Clinical Biochemistry: Hyperuricemia and Gout

Biochemistry · Basic Sciences

How it begins

In-depth study of purine nucleotide metabolism, the kinetics of renal and intestinal clearance of urate, the thermodynamic determinants of monosodium urate crystal nucleation and the biology of sterile inflammation mediated by the NLRP3 inflammasome and proinflammatory interleukins.

What it covers

1. Introduction, Definition and Molecular Epidemiological Context
2. · Historical Evolution of Biochemical Understanding
3. Biochemistry of De Novo Synthesis of Purine Nucleotides
4. · Phases and Enzymatic Flow of De Novo Synthesis
5. · Ring Construction Stoichiometry
6. The Purine Rescue Pathway and its Energy Balance
7. · Enzymology of Recovery
8. · Thermodynamic Interconnection and Cross Control
9. Purine Catabolism and Uric Acid Biosynthesis
10. · Enzymatic Route of Degradation
11. · Xanthine Oxidase: Molecular Biology and Isoforms
12. · The Mutation of the Uricase Gene and its Physiological Impact
13. Excretory Physiology of Urate I: Dynamics of Renal Transport
14. · The Four Component Model of Renal Management
15. · Molecular Biology of the Urate Transportosome
16. Excretory Physiology of Urate II: Intestinal Secretion and Uricolysis
17. · The Enterocyte Secretion Machinery
18. · Uricolysis by the Intestinal Microbiome
19. Etiopathogenesis of Hyperuricemia: Classification of Physiological Basis
20. · 1. Uric Acid Hyperproducers (~10% of gout cases)
21. · 2. Hypoexcretors of Uric Acid (~90% of gout cases)
22. Physical Biochemistry of Urate: Mechanisms of Supersaturation and Nucleation
23. · UMS Crystal Nucleation Physics
24. Pathophysiology of Inflammation Induced by UMS Crystals
25. · Phase I: Crystal Recognition and Phagocytosis
26. · Phase II: The Assembly of the NLRP3 Inflammasome
27. · Phase III: Massive Neutrophil Infiltration and NETosis
28. Immunobiology and Histopathology of Chronic Gouty Tophus
29. · Concentric Architecture of the Gotoso Tofo
30. · Cartilaginous and Subchondral Bone Destruction
31. Clinical Presentations of Gout and its Natural History
32. · Clinical Phases of the Gout Spectrum
33. Kidney Compromise: Urate Nephropathies and Urolithiasis
34. · 1. Acute Uric Acid Nephropathy
35. · 2. Chronic Urate Nephropathy (Interstitial)
36. · 3. Uric Acid Urolithiasis
37. Urate Physiopathology in Cardiovascular and Metabolic Risk
38. · The Urate Paradox: Extracellular Antioxidant vs Intracellular Prooxidant
39. Laboratory Diagnostic Methodologies in Hyperuricemia and Gout
40. · 1. Quantification of Uric Acid in Serum
41. · 2. Characterization of Urate Clearance in 24-Hour Urine
42. · 3. Analysis of Synovial Fluid under Compensated Polarized Light
43. Advanced Diagnostic Imaging: Ultrasonography and DECT
44. · 1. High Resolution Ultrasonography (Joint)
45. · 2. Dual Energy Computed Tomography (DECT)
46. Pharmacology of Acute Gout Attack and Prophylaxis
47. · 1. Colchicine: Molecular Mechanism of Action
48. · 2. Nonsteroidal Anti-Inflammatories (NSAIDs)
49. · 3. Corticosteroids (Glucocorticoids)
50. · 4. Anti-Interleukin-1 Biological Therapy (IL-1 Inhibitors)
51. Chronic Hypoglycemic Therapy (ULT) and New Frontiers
52. · 1. Xanthine Oxidase Inhibitors (IXO)
53. · 2. Uricosuric Agents (URAT1 Inhibitors)
54. · 3. Uricolytic Agents: Uricase Enzyme Replacement