Chemical Pathology Shohaib Flashcards Preview

Year 5 Pathology > Chemical Pathology Shohaib > Flashcards

Flashcards in Chemical Pathology Shohaib Deck (24):
1

Name 3 purines

Adenosine, Guanosine, Inosine

2

What enzyme converts hypoxanthine to xanthine

Xanthine Oxidase (also converts xanthine to urate)

3

Name 2 factors that affect the plasma concentration of urate

1. Temperature (the extremities are colder, so this is why the foot is the site of acute gout presentation-> reach max solubility-> forms crystals)
2. pH

4

What pathways is dominant in purine metabolism

Salvage pathway
the de novo pathway happens in bone marrow, and requires more energy

5

what is the main enzyme of the salvage pathway in purine metabolism

HPRT/HGPRT

6

what is the rate limiting step of purine synthesis

PPRP->IMP (enzyme PAT)
- Increase in end product inhibit PAT
-Increase of PPRP positive feedback on PAT

7

What enzyme is deficient in Lesch Nyham Syndrome

complete HPRT deficency (X linked)

8

Explain why Lesch Nyham syndrome leads to hyperuracaemia

There is a complete def of HPRT!
1. no recycling of guanine of hypoxanthine
2. decrease of IMP/GMP/AMP-> removes negative inhibition on PAT
3.This leads to an increase in de novo synthesis-> increasing IMP
4. IMP goes down the catabolic pathway (xanthine oxidase)
5. Increased urate
(Another reason: remember HPRT needs to be coupled with PPRP to work-> since deficient there is a build up of PPRP which acts as a feed forward for PAT)

9

What symptoms/signs would you see at birth in Lesch Nyham syndrome

none-> normal at birth
see symptoms at 6/12 months
developmental delay, cholifrom movement, mental retardation, self mutilations, hyperuracemia.

10

Causes of hyperuracemia

1) increased urate production
-primary: LNS, glycogen storage disorders,
-Secondary: Increwased cell turnover ( myeloprolif, psorasis, lumphoprolif)
2) decreased excretion
-primary: FJHN
-secondary: chronic kidney disease, diuretics (Thiazides), aspirin, Downs, lead poisoning

11

What is formed in gout

monosodium urate crystals

12

typical presentation of acute gout

rapid buildup of pain, red hot swollen joint
1st MTP-> 50% 1st site, 90% overall

13

Management of acute gout

DECREASE INFLAM
1-> NSAIDs
2->Colchicine
3->steriods
(dont modify plasma urate)

14

how does colchinine work for acute gout

decreases tubulin formation-> inhibits microtubule assembly-> this decreases neutrophil motility-> unable to enter joints-> reduces inflam

15

what is the management of hyperuricamia (non-acute gout)

1)drink water
2)reverse factors putting up urate (diuretics etc)
3)Drugs
-reduce synthesis: Allopurinol (XO inhibitor)
-Increase excretion:probenecid (uricosuric)

16

which medication is a contraindication to prescribing allopurinol

AZOTHIOPRINE->leads to increased BM toxicity (neutropenia)

azothioprine->mercaptopurine (active drug)->thioisinate

mercaptopurine is catabolised by XO-> stopped with given allo> therefore increased-> increasing toxicity

17

under polarized light urate crystals are...

-ve birefringent and needle shaped

18

under polarized light pyrophsphate crystals are...

+ve birefringenet (pseudogout-> seen in pts with osteoarthritis)

19

Which lipid makes up the majority of plasma lipids?

LDL-70%
HLD-17%
VLDL-13%
Chylomicrons-<5%

20

Which is the largest circulating triglyceride?

VLDL-55%

21

Which enzymes control cholesterol absorption in the jejunum?

NPC1-L1-> absorb cholesterol in the jejunum
ABC G5, ABC G8-> moves cholesterol into the jejunum

(BAT in the ileum absorbs bile acid)

22

What is the main mutation that causes familial hypercholestalemia (type II)

LDL receptor mutation (AD)

23

Name 3 AD mutations that can cause familial hypercholesterlemia (type II)

LDL receptor
apoB
PCSK9-> binds to LDLr (increased function, increased cholesterol)

24

Causes of secondary hyperlipadamia

Hormonal->preg, hypothyrodism
Metabolic-> diabetes
Renal Dysfunction->CKD
Obstructive liver disease
Toxins->alcohol
Iatrogenic->HTN, immunosuppressive