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Biochemistry I > Chapter 23: Abnormalities of Purine Metabolism (Gout) > Flashcards

Chapter 23: Abnormalities of Purine Metabolism (Gout) Flashcards

1
Q

Gout

A
  • Chronic systemic disease

- Characterized by buildup of uric acid crystals

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2
Q

Gout is a common form of

A
  • Arthritis

- 5% of all cases

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3
Q

Symptoms of Gout

A
  • Sudden acute attack of unbearable pain
  • Typically in toe, ankle, or knee
  • Comes on overnight
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4
Q

Gout effetcs

A
  • 840/100,000 individuals
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5
Q

Gout is more common in

A
  • Males

- Younger age people

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6
Q

Gout results from

A
  • Overproduction of uric acid
  • Excessive intake of foods that are rich in purines
  • Inability to excrete uric acid
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7
Q

Gout usually only affects

A
  • 1 or 2 joints at a time
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8
Q

Peripheral joints have

A
  • Lower body temperature
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9
Q

Uric acid is overproduced by the

A
  • Liver
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10
Q

Foods rich in purines that may cause Gout

A
  • Red meats
  • Cream sauces
  • Red wine
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11
Q

Gout may occur as a consequence of

A
  • Trauma

- Surgery

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12
Q

Inability of the kidney to excrete uric acid in the urine is due to

A
  • Decreased filtration
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13
Q

Podagra

A
  • Large red swelling on first metatarsal joint
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14
Q

First stage of gout

A
  • Asymptomatic hyperuricemia
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15
Q

Second stage of gout

A
  • Acute symptomatic attacks

- Interrupted by asymptomatic intervals of decreasing length

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16
Q

Third stage of gout

A
  • Intercritical gout

- Symptom free periods for months or years

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17
Q

Untreated gout may result in

A
  • Chronic tophaceous gout with crippling gouty arthritis
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18
Q

90% of patients with gouty arthritis also have

A
  • Renal impairment
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19
Q

Hyperuricemia occurs when

A
  • Serum levels of uric acid are markedly elevated

- Currently affects 18% of the US population

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20
Q

Urate levels may be determined by

A
  • Urate formed minus urate excreted
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21
Q

2/3 of urate excretions occurs in the

A
  • Kidney
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22
Q

1/3 of urate excretion occurs in the

A
  • Gut
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23
Q

Hyperuricemia may be associated with

A
  • Obesity
  • Gender
  • Higher socioeconomic status
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24
Q

Medications that predispose to hyperuricemia

A
  • Levodopa (for Parkinson’s)
  • Diuretics
  • Niacin
  • Aspirin
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25
Q

Radiation therapy for cancer may result in

A
  • Hyperuricemia
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26
Q

Metabolic syndrome/syndrome X can contribute to

A
  • Hyperuricemia
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27
Q

Perfect range of uric acid in US males

A
  • 2.7 - 7.0 mg/dL
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28
Q

Hyperuricemia may be elevatd due to

A
  • Increased formation

- Decreased excretion

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29
Q

Approximately 10% of patients with gout are

A
  • Overproducers
30
Q

Alcohol ingestion increases

A
  • De novo purine production

- Contributes to uric acid overproduction

31
Q

Approximately 90% of patients with gout have a

A
  • Defect in uric acid excretion due to reduced renal clearance
32
Q

Lactic acid may compete with

A
  • Uric acid for renal secretion

- Reduces renal clearance (decreased excretion)

33
Q

Diagnosis of MSU crystals in synovial fluid involves observing

A
  • Symptoms

- Joint examination

34
Q

“Gold standard” for diagnosis

A
  • Joint aspiration
35
Q

Monosodium Urate (MSU) can be demonstrated in

A
  • Fresh synovial fluid
36
Q

Crystals are characteristically

A
  • Long
  • Needle-shaped
  • Birefringent
37
Q

Gout symptoms/diagnosis may be easily confused with

A
  • Rheumatoid arthritis
  • Osteoarthritis
  • Septic arthritis
  • Pseudogout
38
Q

Rheumatoid arthritis or osteoarthritis in elderly can be confused with gout because

A
  • They can present as polyarticular disease
39
Q

Septic arthritis has

A
  • High degree of mortality
40
Q

Pseudogout crystals are

A
  • Calcium pyrophosphate dihydrate
41
Q

Pathogenesis of gout

A
  • Acute inflammatory response
42
Q

The crystalline deposits of urates on bone trigger

A
  • An inflammatory response

- Neutrophils are the “first responders”

43
Q

Knee joint in gout is characterized by

A
  • Chalky tophaceous urate deposits covering the articular surface of the knee joint
44
Q

Dietary measures to help manage gout

A
  • Avoidance of alcohol and relevant drugs (especially diuretics)
  • Weight loss
45
Q

Anti-inflammatory drugs to help manage gout symptoms

A
  • NSAIDs (indomethacin/aspirin)
46
Q

Drugs to help with gout management

A
  • Colchicine

- Corticosteroids (prednisone)

47
Q

Urate-lowering drugs that assist in gout management

A
  • Probenecid
  • Synthetic C-7, N-8 position isomer of hypoxanthine
  • Febuxostat
48
Q

Febuxostat

A
  • Non competitive inhibitor
49
Q

Synthetic C-7, N-8 position isomer of hypoxanthine

A
  • Converts allopurinol to alloxanthine
50
Q

Uric acid is produced from

A
  • Purine nucleotide turnover
51
Q

Final step in uric acid production is catalyzed by

A
  • Xanthine oxidase
52
Q

Enzyme defects involved with gout

A
  • Partially inhibited HGPRT activity
  • Overactive PRPP synthetase
  • Reduced glucose-6-phosphatase activity
53
Q

Overactive PRPP synthetase causes

A
  • Reduced allosteric control
54
Q

Reduced glucose-6-phosphatase activity is characteristic of

A
  • Von Gierke’s disease

- Results in increased PPP activity

55
Q

Lesch-Nyan syndrome

A
  • Inherited disorder

- Sex linked and recessive (more common in males)

56
Q

Lesch-Nyan syndrome is a result of a deficiency of

A
  • HGPRTase

- Prevents salvage of hypoxanthine or guanine

57
Q

Prevention of hypoxanthine/guanine salvage by Lesch-Nyan syndrom causes

A
  • Hyperuricemia due to PRPP accumulation
58
Q

HGPRTase deficiency results in

A
  • An increase in de novo purine biosynthesis
59
Q

Characteristic neurological features of Lesch-Nyan syndrome include

A
  • Self-mutilation
  • Involuntary movements
  • Mental retardation
60
Q

In Lesch-Nyan syndrome, the distal portions of several fingers are often

A
  • Shortened due to prior uncontrolled self-mutilation
61
Q

Patients with Lesch-Nyan syndrome have an increased risk of

A
  • Kidney stones
62
Q

Treatment for Lesch-Nyan syndrome invovles

A
  • Hydration/Allopurinol
  • Management of behavioral concerns is difficult
  • Brain stimulation/antispasticity medications/benzodiazepines
63
Q

Gout is a chronic systemic condition arising from

A
  • The accumulation of monosodium urate crystals in the synovial joints
  • Crystal accumulation causes pain and inflammation
64
Q

A significant number of people with hyperuricemia do not develop gout, and those who suffer from repeated gout attacks have

A
  • Normal or even diminished circulating levels of uric acid
65
Q

The “gold standard” for gout diagnosis is aspirating a sample of

A
  • Joint fluid and observing the presence of monosodium urate crystals in the synovial fluid
66
Q

Crystals are often surrounded by

A
  • Red and white blood cells and are negatively birefringent
67
Q

The most frequently prescribed medications for acute gout attacks are

A
  • NSAIDs

- Colchicine

68
Q

Allopurinol reduces the amount of uric acid in the blood by

A
  • Inhibiting xanthine oxidase and slowing uric acid production
  • May be used for the long-term treatment of gout
69
Q

Febuxostate is a newer, noncompetitive inhibitor of

A
  • Xanthine oxidase
70
Q

Absence of HGPRT due to an inborn error of metabolism results in

A
  • Lesch-Nyan syndrome
71
Q

Lesch-Nyan syndrome is a rare

A
  • X-linked recessive disorder

Biochemistry I (34 decks)

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