11/15: Calcium and Phosphorus II Flashcards
How does chronic kidney disease affect calcium and phosphate homeostasis?
By disrupting the Ca and Pi reabsorption process
What defines hypocalcemia?
When total serum calcium concentrations are less than 8.5 mg/dL
Or serum ionized calcium less than 4.4 mg/dL
What are the symptoms of hypocalcemia?
Muscle cramps
Increased neuromuscular excitability Muscle spams
Fatigue
Cardiac dysfunction
Depression, psychosis, seizures
what is hypoparathyroidism?
Undersecretion of PTH
what leads to hypoparathyroidisms?
Hypocalcemia that also has serum PTH that is really low
what are the common causes of hypoparathyroidisms?
autoimmune
what is DiGeorges syndrome?
Congenital disease that causes a lack of the parathyroid glan
Is hypoparathyroidism associated with CaSR mutations?
yes
how is hypoparathyroidism associated with CaSR mutations?
By consitutively activating CaSR causing hypocalcemia since PTH becomes
inhibited leading to low Ca reabsorption
How do you treat hypoparathyroidism?
Calcium and calcitriol
What occurs in this disease (hypocalcemia)?
Serum PTH is high to overcome the resistance to increase low Ca levels
what can a Vit. D deficiency lead to in children?
rickets
what can a Vit. D deficiency lead to in adults?
Osteomalacia
what is VDDR type 1?
Pseudovitamin D deficiency
what causes VDDR type I
Defect in renal 25-OH-Vit. D 1-alpha hydroxylase
Is 1,25(OH)2D3 high or low in VDDR type 1?
very low
What causes VDDR type 2?
Defect in Vit. D receptor
Is 1,25(OH)2D3 high or low in VDDR type 2?
High
How do you treat primary hyperparathryoidism?
surgery
Can inactivating mutations of CaSR cause familial primary hyperparathryoidism?
yes
What occurs in this disease (hypercalcemia)?
Oversecretion of PTH due to hypocalcemia or decreased 1,25(OH)2D3
b. Renal failure
what defines hypophosphatemia?
<2.5-4.5 mg/dL of Pi
what is X-linked hypophosphatemic rickets (XLH)?
PHEX gene on X-chromosome gets mutated causing bone deformities
what does PHEX normally do?
Inhibits FGF23 production
what does XLH mutation do?
Causes inactive PHEX so FGF23 is increased
How do you treat XLH?
. Phosphate supplementation
b. High calcitriol
What are the two forms of hypophosphatemic rickets?
Autosomal dominant
b. Autosomal recessive
What causes autosomal recessive hypophosphatemic rickets?
a.Mutations in DMP1
i. Causes overproduction of FGF23
What causes hereditary hypophosphatemic rickets?
Loss of function mutations in NaPiIIc
What is tumor induced osteomalacia?
An acquired syndrome of renal phosphate wasting
What does the condition cause?
Secretion of factors into the blood like FGF23
what defines hyperphosphatemia?
Phosphate > 4.5mg/dL or >1.5mM
what are the symptoms of acute hyperphosphatemia?
Hypocalcemia
what are the symptoms of chronic hyperphosphatemia?
Soft tissue calcification
Renal failure
What causes autosomal dominant hypophosphatemic rickets?
Mutations in FGF23 causing its increase
How does renal failure cause hypercalcemia?
Due to the kidneys being unable to produce 1,25(OH)2D3 which inhibits PTH
Is secondary hyperparathyroidism a condition of hypercalcemia?
no
What causes hypercalcemia of malignancy?
Tumors that secrete factors that stimulate bone resorption
What occurs to cause familial primary hyperparathryoidism in this instance?
CaSR inactive so high Ca levels are not sensed leading to elevated PTH since parathyroid gland reads Ca levels as low
What occurs in MEN2A?
Gain of function mutation in RET protooncogene
What occurs in MEN1?
Menin tumor suppressor gene inactivated
What are the two types of familial primary hyperparathryoidism?
MEN1 (Mutiple Endocrine Neoplasia)
b. MEN2A
what can primary hyperparathyroidism cause?
Hypercalcemia
Low Pi
High bone turnover
Kidney stones
what causes primary hyperparathyroidism?
Oversecretion of PTH without a negative feedback on it
what are the symptoms of hypercalcemia?
Fatigue
EKG abnormalities
Nausea, vomiting, constipation Anorexia
Abdominal pain
Hypercaciuria
Calcification of soft tissues Hypercalcemic crisis
what defines hypercalcemia?
Serum total calcium >10.5 mg/dL
Ionized calcium >5.4 mg/dL
What is VDDR type 2?
a. Hereditary vitamin D resistant rickets
what are the two types of Vit. D deficient rickets?
Type 1
Type 2
How does a lack of Vit. D inhibit Ca and Pi uptake?
Due to calcium transport proteins relying on Vit D to function, so without it they do
not work
What causes pseudohypoparathyroidism?
Hypocalcemia due to lack of sensitivity to PTH on tissues
How can you treat hypoparathyroidism?
Calcium and calcitriol supplements
