lecture 85 Calcium, PTH and Metabolic Bone disorders Flashcards
in the post op ICU a patient is noted to have low serum calcium levels, is this normal?
Yes – post op patients may have low albumin; therefore less protein bound calcium and lower serum calcium measurement
when you measure a total serum calcium, what components are you measuring?
what factors might alter these values?
□ Protein Bound Calcium
□ Diffusible Non Ionized
□ Ionized Calcium
Low albumin – lower protein bound calcium; lower total Calcium
Alkalosis – more protein bound calcium, but same Ca overall
Acidosis – lower protein bound calcium, but same Ca overall
if there is low albumin , how do you measure calcium levels ?
“Corrected Ionized Calcium” = Total Calcium + Correction Factor
Correction Factor = (4 - Albumin) x .8
Normal albumin: 3.5 -5.5
what organs control the level of serum calcium?
what hormones control the level of calcium ?
Intestines, bones, kidneys
PTH
1, 25 OH2 Vit D
Calcitonin, PTHRP
describe the generation of the active form of vit D?
function of this active form?
Skin: UV Light converts 7 Dehydroxycholesterol –> Vit D3
Liver: D3 —> 25 OH Vit D
Kidney: 25 OH Vit D –> 1,25 OH2 Vit D (Calcitriol); under control of PTH
§ Gi Tract: Increased Absorption of Ca2+ and PO4
§ Bone – Stimulates Bone breakdown
§ Maintains serum Ca and P
§ Negative Feedback on PTH glands
what form of vit D is measured when measuring vit D values ?
25 OH Vit D (not 1,25 bc the body readily converts this when it needs to)
Effect of PTH on the Kidney
□ Increases conversion of 25 vit D to 1,25 Vit D
□ Reabsorption of Ca2+ increased
□ Decreased Reabsorption of PO4
effect on PTH on bone
§ Bone – Two Opposite Effects – Anabolic and Catabolic – KNOW THIS
□ If Brief Stimulus (eg PTH injection) — bone Formation
® Osteoblasts – make new bone and stimulate Osteoclast activation
□ Prolonged Stimulus — Bone Breakdown
® Stimulation of osteoclast differentiation and Function (increasing blood calcium)
what is the most abundant anion in the body?
‘
too much of this anion in the serum can lead to____
PO4
vascular calcification
how is phosphorous regulated in the body?
§ High Phosphorous –
□ Increased PTH —> Phosph excretion from the kidney
□ FGF23 (made in osteocytes) —> Causes phosph excretion from the kidney
what is the most common cause of outpatient (asymptomatic) Hypercalcemia ?
what is the most common etiology of this ?
at what serum concentration may symptoms begin?
Primary Hyperparathyroidism –
□ 85% – single adenoma
□ 10% hyperplasia
Ca > 12 mg/dl
Signs and Symptoms of primary Hyperparathyroidism
Bones, Stones, Moans, Groans, Psychological Overtones
Asymptomatic – Most
Bones – Osteroporsis, pain and fracture
Stones – kidney stones, polyuria, azotemia
Moans – Neuromuscular weakness, fatigue, Chondrocalcinosis
Groans – constipation/N/V/peptic ulcers
Psychological Overtones -- Mild - depression Severe -- obtundation, coma Other -- eye (band keratopathy) Common cause of death in cancers (PTHRP)
what are three inherited forms of Primary hyperPTH
Rare form: FHH (familial hypocalciuric hypercalcemia) – AD mutation to calcium sensing receptor
MEN1
MEN 2
three non PTH mediated forms of hypercalcemia
what is the most common form of inpatient hypercalcemia
PTH levels are normal
Vit D Mediated - eg VIt D intoxication
PTHRP – most common form of inpatient (symptomatic)hypercalcemia
Other – Milk alkali syndrome, Immobilization, rhabdo
3 REQUIREMENTS for the dx of primary HyperPTH
® Elevated Serum Calcium
® Elevated or Inappropriately Normal PTH
® Elevated or normal Urine Calcium
Treatment of HyperPTH
Mild – none
Symptomatic:
Surgery – Localization of PTH glands by US and Sestamibi Scan, and removal of the glands.
For Poor Surgical Candidates – Cincalcet (calcimimetic agent) that tricks the PTH gland into thinking Calcium levels are sufficient
Treatment of Hypercalcemia
Acute Treatment –
Saline, Loop Diuretics,
IV Bisphosphonates (stbilize bone)
Treat the underlying cause –
Surgery, chemorads, glucocorticoids
what is secondary HyperPTH
Most common etiologies
Complications –
Parathyroid glands are reacting to something else such as low Calcium or Excess Phosphorous
etiologies –
CKD (most common); Hypercalcicuria, Vit D Deficiency
Bone Loss
what is tertiary HyperPTH
§ General: Same as primary hyperPTH, but in a patient who has been through a bout of Secondary HyperPTH
Eg CKD patient who then develops PTH Adenoma == Hypercalcemia
main causes of hypoPTH
Post op (thyroidectomy, head and neck surgery)
Auto Immune
AD CASR Mutaiton which perceives high levels of calcium
Digeorge Syndrome
requirements for dx of hypoPTH
□ Low PTH (Or inappropriately normal)
□ Low serum Ca
High Phosphorous
Hallmark and other symptoms of Hypocalcemia
Symptomatic if acute/severe rate of rise –
® Tetany – HALLMARK (neuromuscular irritability, paraesthesias, Seizures, larygospasm, cardiovascular collapse)
® Widened QT
® Mental Status – Fatigue, anxiety, depression, psychosis
® Intracranial – calcification of the basal ganglia
® Ocular – Cataracts
® Dental – early development = defective enamel
Two bedside signs for hypocalcemia
Chvostek Sign – tap along facial nerve –> ipsilateral twitch
‘
Trousseau Sign – BP cuff –carpal spasm
what is Pseudo-Hypoparathyroidism
Rare resistance to PTH (eg at the level of the kidey)
aka Albright’s Hereditary Osteodystrophy
pseudohypoparathyroid
labs
clinical features
genetics
® Low Serum Ca
® Elevated PO4
® Elevated PTH
® Short stature, short 4-5th metacarpals (seen also in Turner’s)
® Wide space nipples, mental retardation
Autosomal Dominant
Etiologies of Vit D Deficiency
Low Sun
Fat Malabsorption (IBD pts)
Anticonvusalnts (increased Vit D metabolism)
Obesity – Vit D is sequestered in Fat
manifestation of severe vit D deficinecy in adults vs children
Adults – bone pain, fractures
Childhood – Rickets,
2 forms of Hereditary Vit D Resistance
HVDDR Type 1 – alpha 1 hydroxylase deficiency/mutation
HVDDR Type 2 – due to mutation in Vit D receptor
name 2 monogenic Developmental bone disorders
what are the respective mutations?
Osteoporosis Pseudoganglioma Syndrome – LRP5 (Wnt Activator)
Osteogeneiss Imperfecta –
(Type 1 collagen)
Risk factors for osteoporosis
older age, female, fam hx, whites and asians, low body weight, smoking, alcohol, hypogonadism, inactivity, low calcium
A patient has is found to have a fragility fracture, but a T score WNL, does this patient has osteoporosis
describe how the dx of osteoporosis is made
yes – Diagnosis can be made by presence of fragility fracture (hip or spine compressure fracture)
vs DEXA scan T Scores (
what drugs and therapies are used to treat osteoporosis
Bisphosphonates (staibilizes)
Denosumab (RANK Ligand Inhibitor)
SERM (Raloxifene) (estrogen agonist activity on bone)
Teriparatide PTH (activates osteoblasts in the breif, acute setting)
Calcium
Vit D
Exercise
what is Paget’s Disease of the Bone –
genetics?
pathophys?
where does it most commonly occur?
Treatmnet?
AD
Increased rate of bone turnover
but in focal regions
axial skeleton
Lab markers for increased bone foraiton and turnove
ALP and N telopeptide
Pathognominc X ray finding for paget’s bone disease?
Picture frame sign of the vertebrae
Symptoms of paget’s bone disease ?
Treatment?
Who is treated?
Symptoms – bone pain and neurologic symptoms; warmth over bone; neurologic features
ALL patients are treated; even if asymptomatic (bc its progressive)
Treatment – Bisphosphonates
symptomatic management
what is renal oseotodystrophy; what is the classic radiological findng of the skull?
CKD –> poor response to PTH –> continual PTH secretion –> bone disease
Radiology: Salt and pepper of the skull
