Bones & Joints Flashcards
Name 4 categories of Inflammatory BJ and their diseases
Degenerative - Osteoarthritis (Bone + Joint) non-inflammatory
Autoimmune - Rheumatoid Arthritis
Crystal Deposition - Gout, Pseudogout
Infections - Osteomyelitis, Septic Arthritis
Note inflammatory disease - joint pain decrease w movement
Osteoarthritis Pathophysiology and Cause
1: Articular Cartilage! destruction
- cartilage layer over bones @ articulating joint part
2: Cartilage, then exposes Subarticular bones, then Bone undergoes Eburnation, to become ivory/smooth surface - Eburnation + Thickening;
- eburnation: conversion of the sub-chondral bone to an ivory-like surface from friction
- Subchondral Cysts formation
- Subchondral bone thickening - Sclerosis
- Bone Spurs - outgrowth of bone/ bone projections called Osteophytes;
Secondary:
- Synovium thickening, synovitis [Rheumatoid Arthritis is primarily synovium damage, this inflammation is mild compared to RA] - synovium inflammation + fibrosis
- Joint space narrowing
- Muscle atrophy
Primary OA - post menopause
Osteoarthritis Treatment 3 + 3
Symptomatic Treatment:
Inflammation
- Paracetamol, NSAIDs (meloxicam), Corticosteroids;
Extracellular Matrix - think HCG
SYSADOA - Symptomatic Slow-acting Drugs for OA
- Hyaluronic Acid
- Chondroitin Sulfate (sulfated Glycosaminoglycan GAG)
- Glucosamine
Rheumatoid Arthritis Pathophysiology, location, predisposition, features
Both type III and type IV HS
CD4 T Cell, B Cell, responds to self antigens;
T Cell - cytokine mediated inflammation - Type IV HS
B Cell - Rheumatoid Factor is autoantibody against some IgG; also have ACPA - then complex deposits - Type III HS
Chronic Systemic Disease, common at Joints - MCP, PIP
Predispositions
- Genetic: HLA-DR4 (MHC II)
- Env: Antibodies against Citrullinated Peptides; Anticitrullinated Peptides Antibodies - ACPA; smoking, alcohol
- Synovitis! Swelling of synovium, inflammatory cells
- — Basically, the hypertrophied synovium is called pannus; w macrophages and mesenchymal cells for fibroblasts
- Pannus formation - granulation tissue; this destroys the articular cartilage and bone
- Fibrosis after granulation, Ankylosis (fusion of joints)
- Bone erosion, destruction
Systemic:
- Rheumatoid Nodules (usually found at skin)
- Granulomas w Central fibrinoid necrosis
- Vasculitis, necrotizing
- anaemia of chronic disease - hepcidin increased
Differences between OA and RA [2]
Explain
Articular Cartilage vs Swollen inflamed Synovium
Narrow joint spacing, then bone ends rub together + Bone Spurs vs Bone erosion (from Pannus granulation tissue)
Rheumatoid Arthritis treatment
1 + 3 Classes (5)
Recall Pathophysio:
Rhematoid Factor - is an AutoAB against antibodies - forming complexes - Type III HS
- also have ACPA
Anti-inflammatory - NSAIDs, CS
Disease-modifying antirheumatic drug:
conventional synthetic csDMARD - Methotrexate
Block AICAR transformylase; inhibiting purine metabolism - accumulate ADENOSINE
- Adenosine is an anti-inflammatory agent
- Adenosine then activate A2a receptor, inhibiting T cell proliferation and macrophage activation, anti-inflammatory (receptor found on T cells, platelets, others)
targeted tsDMARD - tofacitinib
- oral JAK inhibitor; block transcription of inflammatory mediators
bDMARD;
- TNF alpha inhibitor
- recombinant IL1R antagonist
- IL6R antagonist;
- recall pro-inflammatory cytokines are IL1, IL6, TNF-a
Crystal arteriopathies
- pathophysiology and polarized light appearances
- crystals for immune attack
Gout
- increased serum uric acid
- urate crystal deposition
- Long term joint erosion; nephritis, renal failure
Primary cause - idiopathic but linked to obesity, hypertension, alcohol
Pseudogout
- increased calcium pyrophosphate dihydrate
Primary cause - idiopathic, linked to hyperparathyroidism;
Polarized light:
Strongly birefringent needle-shaped crystals vs Rhomboid weakly birefringent
- Birefringent meaning 2 refractive indices
Gout Treatment
Anti-inflammatory + 3
3 split 1 + 2
Contra I
Gouty Attack
- NSAID, COX2, GC (CS)
- Low-dose Aspirin contraindicated (inhibit uric acid secretion)
- Colchicine - inhibit microtubule formation by tubulin polymerization; to block WBC migration and phagocytosis
Recurrent attacks - decrease production increase excretion
- Allopurinol - decrease uric acid production by blocking Xanthine Oxidase
- Probenecid - block anion transport at proximal tubule to block UA reabsorption; note to drink more water as conc of UA in urine increases
C A P
Pyogenic Osteomyelitis (bone + marrow inflammation) causes and pathophysiology; + Tuberculous OM
Pathophysiological features uwu
Bacteria agents:
- Staph Aureus
- TB (targets spines in adults, if TB, chronic granulomatous inflammation seen)
Pathophysiology:
- Bone necrosis, abscess
- Inflammation, pus, draining sinus - Suppurative Necrosis
- Inflammation/pus spreads under periosteum, lifting it - subperitosteum abscess
- Cuts blood supply, bone necrosis, dead bone called Sequestrum - necrotic bone
- Sleeve of woven bone produced called Involucrum
Name Metabolic Bone Diseases [4]
Osteoporosis
Osteomalacia/Rickets - bone + soft
Osteitis Fibrosa Cystica
Osteitis Deformans / Paget’s Disease
Osteitis is inflammation of bone
Osteoporosis
Pathophysiology
CauseSSSS
Give 3 causative drug classes
- Low bone mineral density but NORMALLY mineralized, thinned and reduced bone trabeculae; quality normal;
- Serum levels normal: Insufficient calcium intake leads to secondary hyperparathyroidism, which increases the rate of bone remodelling to maintain a normal serum calcium levels.
Primary cause
- post-menopausal - estrogen deficiency
- increase RANK, RANKL, TNF, IL1, IL6
- As a decoy receptor for RANKL, OPG inhibits RANK-RANKL interactions thus suppressing osteoclastogenesis and bone resorption; hence post menopause less Oestrogen less OPG, hence RANKL binds to RANK, osteoclast bone resorption - oesteoporosis
Secondary causes
- Decreased calcium, Corticosteroids
- CS leads to decreased Ca absorption and increased Ca excretion; this increases PTH; bone resorption increased, bone formation decreased
- Drugs of levothyroxine and long term Heparin
Osteomalacia/Rickets (kids)
- defect in mineralization, calcification due to Vitamin D deficiency;
- Kidney needed to activate Vit D;
- Rickets: Bone matrix remains not mineralized - cartilage hypertrophy (supposed to apoptosis and be calcified) Endochondral ossification problem, failure of cartilage cells to mature;
VitD: intestinal Ca absorption, increase bone resorption
Osteitis Fibrosa Cystica - serum levels, cause and histological features
weakening of the bones as calcified supporting structures are replaced with fibrous tissue and the formation of cyst-like brown tumors (just a mass from excess OC activity) in and around the bone
- Excessive osteoclastic activity; from hyperparathyroidism;
- High serum calcium, low serum phosphate
- Brown Tumor of cystic solid lesion of masses of osteoclastic giant cells & Fibrotic tissue, brown due to hemosiderin depositions
Hemosiderin and MGC found in benign GCT of bone
Heart failure cells are siderophages generated in the alveoli of patients with left heart failure or chronic pulmonary edema, when the high pulmonary blood pressure causes red cells to pass through the vascular wall
Osteitis Deformans/ Paget’s Disease
enlarged, deformed bones
- Uncoordinated resorption + formation remodeling;
- Haphazard bone architecture, jigsaw irregular pattern, disorganized collagen fibers;
