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RC Peds Endo 2023 > Ca, Phos, Bone > Flashcards

Ca, Phos, Bone Flashcards

1
Q

Causes low ALP

A
  • HPP
    • Congetnital hypophosphatasia
    • Nutritional deficiencies
    • Zine Def
    • Vit C Def
    • Wilson disease
    • Hypothyroidism
    • Celiac Disease
    • Glucocorticoids
    • Bisphosphonates
    • Pernicious anemia
    • Active caloric restriction
    • Multiple myeloma, other cancers
      • Major trauma or surgery
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2
Q

Cause high ALP

A
  • Bone disease
  • GI disease
    ○ biliary tract obstruction - elevated LFTs too
    ○ liver disease (eg, tumor, abscess, granulomas, or amyloidosis) - isolated elevated ALP
  • Transient hyperphosphatasemia of infancy and early childhood (benign)
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3
Q

FGF23 receptor
- what kind of R
- what does it do
- what does it cause

A
  • tyrosine kinase recetpro
  • degradation of NaPi cotransporter
  • lowers [phos]
  • also decreases calcitriol
  • increases 24-OHase
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4
Q

SnS HypoCa

A

irritability
jitteriness
tremors
perioral and acral paresthesia
poor feeding
laryngospasm
muscle cramp
lethargy
seizure

Trousseau’s sign
Chvostek’s sign

prolonged QTc
arrhythmia
bradycardia

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5
Q

Neonatal HypoCa DDx

A
  • Early-Onset (0-72 hours)
    ○ IDM, IUGR, birth asphyxia, prematurity
    ○ Maternal hypercalcemia
    ○ Hypoparathyroidism (transient or permanent)
  • Late-Onset (>72 hours)
    ○ High phosphorus intake - in formula
    § Because this steals all the Ca to complex w so decreases [Ca]
    ○ Low magnesium
    Maternal vitamin D deficiency – Hypoparathyroidism
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6
Q

HyperCa SnS

A

Polyuria, polydipsia
Anorexia, nausea and vomiting
Failure to thrive in infants and toddlers
Constipation
Hypotonia
Irritability/seizure/depression
Renal calculi
Bone pain
Hypertension

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7
Q

how does SCFN cause hyper Ca

A

Granulomatous disease (1-alpha hydroxylase - high levels of 1,25 OH Vit D from macrophages)

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8
Q

how does Williams syndrome cause hyperCa

A

Incr absorption of Ca and dcr clearance

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9
Q

features to distinguish FHH from other causes of hyper Ca

A

Low calcium in urine (hypocalciuria)
Family history of the same (autosomal dominant)
Lower PTH
No findings on ultrasound or imaging (ie: no adenomas)
Hypercalcemia is present from a young age
Elevated Mg (or upper limit of normal)
Typically mild hypercalcemia
Typically asymptomatic

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10
Q

Mgmt HyperCa

A

Acute
– Hydration (normal saline) - (1.5-2xmaintenance)
– Loop diuretics– for fluid overload (not first line) – do not recommend prolonged use
– Oral phosphate for binding of calcium in intestine
– Calcitonin
– Dialysis
– Bisphosphonate

Long term
- bisphosphonates
*denosumab
– Glucocorticoids (inhibits 1 ⍺ hydroxylase activity + decreases GI absorption of Ca)
– Calcimimetic agents (Allosteric activators of CaSR-> reduce PTH secretion)
– Parathyroidectomy
– cinacalcet for neonates/inoperable cases -> Stimulates the CaSR

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11
Q

Hungry bone syndrome

A

After prolonged hyperparathyroid - acute removal of PTH so bones take back up the Ca

– Severe hypocalcemia
– Hypophosphatemia
– Hypomagnesemia
– Elevated alkaline phosphatase

  • Due to chronic increase in bone resorption
  • Bone influx of minerals after acute drop in PTH levels

Hungry bones – rapid aggressive remineralization after prolonged exposure to PTH

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12
Q

sx hypophos

A

Muscle weakness
Fatigue
Acute neurological symptoms – paresthesia, altered mental status, seizures

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13
Q

causes hypophos

A

**Renal phosphate wasting (main cause)
**Acute phosphate redistribution
○ Refeeding syndrome
**High PTH
○ PTH inhibits phosphate reabsorption in proximal renal tubule

**Decreased GI uptake / intestinal absorption
○ Starvation, e.g. AN
○ Vitamin D deficiency
○ Malabsorption
○ Inhibition of phosphate absorption (eg, antacids containing aluminum or magnesium, niacin)
○ Chronic alcoholism
○ Steatorrhea and chronic diarrhea
○ Vitamin D deficiency or resistance (VDDR1: mutation in 1-alpha-hydroxylase)

**Renal losses / increased urinary excretion
○ Hyperparathyroidism – primary and secondary
○ Hypophosphatemic rickets (X-linked and AD)
○ Vit D Def or resistance
○ RTA (fanconi)
○ Diuretic therapy
○ Hypomagnesemia
○ Aldosteronism
○ HHRH : Hereditary hypophosphatemic rickets with hypercalciuria (LOF mutations in Na-Pi IIc)
○ Oncogenic osteomalacia
**Intracellular shifts / internal redistribution
○ Alkalosis (metab or resp)
○ Increased insulin secretion (particularly refeeding)
○ Hungry bone syndrome
○ Administration of corticosteroids, epi, lactate, glucose, insulin
○ Recovery from hypothermia

**Misc
* Acute gout
* Hypokalemia
* Carcinoma – tumor induced osteomalacia
* DKA
* Alcohol withdrawal

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14
Q

what is Fanconi syndrome

A

Renal proximal tubular disorder leading to loss of:
- phos
- gluc
- K
- bicarb
- UA
- AA
- proximal RTA

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15
Q

HypoMg
- what does it do to PTH
- sx

A

Chronic hypoMg -> Decreases PTH secretion and action
==”Stuns the gland”
Acutely hypoMg -> parathyroid increases secretion of PTH

Symptoms of hypocalcemia
* Irritability
* Muscle twitches
* Jitteriness
* Tremors
* Poor feeding
* Lethargy
* Seizures

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16
Q

what does hyperMg do

A

suppresses PTH
Stimulates CaSR

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17
Q

Genetic syndromes assoc w hyperparathyroid

A

MEN 1
MEN 2a
Hyperparathyroidism - jaw tumor syndrome
MEN 4
Familial isolated hyperparathyroidism
Neonatal severe primary hyperpathyroidism
Nonsense PHPT

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18
Q

clinical features of rickets

A

○ Craniotabes
○ Frontal bossing
○ Delayed closure of fontanelles
○ Delayed eruption of teeth with poor enamel formation, pitting
○ Rachitic rosary
○ Harrison’s groove
○ Pectus carinatum
○ Scoliosis and kyphosis
○ Flaring of the metaphyses of the long bones
○ Bowing of legs
○ Poor growth, short stature
○ Muscle hypotonia -> pronounced potbelly and waddling gait
○ Pathologic fracture

adolescents:
○ Bone pain (usually lower spine, pelvis, lower extremities) and muscle weakness
○ Bone tenderness
○ Fracture (rib, vertebrae, long bone)
○ Difficulty walking and waddling gait
Muscle spasms, cramps, a positive Chvostek’s sign, tingling/numbness, and inability to ambulate

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19
Q

Xray of rickets

A
  • Widening of growth plate (metaphysis)
  • Irregularity of the epiphyseal-metaphyseal junctions
  • Metaphyseal cupping, splaying and fraying (vs. sharp demarcation and slightly convexshape)
    -Osteopenia
    -Bowing of long bones (if wt bearing)
    -Pseudofractures (= Looser’s zones or Milkman’s fractures)
    -unhealed microfractures at points of stress or at entry point of blood vessels into bone
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20
Q

Rickets or osteopenia of prematurity

A

causes”
– Prematurity (Failure to accrue bone mineral in third trimester)
– Chronic medical problems; Medications used to treat them
– Inadequate intake of minerals post birth, TPN dependency, aluminum toxicity
= lack of dietary Ca, phos, Vit D + lack of Vit D can cause decreased absorption of Ca and Phos

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21
Q

RF for MBD of prem

A
  • <28 wga
  • <1500g
  • TPN for >4weeks
  • CLD
  • long term diuretic use
  • NEC grade 2 or more
  • fluid restriction (TFI <150)
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22
Q

what do you see on xray in scruvy

A

osteopenic with thin cortices
sclerotic bands

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23
Q

Primary causes of osteoporosis

A

1) OI
2) Idiopathic juvenile osteoperosis

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24
Q

Types of OI

A

○ Mild - type 1
○ Type 2 - lethal
○ Type 3 - severe
○ Type 4 - moderate
○ Type 5 - moderate

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25
Q

Secondary causes of osteoporosis

A

1) Malignancy
- leukemia
- solid tumours
2) Inflammatory disorders
- Rheuatoid arthritis
-IBD
-CF
-Celiac disease
3) Muscle weakness or reduced mobility
-DMD
-CP
-Developmental delay
-Autism
4) Osteotoxic drugs
-Glucocorticoids
-Methotrexate
-GnRH agonists
5) Endocrinopathies
-Hypogonadism
-Hyperthyroidism
-Cushing

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26
Q

Meds causing osteoporosis

A

○ Glucocorticoids
○ Anticonvulsants
○ Methotrexate
○ Antiepileptics
○ Heparin
○ Immunosuppressants: MTX, Cyclosporine A
○ Lithium
○ Antiretrovirals
○ GnRH agonist
○ Sex hormone deprivation with gonadotropin releasing hormone agonists or medroxyprogesterone acetate.
○ Thyrotoxicosis
○ Diuretics
L-thyroxine suppressive therapy (only post menopausal women)

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27
Q

how do GC cause osteoporosis

A

CELLS
- increased apoptosis osteoblasts and chondrocytes
- decreased proliferation osteocytes
- inhibition of osteoblastogenesis
- prolongs osteoclast life
- enhanced osteoclastogenesis

HORMONES/OTHER FACTORS
- decreased OPG
- increased FGF23
- decreased expression type 1 collagen
- decreased WNT signalling

ENZYMES
- impaired 1aOHase

Ca coming into body
- increased Ca excretion in the kidney
- decreased Ca absoriotn in gut

OTHER HORMONES
- impaired androgens
- decreased sex hormones
- decreased GH and IGF1

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28
Q

OI findings

A

○ Craniofacial:
-Triangular facies
-Wormian bones (extra skull bones between normal sutures)
-Macrocephaly
-Chiari malformation
-Hydrocephalus
-Hearing loss

○ Optho:
-Blue sclerae

○ Dental:
-Dentinogenesis imperfecta (teeth discolored and translucent)

○ Respiratory:
-Pulmonary hypoplasia
-Respiratory failure

○ MSK:
-Hypermobility
-Fragility fractures
-Long bone deformities (can have bowing)
-Short stature
-Scoliosis
-osteoporosis
- long bone fractures

29
Q

problems w the bone

A

low bone mass
low bone quality
abnormal bone geometry
bone deformation

30
Q

how do bisphosphates work

A
  • bind to hydroxyapatite
  • stop osteoclasts from binding
  • cause osteoclast apoptosis
31
Q

peds uses of bisphosphanates

A

○ Hypecalcemia
○ Primary Osteoporosis
§ OI
§ OJI
○ Secondary Osteoporosis except eating disorders –
–Fibrous Dysplasia
–Immobilization
– DMD
– CP
– juvenile arthritis
○ Fibrous dysplasia
- juvenile Paget’s (idiopathic hyperphosphatasia)

32
Q

S/E bisphos

A
  • Acute
    ○ Fever
    ○ Myalgia
    ○ Abdominal pain, dyspepsia
    ○ Vomiting
    ○ Hypocalcemia, hypophosphatemia
    ○ Bone pain
    ○ Pain at infusion site
    ○ Headache
    ○ Allergic reaction
    ○ *Acute phase reaction usually only after 1st dose
  • Chronic
    ○ Inflammatory disorders of the eye
    ○ Osteonecrosis of the jaw (in the elderly)
    ○ Induced osteopetrosis
    ○ atypical femur fracture
33
Q

denosumab
- what is it
- when to use
- big issue

A
  • monoclonal ab to RANK-L
  • Giant cell tumour
  • osteoporosis
  • Aneurysmal bone cysts

rebound hyperCa

NOT IN OI anymore

34
Q

osteopetrosis

A
  • Malignant infantile osteopetrosis
  • AD form
  • Xlinked

defect in bone resorption
increased BMD

bone fragility
narrow bone marrow space
- pancytopenia
compression of CN
hypoCa - sz

Infantile: Definitive treatment for most of the genetic lesions is hematopoietic stem cell transplantation.

35
Q

what is seen in PHP w bone

A

fibrous dysplasia

Soft tissue calcification

36
Q

PTH-R activating mutation

A

Jansen’s Metaphyseal Chondrodysplasia

  • short-limbed dwarfism and characteristic skeletal abnormalities

activating mutations in the PTH/PTHrP receptor that result in ligand-independent cAMP accumulation

Hypercalcemia and hypophosphatemia
low or undetectable serum levels of PTH and PTHrP.

37
Q

what meds affect renal Ca excretion

A

corticosteroids: increase Ca excretion

furosemide: increase Ca excretion

thiazide diuretics decrease Ca excretion

38
Q

what happens when PTH acts on the PTH-R

A

PTH-R expresses:
more RANK-L
less OPG
This leads to more osteoclast action and more bone turnover

39
Q

hyper Ca DDx

A

Bone resorption:
- hyperPTH
– primary, MEN, familial isolated
- thyrotoxicosis
- vit D intoxication
- hypervitaminosis A
- immobilization

High Ca intake
- High Ca intakes for phosphate binding in renal failure
- milk alkali syndrome
- vitamin D intoxication

Other:
- subcutaneous fat necrosis
- malignancy (osteolytic mets, PTHrP)
- Williams syndrome
- Familial hypocaliuric hypercalcemia
- Meds: thiazides, lithium, theophylline
- Adrenal insufficiency
- pheochromocytoma
- hypophosphatasia
- rhabdomyolysis
- distal RTA
- Excess PTHrP (ie. tumour induced)
- hyperthyroidism

40
Q

HyperCa in Neonates - DDx

A
  1. Excessive intake of calcium or Vit D’
    - Exogenous
    - Milk-alkali
    - Granulomatous diseases – ectopic production of calcitriol
  2. Phosphate depletion
  3. SC fat necrosis, Granulomatous disease (1-alpha hydroxylase)
  4. Williams syndrome
  5. Endocrinopathies:
    - primary adrenal insufficiency
    - severe hypothyroidism, or hyperthyroidism
  6. Malignancy
    - lytic bone lesions or PTHrP
  7. Meds:
    - thiazides, lithium, Vit A ,Ca, alkali etc.
  8. Genetics
  9. Other:
  10. Immobilization
  11. Persistent PTHrP

Maternal hypoparathyroidism
Maternal pseudohypoparathyroidism

41
Q

Genetic causes of HyperCa in neonates

A
  1. CYP24A1
  2. Jansen metaphyseal chondroplasia (activating mutation of PTH-R)
  3. LCT: Congenital lactase and other disaccharide deficiencies (2/2 increased intestinal absorption of Ca promoted by the disaccharides)
  4. Infantile hypophosphatasia (TNSALP: mutation in AlkPhos)
  5. Mucolipidosis type II
  6. Blue diaper syndrome
    a. defect in absorption of tryptophan, ass/w hypercalcemia and nephrocalcinosis, pathogenesis unclear
  7. Antenatal Bartter syndrome type 1 (SLC12A1) and type 2 (KCNJ1)
  8. Distal RTA
42
Q

Familial Hypocalciuric Hypercalcemia
- gene
- labs

A

Due to dominantly inherited INACTIVATING mutation in the CaSR

Benign elevation in Ca
PTH normal to slightly high

43
Q

Chvostek’s sign

A

Percussing the facial nerve approximately 2 cm anterior to the ear, causes contraction of the ipsilateral facial muscles.

44
Q

Trousseau’s sign

A

Inflate the BP cuff to approximately 20–30 mmHg above systolic for 3 minutes.
Characterized by carpal spasms, with adduction of the thumb, flexion of the metacarpophalangeal joint, extension of the interphalangeal joints, and flexion of the wrist

45
Q

neonatal hypoCa

A

maternal diabetes
maternal hyperparathyroidism
Vitamin D deficiency
High intake of alkali or magnesium sulfate
Use of anticonvulsants

prematurity/LBW
birth trauma/asphyxia
sepsis, toxemia
hypoparathyroidism (DiGeorge)
hypomagnesemia
Acute/chronic renal failure
excessive phos intake
inadequate calcium intake
vitamin D deficiency
hyperphosphatemia
pseudohypoparathyroidism
Vitamin D def or resistance
Osteopetrosis type II

46
Q

where is the GNAS gene imprinted

A

paternal allele imprinted in the kidney (ie silenced)

47
Q

what is the AHO phenotype

A

short stature
round facies
obesity
brachydactyly
developmental delay
dental hypoplasia
basal ganglia calcifications
decreased bone density
subcutaneous calcifications
lenticular opacities
strabismus
cognitive impairment

48
Q

inherited defects in CaSR

A

Inactivating – High PTH & high calcium
1. Neonatal severe hyperparathyroidism (AR)
2. Familial Benign Hypocalciuric hypercalcemia(AD)

Activating – Low PTH & low calcium
1. AD Hypocalcemic hypercalciuria

49
Q

acquired defects in CaSR

A

Autoimmune hypocalciuric hypercalcemia (hyperparathyroidism)
- Blocking Ab vs. CaSR
- Acts like inactivating mutation

Autoimmune acquired hypoparathyroidism
- Stimulating Ab vs. CaSR
- Acts like activating mutation

50
Q

type of R - VDR

A

nuclear steroid hormone receptor

51
Q

definition of rickets

A

1) Deficient mineralization at the growth plate

+ 2) architectural disruption of this structure.

52
Q

signs of low phosphate

A

Muscle weakness/dysfunction/fatigue
Neuro sx if acute hypophos (parathesias, altered mental status, seizure)

53
Q

meds that can cause osteoporosis

A

Glucocorticoids
GnRH agonist
Anticonvulsants
Heparin
Immunosuppressants: MTX, Cyclosporine A
Lithium
Antiretrovirals
Diuretics
L-thyroxine suppressive therapy

54
Q

differentiating features between FHH and primary hyperparathyroidism

A

i) No findings on ultrasound
ii) Lower PTH
iii) Higher urinary calcium excretion
iv) AD family history
v) Hypercalcemia is present from young age (from birth if investigations are done)
vi) Elevated magnesium

55
Q

What medication can modulate CaSR? How does it work?

A

i) Magnesium: binds to CaSR and causes reduced PTH secretion and lower calcium
ii) Cinacalcet: Can upregulate CaSR expression

56
Q

osteogenesis imperfecta
- what protein is implicated
- features of the protein that are important for normal function

A

type 1 collagen

most commonly caused by mutations in genes encoding the alpha-1 and alpha-2 chains of type I collagen or proteins involved in posttranslational modification of type I collagen

i. Has to form helix
ii. Helices have to form triple helix

57
Q

RF for hungry bone syndrome

A

high ALP,
parathyroid adenoma >5 cm,
very elevated calcium and PTH
the osteitis fibrosa cystica

58
Q

what are the bone lesions in hyperparathyroidism?

A

Osteitis fibrosa cystica are the bone lesions seen in the phalanges and skull in hyperparathyroidism

59
Q

how long can nodules appear in SCFN

A

6 weeksw

60
Q

what is craniosyostosis seen in

A

X-linked hypophosphatemic rickets

61
Q

what are causes of bone resorpton

A
  • hyperPTH
    – primary, MEN, familial isolated
  • thyrotoxicosis
  • vit D intoxication
  • hypervitaminosis A
  • immobilization
62
Q

preferred site for DEXA in children

A

lumbar spine and total body

63
Q

acute hypoCa - what to watch for

A

laryngospasm

64
Q

what is Blomstrand chondroplasia

A

(PTHR1–loss of function mutation)
PTH resistance

65
Q

5 factors for osteoporosis in DMD

A

1) reduced muscle tension on bone
2) steroids
3) delayed puberty
4) chronic inflammation (attempted repair of damaged muscle fibres)
5) immobility

66
Q

maternal factors risk of MBD

A

Vitamin D deficiency
Placental insufficiency (impacts mineral transfer)
Pre-eclampsia
Chorioamnitis
Alcohol intake
Smoking

67
Q

neonatal factors factors risk of MBD

A

Vitamin D deficiency
Prematurity </= 28 wks
Birth weight </= 1500g
Immobilization
Prolonged parenteral nutrition (ie: >2 wks)
Inadequate calcium supplementation
Inadequate phosphate supplementation
Necrotizing enterocolitis
Chronic glucocorticoids
Chronic diuretics
Chronic lung disease
Malabsorptionw

68
Q

when does the majority of Ca and phosphate accretion occur

A

third trimester of pregnancy

resulting in bone and growth plate mineralization

69
Q

4 inherited causes of PTH dependent hypercalcemia

A

MEN1 - hyperparathyroidism
Autosomal dominant, MEN1 tumor suppressor gene (menin protein)

MEN2a - hyperparathyroidism
Autosomal dominant, RET (634 most common)

Familial hypocalciuric hypercalcemia
Autosomal dominant, inactivating mutation in CASR

Neonatal severe hyperparathyroidism
Autosomal recessive, inactivating mutation in CASR

RC Peds Endo 2023 (17 decks)

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