Biochemistry: part 1 Flashcards
What is P1NP being used for now?
Used as a predictor of response to anabolic treatments
What is used to measure BMD?
DEXA scans
What is the half-life of PTH?
8 mins
What is the normal range for serum calcium concentration?
2.15-2.56 mmol/L
Which receptors/proteins are involved in mediating the effects of calcitriol on the intestines?
TRPV6
Calbindin
Describe the effect of metabolic alkalosis on calcium distribution.
It makes more calcium bind to plasma proteins thus reducing the free calcium levels
NOTE: venous stasis may elevate free calcium
How does oestrogen deficiency lead to a decrease in bone mineral density?
It increases the number of bone remodelling units
It causes an imbalance in bone remodelling with increased bone resorption compared to bone formation
How many amino acids make up PTH and which part of this is active?
84
Active: N1-34
Which bone diseases will cause a rise in ALP?
Osteomalacia
Bone metastases
Also hyperparathyroidism and hyperthyroidism
Describe the effects of calcitriol on bone and in the kidneys.
Facilitates PTH effect on the DCT in the kidneys (increased calcium reabsorption)
Synergises with PTH in the bone to increase osteoclast activation/maturation
Briefly describe the bone remodelling cycle.
A microcrack crosses the canaliculi and severs the osteocyte processes, inducing osteocyte apoptosis
This signals to the surface lining cells, which release factors to recruit cells from the blood and marrow to the remodelling compartment
Osteoclasts are generated locally and resorb the matrix and the mitrocrack
Then osteoblasts deposit new lamellar bone
Osteoblasts that become trapped in the matrix become osteocytes
What are the clinical features of primary hyperparathyroidism?
Stones, Bones, Abdominal Groans and Psychic Moans
Stones – renal colic, nephrocalcinosis
Bones – osteitis fibrosa cystica
Abdominal moans – dyspepsia, pancreatitis, constipation
Psychic groans – depression, impaired concentration
NOTE: patients may also suffer fractures secondary to the bone resorption
IMPORTANT NOTE: hypercalcaemia also causes diuresis (polyuria and polydipsia)
What is metabolic bone disease?
A group of disease that cause a change in bone density and bone strength by increasing bone resorption, decreasing bone formation or altering bone structure
State some signs and symptoms of Rickets.
Symptoms:
Lack of play
Bone pain and tenderness (axial)
Muscle weakness (proximal)
Sign:
Age dependent deformity
Myopathy
Hypotonia
Short stature
Tenderness on percussion
Which cells produce this factor?
Osteoblast lineage cells
What parameter is used to determine whether a patient is vitamin D deficient?
Deficient < 20 ng/M (50 nmol/L)
Normal > 30 ng/M (75 nmol/L)
What else can the PTH receptor be activated by other than PTH?
PTHrP (PTH related protein)
This is produced by some tumours
What is PTH dependent on?
Magnesium
Describe the effects of PTH in:
a. Bone
b. Kidneys
a. Bone
Acute release of available calcium (not stored in hydroxyapatite crystal form)
More chronically, increased osteoclast activity
b. Kidneys
Increased calcium reabsorption
Increased phosphate excretion
Increased stimulation of 1-alpha hydroxylase (thus increasing calcitriol production)
State some phosphate-related conditions that cause Rickets/Osteomalacia.
X-linked Hypophosphataemic Rickets (mutation in Phex (this cleaves FGF23))
Autosomal Dominant Hypophosphataemia Rickets
Oncogenic Osteomalacia (mesenchymal tumours can produce FGF23)
