Describe the pathological features of gout.
- Acute arthritis
- Precipitation of urate crystals into the joint/s
- An event (sometimes minor trauma) releases crystals into synovial fluid
- Cascade occurs resulting in intense inflammatory reaction (complement activated, chemotaxis of neutrophils and macrophages with phagocytosis and activation of lysosymal enzymes, leukotrienes, prostaglandins and free radicals
- Chronic arthritis and formation of tophi which are urate deposits in synovium and periarticular areas
- Nephropathy – deposition of urate in kidney as well as formation of uric acid stones
What are the causes of gout?
- enzyme defect unknown (90%) (overproduction, underexcretion or increased excretion)
- rare enzyme defect (HGPRT deficiency)
- Secondary (10%)
- Increased nucleic acid turnover e.g leukaemias (overproduction and excretion)
- Chronic renal disease (decreased excretion)
- Inborn error metabolism (complete HGPRT deficiency – Lesch-Nyhan syndrome) overproduction and excretion
- Primary PLUS one secondary to pass
What factors lead to osteoarthritis?
- Genetic & environmental (mechanical)
- Age – virtually ubiquitous (80-90%) after 65
- Other exacerbating diseases e.g. Obesity, diabetes, injury, abnormal joints
Describe the pathological changes that occur in an affected joint.
- Chondrocyte injury
- Early OA: chondrocytes proliferate (cloning) and secrete inflammatory mediators, collagens, proteoglycans, and proteases which initiates secondary inflammatory changes.
- Later OA: repetitive injury and chronic inflammation lead to chondrocyte drop out, marked loss of cartilage, and extensive subchondral bone changes
Describe the major clinical features of osteoarthritis.
- Mostly asymptomatic <50y.o.
- Deep, achy pain worse with use, morning stiffness, crepitus, and limited ROM
- Oligoarthritis 95% ( occas generalized/early)
- Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits.
- Common: hips, knees, lower lumbar and cervical vertebrae, PIP, DIP of the fingers, 1st carpoMC joints, and 1st TarsoMT joints. Not wrists, elbows, shoulders
Describe the morphology of osteoarthritis affecting a major joint.
- Early -1″ chondrocytes, i water, 1 proteoglycans
- Sloughing, bone exposure
- Dislodged cartilage and bone (joint mice)
- Fibrous subchondral bone cysts
- Synovium — fibrotic, inflammatory cells
Pass: 4 of 8
Describe the causes of secondary osteoarthritis.
- congenital or acquired deformity
- Systemic disease eg diabetes
Pass: 2 of 4
Describe the morphology of the joint lesion in Rheumatoid Arthritis.
- Joints — perivascular inflammatory infiltration CD4+ helper T cells, plasma cells, Macrophages.
- increased vascularity
- Organising fibrin, rice bodies
- Neutrophil accumulation
- Osteoclastic – juxta articular erosion, subchondral cysts, osteoporosis
- Fibrous ankylosis —> bony ankylosis
Pass: At least 3
What are the extra articular manifestations of RA?
- Rheumatoid nodules – 25% forearm/elbow/occiput/lumbosacral.
Less frequent — lungs/spleen/heart/pericardium/valves/aorta.
- Fibrinoid necrosis — epithelioid cells/Lymphocytes/ Macrophage.
- Vasculitis- ptupura, ulcers, nail bed infarcts Digital – endarteritis (neuropathy/ulcers/gangrene)
Pass: At least 2
Describe the pathogenesis of gouty arthritis.
- Purine metabolism — 2 pathways.
- Hypoxanthine guanine phosphoribosyltransferase.
- Supersaturation — synovial fluid.
- Chemotactic, complement activation.
Macrophage free radical, leukotrienes, lysosomal enzymes. Hagemann.
- Acute arthritis — cartilage, joint damage
Pass: At least 3
What are the risk factors for primary gout?
- Genetic predisposition
- Lead toxicity
Pass: At least 4
Describe pathogenesis of osteomyelitis.
PROMPT – What organisms cause osteomyelitis?
- Local bone injury and organism entry, blood borne organisms, neighbouring source entry.
- Staphylococcus aureus >80% of pyogenic ones
- Others: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa from IVDU and GU, Haemophilus influenzae, Group B streptococcus
- 50% no organisms found
- Bold + 1 other organism to pass
What changes occur to the bone?
- Acute inflammation
- Involucrum and sequestrum
- Lytic focus and surrounding necrosis – periosteal elevation
- Bold to pass
What are the pathological sequelae of osteomyelitis?
- Chronic – up to 25%
- Deformity and bone destruction
- Severe sepsis
- Pathological fracture
- Bold to pass
A 60 year old woman presents with severe jaw pain following a dental extraction a month earlier and is given IV morphine. Her X-ray reveals evidence of bony destruction in the mandible. Describe the pathogenesis of osteomyelitis.
PROMPT – How would this patient have suffered a bony infection of his jaw?
- Local infection related to extraction of tooth
- Blood borne
- Spread from neighbouring gingival source
What organisms cause osteomyelitis?
- Staphylococcus aureus majority >80% pyogenic
- Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, from genitourinary tract or IV drug use
- Haemophilus influenzae and GBS in neonates
- Viruses, fungi, parasites, tuberculosis, syphilis
- About 50% no organisms found.
- Staph aureus and 1 other
What changes occur in the bone?
- Acute inflammation and necrosis, abscess formation
- Sclerosis and involucrum formation
- Deformity and sequestrum formation, Draining sinus
- Characteristic lytic focus surrounded by zone of necrosis on X-ray, lifting of periosteum
- 5-25% become chronic inflammation
- Bold to pass
What are the clinical consequences of osteomyelitis?
- Resolution after treatment with IV antibiotics and drainage
- Conversion to chronic osteomyelitis
- Deformity and bony destruction
- Severe sepsis syndrome, ARF
- 2 to pass
Describe the steps in fracture repair process.
- Haematoma fills fracture gap – provides fibrin mesh framework (hours)
- Influx of inflammatory cells, fibroblasts, new vessels (days)
- Haematoma organising –> Procallus
- Osteoprogenitors despoti trabeculae of woven bone – ossification –> bony callus (2-3 weeks)
- Callus matures, remodelling (6 weeks)
- 4 of 5 steps
- Logical sequence
How does remodelling of callus occur?
- Initial large volume of callus – portions not physically stressed are resorbed, reducing callus size/altering contour
- Physical stress
What factors can impede the healing of a fracture?
- Inadequate immobilisation
- Marked displacement/soft tissues
- Vascular compromise
- Infection (open fractures/foreign bodies)
- Systemic factors (nutrition, osteoporosis, smoking…)
- 2 bold and 1 other
How are fractures classified?
Describe the abnormality.
- Spiral/oblique fracture mid-shaft left humerus with displacement
Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 18162
What structure may be injured in this fracture?
- Radial nerve