Calcium and PTH Flashcards
Signs + sx of hypocalcemia
Mild hypocalcemia usually asymptomatic
Tetany, seizures, QT prolongation, Chvostek sign (facial twitching), Trousseau sign (spasm upon blood pressure cuff)
Imaging findings for rickets (2)
1) Rachitic rosary
2) Epiphyseal widening + metaphyseal cupping/ fraying
Functions of vitamin D
Generally increases both Ca2+ and phosphate levels in the serum
1) Increase aborption of Ca2+ and phosphate in the instestine
2) Increase renal absorption of Ca2+ and phosphate
3) Increase resorption of bone- provides Ca2+ and phosphate in the serum to mineralize new bone
How does renal failure lead to hyperparathyroidism? (2 ways)
1) Secondary hyperparathyroidism: Renal failure results in phosphate retention, which binds Ca2+ and deposits it in ectopic tissues –> hypocalcemia –> increased PTH (secondary hyperparathyroidism)
2) Tertiary hyperparathyroidism: Chronic renal failure and untreated hyperparathyroidism- autonomous PTH secretion –> hypercalcemia
Functions of PTHrP and when it’s commonly seen
Functions: same as PTH except doesn’t increase Vitamin D production + intestinal Ca2+ absorption
Commonly associated w/ cancers (e.g. small cell carcinoma of lung, renal cell carcinoma, breast CA)
Synthesis of Vitamin D
D3 (from sun, ingestion of fish + plants) + D2 (from plants, fungi, yeasts) are converted to 25-OH in liver then subsequently to 1,25-(OH)2vitamin D (active form) in kidney via 1alpha-hydroxylase
Chvostek sign + Trousseau sign and what do they implicate
Chovestek sign: tapping of facial nerve (tap cheek) –> contraction of facial muscles
Trousseau sign: occlusion of brachial artery w/ BP cuff –> carpal spasm
indicative of hypocalcemia
Causes of secondary hypoparathyroidism
1) Vitamin D deficiency (e.g. Renal failure, inadequate intake)
2) Deficient Vitamin D receptor
3) Albright Hereditary Osteodystrophy
Lab findings of rickets/ osteomalacia (Vitamin D deficiency)
Low Vitamin D
Low serum Ca2+ and Phosphate
High PTH (secondary hyperparathyroidism due to low Ca2+)
high ALP (correlated w/ osteoblast activity)
How alkalosis/ acidosis affects serum Ca2+ levels
Alkalosis- total Ca2+ levels the same; however, low H+ so more Ca2+ binds to albumin –> hypocalcemia
Acidosis- total Ca2+ level the same; however high H+ so less Ca2+ binds albumin –> hypercalcemia
Rachitic Rosary
Rickets
Functions of PTH (4)
Generally, increases serum Ca2+ levels and decreases phosphate levels
1) Bone resorption- stimulates osteoblasts to express RANKL, which binds RANK on osteoclasts, stimulating resorption
2) Increase Renal Ca2+ absorption
3) Increase intestinal Ca2+ absorption- stimulates 1alpha-hydroxylase in the kidney to form more active Vitamin D
4) Decrease phosphate reabsorption in PCT
How does chronic renal failure lead to hyperparathyroidism/ hypercalcemia?
If secondary hyperparathyroidism not treated for a long time, parathyroid gland becomes autonomous w/o regulation via Ca2+ –> increase PTH secretion –> hypercalcemia
What are the etiologies of Vitamin D related hypercalcemia and how does it results in high calcium levels?
1) Granulomatous disease (sarcoidosis)- granulomas express high 1-alpha-hydroxylase activity –> increase Vitamin D activation –> hypercalcemia (normal levels of Vitamin D but active forms increased)
2) Lymphomas– lymphocytes in lymphomas express high 1-alpha-hydroxylase activity –> increase Vitamin D activation –> hypercalcemia (normal levels of Vitamin D but active forms increased)
3) Excess Vitamin D ingestion– high levels of vitamin D + active form
Imaging findings of osteomalacia
Osteopenia + “looser zones” (pseudofractures- decreased density of bones)
Sx/ presentation of rickets (5)
1) Pigeon-breast deformity
2) Rachitic rosary
3) Bowing of legs (genu varum)
4) Frontal bossing
5) Craniotabes (soft skull)
3 forms that Ca2+ exists in the blood
1) Ionized/ free (available Ca2+)- 45%
2) Bound to albumin- 40%
3) Bound to anions- 15%
Etiology of DiGeorge
Develomental failure of 3rd and 4th pharyngeal pouches, leading to thymus and parathyroid aplasia.
Usually sporadic but can be due to 22q11.2
Vitamin D’s effect on PTH
Inhibits transcription of PTH
Lab findings for HHM (PTHrP) – blood Ca2+ and phosphate levels, PTH, urine Ca2+ and phosphate, and urine cAMP
Ca2+ is high, Phosphate is low
PTH is low
urinary cAMP is high (acts on PTH receptors in kideny)
Urine Ca2+ and phosphate are high
Lab findings of Albright hereditary osteodystrophy
High PTH
Low Ca2+
Main problem in pseudohypoparathyoridism type 1A (Albright hereditary osteodystrophy)
Unresponsiveness of kidney to PTH, resulting in hypocalcemia despite high PTH levels. Normally, Gsalpha gene (GNAS) is paternally imprinted in certain areas (e.g. renal cortex, endocrine organs), resulting in shutting off of his genes. In PTHR, father’s shuts off but mother’s is mutated –> kidney is unresponsive to PTH
Defective mineralization of cartilaginous growth plates
Rickets
Function of calcitonin
Decrease bone resorption
Lab findings for familial hypocalciuric hypercalcemia (serum Ca2+, phosphate, PTH, calcitriol, urinary Ca2+)
Elevated serum PTH, Ca2+, Vitamin D
Low urinary Ca2+ excretion- Ca2+ sensing receptors in kidney inactivated –> excessive Ca2+ uptake
Etiology + findings of osteitis fibrosa cystica
Etiology: primary hyperparathyroidism
Findings: Due to increased PTH, there is cystic bone spaces (cortical bone loss) w/ brown fibrous tissues that cause bone pain. Brown fibrous tissues due to BV that are affected, leading to hemorrahge –> hemosiderin deposits.
How does presentation of HHM (PTHrP) of hypercalcemia differ from other causes of hypercalcemia?
Presents as an acute, severe hypercalcemia and is always symptomatic
Source of calcitonin and stimulation
Source: parafollicular cells (C-cells) of thyroid
Stimulation: Increase in serum Ca2+
Causes of primary hypoparathyroidism (4)
1) Accidental surgical excision of parathyroid
2) DiGeorge
3) AD hypoparathyroidism
4) Autoimmune destruction
Causes of hypercalcemia
1) PTH dependent hypercalcemia: Primary hyperparathyroidism, renal failure (tertiary hyperparathyroidism)
2) PTH independent hypercalcemia: HHM (PTHrP), Bone mets, vitamin-D related, Medications (e.g. thiazides)
Embryological origin of parathyroid gland
3rd and 4th pharyngeal pouches
Main problem in pseudopseudohypoparathyroidism and how it’s differnet from Albright hereditary osteodystrophy
Defective GNAS from father- although Gsalpha from father is shut off in renal cortex and endocrine glands, it’s normally not shut off in the periphery. Results in same physical exam features as Albright hereditary osteodystrophy but normal PTH and Ca2+ levels.
Decreased mineralization of osteoid
Osteomalacia
Sx/ presentation of albright hereditary osteodystrophy
Short stature (due to PTH resistance and hypocalcemia)
shortened 4th digit
Sx/ Presentation of osteomalacia
Increased fractures
Lab findings in primary hyperparathyroidism (serum Ca2+, PTH, calcitriol, urine Ca2+ and phosphate, urine cAMP)
Elevated calcium and PTH
Decreased Phosphate
Elevated urine Ca2+ and phosphate*
Elevated urine cAMP
Causes of primary hyperparathyroidism
Most often due to parathyroid adenoma/ hyperplasia (e.g. part of MEN)
Other causes: Familial hypocalciuric Hypercalcemia (FHH)
Inactivating mutation of Ca2+ sensing receptor in multiple tissues, leading to hyperparathyroidism and hypercalcemia
Familial hypocalciuric hypercalcemia
Mg2+ levels and PTH secretion and causes of low Mg2+
Low magnesium levels- stimulate PTH secretion
Very low magnesium levels- inhibit PTH secretion
Causes of low Mg2+: diarrhea, aminoglycosides, diuretics, alcohol abuse
Sx/ Presentation + Imaging finding of DiGeorge
Sx/ Presentation: CATCH-22
- C: Conotruncal abnormalities (e.g. truncus arteriosus, tetralogy of Fallot); most common cause of death
- A: Abnormal facial features
- T: Thymic aplasia –> T cell deficiency (leads to recurrent viral + fungal infections)
- C: Cleft palate
- H: Hypoparathyroidism + hypocalcemia (due to parathyroid hypoplasia)
22: 22q11.2 genetic microdeletion
Imaging: Absent thymic shadow on CXR
Sx of hypercalcemia
Mild hypercalcemia is asymptomatic
Sever hypercalcemia- Stones, thrones, bones, groans, psychiatric overtones
- Stones: hypercalciuria leads to increased risk of calcium renal stones
- Thrones: polyuria
- Bones: Osteitis fibrosa cystica
- Groans: weakness + constipation, abdominal pain/ flank pain
- Psychiatric overtones: depression
What are the causes of hypocalcemia?
1) Primary hypoparathyroidism- Accidental surgical excision of parathyroid glands, autoimmune desutrciton, DiGeorge (agenesis), AD Hypoparathyroidism
2) Secondary hyperparathyroidism- Vitamin D deficiency, Renal failure, deficienct Vitamin D receptor, Albright Hereditary Osteodystrophy
