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.
Nutrients for gout
1) Quercetin 200‒400 mg x 3 daily
* Xanthine Oxidase inhibition and promoted activity of urate excretion transporters.
* Anti-inflammatory activity by targeting NLRP3 inflammasome-IL-1β pathway and TLR signalling.
* Antioxidant properties ― reducing inflammatory effects.
2) EPA 3 g daily
* inhibits urate transporter 1 (URAT1), thus increasing renal urate excretion.
* Anti-inflammatory: Inhibition of the PGE2 pathway; NFκB, TNF-α and interleukin-6.
3) Methyl folate 400‒800 mcg + high dietary folate
* inhibit XO by displacing the enzyme’s cofactor, molybdenum.
4) Tart cherry Up to 3000 mg / day extract
Its polyphenols:
* Inhibit COX-1, COX-2, NFκB and IL-1β.
* Reduce uric acid levels, possibly through XO inhibition or increased renal clearance.
* Reduce oxidative stress.
5) Celery
Reduces uric acid through inhibition of XO activity, reduction in oxidative stress and inflammation (COX and LOX inhibiting), attributed to flavonoids (e.g., apigenin) and phenolic compounds.
What is fibromyalgia? symptoms? and what are the diagnostic criteria?
a condition of chronic widespread pain and abnormal pain-processing mechanisms.
Other key symptoms:
* Fatigue, sleep disturbance, stiffness, headaches, bowel disturbances, anxiety and depression.
:
1. A widespread pain index (WPI) score of 7+ and a symptom severity scale (SS) score of 5+.
2. Symptoms lasting at least three months at a similar level. 3. No other health problem that would explain the symptoms.
Causes/ risk factors for FM?
1) Trauma ― physical and emotional
– links with adversity in early life; excessively activating stress responses during development, hyperalgesic priming. HPAA dysregulation.
– Disrupted cortisol levels are common
2) Hypothyroidism ― thyroid hormones normally inhibit
the secretion of substance P in the dorsal horn of the spinal cord.
3) Intestinal dysbiosis:
* SIBO ― degree of pain in FM
correlates significantly with breath test hydrogen levels.
* altered composition of SCFA-metabolising bacteria. Faecalibacterium prausnitzii and Bacteroides spp. were found in lower relative abundance in FM.
* Gut bacteria could modulate nociception (pain), likely mediated by metabolites including SFCAs, bile acids and neurotransmitters.
4) Infections ― e.g., EBV ― high EBV IgG concentrations in
FM correlate with pain intensity and other key symptoms.
5) Nutritional deficiencies:
‒ Vitamin D ― ↓ PGE2 synthesis, inflammatory cytokines and modulates central pain processing.
‒ Vitamin B12 ― enhances noradrenaline and 5-HT as inhibitory pain signals and supports myelination.
‒ Magnesium ― inhibits NMDA receptors, glutamate & substance P.
6) Gluten reactivity ― in the form of coeliac disease, non-coeliac gluten sensitivity or allergy is common in FM.
7) Genetic SNPs affecting methylation and detoxification, e.g.:
– MTHFR (C667T SNP) = impaired methylation
(detoxification, NT production, e.g., serotonin).
– COMT ― . Val158Met polymorphism plays a role in FM pain sensitivity
– GSTM1 (e.g., absent gene) ― increases the toxic burden.
8) Heavy metals (e.g., mercury) ― ↓ glutathione,
disturbs GABA-glutamate balance and
methylation, ↑ pro-inflammatory cytokines.
Natural dietary approach to fibromyalgia?
1) Follow dietary guidelines outlined for stress, mitochondrial
dysfunction and CFS / ME in stress / fatigue lecture.
2) Gluten-free diets and a low FODMAP diet have
shown clinical improvements i
3) Support the gut if needed.
E.g., 5R protocol; support commensal microbial diversity and SCFA-producers with fibre, polyphenols etc.
4) Reduce glutamate levels ― by increasing glutamate decarboxylase (GAD) co-factors (Mg, vitamin B6, Zn, vitamin C, taurine). Avoiding glutamate sources (e.g., MSG) and alcohol (inhibits GAD).
5) Reduce toxic load; support liver detoxification phases
and elimination pathways
* Optimise levels of Metallothionein (binds to heavy metals) (cysteine, zinc, copper, and selenium)
‒ Antioxidant enzyme status with selenium, zinc, etc.
‒ Chain-breaking antioxidants (vitamin C, E,
flavonoids, carotenoids) with a ‘rainbow’ diet.
* Optimise glutathione levels ― e.g., NAC, silymarin, resveratrol.
6) Support methylation ― for NT synthesis and detoxification: folate, B12, B6, B2, choline, betaine (TMG, e.g., in beetroot) and zinc; Consider methylated B vitamins.
Nutrients for fibromyalgia
1) Magnesium (as malate or citrate) 200‒500 mg / day
* Magnesium blocks NMDA receptor channels
and must be removed for excitation to occur.
This leads to anti-nociceptive and analgesic effects.
2) Vitamin D Optimise levels
* Modulates central pain processing, reduces inflammatory cytokines and PGE2.
3) Vitamin B6 50–100 mg / day
* A co-factor for the glutamate decarboxylase ― needed for the conversion of glutamate to GABA.
4) Coenzyme Q10 300 mg daily
* CoQ10 deficiency is common in FM, correlateswith symptom severity.
* potent antioxidant, deficiency associated with mitochondrial dysfunction.
* Plays a key role in the electron transport chain.
5) 5-HTP 100–300 mg daily
* Low levels of serotonin and L-tryptophan have been observed in the cerebrospinal fluid of FM patients.
* 5-HTP is the direct precursor to serotonin,
which plays a role in descending pain regulation. It also supports melatonin synthesis.
Herbs for fibromyalgia?
1) Ashwagandha 300‒600 mg 1-3 x / day
* Supports the HPAA and restorative sleep through its influence on GABA. Anti-nociceptive effects mediated by the opioidergic system.
2) St John’s wort 600–1200 mg as 3 divided doses daily.
* Interacts with several neuronal systems that modulate nociception. Affinity for GABA and MAO, increases serotonin / dopamine.
3) Devil’s Claw 3‒6 g daily dried herb
* Inhibits: Proinflammatory cytokine release (e.g., IL-1β, IL-6, TNF-α) from macrophages; COX-2 expression and lipid peroxidation.
Which structures are implicated in mechanical back pain , with pain onset and daily patttern
- Structures implicated include:
- Muscles (e.g., muscle strains, spasms) — typically relieved by rest and heat.
- Facet joints — often worse with spinal extension.
- Intervertebral discs (e.g., degeneration, herniation)
- Bones (e.g., vertebral fracture) — look for unremitting pain,
trauma, osteoporosis risks / diagnosis. :
Pain onset:
Gradual without trauma might indicate degenerative picture or muscle fatigue. A sudden onset (e.g., trauma, waking with pain) is likely associated with acute inflammation.
Age:
Spinal joint degeneration begins from the age of about 30. Disc herniations are common around the age of 30‒40 years.
Daily pattern:
If inflammation is a key feature, the pain is often relieved by movement. Morning stiffness is also common with inflammation. A muscular or degenerative issue often worsens through the day.
What are the risk factors/ causes for mechanical back pain?
- Physical trauma — e.g., sports injury, heavy lifting
- Emotional stress — ↑ SNS activity =
↑ muscle tone / shortening. Chronic stress can also alter neurotransmitter levels associated with descending antinociceptive pathways. - Inflammation — (e.g., poor diet, metabolic endotoxaemia, obesity).
