Flashcards in Lecture #4 -- Parathyroid Physiology Deck (79):
How is intracellular calcium controlled?
Pump-leak transport system
--Calcium leads into cytosolic compartment and is actively pumped into storage sites in organelles
What are the three definable fractions of calcium in serum
Ionized Calcium -- 50%
Protein Bound Ca -- 40%
Ca complexed to serum constituients -- 10%
What is protein bound Ca bound to
Remainder to globulins
What serum constituients is Calcium complexed to?
Citrate and Phosphate
Explain the relationship of EC Ca binding to pH
Acute Alkalosis --> more Ca binding, less ionized Ca
Normal blood Ca range?
What type of Ca is biologically active?
Only free, ionized Ca
Physiological importance of Calcium?
Calcium salts provide structural integrity of skele.
Essential for biochemical processes (neura, muscular, coagulation, hormonal secretion, enzymatic rxns)
Where is most Ca found? What does it look like there?
99% Ca is found in the bone in hydroxyapatite crystals
Describe the process of Vitamin D synthesis
Occurs in keratinocytes
7dehydrocholesterol photoconverted to pre-D3
pre-D3 spontaneously converts to D3
How is Vitamin D3 production controlled
UV rays degrade previtamin D3 if present too long
1,25 dihydroxy-D feeds back to inhibit production
Two sources of vitamin D
Produced by skin + UV
Why is Vitamin D a shitty vitamin?
Why is D a shitty hormone?
Bad vitamin -- synthesized de novo
Bad hormone -- not produced/secreted by gland
First hydroxylation of in D3 processing takes place...
What about the 2nd?
What do these make?
in the liver, yielding 25-hydroxy D
in the kidney, making 1, 25 dihydroxy-D
Enzyme responsible for generation of 1,25 dihydroxy-D
Mitochondrial P450 enxyme -- 1 alpha hydroxylase
1-alpha hydroxylase is inhibited by
1, 25 dihydroxy-D
Effects of PTH on Vit D synthesis
Stimulates 1-alpha hydroxylase
Where does Vitamin D promote Ca absorption?
Duodenum > Jejunum > Ileum
Ca absorption is greatest at ____ pH
Blood supply of parathyroid glands?
Clevage of the C-terminal end of PTH yields...
.a biologically inactive peptide
How is PTH release regulated?
G protein coupled Receptor
Activated Phospholipase C, Inhibits Ad. Cyclase
Increase in intracellular Ca, decreased cAMP
These conditions don't allow PTH exocytosis
Overall action of PTH?
Increase plasma Ca levels
Decrease plasma phosphate levels
Three sites of PTH action
- Stims Bone Ca Resorption
- Stims Kidney Ca reabsorption, P excretion
- Stimulates 1, 25 Dihydroxy-D synth
Specific sites in nephron on kidney activities
Ca reabsorbed in distal tubule
P resorption inhibited in the prox (?)
What happens when PTH is secreted continuously?
If cont., Gs in ost.blast increases cAMP, PLS, inhibits fxn
If once daily, the opposite
PTH half life?
Where is PTH broken down?
Liver (2/3) and Kidney (1/3)
Intake range of Ca?
Why is this okay?
Fractional gut absorption will adapt to deprivation or overload
General daily Ca balance
350 absorbed in intestine
750 lost in feces
200 lost in urine
Normal PO4 plasma concentration?
Low Calcium levels in the blood will ______ PTH release
High levels of 1,25 dihydroxy D and Ca have what regulatory power
Inhibition of transcription of PTH
Cell type with Calcium sensing receptor (CaSR)
Parathyroid Chief Cells
What is a Calcium Sensing Recptor (CaSR)
GPCR or Gplc and Gi varieties
Makes inositol 1,4,5-triphosphate
Increases intracellular Ca
Found in thyroid C Cells, Kidney, Brain
Where does calcitonin come from?
What does it do?
Parafollicular C cells of the thyroid
Inhibits osteoclast resorption and promotes renal Ca excretion
Big picture purpose of Calcitonin?
Decreasing plasma Ca
How can parafollicular (C) cells be distinguished in the thyroid?
They are large, pale cytoplasm, and have small secretory granules
What stimulates Calcitonin secretion?
High plasma Ca
Molecular method of Calcitonin action
Increased cAMP concentration to inhibit osteoclast motility and cell shape
This inactivated them
T or F. Calcitonin is necessary for human survival.
It probably isn't
Calcitonin is used clinically to treat.....
List some bone formation stimulants
GH, Insulin-like growth factos, insulin, estrogen, androgens, Vit D
Common bone formation inhibitor?
Common bone reabsorption inhibitors?
Estrogen, Androgen, Calcitonin
Three types of hypocalcemia
Causes of hypoparathyroid hypocalcemia
Causes on Non-parathyroid hypocalcemia
Vit D Deficiency or Resistance
Causes of PTH resistance hypocalcemia
When should we expect to see Parathyroid Hormone Related Protein
Important in deveopment of hypercalcemia of malignancy
Also involved in development and lactation
Primary effects of Hyperparathyroidism
Depressed neuromuscular excitability, lethargy, anorexia, muscle weakness, dulled mentation, constipation, renal stones, ulcers
Primary effects of Hypoparathyroidism?
Increased neuromuscular excitability, hyperreflexia, decreased D3 synth, convulsions
Effects of Vitamin D toxicity?
Excess bone reabsorption and gut absorption of Ca
Increase in plasma Phos
Effects of Vitamin D deficiency?
Decreased plasma (buffered by PTH)
Decreased Bone Mineralization (Rickets/Osteomalacia)
Causes of primary hyperparathyroidism?
15% parathyroid hyperplasia
other -- parathyroid carcinoma
Labs in Primary Hyperparathyroidism?
PTH, Ca, P, Urinary cAMP, Alkaline Phosphotase
Increase Urinary cAMP
Increased alkaline phosphate
treatment for primary hyperparathyroidism?
Surgical excision of the gland
Cinacalcet (Sensipar) for non-surgical candidates
Cause of secondary hyperparathyroidism?
Excess PTH production in resp. to problem outside PT
Two commonly seen sources of secondary parathyroidism?
Chronic Renal Failure
Gastric Bypass Surgery
What causes secondary hyperparathyroidism in renal insufficiency>?
Decreased P excretion by kidneys
Increased serum phosphate binds free Ca
Lower free Ca level stimulates PT to produce PTH
Labs in secondary hyperparathyroidism
PTH, Ca, P, Alkaline Phos.
Inc. alkaline phosphatase
Three primary causes of hypoparathyroidism?
Autoimmune hypoparathyroidism, surgical excision, digeorge syndrome
Features of a DiGeorge syndrome patient?
Congenital heart defects
Hypoparathyroidism with hypocalcemia
Cognitive, Behavioral, and psychiatric problems
Increased Susceptability to infections
Physical exam findings in a hypoparathyroidism patient?
Tetany, carpopedal spasms
Decreased PTH, Ca
How is hypoparathyroidism treated?
Calcitrol and Ca supplements
What is pseudohpoparathyroidism
End Organ Resistance to PTH
Hypocalcemia and Increased PTH
Give patient short stature and short 4th and 5th digits
Review the charts on diagnosing with PTH and Ca levels
That'll probably be testable
What is osteoporosis?
Disease characterized by low bone mass and micro-architectural deterioration of boen tissue
Causes reduced bone strength and increased fracture risk
Presentation of Rickets, Osteomalacia
Insufficient mineralization of bone
Rickets is in children before growth-plate fusion
Osteomalacia occurs in patients of any age
Causes of Rickets, Osteomalacia?
Nutritional Def (D, Calcium Chelators, Antacid overuse)
GI Abs. Defects (Gastrectomy, Biliary disease, liver probs)
Renal tubular defects
Clinical features of Rickets
Convulsions, Failure to Thrive, Tetany
Bowing of Long Bones
Clinical features of Osteomalacia
Aches and Pains
Loss of Height, Stree Fractures
What is Paget's Disease?
A disease of bone remodeling
Accelerated bone resorption and formation causes bone to be disorganized with more vascularity
Cause of Paget's Disease?
Blamed on a Virus
How would you treat Paget's disease?
Bisphosphonates to decrease bone turnover
Clinical manifestations of Paget's disease?
Other name for osteogenesis imperfecta
brittle Bone Disease
What is Osteogenesis imperfecta?
heritable disorder of connective tissue with 4 subtypes