesia (tingling “pins & needles”
sensation)
Seizures
Laryngospasm/Bronchospasm
```
57
hypocalcemia affects cvs
Heart Failure
58
hypocalcemia affects muscle
```
Muscle cramps (Chovtek’s sign,
tetany)
Hyperactive tendon reflex
```
59
ABNORMALITIES IN PLASMA CALCIUM LEVEL
| hypercalcemia
cns, cvs, muscle, kidney + git
60
hypercalcemia affects cns
↓concentration, ↑drowsiness
| Depression, Confusion & Coma
61
hypercalcemia affects cvs
Cardiac Arrythmias
| Bradycardia
62
hypercalcemia affects muscle
Muscle weakness
| Bone pain, kidney stones
63
hypercalcemia affects git & kidney
Polyuria, polydipsia (thirst)
| Dyspepsia (e.g gastrin )
64
Chvostek’s sign
```
Abnormal reaction to the stimulation
of the facial nerve hyperexcitability.
The facial nerve is tapped at the
angle of the jaw, the unilateral facial
muscles will contract momentarily.
A positive response varies from
twitching of the lips at the corner of
the mouth to spam of all facial
muscles, depending on the severity of
hypocalcaemia.
```
