Biochemistry

Question 1

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Answer 1

!!!

Question 2

Osteoporosis

• what is it- define (2)
• name the intermediate stage
• occurs due to (2)
• types (2)
• secondary causes (8)
• presentation (4)
• diagnosis (1)
• management- drugs and their action (9)

Answer 2

-reduced bone mineral density and increased porosity
less than 2.5 SD below mean peak value for age and sex

• osteopenia, 1-2.5 SD
• slowing of osteoblast activity, females affected more after menopause due to increase osteoclastic bone resorption as less oestrogen
• type 1: post menopausal
  type 2: osteoporosis of old age

-corticosteroid use, alcohol abuse, malnutrition, CKD

-calcium and vitamin D supplements (if dietary intake is poor),
bisphosphonates (alendronate, risedronate, etidronate) which reduce osteoclastic resorption,
Desunomab (a monoclonal antibody which reduces osteoclast activity)
strontium (which increases osteoblast replication and reduces resorption).
Zoledronic acid is a once yearly intravenous bisphosphonate (++£)

Question 3

Osteomalacia & rickets

• what is it
• due to
• causes (3) examples (6)
• presentation (5)
• blood biochemistry
• management
• symptoms of hypocalcaemia (6)

Answer 3

• abnormal softening of the bone
• due to deficient mineralisation of osteoid secondary to inadequate amounts of Ca and phosphate

-insufficient Ca absorption
deficiency/resistance to Vit D
phosphate deficiency
E.g. malnutrition, malabsorption, lack of sunlight exposure, hypophosphateamia (renal tubular acidosis), CKD

-bone pain
deformity from soft bones
pathological fracture
hypocalcaemia 
\+ pseudo fractures of pubic rami, proximal femur, ulna and ribs

-low Ca
low Ph
high Alk phos

• Vit D therapy and Ca and phosphate supplemetation
• parasthesia, muscle cramps, irritability, fatigue, seizures, brittle nails

Question 4

Hyperparathyroidism

• high levels of what hormone?
• primary causes (3) and biochem (3)
• secondary causes (2)
• tertiary causes (2)
• name the tumour caused
• treatment of v high Ca levels (3)

Answer 4

-PTH

-benign adenoma, hyperplasia, malignancy
high PTH causes hypercalcaemia 
(fatigue, depression, bone pain, myalgia, nausea, thirst, polyuria, renal stones, osteoporosis)
elevated PTH
high Ca
low/normal phosphate

-overproduction of PTH secondary to hypocalcaemia
generally caused by Vit D deficiency or CKD

• in chronic secondary hyperparathyroidism (CKD), they develop an adenoma which continues to secrete PTH
• Brown tumour, might cause fragility fracture

-IV fluid
bisphosphonates
Calcitonin

Question 5

Renal dystrophy

-describe

Answer 5

in CKD, reduced phosphate excretion and inactive activation of Vit D causes secondary hyperparathyroidism and osteomalacia, sclerosis of bone and calcification of soft tissues

Question 6

Paget’s disease

• what is it
• aetiology (2)
• pathogenesis (4)
• location (5)
• presentation (6)
• biochem
• X ray findings
• treatment

Answer 6

• chronic, results in thickened brittle and misshapen bone
• viral infection and genetics

-increased osteoclast activity
causes increased bone turnover
osteoblasts become more active to try and correct the excessive bone resorption
new bone formed but it fails to remodel sufficiently and the resulting bone is brittle and can fracture easily

• pelvis, femur, skull, tibia, ear ossicles
• asymptomatic, arthritis, pathologic fracture, pain, deformity and increased CO

-alk phos high
Ca normal
Phosphate normal

-enlarged bone
thickened cortices
coarse, thickened trabeculae
mixed areas of lysis and sclerosis

-bisphosphonates (inhibit osteoclasts)
calcitonin if extensive
joint replacement might be necessary