Musculoskeletal Flashcards
What is osteoarthritis, with key signs and symptoms?
degenerative arthritis of the articular cartilage, typically affecting the weight-bearing (larger) joints and seen mostly over the age of 45 years.
- Joint pain (e.g., knee, hip) with a gradual onset unilaterally. Often worsened by activity and relieved by rest.
- Associated joint stiffness.
- Joint swelling, deformity (due to osteophytes)
- Heberden’s nodes: Swelling at the distal interphalangeal joints.
What mediates the normal turnover of matrix components? Describe the pathophysiology of osteoarthritis
The normal turnover of matrix components is mediated by chondrocytes, which synthesise ECM components and the proteolytic enzymes responsible for their breakdown.
1) The proteolytic breakdown of cartilage matrix begins (this is made up of extracellular matrix (water, collagen and proteoglycans) and chondrocytes.
2) Matrix metalloproteases (MMP) such as collagenase degrade the ECM, releasing fragments into synovial
fluid → release of pro-inflammatory mediators (e.g., IL-1β, TNF-α).
3) The level of proteoglycans (formed of glycosaminoglycan (GAG) chains such as chondroitin sulphate) continue to drop, causing the cartilage to soften, thin and lose elasticity, compromising joint surface integrity. Fibrillations (vertical clefts) develop
4) Over time, the loss of cartilage results in loss of joint space. Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed.
5) Subchondral bone responds with vascular invasion and increased cellularity. Bone thickening (‘eburnation’) and osteophyte (bone spur) formation occurs.
Causes and risk factors for OA?
1) Increasing age ― age-related loss of chondrocyte function
is characterised by erosion of chondrocyte telomere length and mitochondrial dysfunction due to oxidative damage.
2) Previous joint trauma ― associated
with joint inflammation and the onset of cartilage degradation.
3) Overweight / obesity ― direct effect of mechanical load on cartilage.
4) T2DM ― insulin stimulates chondrocytes
to synthesise proteoglycans.
5) Genetics ― a number of OA genetic risk loci
6) Drivers of chronic inflammation e.g., metabolic endotoxemia.
7) Other joint diseases ― e.g., gout, RA.
8) Nutritional deficiencies ― e.g., vitamin D;
prevents articular cartilage erosion by
regulating collagen II turnover and bone metabolism.
How can OA be diagnosed?
Radiography: Key x-ray findings include joint-space narrowing, osteophytes and subchondral sclerosis.
* However, there is a lack of correlation between severity and findings
Dietary suggestions for OA?
CNM Naturopathic Diet with a focus on supporting an anti-inflammatory environment, sufficient level of hydration for synovial support.
- Address the cause/s ― e.g., manage weight and improve insulin sensitivity address dysbiosis / intestinal permeability (e.g., 5R protocol).
- Change dietary fats and oils ― decrease arachidonic acid as it’s a precursor to the inflammatory PGE2 series. Instead, increase dihomo-gamma-linolenic acid (DGLA) ― precursor to PGE1 series and eicosapentaenoic
acid (EPA) ― precursor to PGE3 series.
Lifestyle suggestions for OA?
1) Hydrotherapy ― contrast showers (starting
with heat, ending with cold, and with heat being 3–4 x longer than cold) to areas of pain.
2) Epsom salt baths (500g–1kg).
3) Tissue salts (1 each x 3 daily):
- Ferrum phos ― for inflammation and pain that comes with advanced OA.
- Calc. phos and calc. fluor ― for reduction of joint degeneration.
4) Exercise ― low-moderate intensity. Swimming, and practices such as yoga, Tai Chi and Pilates all increase joint
circulation and strengthen surrounding muscles.
5) Topical Warming oil blend, e.g., rosemary, ginger, cayenne
(used cautiously) to encourage vasodilation / blood flow.
6) Essential oils, e.g., peppermint, wintergreen, frankincense,
basil. Add drops into a carrier oil or cream. Anti-inflammatory, blood circulation promoting and muscle relaxing effects.
Nutrients for OA?
1) Glucosamine sulphate 500 mg x 3 daily
- Used for GAG and hence proteoglycan synthesis,
-stimulates chondrocyte production of collagen.
- A provider of sulphate ions for the synthesis of the chondroitin sulphate.
* Inhibits: MMPs (e.g., collagenase), reducing cartilage degradation; COX-2, PGE2 and downregulates NF-kB in chondrocytes.
2) Chondroitin sulphate 200–400 mg / day
* Chondroitin increases the amount of hyaluronic acid in joints ― keeping synovial joints lubricated.
* Inhibits many cartilage-degrading enzymes.
3) Methylsulfonyl- methane (MSM) 1 g / day, building to 3–4 g / day
* Anti-inflammatory effects- NF-κB inhibition and free radical scavenging.
* Stimulates proteoglycan and hyaluronic acid synthesis; inhibits proteolytic enzymes.
4) Vitamin C 1–5000 mg / day
* Anabolic effect on cartilage; required for chondrocyte protein synthesis (e.g., collagen).
* Antioxidant properties reduce impact of ROS on genomic stability in chondrocytes.
5) Vitamin D 2000–10,000 iu depending
* Prevents articular cartilage erosion by regulating collagen II turnover and bone metabolism.
6) Tart cherry Up to 3000 mg / day extract
* Rich in anthocyanins and other flavonoids.
* Anti-inflammatory: Shown to inhibit COX, inhibit
NF-κB and reduce IL-6. Antioxidant effects.
What is the pathophysiology of rheumatoid arthritis? How is it defined?
a chronic inflammatory autoimmune disease characterised by synovial joint inflammation, potentially affecting all organs except the brain.
Pathophysiology:
1) Arginine converts to citrulline (citrullination) , mediated by genetics and environmental factors
2) Antigen presenting cells recognise the cirtrulline in regions of several proteins including collagen and fibrin, as foreign
and present the antigens to CD4+ T cells, triggering T-cell differentiation.
3) B-cells are activated leading to production of autoantibodies (anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor).
4) T-cells stimulate macrophages in synovial joints to produce inflammatory cytokines (e.g., TNF-a, IL-1, IL-6), these stimulate fibroblast-like synoviocytes (FLS), which
degrade cartillage
5) together with the cytokines they increase RANKL expression ( this increasing osteoclasts and bone destruction).
Causes and risk factors of RA
1) Genetics:
– HLA-DRB1 alleles contribute at least 30% of the total genetic component of this disease.
– PTPN22 SNP – the largest non-HLA genetic association in RA.
2) Smoking ― oxidative damage; raised
pro-inflammatory cytokines (e.g., IL-17);
increased MMP expression; epigenetic changes.
3) Porphyromonas gingivalis
(periodontitis) ― produces the enzyme peptidylarginine deiminase (PAD), which induces citrullination.
4) Silica dust exposure ―
increases inflammatory cytokines (e.g., TNF- α) and MMP activity.
5) Intestinal dysbiosis:
‒ Prevotella copri is often abundant in RA, can induce Th17-related cytokines.
‒ Raised Collinsella increases gut permeability and IL-17.
‒ Reduced Bacteroides spp. and Bifidobacterium spp. abundance.
Disturbed gut barrier function (e.g., →
metabolic endotoxaemia) and intestinal inflammation.
Which blood tests might indicate RA?
- Raised inflammatory markers (ESR / CRP).
- Rheumatoid factor (RF) in 70% of cases ― an IgM antibody
- Anti-citrullinated protein antibodies (ACPAs) ― can be present in the serum up to 10 years before the onset of clinical symptoms.
Natural approach to RA?
1) CNM Naturopathic Diet with a focus on reducing inflammation (e.g., no refined sugar, trans fats, dairy, limited red meat; high omega-3, etc.).
2) Abundant antioxidants (rainbow diet) ―
RA sufferers have low serum levels of antioxidants, and high levels of oxidative stress, contributes to tissue damage.
3) Gluten-free ― as gluten is a key food source of molecular mimicry and inducer of intestinal permeability (triggering zonulin release).
4) Oral microbiome support if needed
– Anti-microbials and biofilm disruptors
Ginger, turmeric, aloe vera, clove, garlic and neem have demonstrated anti-microbial effects against P. gingivalis.
– Oral probiotic and immune support (e.g., vitamin C).
5) Stop smoking
6) stress management
7) Gut barrier and microbiome support
Nutrients for RA?
1) Vitamin D
* A potent inhibitor of Th17 pathogenicity and promotes Treg differentiation.
* Shown to lower the levels of RANKL.
2) Omega-3 1 g+ of actual EPA
Anti-inflammatory effects, beneficial in RA:
* Reduce Th17 cells and IL-17 levels.
* Inhibit PGE2, NFκB, TNF-α and Interleukin-6.
3) GLA Borage oil 1–2 g daily
* Shown to reduce pain, stiffness and swelling in RA.
* Converted to DGLA, which forms
the anti-inflammatory PGE1. It inhibits 5-LOX and reduces NF-kB activity.
4) Resveratrol 200 mg / day
* A polyphenol that reduces Th17 cells; downregulates NF-KB and COX-2.
5) Alpha lipoic acid Up to 1200 mg / day
* Potent fat- and water-soluble antioxidant, raising intracellular glutathione.
* Anti-inflammatory ― shown to downregulate NFκB and reduce inflammatory markers such as CRP.
6) Quercetin 1.5–3 g / day
* Anti-inflammatory: Inhibits NF-kβ and COX-2, as well as various inflammatory cytokines e.g., IL-17, TNF-α.
* Shown to inhibit the invasion of FLSs.
7) Zinc (e.g. citrate) 15–30 mg / day
* Deficiency predispose to inflammation. Delta-6-desaturase activity decreases.
* Low levels are associated with increased: NF-kb activation, CRP, IL-1β, and TNF-α.
8) Probiotics ― e.g., Lactobacillus casei ↓inflammatory cytokines such as TNF and Il-6, L. rhamnosus GG also effective.
9) Anti-inflammatory herbs: Turmeric, Devil’s Claw, boswellia and ginger (see OA).
What is gout, and what are the main signs and symptoms?
arthritis due to deposition of monosodium urate (MSU) crystals within joints causing acute inflammation.
Signs / symptoms:
* Monoarticular arthritis most commonly affecting the 1st metatarsophalangeal joint (big toe). Most often affecting men.
* Pain, swelling, redness and heat. Shiny skin. Can awaken patients from sleep.
* Can affect other joints (e.g., knee).
* Reaches its peak within 24 hours, often with fever and malaise.
Pathophysiology of gout?
1) Purines are part of the chemical structure of DNA and RNA found in all of the body’s cells, and in virtually all foods,
2) when cells die, the purines are released , and uric acid is the final breakdown product of purine meabolism
3) High serum uric acid (Hyperuricaemia) leads to monosodium urate (MSU) crystal formation, and gout.
4) Inflammation is mediated by cytokine Interleukin-1β
Causes and risk factors of gout?
1) uric acid overproduction:
* Dietary purines ― e.g., meat, organ meat, seafood (e.g., shellfish).
* High cell turnover disorders ― e.g., leukaemia,
haemolytic anaemias, psoriasis.
* Fructose increases ATP degradation to AMP, a uric acid precursor.
2) underexcretion of uric acid:
* Medication side effects ― e.g., diuretics, aspirin (low dose)
and ACE inhibitors increase urate renal retention.
* Renal insufficiency (CKD) ― impairs uric acid excretion.
* Alcohol (e.g., beer) ― decreases urate excretion and increases urate production.
* Genetics SNPs in ABCG2: mediates urate secretion primarily in proximal renal tubule cells.
* Obesity and insulin resistance (IR) ― reduces urate renal excretion.
* Dehydration.
Natural approach to gout
1) Avoid / minimise: Alcohol, fructose-containing beverages, pro-inflammatory foods (e.g., refined carbohydrates, trans fats).
2) Low purine diet
3) Optimise omega-3:6 ratio to reduce inflammation
4) Minimum of 2L of water daily ― dilutes urine
and promotes uric acid excretion.
5) Protein intake should not be excessive
(i.e., not >0.8 g / kg body weight), as this may accelerate uric acid synthesis. However, sufficient protein is needed to decrease resorption of uric acid in the renal tubules.
6) Avoid the feet getting cold ― uric acid is a highly water insoluble molecule which deposits easily in
cold weather.
