Biochemistry Flashcards
List the biochemical features of primary hyperparathyroidism
High calcium
High PTH
High or NORMAL alkaline phosphatase
LOW phosphate
List the biochemical features of secondary hyperparathyroidism
High PTH
Low calcium
Low or normal phosphate
List the biochemical features of Paget’s disease
High alkaline phosphatase
NORMAL calcium
NORMAL phosphate
List the biochemical features of osteomalacia
Low vitamin D
Low phosphate
Low or normal calcium
HIGH PTH
High alkaline phosphatase
List the biochemical features of osteoporosis
Normal calcium
Normal phosphate
Normal alkaline phosphatase
List the biochemical features of bone metastases
High calcium
High phosphate
High alkaline phosphatase
What actions does PTH have on the kidney? State how it has its effects on phosphate and where it has its effects on calcium.
Calcitriol formation
Calcium resorption in distal tubule
Phosphate excretion (blocks the sodium phosphate transporter)
How many amino acids does PTH contain?
84 amino acids
PTH is dependent upon which ion and who is this particularly bad for?
Dependent upon Mg
Bad for alcoholics
What’s the half life of PTH?
8 minutes!
What else activates the PTH receptor and when is it released?
PTHrP
(parathyroid hormone related peptide)
Released in pregnancy to supply calcium to the milk
How does the parathyroid hormone monitor levels of calcium?
Via the calcium sensing receptor
What effect does PTH have on bone?
Increased cortical bone resorption due to:
PTH binds to receptors on osteoblasts and stimulates RANKL production.
This increases osteoclast stimulation and resorption.
Primary HPT is more common in males or females and at what age?
Females (3:1)
Aged 50, after menopause
List four causes of primary hyperparathyroidism
Parathyroid adenoma
Parathyroid hyperplasia
Parathyroid cancer
Familial syndromes
List three familial syndromes causing primary hyperparathyroidism
MEN 1
MEN 2A
HPT-IT
What are the symptoms of primary hyperparathyroidism?
High calcium
Therefore:
Stones - renal colic, nephrocalcinosis, chronic renal failure
Moans - pancreatitis, dyspepsia, constipation, nausea, anorexia
Groans - depression, impaired concentration, drowsiness, coma
Also: Thirst polyuria Tiredness Fatigue Muscle weakness
Why does primary HPT cause polyuria?
High serum calcium stops potassium, recycling in the loop of Henle, which in turns prevents the Na/Cl/K cotransporter from working, thus leading to diuresis.
What are the downstream effects of calcitriol in the intestine?
Increased calcium and phosphate absorption
via TRPV6 and calbindin
Where in the gut is calcium mostly absorbed, and through what type of transport?
Duodenum/jejunum
Colon
Passive paracellular linear transport (60%) Active transport (40%)
What is the effect of vitamin D on bone?
Maintains calcium in bone (increases osteoblast differentiation and bone formation)
(also works with PTH to increase calcium and phosphate release from bone if needed via RANKL and osteoclasts)
What is the effect of Vitamin D on the kidney?
Increased calcium reabsorption from distal tubule via TRPV5, calbindin
Vitamin D causes the production of what from the bone? Name the type of cell which produces this.
FGF-23 from osteoblasts in long bones
What are the effects of FGF-23?
Inhibits sodium phosphate transporter in the proximal convoluted tubule
Also provides negative feedback to decrease calcitriol synthesis
What are the symptoms of rickets?
Bone pain and tenderness (axial)
Muscle weakness
Lack of play
What are the signs of rickets?
Myopathy
Hypotonia
Short stature
Tenderness on percussion
What are the causes of vitamin D deficiency?
Small bowel malabsorption
Pancreatic insufficiency
Liver/kidney problem
Drugs e.g. phenytoin/phenobarbitone
What are the rare hereditary causes of rickets?
Type 1 - 1 alpha hydroxylase deficiency
Type 2 - Defective vitamin D receptor
Name three causes of rickets which cause chronically high levels of fibroblast growth factor
X-linked hypophosphatemic rickets (XLHR)
Autosomal dominant hypophosphatemic rickets (ADHR)
Oncogenic osteomalacia (mesenchymal tumours)
What is X-linked hypophosphatemic rickets caused by?
Mutations in PHEX (phosphate-regulating endopeptidase)
How does X-linked hypophosphatemic rickets present?
In toddlers, with: Hypophosphatemia Leg deformity Enthesopathy Dentin anomalies
Explain the problem in autosomal dominant hypophosphatemic rickets
Cleavage site of FGF-23 is mutated, therefore you get high levels of FGF-23
When does ADHR present?
Age of onset is variable
Explain oncogenic osteomalacia
Mesenchymal tumours produce FGF-23 which stops 1 alpha hydroxylase and causes phosphaturia
Therefore you get low phosphate and calcium, causing decreased mineralisation and osteomalacia
What is the most common cause of damage to the proximal convulted tubule?
Fanconi syndrome
What are the causes of Fanconi syndrome?
Multiple myeloma
Heavy metal poisoning
Drugs
Congenital diseases
What drugs can cause Fanconi syndrome?
Tenofovir
Gentamycin
What congenital diseases cause Fanconi syndrome?
Wilsons disease
Glycogen storage diseases
What is Wilson’s disease?
A genetic disorder where excess copper builds up in the body
