Gout & Crystal Arthropathies

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30 Questions

What is the result of PRPP accumulation and stimulation of purine nucleotide production?

Triggering of gouty arthritis

Which condition could arise as a result of hyperuricemia?

Urolithiasis

What is another name for Calcium pyrophosphate crystal deposition disease (CPPD)?

Pseudogout

What is the most common genetic component associated with CPPD?

Autosomal dominant inheritance

Where do calcium pyrophosphate crystals deposit in CPPD?

Connective tissue of the joint

What is the main adverse effect of Colchicine?

Bone marrow depression

Why can Allopurinol precipitate an attack of gout at the beginning of therapy?

It inhibits xanthine oxidase leading to crystal dissolution

Which of the following coenzymes supplies C, H, O, and N during purine de novo synthesis?

Folic acid

What is the mechanism of action of Uricosurics?

Block tubular reabsorption of uric acid

Why is patient blood count monitoring necessary with Colchicine?

To assess degree of bone marrow depression

How does aspirin help in the beginning of Allopurinol therapy?

By reducing pain associated with a potential gout attack

What enzyme is used to transfer an N to phosphoribosyl pyrophosphate during purine de novo synthesis?

Phosphoribosylpyrophosphate amidotransferase

Which nucleotide is the end product of purine de novo synthesis?

Inosine monophosphate (IMP)

Which medication competitively inhibits xanthine oxidase?

Allopurinol

Which nucleotide base is built on the N in phosphoribose during purine de novo synthesis?

Adenine

What is the general structure (number of rings) of purines?

Two rings

Which of the following statements is true regarding pyrimidines?

Includes cytidine, thymidine, and adenosine

Adenosine triphosphate is an example of which type of nucleotide?

Nucleotide

Which of the following is analyzed in a synovial fluid analysis?

All of the above

In which situation is synovial fluid analysis typically done?

When there is suspicion of hemarthrosis

Which condition is NOT mentioned as a reason for synovial fluid analysis in the text?

Acute bronchitis

What should be analyzed under microscopy during synovial fluid analysis to aid in diagnosing gout or pseudogout?

Crystals

Why is reciprocal control between ATP and GTP important in the synthesis of AMP and GMP?

To ensure balanced production of AMP and GMP based on cellular energy needs

What is the primary function of the purine salvage pathway in nucleotide synthesis?

To conserve energy by utilizing existing purine bases

What is the role of Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in the salvage pathway?

Facilitates the addition of phosphoribose to hypoxanthine or guanine

What is the main difference between pyrimidine and purine nucleotide synthesis pathways?

Purine ring is constructed on the ribose-5-P directly

What are the substrates required for initiating pyrimidine ring formation in de novo synthesis?

Carbomyl phosphate and aspartate

What is the significance of reciprocal control mechanisms in nucleotide biosynthesis pathways?

Balancing the production of different types of nucleotides in response to cellular conditions

Which enzyme is responsible for attaching phosphoribose to adenine in the purine salvage pathway?

Adenine phosphoribosyltransferase (APRT)

Synovial fluid analysis is a good test to distinguish between an acute flare of _______ and septic arthritis

Gout

Study Notes

Nucleotide Metabolism

  • Nucleotides consist of a sugar molecule (ribose or deoxyribose), a phosphate group, and a nitrogenous base (purine or pyrimidine)
  • Purines (double ring structure): adenine (A) and guanine (G) found in DNA and RNA
  • Pyrimidines (single ring structure): cytosine (C), thymine (T), and uracil (U), with T only in DNA and U only in RNA
  • Nucleosides: sugar + base (e.g., adenosine = adenine + ribose)
  • Nucleotides: nucleoside + 1-3 phosphates (e.g., adenosine triphosphate)

Purine Nucleotide Biosynthesis

  • De novo synthesis: glutamine is used to transfer an N to phosphoribosyl pyrophosphate (PRPP)
  • IMP (inosine monophosphate) is the nucleotide product, which can be converted to AMP or GMP
  • Salvage pathway: uses hypoxanthine, guanine, and adenine bases, adding phosphoribose from PRPP to form IMP, GMP, or AMP
  • Enzymes: hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and adenine phosphoribosyltransferase (APRT)

Pyrimidine Nucleotide Synthesis

  • De novo pathway: involves making an intermediate pyrimidine ring, then attaching a ribose-5-P from PRPP
  • Substrates: carbamoyl phosphate (made from glutamine, ATP, and CO2), and PRPP

Crystal Arthropathies

Gout

  • Hyperuricemia can cause urolithiasis and gouty arthritis
  • Management: colchicine, allopurinol, and uricosurics (e.g., probenecid)

Pseudogout (Calcium Pyrophosphate Crystal Deposition Disease or CPPD)

  • Epidemiology: common, prevalence increases with age
  • Etiology: sporadic, autosomal dominant, or associated with hyperparathyroidism, hemochromatosis, and diabetes
  • Pathology: crystals deposit in joint matrix, eliciting inflammation
  • Clinical features: can be asymptomatic, asymmetric, and monoarticular or polyarticular
  • Treatment: symptomatic, no therapy prevents damage

Synovial Fluid Analysis

  • Done to distinguish between septic arthritis, gout, pseudogout, hemarthrosis, and rheumatic joint diseases
  • Analyze crystals, cells (RBCs and leukocytes), and culture for microorganisms

Pharmacologic Agents for Gout

  • Colchicine: terminates an attack, reduces frequency of attacks; adverse effects: bone marrow depression, nausea, vomiting, abdominal pain, and diarrhea
  • Allopurinol: competitive inhibitor of xanthine oxidase, useful prophylactically and acutely; can precipitate an attack at the beginning of therapy
  • Uricosurics (e.g., probenecid): block tubular reabsorption of uric acid, increasing excretion; useful prophylactically and acutely

Explore the process of purine metabolism and its association with disorders like hyperuricemia, urolithiasis, gouty arthritis, and Calcium pyrophosphate crystal deposition disease (CPPD). Understand the epidemiology and etiology of CPPD, also known as pseudogout.

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