Bones Flashcards
What hormones increase and decrease Ca and where are they produced?
Increase:
- PTH → produced by parathyroid glands
- Calcitriol (activated vitamin D)
Decrease:
- Calcitonin (parafollicular cells - part of thyroid gland)
How is vitamin D activated?
Vitamin D3 comes from:
- Diet
- Precursor in skin → converted to vitamin D3 by UV light
Vitamin D3 → 25 OH-D3 in liver → 1,25 (OH)2-D3 in kidneys
1,25 (OH)2-D3 = active vitamin D3 = calcitriol
How does PTH work and what does that result in?
Kidneys: - Stimulates kidneys to hydroxylate and activate vitamin D → increased calcitriol - Stimulates Ca reabsorption - Stimulates phosphate excretion (Phosphate Trashing Hormone)
Bone:
- Increased bone resorption (breakdown)
Small intestines:
- Increased Ca absorption
Overall effect:
- Increased Ca (a lot)
- Decreased phosphate
How does calcitriol work and what does that result in?
Kidneys:
- Increased Ca reabsorption
Bone:
- Increased bone formation
Small intestine:
- Increased Ca AND phosphate absorption
Overall effect:
- Increased Ca (a lot)
- Increased phosphate
Describe the process of PTH secretion.
- Parathyroid glands detect low serum Ca
- Stimulates them to release PTH
- PTH acts to increase serum Ca AND stimulates formation of calcitriol
- Increase detected by PT glands and inhibits further PTH release AND calcitriol has a negative feedback effect on the PT glands
What are the 3 types of hyperparathyroidism? What do they result in? What are their causes?
Primary → parathyroid adenoma OR hyperplasia:
- high Ca
- low phosphate
Secondary → vitamin D deficiency, CKD, liver disease - LOW CALCITRIOL:
- low calcium
- vitamin D deficiency → low phosphate
- CKD → high phosphate
Tertiary → CKD:
- high calcium
- high phosphate
What are the causes of hypercalcaemia?
High PTH:
- primary hyperparathyroidism
- tertiary hyperparathyroidism
Low PTH:
- malignancy
- sarcoidosis
- thiazide diuretics
What are the causes of hypocalcaemia?
High PTH:
- secondary hyperparathyroidism
Low PTH:
- surgical complications (iatrogenic)
- autoimmune hypoparathyroidism
What are the symptoms and signs of hypocalcaemia?
CATS go numb:
Convulsions
Arrhythmia (prolonged QT interval)
Tetany
Paraesthesia (hands, mouth, feet, lips) - go numb
Signs:
Trousseau’s sign = inflation of cuff to high BP causes contraction of wrist and fingers
Chvostek’s sign = tapping facial nerve (1cm below zygomatic process) causes twitch of facial muscle fibres
What are the risk factors and symptoms of primary
hyperparathyroidism?
Risk factors:
MEN-1 or MEN-2 gene mutations
Symtpoms:
- often asymptomatic
- symptoms of hypercalcaemia
What are the symptoms of hypercalcaemia?
Stones, abdominal moans and psychic groans
Stones - renal effects:
- polyuria & thirst
- nephrocalcinosis, renal colic, chronic renal failure
Abdominal moans - GI effects:
- anorexia
- nausea
- dyspepsia
- constipation
- pancreatitis
Psychic groans - CNS effects:
- fatigue
- depression
- impaired concentration
- altered mentation
- coma (usually >3mmol/L)
What are the causes and signs/symptoms of secondary hyperparathyroidism?
Cause - LOW CALCITRIOL: - vitamin D deficiency poor dietary intake poor sunlight malabsorption - chronic kidney disease - liver disease
Signs and symptoms:
Lack of mineralisation in bone:
→ osteomalacia in adults
bone deformities (softening of bone)
bone pain
fractures
→ rickets in children
bowed legs
knock knees
Also in adults:
- proximal myopathy
- fatigue
- symptoms of hypocalcaemia (CATS go numb)
What investigations would you do for hyperparathyroidism and what would you expect to see?
Investigations:
- bloods (the ones below and U&Es for kidney function)
- imaging
Bloods:
Primary:
- high Ca
- low phosphate
- high PTH or inappropriately normal (i.e. should be low)
- normal ALP
Secondary:
- low calcium
- vitamin D deficiency → low phosphate
- CKD → high phosphate
- high PTH
- high ALP
Imaging:
- x-rays/CT (extent of bone disease)
- cervical ultrasound (before surgery)
Primary - x-rays:
- subperiosteal bone resorption
- acro-osteolysis (i.e. resorption of distal phalanges)
- pepper pot skull
Secondary - x-rays:
- rachitic rosary = nodularity at costochondral junctions
- looser’s pseudofractures
What is the management of primary hyperparathyroidism?
Acute hypercalcaemia:
- IV fluids
- bisphosphonates (if calcium remains high)
Surgical (1st line):
- total parathyroidectomy
Medical (if unsuitable for surgery):
- cinacalcet (drug class: calcimemetic)
What is the management of secondary hyperparathyroidism?
Acute hypocalcaemia
- IV calcium infusion (calcium gluconate)
Medical:
- calcium
- vitamin D (inactive - ergocalciferol)
If due to CKD - medical:
- calcium
- vitamin D (active - alfacalcidol)
- treat CKD
What is Paget’s disease and what is the pathophysiology?
Paget’s disease is a disorder of bone remodelling
Pathophysiology:
1. Lytic phase:
hyperactive osteoclasts → resorption
2. Mixed phase:
lytic phase + sclerotic phase
(i.e. both phases happening at the same time)
3. Sclerotic phase:
hyperactive osteoblasts → formation
(disorganised deposition of collagen fibres - woven
bone, not lamellar)
What are the risk factors and signs and symptoms for Paget’s disease?
Risk factors:
- elderly
- family history (i.e. genetic factor)
Symptoms:
- often asymptomatic (early on)
- fragility fractures
- bone pain (insidious onset)
skull, pelvis, femur
- nerve compression
hearing loss (sensorineural)
sciatica
Signs:
- bone enlargement
- warm skin over painful area (high metabolic activity)
What investigations would you do for Paget’s disease and what would you expect to see?
Bloods:
- LFTs (ALP) → high ALP
- Calcium → normal
- Phosphate → normal
- PTH → normal
- serum CTX (bone resorption marker) → high
- serum P1NP (bone formation marker) → high
Imaging: X-rays - to visualise changes in bone STRUCTURE Bone scan (Tec99) - to visualise changes in bone ACTIVITY (tracer taken up by areas of bone remodelling)
What is osteoporosis and what are its causes?
Osteoporosis is when bone reabsorption exceeds formation → decreased bone MASS
Causes:
Primary:
- post-menopausal
- elderly
Secondary:
- drugs (steroids, thyroxine, alcohol)
- endo (Cushing’s disease, hyperparathyroidism, hyperthyroidism)
- GI (coeliac disease, IBD)
What are the signs and symptoms of osteoporosis?
Often asymptomatic (unless fracture)
Fragility fractures
- vertebral fractures → back pain
Classic osteoporosis fracture types:
- hip (neck of femur)
- wrist (Colles’ fractures)
- lumbar spine (vertebral wedge fractures)
- shoulder (neck of humerus)
What investigations would you do for osteoporosis and what would you expect to see?
Bloods - should be NORMAL
- calcium
- phosphate
- PTH
- ALP
Imaging:
- x-rays
- DEXA scan (T-score < -2.5 = osteoporosis)
