chemical pathology: uric acid

Question 1

What is the components of nucleotides

Answer 1

Nucleobase (purine & pyrimidine) sugar & one + phosphate group

Question 2

What is the difference between purine & pyrimidines

Answer 2

Purine: two carbon rings
Pyrimidines: one carbon ring

Question 3

What is the purine synthesis pathway

Answer 3

1. De novo synthesis
2. Catabolism
3. Salvage

Question 4

What four factors influence purine levels

Answer 4

1. Purine intake
2. Alcohol intake
3. Insulin
4. Fructose intake

Question 5

What does other animal contain that humans are deficient of

Answer 5

Uricase
An enzyme that is able to further breakdown uric acid

Question 6

What is uric acid

Answer 6

Nitrogen containing waste products

Question 7

How is uric acid form

Answer 7

Produced from breakdown of purine nucleotides in liver & intestinal mucosa

Question 8

What is uric acid form in blood

Answer 8

Sodium urate

Question 9

What form of uric acid is in the urine

Answer 9

Monosodium urate

Question 10

What other factor influences sodium urate precipitation risk

Answer 10

Temperature

Question 11

What happens when sodium urate precipitate

Answer 11

Forms urate crystals that results in gout

Question 12

Is monosodium urate or sodium urate at higher risk for percipitation

Answer 12

Monosodium urate

Question 13

What happens when monosodium urate precipitate

Answer 13

Uric acid kidney stones

Question 14

What organs excrete uric acid

Answer 14

Kidneys & in the intestines

Question 15

How much uric acid is excreted

Answer 15

10% is filtered

Question 16

Why does humans have higher uric acid levels

Answer 16

No uricase & renal handling

Question 17

How is renal uric acid excreted

Answer 17

1. Freely filtered at glomerulus
2. Active reabsorption in PCT
3. Active secretion in PCT
4. Post secretory reabsorption

Question 18

What is four causes of hyperuricaemia

Answer 18

1. Under excretion: primary (idiopathic) or renal insufficiency, ketoacidosis or diuretics
2. Over production: increased catabolism of purines or increased de novo synthesis/decreased salvage of purine
3. Over consumption
4. Multiple mechanisms: alcohol, obesity or fructose

Question 19

What is the explanation of alcohol causing hyperuricaemia

Answer 19

Increase lactic-/keto acidosis that competes for excretion

Question 20

What is the explanation of obesity causing hyperuricaemia

Answer 20

1. Increased purine turnover
2. Insulin resistance & reduced uric acid excretion
3. Fructose & sugar intake
4. Chronic low grade inflammation

Question 21

What is gout

Answer 21

Deposition of monosodium urate crystals causing acute painful arthritis in single joint

Question 22

Where is gout common & why

Answer 22

Big toe as it is the furthest away from circulation with lower temperatures

Question 23

What is Gouty Tophi

Answer 23

Late complication of gout that can cause local destruction & loss of function

Question 24

What is used for diagnosis of gout

Answer 24

1. Clinical features
2. Joint fluid aspirate for uric acid crystals
3. Elevated serum levels (not accurate)

Question 25

What is the treatment plan for gout

Answer 25

**Pain** give colchicine **Long term** allopurinol **Reduce reabsorption** uricosurics (can increase uric acid renal stones risk) **General** lose weight, decrease alcohol, fructose & purines

Question 26

What is tumour lysis syndrome

Answer 26

Group of metabolic complication caused by rapid lysis of malignant cells that release of breakdown products & intracellular content of dying cells

Question 27

What is precipitating events of tumour lysis syndrome

Answer 27

Chemotherapy/radiotherapy/steroids within 72 hrs of treatment or spontaneous

Question 28

What is the laboratory diagnosis of tumour lysis syndrome

Answer 28

2+ within 3 days prior or 7 days after treatment Hyperkalemia, hyperuricemia, hypocalcaemia & hyperphosphatemia

Question 29

What is the complications of hyperkalemia

Answer 29

Cardiac dysrhythmia (peaked T wave, widened QRS & asystole)

Question 30

What is the complications of hyperuricemia

Answer 30

Inflammation & release of cytokines that attract WBC causing systemic immune response

Question 31

What does hyperphosphatemia cause

Answer 31

Binding to Ca that causes hypocalcemia

Question 32

What is the complications of hypocalcemia

Answer 32

Neuromuscular irritability, cardiac dysrhythmia & seizures (QT prolonged)

Question 33

What is the clinical diagnosis if tumour lysis syndrome

Answer 33

Laboratory & 1+ renal failure (elevated creatinine & urea) seizures, cardiac dysrhythmia & death

Question 34

What is the two pathophysiologies of tumour lysis syndrome

Answer 34

1. **Crystal dependent injury:** uric acid crystallization in renal tubules can obstruct urine flow causing AKI 2. **Crystal independent injury:** renal vaso-constriction & impaired autoregulation, decreased renal blood flow, oxidative stress & inflammation

Question 35

What is the management of tumour lysis syndrome

Answer 35

Anticipation & diagnose Adequate IV hydration Monitor renal function & electrolytes Reduce uric acid with allopurinol AKI hemodialysis

Question 36

What is a multiple myeloma

Answer 36

Uncontrolled proliferation of one clone of plasma cell in bone marrow called **monoclonal expansion** instead of normal polyclonal expansion

Question 37

What is the diagnosis methods for multiple myeloma

Answer 37

1. Clonal bone marrow plasma cells >10% 2. CRAB/MDE criteria

Question 38

What is the CRAB criteria

Answer 38

1. Hypercalcemia 2. Renal insufficiency 3. Anaemia 4. Bone lesions

Question 39

What is MDE criteria

Answer 39

1. Sixty percent or more clonal plasma cells in bone marrow 2. Abnormal light chains : normal light chains ratio 3. > 1 focal lesion on MRI