PATHO-PHYSIOLOGY OF RHEUMATOID ARTHRITIS, GOUT & ANEMIA

1. RHEUMATOID ARTHRITIS- CAUSES, SIGNS & SYMPTOMS, PATHOLOGY, CLINICAL FINDINGS
2. GOUT- CAUSES, SIGNS & SYMPTOMS, PATHOLOGY, CLINICAL FINDINGS
3. ANEMIA- CAUSES, SIGNS & SYMPTOMS, PATHOLOGY, CLINICAL FINDINGS

1. RHEUMATOID ARTHRITIS, GOUT & ANEMIA Unit- 10 pathophysiology (pc- 511) m.s. (pharm)- pharmacology & toxicology Niper- guwahati

2. RHEUMATOID ARTHRITIS

3. WHAT IS RHEUMATOID ARTHRITIS

4. INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints & can also cause inflammation of the tissue around the joints, as well as in other organs in the body . (An autoimmune disease is a disease where the immune system attacks healthy parts of the body) As it can affect multiple other organs of the body, RA is referred to as a systemic illness and is sometimes called rheumatoid disease

5. STAGES OF RHEUMATOID ARTHRITIS

6. PATHOGENESIS OF RHEUMATOID ARTHRITIS

7. HEALTHY v/s ARTHRITIC JOINT

8. GENETIC PREDISPOSITION OF R.A.

9. RHEUMATOID ARTHRITIS- PATHOGENESIS Rheumatoid arthritis (RA) is a chronic, inflammatory disease that causes degeneration of connective tissue . The connective tissue usually destroyed first is the synovial membrane, which lines the joints. In RA, the inflammation becomes unrelenting and spreads to the surrounding structures of the joint, including the articular cartilage and the fibrous joint capsule. Eventually, the ligaments and tendons become inflamed.

10. The inflammation is characterized by white blood cell accumulation, complement activation, extensive phagocytosis, and scarring. With chronic inflammation, the synovial membrane undergoes hypertrophy and thickens, occluding blood flow and further stimulating cell necrosis and the inflammatory response . The thickened synovium becomes covered by inflammatory granular tissue called pannus . Pannus may spread throughout the joint, leading to further inflammation and scarring . These processes slowly destroy the bone and cause great pain and deformity. PATHOGENESIS OF RHEUMATOID ARTHRITIS

11. Rheumatoid arthritis is an autoimmune disease that develops in susceptible individuals after an immune response against an unknown triggering agent. The triggering agent may be a bacterium, mycoplasma, or virus that infects the joints or resembles the joint antigenically. Typically, the original antibody response to the microorganism is IgG mediated . Although this response may successfully destroy the microorganism, individuals who develop RA begin to produce other antibodies, usually IgM or IgG, against the original IgG antibody. These self-directed antibodies are called rheumatoid factors (RFs). The RFs persist in the joint capsule, causing chronic inflammation and destruction of the tissue . RA is thought to result from a genetic predisposition to autoimmune disease. There is strong evidence to suggest that various cytokines, especially tumor necrosis factor alpha (TNF- α ) , contribute to the cycle of inflammation and joint destruction PATHOGENESIS OF R.A. contd…

12. ETIOLOGY The cause of RA is unknown . It is assumed that a genetically susceptible host is exposed to an unknown antigen & this interaction gives rise to a persistent immunological response. The activation of immune response is triggered by the following factors. They are:- GENETIC FACTORS : - RA is documented by presence of immune cell reactivity and production of antibodies to endogenous elements such as immunoglobulins, collagen, and cellular components

13. ETIOLOGY CONTD… PRESENCE OF HLA (human lymphocyte antigen ):- The most definite genetic association with RA is with HLA alleles. The HLA-DR4 allele is associated with development & severity of RA . Risk of an individual with HLA-DR4 to develop the disease is between 2 & 6. In American Whites , 60-70 % of RA patients are positive for HLA-DR4 . Frequency of this allele among Dutch patients is greater than 90% .

14. ETIOLOGY CONTD … There is a 30% concordance in monozygotic (identical) twins compared to 5% in fraternal twins and first degree relatives. First degree relatives of patients develop RA at 4-6 times the rate of standard population rate. INFECTIOUS FACTORS :- Presence of Epstein-Barr virus as antigen. Of patients with RA ,80% have a circulating antibody directed against antigens specific for this virus. Parvovirus particularly B19 & also Mycobacteria(as it expresses HSP,heat sensitive protein ) have been linked to RA.

15. ETIOLOGY CONTD … ENDOCRINOLOGIC FACTORS : - D isease may improve during pregnancy and flare after pregnancy. Breastfeeding may also aggravate the disease Contraceptive use reduces the risk of developing RA. This suggests possible deficiencies or changes in certain hormones, may promote the development of RA ENVIRONMENTAL FACTORS :- Changes in barometric pressures are associated with acute worsening of RA. Besides climate,diet,trauma are also known to influence RA.

16. RISK FACTORS Gender Age Family history Smoking Overweight HLA gene

17. EROSIVE CHANGES GIVE RISE TO JOINT INSTABILITY &SUBLUXATION . CHARACTERISTIC DEFORMITIES INCLUDE ULNAR DEVIATION , SWAN NECK , BOUTONNIERE SYNDROME .

18. DIAGNOSIS Are made after a full medical and family history and physical and diagnostic testing are evaluated by a qualified health care professional . Medical testing may include a wide variety of tests like:- ESR (Erythrocyte Sedimentation Rate) CRP ( C–Reactive protein ) INFLAMMATORY RF (Rheumatoid factor)blood tests MARKERS ANA (Anti nuclear antibodies) JOINT X-RAYS MRI (Magnetic resonance imaging) & US (ultra sound)

19. DIAGNOSIS A) By imaging: -X-ray -MRI -Ultra sound B) By Blood tests: a ) Inflammatory markers: -ESR(erythrocytes sedimentation rate) -C reactive protein(CRP) -ANA(anti-nuclear antibody) b) Rheumatoid factor c) Anti-CCP antibodies d ) Anti-MCV assay

20. DIAGNOSIS CONTD… b ) Rheumatoid factor : In 75-80 %, gives +ve result. Low sensitivity, because it gives +ve result in some other diseases like hepatitis , S jogren’s syndrome c)Anti-CCP antibodies : In 99% gives +ve result. Specificity is 95%. Modification : Anti-MCV assay (anti-Mutated citrullinated Vimentin) Sensitivity-72% Specificity-99.7%

21. DIAGNOSIS CONTD … ESR … It is a test that measures how fast red blood cells (erythrocytes) drop to the bottom of a collection tube . CRP … C-reactive protein, another common test for inflammation is useful both in making a diagnosis and monitoring disease activity and response to anti-inflammatory therapy . RA FACTOR … is an autoantibody that is present in the blood of most people with RA & directed against host immunoglobulin & present in 75-80% in patients with RA .

22. DIAGNOSIS CONTD … ANA (Anti nuclear antibodies) ….These are investigated to rule out possibility of other connective tissue disorders like SLE (Systemic lupus erythematosus). ANA’s are raised in 80% of patients with SLE & 20% of patients with RA. X-RAYS …. Erosions can be seen at the joint margins & loss of joint space due to erosion of cartilage & bone may be identified. MRI & US SCAN … used to detect inflammatory activity. so these are increasingly used to detect early changes in RA patients.

23. DIAGNOSIS CONTD … Laboratory tests include an elevated alkaline phosphatase , elevated platelet count, decreased serum albumin level Anti-CCP antibodies : This blood test detects antibodies to cyclic citrullinated peptide (anti-CCP). Highly sensitive and this test is positive in most people with RA . Anti-CPP antibodies, which have been detected very early in RA, appear to be a good prognostic marker for the disease and discriminate between erosive and non-erosive forms of the disease.

24. GOUT

25. INTRODUCTION

26. PRIMARY v/s SECONDARY HYPERURICEMIA

27. URIC ACID PRODUCTION AND EXCRETION

28. PATHOPHYSIOLOGY

29. PATHOPHYSIOLOGY

30. PATHOPHYSIOLOGY   ** A deposit of monosodium urate crystals , in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout.

31. Acute Gout

32. Chronic Gout

33. DIAGNOSIS

34. ANAEMIA

35. OBJECTIVES

36. DEFINITION

37. PATHOGENESIS

38. PATHOLOGY

39. NORMAL VALUES

40. CLASSIFICATION

41. TYPES OF ANEMIA

42. TYPES OF ANEMIA CONTD…

43. CAUSES

44. CAUSES

45. SYMPTOMS

46. SIGNS OF ANEMIA

47. SYMPTOMS

48. INVESTIGATIONS

49. INVESTIGATIONS

50. NORMAL VALUES