purine metabolism Flashcards

1
Q

Name the three (3) pathways that together ensure the continuing balanced supply of purine nucleotides to the cell. State which pathway is the most energy expensive (2)

A

Pathways: De novo synthesis, Salvage, Catabolism. Most energy expensive: De novo synthesis

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2
Q

Briefly describe three (3) processes leading to uric acid excretion and where each process takes place (3)

A

Glomerular filtration 100% (Renal glomerulus), Active reabsorption almost 100% (Proximal convoluted tubule), Active secretion (PCT)

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3
Q

Name the immediate metabolic complication (syndrome) that may arise following successful treatment of leukaemia with cytotoxic drugs (1)

A

TLS

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4
Q

If a patient were to develop an acutely painful big toe within a week of treatment for leukaemia, name 2 possible diagnoses (2x½ = 1)

A

Gout, Septic arthritis

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5
Q

List four (4) cardinal (main) biochemical features/ -abnormalities/ metabolic complications of TLS and explain the mechanisms behind these abnormalities [8x½ = 4] (Super NB)

A

Hyperkalaemia: From release of intracellular K+

Hyperphosphataemia: Tumour cell lysis leads to release of intracellular phosphate

Hypocalcaemia: Sequestration of plasma calcium in dead & dying tumour cells/ Precipitation with phosphate intracellular protein that has been released/ Calcium phosphate precipitation due to the raised phosphate concentration

Hyperuricaemia: Tumour cell lysis   DNA breakdown  increased purine catabolism  increased uric acid

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6
Q

List the two (2) broad groups of causes (based on the mechanism for the biochemical derangement) for the derangement resulting in gout and two (2) causes from each group (6x½ = 3)

A
  • Increased production of uric acid: Tumours, infection, chronic haemolytic anaemias, psoriasis, enzyme defects, obesity
  • Decreased excretion of uric acid: Renal failure, renal tubular defect, competitors e.g. lactate, ketones, aspiri
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7
Q

Choose the metabolic complication of TLS which is most readily preventable. Which organ is particularly at risk of damage from a raised level of this waste product (1)

A

Hyperuricaemia (uric acid). Kidney.

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8
Q

Name the organ that is particularly susceptible to damage by TLS, and explain why it is so susceptible (3)

A

Kidney, mainly because of uric acid (urate nephropathy). Also possibly metastatic calcification induced by hyperphosphataemia

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9
Q

Indicate two potential clinical consequences of TLS, & describe any steps that can be taken to minimise their impact [4] (NB)

A

Hyperkalaemia  Cardiac arrhythmias - treat with fluids, K+ losing diuretics, glucose + insulin

Hyperuricaemia  Gout, renal damage and/or stones (urate nephropathy) - treat by promoting diuresis, block urate production with allopurinol

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10
Q

State two (2) possible clinical consequences of the elevated plasma uric acid, and explain the rationale for drug therapy aimed at reducing the plasma uric acid (4)

A

Acute gouty arthritis, acute renal failure (gouty nephropathy), urate kidney stones; allopurinol that inhibits formation of uric acid from purine precursor (hypoxanthine) OR uricosuric drugs that promote renal excretion of uric acid

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11
Q

Outline the possible mechanisms for the development of renal failure in a patient with TLS (2)

A

Ca/ phosphate deposition  metastatic calcification in renal tubules. Uric acid crystal deposition in renal tubules

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12
Q

Explain the mechanism by which allopurinol treatment may prevent TLS/ Discuss why it should be commenced prior to chemotherapy (2) (Super NB)

A

Inhibits xanthine oxidase (which converts hypoxanthine to uric acid), thereby preventing accumulation of uric acid from DNA released from tumour cells killed by chemotherapy (in the purine breakdown pathway)

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13
Q

Explain why it is important to maintain a high urine flow rate and alkaline pH to prevent TLS (1)

A

To minimize precipitation of uric acid in the renal tubules (urate nephropathy)

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14
Q

List four modalities used in the acute treatment of severe hyperkalaemia & for each state the mechanism (4x1½ = 6) (NB)

A

 Insulin and glucose  Increased cellular uptake of glucose, leading to glycolysis and phosphorylated intermediates which encourage potassium uptake by cells.

Beta 2 agonists  Stimulates glycogenolysis, in so doing, increasing phosphorylated intermediates and therefore promoting potassium uptake by cells.

Diuretics plus saline infusion: Promotes renal potassium excretion

Bicarbonate infusion  Induces alkalosis which promotes glycolysis, leading to potassium uptake by cells

Dialysis  Removes potassium (diffuses down concentration gradient into dialysis fluid)

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15
Q

State the most likely biochemical cause for the inflamed joint (½)

A

Elevated uric acid

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16
Q

In this particular patient, state the most likely clinical cause for this condition, and the mechanism (2½) [cancer - gout]

A

Leukaemia-associated tumour lysis, increased cell turnover leading to increased DNA breakdown and therefore increased production of uric acid.