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Path - Chempath > Uric acid metabolism > Flashcards

Uric acid metabolism Flashcards

1
Q

What are the three main purines?

A

Adenosine
Guanosine
Inosine

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2
Q

What are the key roles of purines?

A 
Genetic code (A, G)
Messengers for hormone action (cAMP, cGMP)
Energy transfer (ATP)
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3
Q

What enzyme breaks down hypoxanthine to xanthine?

A

Xanthine oxidase

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4
Q

What enzyme breaks down xanthine to urate?

A

Xanthine oxidase

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5
Q

What enzyme breaks down urate to allantoin?

A

Uricase

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6
Q

Which gender is gout more common in?

A

Males

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7
Q

Which enzyme in the urate metabolism process is inactive in humans?

A

URICASE

this means there is a buildup of urate

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8
Q

What concentration does urate circulate at in blood?

A

At the limit of solubility

Urate is INSOLUBLE

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9
Q

How does solubility of urate change based on temperature?

A

At colder temperatures, solubility DECREASES

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10
Q

What is the most commonly affected joint in gout? Why?

A

First metatarsophalangeal joint

Because it is at the extremity of the body > colder > urate is more likely to precipitate

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11
Q

Is urate reabsorbed/secreted by the kidney?

A

BOTH occur in the PCT
Only 10% of urate is filtered our
This is why urate concentration is so high

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12
Q

What is the fractional excretion of uric acid (FEUA)?

A

The fraction of filtered urate

The urate present in urine, so 10%

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13
Q

What are the two pathways for purine synthesis?

A

De novo purine metabolism

Salvage pathway

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14
Q

Compare metabolic demands of the two pathways for purine synthesis

A

De novo - VERY metabolic demanding, inefficient

Salvage - highly energy efficient

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15
Q

Which purine pathway predominates?

A

SALVAGE pathway

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16
Q

Where does the de novo pathway predominate?

A

in the bone marrow

due to high requirements

17
Q

What is the rate limiting enzyme for the de novo pathway?

A

PAT

18
Q

What exerts negative / positive feedback on PAT?

A

Neg feedback: AMP, GMP

Positive feedback: PPRP

19
Q

What is the rate limiting enzyme in salvage pathway?

A

HPRT

20
Q

What is Lesch–Nyhan syndrome?

A

ABSOLUTE DEFICIENCY in HGPRT

21
Q

What is the method of vertical transmission of LNS?

A

X linked recessive

22
Q

What are clinical features of LNS?

A 
Normal at birth 
Development delay at 6m
Hyperuricaemia 
Choreiform movements 
Spasticity, mental retardation 
SELF HARM
23
Q

What is the biochemical basis of LNS?

A

Lack of HPRT > guanine not converted back to GMP > no GMP, AMP > no negative feedback

Also PPRP buildup

Overall, sends de novo pathway into overdrive

24
Q

What are causes of secondary hyperuricaemia due to increased urate production? Why

A

Conditions lke Myeloproliferative disorders, Lyphoprolif disorders

Because there is an increase in cell turnover > excess urate > inability to excrete urate last enough

25
Q

What toxin can cause gout?^

A

LEAD poisoning

causes saturnine gout

26
Q

What drug can cause gout?

A

Diuretics, due to decreased urate excretion

27
Q

What kind of crystals form in gout?

A

monosodium urate

28
Q

What is the shape of crystals in gout?

A

needle shaped

29
Q

What are the two diseases u can get from gout?

A

PODAGRA - acute

TOPHACEOUS gout - chronic

30
Q

What are clinical features of gout?

A

Rapid build up of pain
Hot swollen painful joint
Typically 1st MTP (first to appear, most common)

31
Q

How do gout crystals show up in polarised light?

A 
NEGATIVE BIOREFRINGENCE (so perpendicular to compensator axis) and BLUE 
Parallel to compensator if YELLOW
32
Q

How do pseudogout crystals show up in polarised light?

A

POSITIVE BIOREFRINGENCE (blue and parallel to compensator)

33
Q

What substance are pseudo gout crystals made up of?

A

calcium pyrophosphate

34
Q

What tx work for acute gout?

A

NSAID
Colchicine
Glujcocorticoid

35
Q

What tx works for chronic gout=?

A

Allopurinol

Probenecid

36
Q

What kind of medication is allopurinol?

A

XANTHINE OXIDASE inhibitor

so reduces urate synthesis

37
Q

What medication must you never give with allopurinol?

A

AZATHIOPRINE

BECAUSE azathioprine is toxic to BM at high doses
Allopurinol blocks mercaptopurine secretion (mercaptopurine is product of azathioprine) thereby massively increasing its effecxt

38
Q

What is the MOA of probenecid ?

A

URICOSURIC drug

increases secretion of urate in urine (increases FEUA)

39
Q

describe what occurs in pseudogout

A

in patients with osteoarthritis

deposition of calcium pyrophorphate crystals

Path - Chempath (23 decks)

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