Ca-Po4 Flashcards
the journey of Vit D that’s absorbed
A) skin 80% - makes it colecalciferol (D3)
B) dietary <20% (D2, ergocalciferol)
- both go to liver - stores it as 25-OH (=calcidiol) via 25 hydroxylase!
- kidney hydrolyses 25-OH > 1,25-OH (=cantriol) via ONE alpha hydroxylase!
Action on 1,25-OH:
1) bones: resorption
2) kidneys: less Ca/PO4 excretion
3) intestines: absorb Ca
when to use 25-OH vs 1,25-OH Vit D tests
25-OH reflection of stores
1,25-OH = active Vit D, tests renal disease
Ca regulation in body e.g. low Ca
low Ca > inc PTH:
1) bones: resoprtion in MINUTES
2) kidneys: inc Ca abs, decr PO4 abs, inc 1,25-OH creation in DAYS
3) gut: inc Ca and PO4 abs in MINUTES
what does pH do to Ca?
alkalosis increases anionic binding sites, so inc Ca binding, reducing ionised Ca
Ca vs PO4 absorption by gut
Ca poorly absorbed by GIT - only 20-30%
PO4 easily absorbed
Stimuli for increased vs decreased PTH release
Inc PTH: dec CALCIUM, and INC phos
Dec PTH: inc Calcium, and calcitriol
overall action of the following on Ca and PO4:
1. PTH
2. Vit D
3. Calcitonin
- PTH: inc Ca, reduces PO4
- Vit D: inc Ca, INC PO4
- calcitonin: reduces Ca, reduces PO4
PTH action in kidneys: where??
inc Ca abs from DCT!
INHIBITS PO4 abs PCT!
how do glucocorticoids cause osteoporosis?
- bones: increase resorption, inhibit osteoblasts
- gut: less Ca absorption
- kidney: decreased Ca absorption
what are some clinical exam signs for spasm with hypoCa?
- Trousseau’s sign = carpal spasm from inflated BP cuff for 3-5mins >15mmHg above SBP
- Chovstek’s sign = facial spasm from tapping facial nerve in front of ear
why do we correct calcium?
for albumin, as Ca binds to it
= Ca total + (40-alb) x 0.02
neonatal hypocalcaemia - causes
early hypoCa (D2-3):
- prematurity
- FGR
- GDM
- hypoPTH or maternal hyPERPTH
- hypoMg (–> less and resistance to PTH)
late hypoCa (D7):
- hypoPTH
- PTH resistance
- high PO4 intake (cow’s milk)
- hypoMg
- mat Vit D deficiency
- DiGeorge
familial hypocalcaemia - key features
- AD (gain of function) mutation of CaSR > change in set point for PTH release
- low Ca
- normal/low PTH
- high Ca urinary excretion (rather than expected low excretion!)
APECED - key features
- AR mutation in AIRE
- candidiasis, hypoPTH, addison’s (late)
- and alopecia, malabsorption, vitiligo, T1DM etc
causes of high PTH
- vit D deficiency (diet/skin/malabs)
- abnormal Vit D metabolism (liver, kidneys, or genetic)
- pseudohypoparathyroidism
types of genetic Vit D abnormal metabolism
1-alpha hydroxylase deficiency = VDDR type 1. Can’t produce 1,25-OH Vit D
Hereditary resistance to vitamin D (HRVD) = VDDR type 2. Vit D receptor sucks, so 1,25-OH is actually high.
pseudohypoparathyroidism - key features
end organ resistance to PTH:
1. hypocalcaemia
2. hyperphosphataemia
3. elevated PTH
what is the most common type of pseudohypoparathyroidism? key features.
type 1a = albright hereditary osteodystrophy:
- AD GNAS1 MATERNAL mutation > Gs protein cannot signal > PTH receptor cannot couple cAMP
- short stature, short 4th 5th digits, obese and round face, and other hypoCa signs
- also get other end organ resistance: PTH > TSH > LH/FSH, GHRH
what is pseudo-pseudohypoparathyroidism?!
subtype of albright osteodystrophy
gene is PATERNAL
no PTH resistance - normal PTH and Ca
Mg and Ca relationship
hypoMg causes:
1) PTH resistance
2) reduced PTH
3) less 1,25 vit D
all of which > hypoCa
hypoMg could be congenital absorption problem (will respond to Mg supps), but if acquired/renal, then won’t work
FRACP: syndrome for hyper vs hypoCa
hyperCa = Williams
hypoCa = DiGeorge
hypercalcaemia symptoms / signs
stones, bones, groans, abdo groans (n,v, pancreatitis), and psychic moans
… and short QT
how to treat hypercalcaemia
if really bad >3.5: HYDRATE +/0 diuretics
long term: low Ca diet, steroids and bisphosphonates (peak in a week)
neonatal hypercalcaemia - what could be causing it?
- neonatal hyperPTH 13q13
- transient hyperPTH
- Williams
- fat necrosis! esp after delivery trauma
- familial hypocalciuric hypercalcaemia (FHH)
outside of neonatal period, causes of hypercalciuria (think pathophys)
- inc vit D - Vit D toxicity (granulomatous disease!!), Williams
- inc PTH - hyperPTH, adenoma, MEN
- inc bone turnover - immbolisation
- malignancy
hyperPTH - MEN1 or 2?
MEN1 90%, less common in MEN2 which is more malignant driven
what is the problem in familial hypocalciuric hypercalcaemia?
AD INACTIVATVING mutation in Ca sensing receptor > change in set point: high Ca, normal PTH
biggest risk factor for neonatal vit d deficiency?
maternal vit D def! foetal levels come from placenta, and last for 3mo. premmies bad bc less time to accumulate levels
ways you can get low Vit D
- not enough in e.g. diet, prem, BF, skin type, sun
- can’t get it in e.g. malabs, CF
- can’t make it right - genetic disorders
- can’t recognise it
- meds - steroids!
normal vit D minimum level?
50nmol/L
when to give vit D in asymptomatic neonate?
exclusively breastfed + one other risk factor (no sun, skin, medical conditions) > 400IU daily until 12mo
rickets vs osteomalacia
Rickets = deficient mineralisation at the growth plate i.e. only in growing bones!
Osteomalacia = impaired mineralisation of the bone matrix
signs/symptoms of rickets
- head: delayed fontanelle clousre, frontal bossing, craniotabes
- delayed dentition
- rachitic rosary
- initially manifest bone pain: distal forearm, knee > #
- radiologcal fraying, cupping, widening of growth plate
- genu varum (bowed legs in toddler)
- If hypocalcaemic > Sx
- if phosphopenic > dental abscess
best biochem marker of rickets
ALP
Ca, PO4 and PTH levels in hypoCa vs hypoPO4 rickets
- PO4 = ↓ calcipenic ↓ phosphopenic
- Ca = ↓ or N in calcipenic, usually N in phosphopenic
- PTH = usually ↑ calcipenic rickets, N or mildly ↑in phosphopenic
most common pathophys of phosphopenia?
renal wasting - thinkg e.g. fanconi, distal RTA
where will you find the calcium sensing receptors?
parathyroid chief cells, renal tubular cells, c-cells of thyroid
