Locomotor 2 wk1+2 Flashcards
what nerve innervates gluteus maximus
inferior gluteal nerve (L5,S1,S2) innervates gluteus maximus
what nerve innervates gluteus medius, gluteus minimus and tensor fascia latae
superior gluteal nerve (L4,L5,S1) innervates gluteus medius, gluteus minimus and tensor fascia latae
what does a positive trendelenburg sign mean?
A positive Trendelenburg sign= when you ask patient to stand on 1 leg, the pelvis drops on the unsupported side
A person may present with a waddling gait or Trendelenburg gait where the trunk leans toward the weakened side during walking to compensate for the muscle weakness.
+ve Trendelenburg indicates damage to superior gluteal n. or weakness in the hip abductor muscles (gluteus medius and gluteus minimus)
n.b. a normal person= -ve Trendelenburg= when asked to stand on 1 leg, gluteus medius + minimus on other side contract to stop pelvis from dropping
Causes of a Positive Trendelenburg Sign:
- Superior gluteal nerve injury (innervates gluteus medius and minimus)
- Hip abductor weakness (due to muscle atrophy, hip osteoarthritis, or muscle tears)
- Hip joint pathology (e.g., hip dysplasia, hip dislocation)
- Post-surgical complications (e.g., after hip replacement)
what is the blood supply + innervation of anterior compartment of the thigh
anterior thigh:
femoral nerve (L2-L4)
femoral artery
main action is extension of knee + flexion of hip
what is the blood supply + innervation of posterior compartment of the thigh
posterior thigh:
sciatic nerve (L4-S3)
inferior gluteal artery + deep femoral artery
main action is flexion at knee; and extension at hip
what is the blood supply + innervation of medial compartment of the thigh
medial thigh:
obturator nerve (L2-L4)
obturator artery
main action is hip adduction
what muscle is the landmark for the sciatic nerve
piriformis is the landmark for the sciatic nerve
what is the blood supply + innervation of posterior deep compartment of the leg
posterior deep leg:
tibial nerve (L4-S3)
posterior tibial artery
main actions:
- a little plantarflexion
- mainly INVERSION of foot
- flexion of digits (toe curl)
what is the blood supply + innervation of anterior compartment of the leg
anterior leg:
deep fibular/peroneal nerve (L4-S2)
anterior tibial artery
main actions;
- dorsiflex foot
- extend digits
what is the blood supply + innervation of lateral compartment of the leg
lateral leg:
superficial fibular/peroneal nerve (L5-S1)
fibular artery
main actions;
- EVERT foot
what is the blood supply + innervation of posterior superficial compartment of the leg
posterior superficial leg:
tibial nerve (L4-S3)
posterior tibial artery
main actions:
- plantarflexion
- inversion of foot
What does a femoral nerve palsy present as? + some causes
femoral nerve palsy (L2,L3,L4)= damage to anterior compartment of thigh i.e.
- paralysis of quadriceps (no extension or flexion of knee)
- sensory loss of anterior thigh + medial leg
causes:
- compression (resulting from congenital hip dysplasia treatment)
- pelvic fractures
- anterior hip dislocation (V RARE)
What paralysis + sensory loss will you see in a tibial nerve palsy (+ causes)
tibial nerve palsy (L4-S3)= damage to posterior deep + superficial compartment of leg i.e.
- paralysis of plantarflexion + foot inversion
- sensory loss to back of leg + sole of foot
causes:
- fracture of tibia
- compression of tarsal tunnel
What paralysis + sensory loss will you see in a common fibular/peroneal nerve palsy
common fibular/peroneal nerve palsy (L4,L5,S1,S2)= damage to lateral + anterior compartment of leg i.e. unopposed plantarflexion= FOOT DROP!
- paralysis of dorsiflexion, eversion + can’t extend digits
- sensory loss to foot dorsum
What paralysis + sensory loss will you see in a sciatic nerve palsy
sciatic nerve palsy (L4-S3)= damage to posterior thigh + all sensations below knee except medial compartments of leg + foot i.e.
- paralysis of hamstrings + calves= loss of dorsiflexion + plantarflexion
- loss of Achilles reflex
- weak knee flexion
- foot drop
- all sensations below knee lost EXCEPT medial leg + foot
What is the role of the anterior cruciate ligament (ACL) + what sign will u see if damaged
ACL= prevents the femur from sliding posterior on the tibia
Rupture of ACL= anterior drawer sign
What is the role of the posterior cruciate ligament (PCL) + what sign will u see if damaged
PCL= prevents the femur from sliding anteriorly on the tibia
Rupture of PCL = posterior drawer sign
what movements can the ball+socket joint of the hip perform?
ball+socket synovial hip joint can do:
- flexion
- extension
- abduction
- adduction
- circumduction
What type of hip dislocation is more common?
posterior hip dislocations are more common because anterior ligaments are stronger (iliofemoral ligament located anteriorly= strongest ligament in the body)
posterior hip dislocations cause sciatic nerve palsy (L4-S3)
Which fracture of the neck of the femur is more at risk of avascular necrosis
INTRACAPSULAR FRACTURES= occurs within capsule of hip joint
can damage medial femoral + circumflex artery= can cause avascular necrosis (AVN) of femoral head
n.b. whereas extracapsular fractures (occur outside the joint capsule) so blood supply to head of femur intact (v rare complication AVN)
what are the nerve roots and what plexus do the following nerves belong to:
- femoral n.
- superior gluteal n.
- inferior gluteal n.
- obturator n.
- sciatic n.
ALL part of lumbosacral plexus
femoral n. (L2-L4)
superior gluteal n. (L4-S1)
inferior gluteal n. (L5-S2)
obturator n. (L2-L4)
sciatic n. (L4-S3)
What nerve is damaged in a ankle fracture + what sign will u see?
ankle fracture= common peroneal n. (L4-S2)
💡 Clinical Sign:
If deep fibular nerve is damaged:
- Foot Drop:
Inability to dorsiflex the foot (toes drag when walking).
- Loss of sensation in the first web space (between the first and second toes).
If superficial fibular nerve is damaged:
- Numbness or tingling over the dorsum of the foot.
- Weakness in foot eversion (turning the foot outward).
What nerve is damaged in a calcaneus fracture + what sign will u see?
calcaneus fracture= tibial n. (L4-S3)
💡 Clinical Sign:
If tibial nerve or its branches are damaged, the key signs are:
1) Tarsal Tunnel Syndrome:
- Pain, burning, or tingling along the sole of the foot.
- Numbness or paresthesia in the heel, arch, and toes.
- Weakness of intrinsic foot muscles (affecting toe flexion and foot stability).
2) Loss of Plantarflexion & Toe Flexion (Severe Cases):
- If the tibial nerve is severely damaged, loss of plantarflexion (pointing toes down) and toe flexion may occur.
- Rare but significant weakness in the calf muscles (gastrocnemius and soleus).
What nerve is damaged in a metatarsal fracture + what sign will u see?
plantar nerves (medial + lateral) (L4-S3) aka Digital Nerves
Clinical signs of Digital Nerve Injury (Plantar Nerves):
- Burning or shooting pain in the toes.
- Numbness on the plantar surface of the toes.
- Morton’s Neuroma can mimic these symptoms if caused by nerve compression rather than fracture.
What nerve is damaged in a lisfranc fracture + what sign will u see?
deep peroneal/fibular n. (L4-S1) OR tibial n. (L4-S3)
Deep Fibular Nerve Injury (Anterior Tarsal Tunnel Syndrome):
- Numbness or tingling in the first web space (between the big toe and second toe).
- Weakness in toe extension
- Pain on the dorsum of the foot that worsens with pressure or wearing tight shoes.
- In severe cases= foot drop
What nerve is damaged in a tibia fracture + what sign will u see
deep peroneal nerve (L4-S1)
- foot drop
- anterior compartment of leg effected; no longer dorsiflex foot
nor extend digits
What nerve is damaged in a femoral shaft fracture + what sign will u see?
SCIATIC NERVE (L4-S3)
Signs its sciatic nerve:
- foot drop
- weak plantarflexion
- weak toe flexion
- foot slap gait
Sometimes, but v rarely femoral nerve (L2-L4) because it lies protected within the pelvis and posterior to the femur
Signs its femoral nerve: Weak knee extension (quad riceps) + anterior thigh numbness.
what structures are most at risk in a surgical neck fracture of humerus
surgical neck fracture of humerus (common in elderly);
axillary nerve (C5-C6)
what structures are most at risk in a midshaft fracture of humerus
midshaft fracture of humerus (as it travels down radial groove)
radial n. C5-T1= wrist drop
what structures are most at risk in a supracondylar fracture of humerus
supracondylar fracture of humerus (common in kids)= increased risk of volkmaan’s ischemic contractures
median/ radial n. + brachial artery most at risk!
what structures are most at risk when the medial epicondyle (of humerus) is damaged
medial epicondyle;
ulnar n. (C8-T1) = claw hand
what structures are most at risk when the lateral epicondyle (of humerus) is damaged
lateral epicondyle
radial n. (C5-T1)= wrist drop
a patient fractures their fibular neck + has foot drop. What altered sensation would they have?
loss of sensation to dorsum of foot
how do you tell short and great saphenous apart
short saphenous vein is on the lateral aspect of leg
great saphenous on the medial aspect of leg
anterior dislocation of hip is rare, but when it does happen what nerve most at risk
anterior dislocation= FEMORAL nerve (L2-L4) injury
posterior dislocation of hip damages which nerve?
sciatic nerve
the scapulo-humeral rhythm moves in what ratio?
the scapulo-humeral rhythm moves 1:2 ratio. When arm is abducted 180 degress, 60 degrees occurs by rotation of scapula and 120 degrees by rotation of humerus at shoulder joint
winging of the scapula is caused by damage to what nerve + muscle dysfunction
wingning of the scapula is due to damage to long thoracic nerve
serratus anterior dysfunction
what nerve innervates the ‘regimental badge’ and what muscle is this
regimental badge= deltoid
innervated by axillary n. (C5-C6)
damage to what nerve causes shoulder drop?
spinal accessory nerve (CN XI)
what is the Allen test used to assess
The Allen test (and MAT) assess adequate collateral circulation in hand and the presence of a complete palmar arch before performing any any procedure that could potentially disrupt blood flow in the radial or ulnar arteries.
Positive modified Allen test – If the hand flushes within 5-15 seconds it indicates that the ulnar artery has good blood flow; this normal flushing of the hand is considered to be a positive test.
Normal test (Positive Allen test):
Hand flushes pink within 5–7 seconds, indicating good ulnar artery collateral flow.
Abnormal test (Negative Allen test):
Hand remains pale >7–10 seconds, suggesting insufficient ulnar artery circulation.
What type of collagen is
- cartillage
- bone
- smooth muscle e.g. blood vessels
made up of?
cartillage= type II collagen
bone= type I collagen
smooth muscle= type III collagen
how many bones do we have at birth vs how many bones do adults have
275 bones at birth (lots of cartillage in babies) then become 206 bones (less cartillage) at adulthood
baby’s bones will fuse together as they grow
kids have a lot of WOVEN bone (their bones are bendy + disorganised layers)
what type of bone remodels faster; trabecular or cortical
trabecular bone remodels 3-10 times faster than cortical bone
What is Pott’s disease
Pott’s Disease, also known as tuberculosis spondylitis (rare) caused by mycobacterium tuberculosis infecting the spine= arthritis + vertebral osteomyelitis (infection in bone)
symptoms:
- Vertebral damage leading to an increased kyphotic deformity and subsequent back pain.
- Excessive spinal curvature can also compress spinal nerves which may lead to paraplegia.
- Systemic symptoms, such as malaise, fever, appetite loss. haemoptysis, night sweats and weight loss.
Infection results in the vertebral bodies collapsing, compressing and damaging the neural tracts travelling through the spine. The anterior corticospinal tracts are typically affected first resulting in an increase in spasticity which is denoted by exaggerated reflex responses as well as extension of the big toes (Babinski sign). Subsequently, the anterior and lateral spinothalamic tracts are affected leading to loss of crude touch, temperature, and pain detection. Finally, the dorsal column medial lemniscus located posteriorly is damaged causing loss of fine touch and proprioception in the upper and lower body.
Sphincter control over the bladder and the bowel is also affected. The complete compression of the spinal cord results in a transition from spastic paralysis to flaccid paralysis. The stages of neurological deficit are broken down in the modified Tuli classification.
what is a characteristic feature of Diffuse Idiopathic Skeletal Hyperostosis (DISH)
A characteristic feature of Diffuse Idiopathic Skeletal Hyperostosis (DISH) is ossification of the anterior longitudinal ligament.
DISH is a type of arthritis that is characterised by abnormal calcification and ossification of the entheses of the spine. DISH causes the tendons and ligaments around the spine to calcify and form abnormal new bone growth called bone spurs at their attachment points to the bone. It causes the ligaments to harden in areas where they attach to the spine. This is caused by the buildup of calcium salts in these areas causing calcification and overgrowth of bone. DISH can also affect the appendicular bones like the hips, knees, shoulders, and feet, and hands, and is more common in elderly men.
Which meds can cause necrotising autoimmune myopathy (NAM)
Necrotising autoimmune myopathy (NAM) is an inflammatory condition resulting in the degeneration of muscle fibers. Statins (e.g. Atorvastatin) are one of the main medications that can cause this type of myopathy
Other associated medications include colchicine (anti-gout), phenytoin (sodium channel blocker), cimetidine (histamine H2 receptor antagonist) and chloroquine (anti-malarial).
what cell lineage are osteoclasts derived from?
hematopoeitic stem cells -> monocytes -> osteoclasts (bone resorption)
what cell lineage are osteoblasts, osteocytes and osteoprogenitor cells derived from?
mesenchymal cells (embryonic mesoderm) -> osteoprogenitor cell -> osteoblast (bone formation) -> osteocyte (maintain bone)
what 2 things do osteoclasts need for activation
Osteoclasts need the following for activation:
M-CSF (macrophage colony stimulating factor)
RANKL (Receptor activator of nuclear factor kappa-B ligand)
What monoclonal antibody inhibits sclerostin; how does sclerostin work?
Romosozumab (stimulates bone formation while suppressing bone resorption; treatment for osteoporosis)
n.b. Sclerostin is a SOST gene product that reduces osteoblastic bone formation by inhibiting canonical Wnt/β-catenin signaling. Investigational monoclonal antibodies to sclerostin have been to shown to increase bone formation markers and decrease bone resorption markers, with an increase in bone mass
What is the role of RANKL in the body?
Bone Metabolism: Promotes osteoclast formation, activation, and survival, enabling bone resorption. Balanced by Osteoprotegerin (OPG), which inhibits RANKL.
Immune System: Influences dendritic cell survival and T cell responses, linking bone and immune systems (osteoimmunology).
Physiological Roles: Essential for mammary gland development, thermoregulation, and fever response.
Pathology: Overexpression leads to osteoporosis, rheumatoid arthritis, and bone metastases in cancers. Targeted by denosumab for therapeutic purposes.
Calcium Homeostasis - Key Medical Details
Calcium Homeostasis
Regulating Hormones:
Parathyroid Hormone (PTH): Increases blood calcium via bone resorption, kidneys, and vitamin D activation.
Calcitriol (Vitamin D): Enhances intestinal absorption of calcium.
Calcitonin: Lowers blood calcium by inhibiting osteoclasts.
FGF23: Regulates phosphate elimination, decreasing calcium indirectly.
Calcium Distribution: 99% in bones/teeth, 1% in blood and fluids
Daily Requirement: 500-1300 mg/day
Excretion: Kidneys (~200 mg/day), Gut (600-800 mg/day)
Where is parathyroid hormone (PTH) produced? What is the half-life of PTH?
In the four parathyroid glands located behind the thyroid.
half-life; About 4 minutes.
How does PTH increase blood levels in the short term vs the long term?
short term: By making the kidneys excrete phosphate/ PO4 and reabsorb Ca2+ from the distal tubule.
long term: By activating osteoclasts to release CA2+ from bone and by increasing active vitamin D (via 1-α hydroxylase) to enhance intestinal CA2+ absorption.
What happens when free CA2+ binds to the calcium-sensing receptor CaSR on parathyroid chief cells?
It decreases PTH production.
What is the drug cinacalcet used for, and how does it work? What effect does cinacalcet have on the CaSR response curve?
It treats secondary hyperparathyroidism in kidney failure patients by binding to calcium-sensing receptor (CaSR), making it more sensitive to calcium, thus reducing PTH secretion.
effect cinacalcet has on CaSR response curve:
shifts the curve leftward, meaning less extracellular calcium is needed to suppress PTH secretion.
Why do failing kidneys lead to increased PTH secretion?
They reduce phosphate excretion and vitamin D activation, causing low blood Ca2+ and high phosphate, which stimulates PTH release.
What is the primary source of Fibroblast growth factor-23 (FGF23), and what stimuli trigger its production?
FGF23 is produced by osteocytes and osteoblasts. Its secretion is stimulated by calcitriol (active vitamin D3) and dietary phosphate loading.
How does Fibroblast growth factor-23 (FGF23) regulate phosphate and calcium levels in the body?
Phosphate: Reduces renal phosphate reabsorption by decreasing Na/phosphate cotransporters in the proximal tubule (similar to PTH).
Calcium: Inhibits 1α-hydroxylation of vitamin D → lowers calcitriol → reduces intestinal Ca²⁺ absorption.
What role does FGF23 play in chronic kidney disease-mineral and bone disorder (CKD-MBD)?
In CKD-MBD, FGF23 levels rise due to impaired phosphate excretion and calcitriol deficiency. This further suppresses calcitriol, exacerbating secondary hyperparathyroidism (↑ PTH) and bone demineralization.
Explain the pathophysiology of X-linked hypophosphatemia (XLH) and its treatment.
Cause: Mutations in the PHEX gene (a phosphate-regulating peptidase) lead to unchecked FGF23 activity → excessive renal phosphate wasting.
deficiency= hyperactive FGF23 leads to renal phosphate loss!
Effect in children: Causes vitamin D-resistant rickets.
Treatment: Burosumab, a monoclonal antibody that neutralizes FGF23.
n.b. u cant give them vitamin D supplement because kidney (FGF23) is inhibiting 1α-hydroxylase enzyme so conversion to 1,25 dihydroxyvitamin D not taking place
Compare and contrast the effects of FGF23 and PTH on phosphate and vitamin D metabolism.
Shared effect: Both increase renal phosphate excretion.
Opposing effects:
PTH stimulates 1α-hydroxylase → ↑ calcitriol → ↑ intestinal Ca²⁺ absorption.
FGF23 inhibits 1α-hydroxylase → ↓ calcitriol → ↓ intestinal Ca²⁺ absorption.
What are the sources, triggers, and physiological effects of calcitonin? How does it compare to PTH in calcium regulation?
Source: Secreted by parafollicular C-cells of thyroid in response to high serum Ca²⁺ (>2.25 mmol/L).
Effects:
- Bone: Inhibits osteoclasts → ↓ bone resorption (weak effect).
- Kidney: ↑ Ca²⁺ excretion (inhibits reabsorption).
- Intestine: ↓ Ca²⁺ absorption.
Clinical Use: Second-line treatment for osteoporosis (limited efficacy cuz calcitonin effects on bone metabolism v minimal).
vs. PTH:
- Calcitonin lowers blood Ca²⁺ (short-term, mild).
- PTH raises blood Ca²⁺ (dominant, via bone/kidney/vitamin D
MNEMONIC: Calcitonin Tones Down Calcium (T= thyroid)
How do GH and IGF-1 promote bone growth, and what are their target cells?
GH stimulates hepatocytes to produce IGF-1 and directly promotes growth in cartilage/bone.
IGF-1 acts on:
Chondrocytes (epiphyseal plate) → longitudinal bone growth.
Osteoblasts → proliferation and bone formation.
What are the effects of thyroid hormone on bone, and what pathologies arise from its imbalance?
Targets: Chondrocytes, osteoblasts, osteoclast precursors, and bone marrow stromal cells.
Hypothyroidism (children): Dwarfism (impaired bone growth).
Hyperthyroidism: Secondary osteoporosis (excessive bone resorption).
How do estrogens and progesterone protect bone, and what is FSH’s role?
Estrogens:
↑ Intestinal Ca²⁺ absorption.
Directly stimulate osteoblasts and inhibit osteoclasts (↓ M-CSF, IL-1, IL-6, TNFα).
Progesterone: Adds to bone density (used in osteoporosis therapy).
FSH: Stimulates osteoclasts, but estrogens compensate anabolically.
How do androgens (e.g., testosterone) influence bone health?
Converted to estrogens (via aromatase) → bone-protective effects are largely estrogen-mediated.
Why do glucocorticoids cause osteoporosis?
↓ Bone formation: Kill osteoblasts and shorten their lifespan.
↑ Bone resorption: Induce RANKL → activates osteoclasts.
Rank these hormones from most anabolic to most catabolic for bone: GH, estrogens, cortisol, PTH
GH/IGF-1 (strong anabolic).
Estrogens (net anabolic via osteoblast stimulation).
PTH (mixed: catabolic in chronic high doses, anabolic in pulses).
Cortisol (strongly catabolic).
Mnemonic for bone-resorbing hormones: “Cortisol PTHs FSH” (Catabolic: Cortisol, PTH-high, FSH).
Internal (medial) rotation of the shoulder is facilitated by which muscles? (think of it like going to reach your bra strap)
Internal (medial) rotation of the shoulder is facilitated by subscapularis (chief internal rotator), teres major, latissimus dorsi, pectoralis major and deltoid. Subscapularis is an anterior rotator cuff muscle, and it is the most important muscle with regards to internal rotation of the shoulder.
External (lateral) rotation of the shoulder is facilitated by which muscles?
External (lateral) rotation of the shoulder is facilitated by infraspinatus (chief external rotator), teres minor and deltoid muscles. Infraspinatus and teres minor are posterior rotator cuff muscles.
what is ‘trigger finger’ caused by
“Trigger finger” or stenosing tenosynovitis is typically caused by inflammation of the flexor digitorium tendon and its sheath
Stenosing tenosynovitis typically occurs in young adults to middle-aged patients who have occupations or hobbies that involve repetitive and prolonged gripping and grasping
Trigger finger can be caused by other things that disrupt the gliding of the tendon within the sheath, such as a leiomyoma.
what muscles carry out
- extension of elbow
- flexion of elbow
Extension of the elbow is carried out by triceps brachii and anconeus, flexion of the elbow is carried out by biceps brachii, brachialis, and brachioradialis.
Pain and tenderness upon palpation of the anatomical snuffbox may indicate a fracture to what bone?
Pain and tenderness upon palpation of the anatomical snuffbox may indicate a scaphoid bone fracture.
what cells is alkaline phosphatase made by and what does its level indicate?
alkaline phosphatase is made by osteoblasts (marker of how active osteoblasts are) + by the liver
Bone mineral density can be expressed as either the T or Z score. What does each mean?
T-score= number of standard deviations from the mean young (30yr) same gender + ethnicity
Z-score= number of standard deviations from same age, gender + ethnicity (used when u have osteoporosis in a young person)
n.b. WHO-T score is 25% lower than average= osteoporosis diagnosis
what is the precursor to osteoporosis?
precursor to osteoporosis is osteopenia (low bone density)
Dual energy X-ray absorptiometry/ DEXA scans are performed on areas of the body with high levels of trabecular bone (because high turnover rate means pathological changes seen here first); what 3 areas are the scans performed?
- neck of the femur
- lumbar vertebra (L1-L4)
- distal radius at wrist
bone biopsies are usually taken from what bone?
iliac crest
Osteoporosis; causes, symptoms, treatment
Osteoporosis= metabolic bone disease causing porous bone that can lead to fractures
1) Primary Osteoporosis: Age-related (postmenopausal women and elderly men)
2) Secondary Osteoporosis: Due to chronic conditions or medications (e.g., glucocorticoids, hyperthyroidism, malabsorption)
Risk Factors:
- Female gender, advanced age, family history
- Low body weight, smoking, alcohol abuse
- Vitamin D or calcium deficiency, sedentary lifestyle
Symptoms:
- Often asymptomatic until fracture occurs
- Common fractures: Hip, spine, wrist
- Chronic pain, loss of height, kyphosis (hunchback)
Diagnosis:
- DEXA scan (T-score ≤ -2.5 confirms osteoporosis)
- Lab Tests: Calcium, vitamin D, thyroid, renal function
Treatment:
- Adequate calcium (1200 mg/day) and vitamin D (800-1000 IU/day)
- 1ST LINE MED: Bisphosphonates (e.g., Alendronate, Risedronate): First-line for reducing fracture risk
- Denosumab injection every 6 months: Monoclonal antibody binds to RANKL ; For patients intolerant to bisphosphonates
- Selective Estrogen Receptor Modulators (SERMs): For postmenopausal women
- Teriparatide (PTH analog) & Romosozumab: For severe cases
- Strontium ranelate (increases expression of Wnt proteins, activates CaSR= increased collagen type I synthesis)
Osteomalacia; causes, symptoms, treatment
Osteomalacia= a metabolic bone disease characterized by defective bone mineralization leading to soft, weak bones.
Causes/Risk Factors:
- Vitamin D Deficiency: Most common cause (dietary lack, malabsorption, lack of sunlight)
- Chronic Kidney Disease (CKD): Impaired vitamin D activation
- Hypophosphatemia: Renal phosphate wasting or poor intake
Medications: Anticonvulsants (phenytoin), aluminum-containing antacids
Genetic Disorders: Rare forms (e.g., hereditary hypophosphatemic rickets)
Symptoms:
- Bone pain and tenderness (especially hips, legs, and ribs)
- Muscle weakness (proximal myopathy)
- Difficulty walking, waddling gait
- Fractures and bone deformities
Diagnosis:
Laboratory Tests:
- Low serum calcium and phosphate, high alkaline phosphatase (ALP)
- Low vitamin D (25-hydroxyvitamin D < 20 ng/mL)
Radiology: Looser’s zones or pseudofractures on X-rays
Treatment:
-Vitamin D Supplementation:
Cholecalciferol (D3) first-line (n.b. use Ergocalciferol (D2) for vegans)
Calcitriol in CKD or hypoparathyroidism
Calcium and Phosphate Supplements: As needed
Treat Underlying Causes: CKD management, phosphate binders
Lifestyle Modifications: Sunlight exposure, dietary adjustments
Prevention:
- Adequate vitamin D and calcium intake
- Regular sunlight exposure
intermittent exposure to PTH activates – more than —
intermittent exposure to PTH activates osteoblasts more than osteoclasts
Pagets disease
Definition: A chronic bone disorder characterized by excessive bone remodeling, where bone becomes enlarged, weak, and structurally abnormal
Causes/Risk Factors:
Genetic Factors: SQSTM1 gene mutations (codes for protein p62/ sequestosome 1) linked to increased osteoclast activity
Viral Hypothesis: Possible link to paramyxovirus infection (e.g., measles virus remnants in osteoclasts)
Age & Gender: More common in older adults (>55 years), men > women
Ethnicity: Higher prevalence in European populations
Pathology:
Excessive osteoclastic resorption
Compensatory disorganized osteoblastic formation
Symptoms:
- Often asymptomatic, diagnosed incidentally on imaging or labs
- Bone pain (pelvis, spine, skull, long bones)
- Bone deformities (bowing of legs, skull enlargement)
- Increased risk of fractures
Diagnosis:
Laboratory Tests:
- Elevated serum alkaline phosphatase (ALP) with normal calcium and phosphate
Imaging:
- X-ray: Cortical thickening, bone expansion, lytic and sclerotic lesions
Treatment:
- Bisphosphonates (First-line therapy):
- Zoledronic acid (most effective, single-dose infusion)
- Alendronate, risedronate (oral options)
- Pain Management: NSAIDs, analgesics
- Calcium & Vitamin D Supplementation: To prevent secondary deficiencies
monitor ALP levels regularly through life
3 phases of Pagets disease
1) Lytic Phase (Initial)
- Excessive bone resorption due to giant, hyperactive osteoclasts (possibly triggered by viral infection/genetics).
2) Mixed Phase (Compensatory/Proliferative)
- Disorganized bone formation attempts to compensate for resorption → “Mosaic” pattern of woven bone.
3) Sclerotic Phase (“Burnt Out”)
- Dense, sclerotic “Pagetic bone” with:
- Thickened, irregular trabeculae
- Fibrovascular marrow replacement
- Prominent cement lines
Legg-Calvé-Perthes disease
Legg-Calvé-Perthes disease, also known as Perthes disease, is a childhood hip disorder where the blood supply to the femoral head (the ball of the hip joint) is temporarily disrupted, leading to bone death, collapse, and potential long-term hip problem
What is Thomas’ Test used to assess, how is it performed, and what are the key interpretations? What patients cant have the test performed on them?
DO NOT PERFORM THOMAS’ TEST ON PATIENT WITH HIP REPLACEMENT! (risk of dislocation)
Purpose: Detects fixed flexion deformity of the hip (e.g., iliopsoas tightness or contracture).
Contraindication: Do not perform in patients with hip replacements.
Steps:
- Place hand under the patient’s lumbar spine (assesses lordosis).
- Passively flex one hip maximally toward the chest.
- Observe the contralateral (opposite) hip.
Normal: Contralateral/other hip should remain on the bed (no deformity).
Abnormal: Contralateral/other hip raises off the bed → fixed flexion deformity (e.g., iliopsoas tightness).
Key Insight:
- The test eliminates lumbar lordosis to isolate hip flexion deformity.
- Lifting of the opposite hip indicates loss of extension in that hip. (so u are lifting leg on ‘healthy side’ and looking at hip on other side to see if its fucked)
What is the purpose, technique, and interpretation of the Straight Leg Raise (SLR) test?
Purpose: Assesses sciatic nerve compression (L4–S1), commonly due to:
- Lumbar radiculopathy (e.g., herniated disc).
- Piriformis syndrome (sciatic nerve entrapment).
Technique:
- Patient lies supine.
- Passively raise the straightened leg (30°–70° range).
- Observe for reproduction of radicular pain (shooting down the leg). if there is pain ask them to dorsiflex at the height they feel the pain and if it gets worse this will confirm its sciatic (Braggard)
Confirmatory maneuvers:
Bragaard’s Test: Dorsiflex the foot during SLR → ↑ sensitivity.
Pain relief on knee flexion → supports neurogenic etiology.
Interpretation:
Normal: No pain, full ROM (Range Of Motion)
Abnormal: Radicular pain (suggests nerve root irritation).
How is the Painful Arc Test performed and what does it indicate?
Method: Patient raises arm sideways (0-180°).
Positive: Pain between 60-120° = subacromial impingement. Pain after 120° = AC joint issue.
What does Neer’s Test check, and how is it done?
Method: Examiner lifts patient’s straight arm up while holding the scapula.
Positive: Pain at top = subacromial impingement (causes shoulder pain, occurs when rotator cuff muscles’ tendons are compressed as they pass through the area beneath the acromion bone aka subacromial space)
Describe the Hawkins-Kennedy Test.
Method: Arm bent 90° at shoulder/elbow, palm down. Examiner twists arm inward.
Positive: Pain = supraspinatus tendon impingement.
What does the Empty Can Test assess?
Method: Arms at 90°, thumbs down (like emptying a can). Resist upward movement.
Positive: Pain/weakness = supraspinatus tear.
What muscle does Gerber’s test target?
Method: Hand on lower back, push backward against resistance.
Positive: Pain/weakness = subscapularis tear.
What does the Scarf Test check?
Method: Bring arm across chest (like a scarf).
Positive: Pain = AC joint problem (e.g., arthritis).
What does the Speed Test diagnose?
Method: Arm forward, palm up. Resist downward push.
Positive: Pain = biceps tendonitis or labral tear.
First-line medication for each of the following:
- pagets disease of bone
- osteoporosis
- osteomalacia
pagets= IV Zoledronic acid 5mg infusion (bisphosphonate)
osteoporosis= alendronate or risedronate (bisphosphonate)
osteomalacia= Vitamin D Supplementation – Cholecalciferol (Vitamin D3)
What are the vascular and neural properties of normal articular cartilage? What is the structure of normal articular cartilage?
Normal articular cartillage is avascular (no blood supply) and aneural (no nerve supply)
normal articular cartillage:
Hyaline cartilage: 2–4 mm thick, avascular/aneural, low-friction surface.
ECM composition: Type II collagen (strength) + proteoglycans (resilience/squishy), maintained by chondrocytes.
Tidemark: Boundary between uncalcified and calcified cartilage.
what cells make extracellular matrix in
- bone
- cartillage
bone= OSTEOBLASTS make the ECM in bone by producing;
- organic matrix (called osteoid); made of type I collagen, osteocalcin, osteonectin, and proteoglycans
- Once the osteoid is laid down, osteoblasts help mineralize it with calcium and phosphate
cartillage= CHONDROCYTES make the ECM in cartillage by producing;
- Type II collagen
- Proteoglycans (like aggrecan)
What are the 3 phases of macroscopic cartilage degeneration in OA?
Fibrillation (surface splits).
Erosion/cracking (deep fissures).
Eburnation (bone exposure, polishing).
How does HMGB2 loss (natural part of ageing) contribute to OA?
With age or injury, HMGB2 levels decrease → chondrocytes start to die off.
HMGB2 (high-mobility group protein 2) loss=> Superficial chondrocyte death + progenitor cell loss → Reduced ECM synthesis → Cartilage disruption.
HMGB2 helps maintain the survival of chondrocytes in the superficial zone of articular cartilage.
summary:
↓ HMGB2
↓ Chondrocyte survival
↑ Cartilage degradation
↑ Risk of developing OA
What is the role of MMP-13 in normal cartilage vs. OA?
MMP-13 should NOT be present in normal cartilage
Osteoarthritis (OA):
MMP-13 overexpression:
Primary collagenase targeting type II collagen → catastrophic ECM degradation.
Driven by:
- Pro-inflammatory cytokines (IL-1β, TNF-α).
- Mechanical stress.
- Chondrocyte senescence.
Results in:
Cartilage fibrillation → eburnation.
Shift to weak type I collagen (fibrocartilage).
Clinical Relevance: MMP-13 is a therapeutic target (e.g., inhibitors in trials).
What are the key subchondral bone changes in osteoarthritis (OA)?
1) Cartilage erosion → Exposed bone (eburnation).
2) Microfractures of trabeculae due to abnormal loading.
3) Subchondral sclerosis: Increased osteoblast activity → thickened, dense bone.
4) Cyst formation: Focal pressure necrosis → “subarticular cysts.”
5) Vascular changes: Engorgement + slowed blood flow → bone marrow edema (painful!).
Mechanism:
- Biomechanical stress + inflammation → bone remodeling imbalance.
Clinical:
- Sclerosis/cysts visible on X-ray/MRI; marrow edema correlates with pain.
what are the molecular drivers of OA
Molecular Drivers:
TGF-β↑: Drives osteoblast activity → sclerosis
RANKL/OPG imbalance:
↑RANKL → Osteoclast activation → microfractures
↓OPG (osteoprotegerin) → Unchecked bone resorption
VEGF↑: Vascular invasion → edema & cysts
Pro-inflammatory cytokines (IL-1β, TNF-α):
Stimulate MMPs (e.g., MMP-13) → degrade cartilage-bone interface
Wnt/β-catenin pathway:
Dysregulation → abnormal bone formation
Clinical Link:
- Sclerosis/cysts seen on X-ray; marrow edema on MRI (pain correlate).
- Therapeutic targets: Anti-TGF-β, anti-RANKL (e.g., denosumab).
What do tendons attach?
What do ligaments attach?
tendons (a little less elastic than ligaments) attach Muscle ➝ Bone
ligaments attach Bone ➝ Bone
What is the difference between tendinitis and tendinosis?
✅ Tendinitis
* 🔥 Acute inflammation of a tendon
* Caused by microscopic tears
* No permanent structural damage to the tendon
* 📍 Common sites:
- Lateral epicondyle (tennis elbow)
- Achilles tendon
- Supraspinatus tendon
* ⚠️ Causes:
- Overuse
- Collagen disorders
- Renal dialysis (rare but recognized risk)
* 🧰 Treatment:
- RICE (Rest, Ice, Compression, Elevation)
- NSAIDs and analgesia
- Stretching and physiotherapy
- Surgery in refractory cases
- NICE management is often conservative, focusing on inflammation control and rehab.
🧱 Tendinosis
* 🕒 Chronic, degenerative condition from failed healing
* Histology: Disorganized collagen fibers
* Tendon appears thickened, rubbery, and scarred
* ❗️May lead to partial or full-thickness tendon tears
* Less responsive to anti-inflammatory treatment (as there is minimal inflammation)
Studies show altered cell morphology and increased matrix metalloproteinase (MMP) activity in tendinosis tissue.
🧠 Clinical Tip:
If symptoms have persisted for >6 weeks and imaging shows degenerative changes, think tendinosis, not tendinitis.
Etodolac drug mechanism of action (MoA)
Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain, and helps to relieve symptoms of arthritis (eg, osteoarthritis and rheumatoid arthritis), including inflammation, swelling, stiffness, and joint pain.
Etodolac MoA= works by inhibiting cyclooxygenase (COX) enzymes, specifically COX-2, which reduces the synthesis of prostaglandins, thereby alleviating pain, inflammation, and fever
difference between a direct + indirect enthesis
Direct Enthesis:
- Insertion shows a gradual transition (as in fibrocartilage)
- Better for high-stress areas; allows smooth force transfer
Indirect Enthesis:
- tendon/ligament attaches to periosteum or diaphysis, often via Sharpey’s fibers
- More abrupt; common in fibrous entheses
What is heterotopic ossification (HO)? How does COX-2 contribute to heterotopic ossification?
heterotopic ossification:
Pathologic bone formation in soft tissues (e.g., muscles, tendons) after trauma, surgery (e.g., hip arthroscopy), or neurologic injury.
Example: Seen in a 20-year-old post-hip arthroscopy (left side developed HO; right side had NSAID prophylaxis).
COX-2 2 contribution:
COX-2 → Prostaglandins (PGE₂) → Promotes:
Chondrocyte differentiation/hypertrophy (via VEGF, RANKL).
Angiogenesis & osteoclast recruitment → Fracture bridging.
Why are NSAIDs used to prevent HO?
NSAIDs (e.g., Etodolac) inhibit COX-2 → Reduce PGE₂ → Block:
Mesenchymal stem cell differentiation into osteoblasts.
Inflammatory signals (IL-1, IL-6) that drive HO.
Dose: Etodolac 600 mg daily for 2 weeks post-op (per case example).
What are Sharpey’s fibers?
They are strong collagen fibers (mainly type I collagen)
Anchor tendons, ligaments, and periosteum to bone
Insert deep into the cortical bone, ensuring stable attachment
Often found in indirect entheses (e.g. where the tendon inserts into the bone via the periosteum)
What is the pathogenesis of enthesitis?
1) Mechanical injury at the enthesis (bone-tendon junction) triggers stress sensing.
2) Inflammation: Transcortical vessels (TCVs) dilate, allowing immune cell efflux (e.g., neutrophils).
3) Mesenchymal stem cells (MSCs) proliferate and differentiate into osteoblasts.
4) New bone formation: Osteoblasts deposit bone at the enthesis, driven by inflammation and mechanical stress.
Key Players:
- Transcortical vessels (TCVs; small blood vessels crossing cortical bone at the enthesis): Activate vasodilation and immune cell recruitment.
- Mesenchymal stem cells (MSCs; Multipotent cells in bone marrow/entheseal tissues) → Osteoblasts: Drive pathologic bone formation.
Hypertrophic chondrocytes: May contribute to entheseal thickening.
Clinical Link: Seen in spondyloarthritis (e.g., ankylosing spondylitis).
CAUSES OF ENTHESITIS:
- recurring stress/ microdamage
- associated with HLA B27 anthropathies
What is the key difference between enthesophytes and osteophytes?
- Enthesophytes:
Origin: Form at the insertion site of tendons, ligaments, or joint capsules into bone.
Location: Do not involve the articular border (joint surface).
Associated with: Mechanical stress, enthesitis (e.g., spondyloarthritis).
- Osteophytes:
Origin: Arise from the articular cartilage border (joint margin).
Location: Project into the joint space.
Associated with: Osteoarthritis (OA), joint degeneration.
Key Distinction:
Enthesophytes = Tendon/ligament insertion (non-articular).
Osteophytes = Joint margin (articular cartilage).
Visual Clue:
Enthesophyte: “Where tendon meets bone.”
Osteophyte: “Where cartilage degenerates.”
What are the treatment options for enthesitis?
- Mechanical/Traumatic Enthesitis
- RICE (Rest, Ice, Compression, Elevation)
- NSAIDs (e.g., Ibuprofen, Naproxen) – First-line for pain/inflammation.
- Inflammatory/Autoimmune Enthesitis (e.g., Spondyloarthritis, Ankylosing Spondylitis)
- Disease-Modifying Anti-Rheumatic Drug (DMARDs): Sulfasalazine or Methotrexate (for peripheral joint involvement).
- Biologics:
Anti-TNF therapy (e.g., Adalimumab, Infliximab)
For severe, refractory cases. - Local Therapies:
Corticosteroid injections (short-term relief).
Hyperosmolar dextrose injections (prolotherapy, experimental).
Radiotherapy (rare, for resistant cases).
Key Points:
Anti-TNF can resolve inflammation and halt osteoproliferation (e.g., visible improvement in ankylosing spondylitis at 24 weeks).
HLA-B27+ patients often require systemic treatment (linked to autoimmune pathogenesis).
Visual Summary:
Mechanical → NSAIDs/RICE
Inflammatory → DMARDs → Anti-TNF
Clinical Pearl:
If enthesitis is part of ankylosing spondylitis, prioritize anti-TNF over local therapies.
What does DMARD stand for, and how is it used in enthesitis treatment?
DMARD = Disease-Modifying Anti-Rheumatic Drug
Purpose: Slows disease progression in inflammatory enthesitis (e.g., ankylosing spondylitis, psoriatic arthritis) by targeting the underlying immune dysfunction.
Types Relevant to Enthesitis:
Conventional DMARDs:
- Methotrexate (first-line for peripheral joint involvement). MoA; folate antagonist that inhibits dihydrofolate reductase (DHFR) -> this stops tetrahydrofolate production-> stops DNA synthesis/cell division
- Sulfasalazine (especially in axial spondyloarthritis with peripheral symptoms).
Biologic DMARDs:
Anti-TNF agents (e.g., Adalimumab, Infliximab) – For severe, refractory enthesitis.
Key Difference:
- NSAIDs (e.g., Ibuprofen) only reduce symptoms.
- DMARDs modify the disease course by suppressing inflammation.
Clinical Context:
DMARDs are used when enthesitis is part of systemic autoimmune disease (e.g., HLA-B27-associated spondyloarthritis).
What is Systemic lupus erythematosus? What are key signs/symptoms of SLE?
SLE= a chronic autoimmune disease causing multi-system inflammation due to immune complex deposition and autoantibodies (e.g., anti-dsDNA, anti-Sm).
clinical presentation of joint pain and stiffness, fatigue, headache, fever, weight loss, and a distinct rash on face common presentation.
Classic Triad:
1) Malar rash (butterfly rash).
2) Photosensitivity.
3) Non-erosive arthritis (Jaccoud arthropathy, 90% of patients).
Systemic Involvement:
- Renal: Glomerulonephritis.
- Hematologic: Anemia, thrombocytopenia.
- Neuropsychiatric: Cognitive dysfunction.
- Mucocutaneous: Oral ulcers, discoid rash, alopecia.
SLE is associated with alopecia, arthralgia, glomerulonephritis, and pleurisy.
What is Systemic lupus erythematosus (SLE) diagnosed? And what type of arthritis do these patients suffer from?
1) ANA positivity (>95% sensitive, but nonspecific).
2) Specific antibodies:
- Anti-dsDNA (SLE-specific).
- Anti-Smith (Sm) (highly specific).
N.B SLE is associated with alopecia, arthralgia, glomerulonephritis, and pleurisy.
arthritis= Jaccoud’s arthritis/arthropathy is a type of non-erosive arthritis seen in SLE
MNEMONIC; SOAP BRAIN MD;
Serositis → pleuritis, pericarditis
Oral ulcers
Arthritis → e.g. Jaccoud’s arthritis
Photosensitivity
Blood Disorders → anaemia, thrombocytopenia, leucopenia, lymphopenia
Renal Disorder → proteinuria, glomerulonephritis,
Antinuclear Antibodies (ANA) - positive
Immunological disorder → Anti-dsDNA, Anti-Sm, Antiphospholipid antibodies
Neurological disorder → seizures, psychosis
Malar (Butterfly) Rash
Discoid Rash
the following drugs are used in severe SLE (nephritis, CNS lupus) what is there MoA
- Belimumab
- Rituximab
Belimumab (fully human): Inhibits B-cell survival (BAFF/BLyS blocker).
Rituximab (chimeric i.e. mouse/human): Depletes B-cells (anti-CD20).
n.b. both are monoclonal antibodies (mAbs)
What happens to muscle fibers when a motor neuron is lost in adults?
Fibers become small/angulated; remaining motor axons sprout to re-innervate them, forming enlarged motor units. If re-innervation fails → group atrophy.
What links Congenital Fiber Type Disproportion (CFTD) to infantile hypotonia, and what are the key features?
Infantile Hypotonia (“floppy baby”):
- 15% are myopathic (e.g., CFTD).
- Biopsy shows small/round fibers + rare hypertrophic fibers.
CFTD comes in 2 Types:
- Classic (common): Small type 1 fibers, normal/large type 2.
- Rare form: Large type 1 fibers, small type 2.
Note: Hypotonia causes: 68% CNS, 15% muscle/nerve (e.g., CFTD), 17% unknown.
What is sarcopenia, and how does aging affect it?
Age-related muscle loss (0.5–5%/year after 50); type II fibers atrophy more. By 70, 40% mass may be lost.
Key features of polymyositis/dermatomyositis (aka inflammatory myopathies)?
Polymyositis and dermatomyositis are both autoimmune diseases causing muscle inflammation and weakness, but dermatomyositis also involves characteristic skin changes, like a rash, while polymyositis primarily affects muscles
Presentations:
- Proximal weakness, elevated CK, lymphocyte infiltration (CD8+ T cells in polymyositis).
- Dermatomyositis: Rash (heliotrope eyelids), anti-Jo1antibodies, subcutaneous calcifications.
TREATMENT IS HIGH DOSE CORTICOSTEROID (PREDNISOLONE) TILL CREATINE KINASE GOES BACK TO NORMAL
What is unique about Inclusion Body Myositis (IBM) biopsy findings?
Vacuoles, amyloid-like inclusions (β-amyloid, hyperphosphorylated tau proteins, apoliprotein E, presenillin 1, prion protein) deposited in muscles; affects finger/wrist flexors more than extensors.
IBM is the most common muscle disease of elderly it has poor prognosis; more common in males; mild elevation in creatine kinase, muscle weakness, dysphagia, loss of quadriceps reflex
What is Duchenne Muscular Dystrophy (DMD)?
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness caused by a mutation in the DMD gene which leads to the deficiency of the structural protein, dystrophin.
X-linked recessive; 1:3,500 males; proximal weakness by age 2; death by 30s; fibrosis/fat replace muscle; elevated CK.
histology: variation in myofibre size, with small fibres and large, rounded fibres. Furthermore, there is also increased fatty replacement of myofibres and regeneration and increased endomysial connective tissue between muscle fibres.
N.B. Dystrophin is key to the structural and functional integrity of the muscle fibres. The absence of dystrophin leads to damage of muscle cells followed by degeneration of muscle cells. The muscle regenerates new fibres which lead to the formation of many small muscle cells and replacement of muscle tissue by connective tissue.
Which drugs cause myopathies, and how?
Statins: Rhabdomyolysis (type II fibers).
Corticosteroids: Type II atrophy.
Alcohol: Acute/chronic proximal weakness.
Diagnostic criteria and proposed pathophysiology of fibromyalgia?
Widespread pain + 11/18 tender points; CNS sensitization (neurotransmitter/HPA axis dysfunction).
- 50% patients positive for antipolymer antibodies
80–90% female; treated with antidepressants (TCAs; amitriptyline first line) + exercise.
what is Spondyloarthritis and what gene is it associated with?
Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases that primarily affect:
- The spine (especially the sacroiliac joints)
- Entheses (where ligaments and tendons attach to bone)
- Peripheral joints (in some subtypes)
It’s a seronegative arthritis group (negative for rheumatoid factor, RF), often associated with the HLA-B27 gene.
Key Features of SpA:
- Inflammatory back pain (better with exercise)
- Morning stiffness >30 minutes
- Enthesitis (e.g., Achilles tendon)
- Dactylitis (“sausage digits”)
- Extra-articular: uveitis, psoriasis, IBD
- HLA-B27 positivity (not always, but common)
Skeletal muscle contains type I and type II muscle fibers. Explain the difference
Type I fibers:
- slow twitch
- aerobic metabolism
- red (darker when stained with NADH stain)
- With an ATPase stain at a pH of 9.4, type I fibers stain lightly compared to type II
- fatigue slowly
- contain large numbers of mitochondira
type II fibers (u lose these faster with age):
- fast twitch
- anaerobic metabolism
- white (paler when stained with NADH)
- With an ATPase stain at a pH of 9.4 type II fibers stain darker than type I
- fatigue rapidly
- contain low numbers of mitochondria
popliteal artery entrapment symptom
popliteal artery entrapment clinical symptom is cold feet following exercise, paraesthesia of the leg, calf numbness
what is the composition + appearance of the following:
- nucleus pulposus
- Outer ring of annulus fibrosus
- Inner ring of annulus fibrosus
Nucleus pulposus;
- Composition: predominantly type II collagen
- Abundant in chondrocytes
Outer ring of annulus fibrosus;
- Composition: predominantly type I collagen
- Appearance: oblong-shaped
Inner ring of annulus fibrosus;
- Composition: predominantly type II collagen
- Appearance: round-shaped
What are the key non-pharmacological treatments for osteoarthritis (OA)?
Exercise!! (local muscle strengthening, aerobic fitness)
Weight loss (aim for 5% loss if BMI ≥25)
Use of aids (walking sticks, orthopaedic insoles)
TENS for pain relief
Thermotherapy (heat/cold)
Mediterranean diet (anti-inflammatory foods)
What is the first-line pharmacological management for OA pain?
Paracetamol and/or topical NSAIDs.
If ineffective, switch to oral NSAID/COX-2 inhibitor e.g. celecoxib (lowest dose, shortest duration) + PPI.
Avoid long-term use due to comorbidities/side effects.
When is surgical referral considered for OA?
When pain/stiffness significantly impact quality of life (e.g., night waking because of pain will send them to orthopoedic team!). Options include:
- Arthroscopic lavage/debridement
- Joint replacement (last resort; 15–20-year lifespan)
- microfracture (drill holes into subchondral bone + drill the bone marrow pluripotent stem cells; stimulates repair of articular cartilage)
What are some emerging biological treatments for OA, and their limitations?
IL-1/TNF inhibitors (e.g., adalimumab) – Limited by variable low-grade inflammation.
TNF inhibition; Adalimumab (cost a lot)
Platelet-rich plasma (PRP) injections
Nerve Growth Factor (NGF) – Used in dogs and cats lol; awful adverse effects limit human use.
How does viscosupplementation work, and what are its pros/cons?
viscosupplementation:
Mechanism: Hyaluronic acid injections restore synovial fluid viscosity.
Pros: Pain reduction, delays joint replacement.
Cons: NHS rarely covers it; less effective in severe OA.
what are syndesmophytes?
Syndesmophytes are bony outgrowths, or calcifications, that form within the spinal ligaments (osteophytes of the spine basically)
what is polyarticular osteoarthritis aka polyarthritis
what mutations cause premature polyarthritis?
Polyarticular osteoarthritis, aka polyarthritis, refers to osteoarthritis affecting five or more joints simultaneously, characterized by pain, stiffness, and potentially inflammation, and can be either inflammatory or non-inflammatory
inherited type II collagen defects cause premature polyarthritis
why are women more susceptible to knee osteoarthritis?
because women have wider pelvis so femur has to angle more to get to knee joint; more weight on medial compartment of knee in females! This is calculated as the q-angle:
- a is line drawn from ASIS to center of patella
- a is line drawn from the tibial tuberosity to center of patella
normal q angle: between 15-20 (angle is bigger in females than males)
normal q angle male between 8-12
where do you find
- Herberden’s node
- Bouchard’s node
distal interpharengeal/DIP joint= Herberden’s node
proximal interpharengeal/PIP joint= Bouchard’s node
mnemonic:
Heberden’s = High up (DIP)
Bouchard’s = Below (PIP)
How can you tell the difference between Erosive OA and Rheumatoid Arthritis (RA)?
🦴 Erosive Osteoarthritis (EOA) (a rare type of OA):
- Affects DIP & PIP joints (causes bony nodules)
- Central erosions → “Gull-wing” sign on X-ray
- No systemic symptoms
- Sudden joint pain/swelling
- linked to dyslipidemia and metabolic syndrome
🧬 Rheumatoid Arthritis (RA):
- Affects PIP & MCP joints (causes soft tissue swelling)
- Marginal erosions, joint space narrowing
- Systemic symptoms (fatigue, morning stiffness >1 hr)
- Autoimmune disease
🔍 Why are they often confused with eachother?
- Both cause joint pain, swelling, and erosions
- Both can affect hand joints
N.B. EOA is LOCALISED INFLAMMATION OF HANDS WHEREAS RA IS SYSTEMIC INFLAMMATION
What is the mechanism of action of NSAIDs?
Inhibit cyclooxygenase (COX) enzymes, blocking prostaglandin synthesis from arachidonic acid.
COX-1 inhibition= ↓ Clotting (↓ TXA2), ↑ GI risk
COX-2 inhibition= ↓ Inflammation, pain, fever
How do steroids and NSAIDs differ in their anti-inflammatory mechanisms?
NSAIDs:
- Inhibit cyclooxygenase (COX) enzymes pathway (COX-1/COX-2).
- Block prostaglandin (PG) synthesis from arachidonic acid → reduce pain, fever, inflammation.
Example: Ibuprofen (reversible COX inhibition), aspirin (irreversible COX-1 inhibition).
Steroids (e.g., glucocorticoids):
- Bind intracellular receptors → regulate gene transcription.
- Downregulate phospholipase A2 (PLA2) → reduce arachidonic acid release → suppress both cyclooxygenase pathway which produces prostaglandins AND lypoxygenase pathway which produces leukotriene production.
- Broad anti-inflammatory effects: inhibit cytokines (IL-1, TNF-α), immune cell migration, and COX-2 expression.
Key Difference:
NSAIDs target downstream PG production (COX only), while steroids act upstream (PLA2 inhibition) and have broader immunosuppressive effects.
Compare COX-1 vs. COX-2 inhibitors with examples.
Non-selective (COX-1 & COX-2): Ibuprofen, naproxen, aspirin → GI/CV risks.
COX-2 selective: Celecoxib, etoricoxib → lower GI but ↑CV risk (e.g., rofecoxib withdrawn).
Aspirin: Irreversibly inhibits COX-1 (antiplatelet effect).
How do NSAIDs differ in their kinetic inhibition of COX?
Reversible competitive: Ibuprofen (short-acting).
Time-dependent reversible: Diclofenac (high affinity, slow dissociation).
Irreversible: Aspirin (covalent modification; platelet COX-1 inhibition lasts 7–10 days).
Explain the difference between 75mg aspirin and 300mg aspirin effects
Low-dose aspirin is cardioprotective (unique among NSAIDs). (only inhibits COX-1 i.e. antiplatelet at 75mg)
High-dose aspirin (300mg) behaves like other NSAIDs (↑ CV/GI risks) inhibits COX-2 i.e. anti-inflammatory as well.
Not a first-line painkiller due to bleeding risks (use paracetamol/NSAIDs instead).
What are the major actions of the following prostaglandins?
PGE₂
PGD₂
PGI₂ (Prostacyclin)
PGF₂α
TXA₂ (Thromboxane A₂)
PGE₂:
Vasodilation (renal), immunosuppression (↓ lymphocytes), pain sensitization, ↓ gastric acid, FEVER, uterine relaxation.
PGD₂:
Vasodilation, bronchoconstriction (10× higher in asthma).
PGI₂ (Prostacyclin):
Vasodilation (renal), antiplatelet, bronchodilation, ↓ gastric acid, pain sensitization.
PGF₂α:
Mixed vascular effects, bronchoconstriction, uterine contraction.
TXA₂ (Thromboxane A₂):
Vasoconstriction, pro-thrombotic (platelet aggregation), bronchoconstriction, uterine contraction.
mnemonics:
PGE₂ = FEVER” (Fever, Uterine relaxation, Gastric protection).
“PGI₂ vs. TXA₂” (Yin-Yang):
- PGI₂: Vasodilate + Antiplatelet.
- TXA₂: Vasoconstrict + Pro-thrombotic.
Asthma Triggers: PGD₂, PGF₂α, TXA₂ → bronchoconstriction.
COX catalyses the formation of prostaglandins from what substrate
the subrstrate= arachidonic acid
COX catalyses the formation of prostaglandins from arachidonic acid
What is paracetamol’s drug class and its proposed mechanism of action?
Paracetamol (acetaminophen)= non-opioid analgesic & antipyretic (NOT NSAID)
Mechanism:
- Central COX-2/COX-3 inhibition in brain/spinal cord → ↓ PGE₂ in hypothalamus (antipyretic/analgesic)
Alternative pathways:
- TRPV1 channel modulation (pain)
- Serotonergic (5-HT) system effects
- Endocannabinoid system activation
- Weak/no peripheral COX inhibition → No GI/platelet effects
Key Distinction:
Unlike NSAIDs: No significant COX-1 inhibition → safer for GI/bleeding risks
Unlike opioids: No μ-opioid receptor activity → no respiratory depression
What are the key structural features of a normal synovial joint?
Synovium: 1-3 cell layers (Type A macrophages + Type B fibroblasts)
Subintima: Loose connective tissue with fenestrated capillaries
Synovial fluid: Ultrafiltrate of plasma + hyaluronan/lubricin
Functions: Lubrication (“weeping”), nutrient diffusion, low friction
What drives joint destruction in RA?
Pannus formation: Invasive synovial tissue (Th17 cells → IL-17 → RANKL → osteoclasts)
Autoantibodies: RF/ACPAs → osteoclast activation + NETosis
Cytokines: TNF-α/IL-1/IL-6 → MMPs → cartilage/bone erosion
Dkk-1/sclerostin → inhibits osteoblasts
Match these mediators to their role in RA:
- IL-17
- RANKL
- Anti-citrullinated protein antibodies (ACPAs)
- NETosis
IL-17: Th17/ CD4+ T cells → synovitis → RANKL expression
RANKL: Osteoclast differentiation → bone erosion
ACPAs: Bind osteoclasts → IL-8 → pain/neutrophil recruitment
NETosis: Neutrophil death → autoantigen release → more ACPAs
Why is pannus destructive in RA?
pannus= (like a tumour) abnormal, hyperplastic synovial tissue that forms in RA joints (caused by chronic synovitis activating osteoclasts)
Contains Th17 cells, plasma cells, fibroblasts
Secretes:
- MMPs (cartilage/bone degradation)
- RANKL (osteoclast activation)
- Dkk-1 (blocks bone repair)
Invades bone at synovium-bone interface
n.b. pannus is destructive (secretes cytokines, autoantibodies) + is involved in the erosion of articular cartilage + bone, eventually destroying the joint
How does synovial fluid differ in RA vs. normal?
Normal Synovial Fluid:
- Appearance: Clear, pale yellow
- WBC count: <200/mm³ (mostly phagocytes)
- Viscosity: High (intact hyaluronan)
- Mucin clot test: Forms a firm clot
RA Synovial Fluid:
- Appearance: Cloudy/yellow (inflammatory)
- WBC count: >2000/mm³ (neutrophil-predominant)
- Viscosity: Low (hyaluronan degraded by free radicals)
- Mucin clot test: Friable or no clot (due to inflammation)
In RA there are 2 types of fibroblast causing havoc, what is there unique role:
- lining fibroblasts
- subintimal fibroblasts
lining fibroblasts= bone erosions
subintimal fibroblasts= cytokines + inflammation
What drives pannus formation in RA?
Invasive synovial tissue fueled by Th17 cells (→ IL-17 → RANKL → osteoclasts).
Activated synovial fibroblasts stimulate osteoclasts and MMPs (→ cartilage/bone erosion).
How do autoantibodies worsen RA?
RF/ACPAs → osteoclast activation + NETosis (neutrophil death → autoantigen release → more ACPAs).
ACPAs bind osteoclasts → IL-8 → pain/neutrophil recruitment.
Key cytokines in RA and their effects?
TNF-α/IL-1/IL-6 → MMPs → cartilage/bone erosion.
IL-17 (Th17 cells) → synovitis + RANKL → osteoclasts.
What inhibits bone repair in RA?
Dkk-1/sclerostin block Wnt signaling → suppress osteoblasts.
Role of immune cells in RA?
B-cells → produce RF/ACPAs.
T-cells (Th17) → pro-inflammatory cytokines (IL-17, TNF-α).
Macrophages → cytokines + can become osteoclasts.
Neutrophils → NETosis (→ autoantigens) + ROS damage.
How do neutrophils contribute to RA initiation?
NETosis: Releases citrullinated proteins (via PAD4) → triggers ACPAs.
Synovial fluid neutrophils are activated, prolonged survival, and secrete inflammatory mediators.
Links: Smoking/infection → NETosis → autoantigen exposure → ACPA production.
How do ACPAs drive joint damage?
Bind osteoclasts → promote bone erosion.
Enhance NETosis → perpetuates autoantigen release.
Activate complement → chronic inflammation.
What are the key autoantibodies in RA, and their clinical significance?
ACPAs: 98% specific for RA; predict progression (90% of ACPA+ asymptomatic patients develop RA within 3 years).
Rheumatoid Factor (IgM): Less specific (60-80% of RA patients); correlates with severity.
Anti-CarP: Associated with smoking; 96% specificity.
Triple positivity (RF/ACPA/A-CarP): Nearly pathognomonic for RA.
PAD4 autoantibodies= associated with more severe, erosive RA that persists despite treatment with TNF inhibitors
First-line treatment for RA and how autoantibodies guide therapy?
1) Methotrexate/MTX (DMARD): Works in seropositive/negative RA; higher doses may be needed for ACPA+ patients.
2) Triple therapy: MTX, cyclosporine (immunosuppresant) + prednisolone (corticosteroid)
Biologicals:
- B-cell/T-cell targeted (e.g., rituximab) → better for seropositive RA.
- Cytokine inhibitors (anti-TNF/IL-6) → effective in both subtypes.
Relapse risk: Increases with number of AMPAs (≥5 AMPAs → 55% relapse risk).
Extra-articular manifestations of RA?
Anaemia of chronic disease: Normocytic → hypochromic (blunted EPO, iron dysregulation).
Rheumatoid nodules: Subcutaneous, non-tender (20% of patients; linked to severe disease).
Systemic effects: Fatigue, osteoporosis, thrombocytosis (due to IL-1/IL-6/TNF-α).
Emerging therapies targeting NETosis in RA?
PAD4 inhibitors (e.g., GSK484, Cl-amidine).
DNase I, myeloperoxidase (MPO) inhibitors.
Goal: Reduce autoantigen release and inflammation.
What is the DAS-28 score in RA?
Quantitative measure of RA activity (tender/swollen joints, ESR/CRP, patient GH).
Scores: ≤2.6 = remission; >5.1 = high activity.
Use: Guides treatment decisions and monitors therapy response.
What is the typical presentation and management of pediatric flat foot?
Most babies have flat feet (fat pad); arches develop with walking.
Persistent cases: “weak ankles,” weight on medial foot.
Tx: Orthotics or surgery if severe.
When is toe walking pathological, and how is it managed?
Normal in toddlers; resolves by age 2.
Pathologic if persistent: Cerebral palsy, DMD, or idiopathic.
Tx: Casting, physiotherapy, or calf muscle surgery.
What are key features and treatment of club foot (talipes equinovarus)?
Presentation:
Fixed varus (inward) and equinus (downward) deformity of the foot.
Often with calf underdevelopment.
Involves adduction and plantarflexion of one or both feet.
Epidemiology:
- Fairly common
- Twice as common in males
~50% bilateral
Associations:
- Breech presentation
- Oligohydramnios
- Trisomy 18 (Edwards syndrome)
Mnemonic – CAVE:
- Cavus – High medial arch due to plantarflexed 1st metatarsal
- Adductus – Forefoot turns inward (midfoot)
- Varus – Hindfoot turns inward (calcaneus)
- Equinus – Ankle in plantarflexion (toes point downward)
Treatment:
! Ponseti method: Serial casting and manipulation over ~5 weeks
Near 100% success rate if started early
How is Congenital Hip Dysplasia (CHD) diagnosed and treated in infants?
Risk factors: Female, breech, oligohydramnios, family history, 1st born.
Tests: Barlow (adduct + push; dislocate hip), then do Ortolani (abduct hips to try and relocate hip), ultrasound (Graf grading= 60 degrees or more is normal Grad I graf… anything below 60 degrees is pathological).
GALEAZZI SIGN= one knee is longer than other when you bend leg
Tx: Most spontaneuosly resolve by 2-8wks, Pavlik harness puts bby in abduction + hip flexion) (0-6 months); spica (plaster cast in abduction + hip flexion)/open reduction if older.
if all this doesn’t work= osteotomy
What is Perthes disease, and how is it managed?
AVN of femoral head, ages 4-8, ♂ >♀.
Tx: Observation (<5yo), braces, or osteotomy (older).
What are the key points about SUFE (Slipped Upper Femoral Epiphysis)?
What are the key points about SUFE (Slipped Upper Femoral Epiphysis)
Who: Obese adolescents/ puberty (♂ >♀), often bilateral, more common on left hip
Etiology: Salter-Harris type I fracture.
Tx: Surgical fixation (screws), prophylactic pinning.
memory tip: its like the ice cream fell off the cone
What causes Blount’s disease, and how is it treated?
Causes tibia varus/ Tibia vara from growth plate dysfunction (obesity risk)
Tx: Bracing (early), osteotomy (if progressive).
What is the cause and management of Osgood-Schlatter?
Traction apophysitis of tibial tubercle (10-15yo).
Tx: Rest, NSAIDs, physiotherapy (self-limiting).
What is Severs disease, and who is at risk?
Calcaneal apophysitis (painful inflammation of the growth plate in the heel bone/ aka calcaneus) from running/jumping.
Sx: Heel pain worsened by activity.
Tx: Rest, heel pads, stretching.
Compare Kohler’s and Kienbock’s diseases.
Kohler’s: AVN of navicular (foot bone) (4-7yo, ♂ >♀).
Kienbock’s: AVN of lunate (wristbone) (wrist pain, ↓grip).
what is a Boutonniere Deformity characterised by + causes
A Boutonniere Deformity is a clinical sign characterised by:
- Proximal Interphalangeal (PIP) → flexion
- Distal interphalangeal (DIP) → hyperextension
Mechanism:
A tear of the central slip of the extensor tendon over the PIP joint.
Causes:
- Rheumatoid Arthritis
- Trauma
- Genetic Conditions (Ehlers-Danlos Syndrome)
calcaneal avulsion fractures are caused by the contraction of which muscles?
Calcaneal avulsion fractures are caused by the contraction of gastrocnemius and soleus muscles
Herniation of an intervertebral disc can compress nerve roots exiting the spine. In particular, entrapment of the S1 spinal nerve can lead to:
Pain in the posterior aspect of the leg (the sacroiliac joint, the hip and the posterolateral parts of the thigh and the leg)
Numbness in the posterior aspect of the leg (the calf and the lateral part of the heel)
Atrophy of the gastrocnemius and soleus muscles
Loss of plantar flexion
Loss of the Achilles reflex
Muscles of the Posterior Compartment of the Thigh
Overview
Collectively known as “the hamstrings”.
3 Muscles:
- Biceps Femoris
- Semitendinosus
- Semimembranosus
Function:
- Flexion of the Knee Joint
- Extension of the Hip Joint
- Reinforcement of Collateral Ligaments of Knee
Origin & Insertion:
All hamstring muscles (except for the short head of the biceps femoris) originate from the ischial tuberosity in the hip.
The common origin and insertion points on the medial and lateral aspects of the knee mean that the hamstrings form the superior part of the diamond shape surrounding the popliteal fossa.
what nerve is most susceptible to injury if the medial epicondyle is damaged?
The ulnar nerve is most susceptible to injury at the medial epicondyle.
clavicular elevation is a sign of what joint dislocation?
Clavicular elevation is a pathognomonic sign of acromioclavicular joint dislocation.
what bacterium causes gas gangrene
Clostridium perfringens is a bacterium responsible for causing gas gangrene.
Septic arthritis is an inflammatory condition caused by infection of the joint; what bacterium is usually responsible?
Septic arthritis is an inflammatory condition caused by infection of the joint. In the majority of people, the causative organism is Staphylococcus aureus
a fall on an outstretched hand when the wrist is in extension will most likely result in what fracture? VS a fall on an outstretched hand when the wrist is in flexion
fall on an outstretched hand when the wrist is in extension = Colles’ fracture; this patient will have a dinner-fork deformity A fracture of the distal radius (metaphysis part), 2-3cm from the articular surface. It is the most common wrist fracture (75% of wrist injuries).
fall on an outstretched hand when the wrist is in flexion= Smith’s Fracture. A fracture of the distal radius caused a fall on an outstretched hand whilst the wrist is flexed, whereby the forearm becomes angled anteriorly (volar) relative to the wrist.
What are the following fractures:
- Boxer’s fracture
- Galeazzi fracture
- Pott’s fracture
- Smith’s fracture
Boxer’s Fracture → a fracture of the 5th metacarpal bone (or sometimes the 4th metacarpal bone) of the hand.
Galeazzi Fracture →a fracture of the distal part of the radius with dislocation of the distal radioulnar joint.
Pott’s Fracture → a fracture affecting one or both of the malleoli.
Smith’s Fracture → a fracture of the distal radius caused a fall on an outstretched hand whilst the wrist is flexed, whereby the forearm becomes angled anteriorly (volar) relative to the wrist.
What is Pseudogout (Calcium Pyrophosphate Deposition Disease)?
Pseudogout is a type of arthritis that is caused by the accumulation of calcium pyrophosphate crystals, which deposit in soft tissues and joints.
This results in inflammation of the joints, causing joint damage and pain. Joint involvement is typically symmetrical and a layer of calcification can often be seen between articulating surfaces (as shown in this image), which will cause narrowing of the joint space.
Subchondral cysts, can also be seen on an X-ray as radiolucent regions within the bone.
Key Note: The knee joint is the most commonly affected site in pseudogout.
which pathogen causes Lyme disease?
caused by bacteria; Borrelia Burgdorferi
The classical sign of Lyme disease is an expanding target-like/bull’s eye rash, known as ‘Erythema migrans’. The Borrelia genus of bacteria is the causative agent of Lyme disease.
what is the classical triad of reactive arthritis (Reiter’s syndrome)
conjunctivitis, urethritis (or cervicitis in women), and arthritis
CAN’T SEE, CAN’T PEE, CAN’T CLIMB A TREE
usually caused by Sterile inflammation post-GI/GU infection (Salmonella, Chlamydia). HLA-B27 linked (60-80%).
differentials from septic arthritis: in reactive arthritis there is NO FEVER, normal blood glucose.
Whereas in septic arthritis patient has fever and low blood glucose
Septic arthritis
septic arthritis:
- Bacterial infection (S. aureus, N. gonorrhoeae). Medical emergency
- Monoarthritis (knee/hip), fever, hot/swollen joint, systemic symptoms
- WBC >50,000/mm³ (often >100K), culture+ (50-70%), low glucose
- ↑CRP/ESR, blood cultures+ (50%). MRI: Bone edema/abscess
- IV antibiotics (vancomycin + ceftriaxone) + urgent drainage
mnemonic “SEPTIC”: Sudden, Elevated WBC, Purulent, Temperature, Immunocompromised, Culture+
What are the two main classes of DMARDs?
Conventional: Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide (aka A77 1726) .
Biologicals: TNF-α inhibitors, IL-1/6 blockers, B/T-cell modulators, JAK inhibitors
Key facts about Methotrexate (MTX) in RA?
1st-line, weekly oral (start 5-10mg → max 20-25mg).
PREGNANCY TEST BEFORE U START; KNOWN TERATOGEN
comes as tablet or IV
MOA: Folic acid antagonist → inhibits DHFR which stops tetrahydrofolate production → inhibits DNA/RNA synthesis, ↓IL-1/NF-κB.
SEs: Hepatotoxicity, myelosuppression (monitor LFTs/CBC q1-3mo).
Pregnancy contraindicated.
How does sulfasalazine work?
Gut bacteria split it into sulfapyridine (systemic) + 5-ASA (gut anti-inflammatory).
MOA: ↓Superoxide radicals, cytokines (IL-8), IgM/IgG.
used in leaky gut syndrome; e.g. in patients with ulcerative colitis + also treats ulcerative colitis.
Hydroxychloroquine; mechanism + use
Anti-malarial; ↑lysosomal pH → blocks TLR9 (↓dendritic cell activation).
Slow onset (12 weeks); used for mild RA/SLE.
TNF-α Inhibitors; examples + key features
Etanercept: Fusion protein (TNF-R2 + IgG1), weekly SC.
Infliximab: Chimeric mAb, IV q2-6wks.
Adalimumab: Human mAb, SC q2wks.
SEs: ↑Infection risk (TB reactivation).
Compare anakinra vs. canakinumab (IL-1 inhibitors)
Anakinra: IL-1 receptor antagonist, daily SC.
Canakinumab: mAb vs. IL-1β, off-label for gout/autoimmune
How does rituximab work?
Anti-CD20 mAb → B-cell depletion (lasts 6-12mo).
Used with MTX; effects seen at 3 months.
What is abatacept’s mechanism?
CTLA-4-Ig fusion → blocks CD80/86 on APCs, preventing T-cell co-stimulation.
IV monthly; slower onset than TNF inhibitors
IL-6 & JAK Inhibitors; drugs used in RA?
Tocilizumab: Anti-IL-6R mAb, IV monthly.
JAK inhibitors (tofacitinib): Oral, rapid onset, comparable to TNF blockers.
How do Anti-drug antibodies (ADAs) affect biologics?
Neutralizing: Block drug action.
Non-neutralizing: ↑Clearance (immune complexes).
Rheumatoid arthritis diagnostic criteria: 2020 ACR/EULAR Criteria for RA
Total score ≥6/10 points = RA
1) Joint Involvement (0-5 points)
- 1 large joint= 0
- 2-10 large joints = 1 point
- 1-3 small joints = 3 points
- >10 joints (at least 1 small joint) = 5 points
2) Serology (0-3 points)
- Negative RF + negative ACPA = 0
- Low positive RF or low positive ACPA= 2
- High positive RF or high positive ACPA= 3
3) Acute Phase Reactants (0-1 point)
- Normal CRP/ESR = 0
- Elevated CRP/ESR = 1
4) Duration of Symptoms (0-1 point)
<6 weeks = 0
≥6 weeks = 1
leflunomide aka A77 1726 (2nd line DMARD) mechanism of action
Leflunomide is metabolized to its active form A77 1726, which inhibits dihydroorotate dehydrogenase (DHODH) — a key mitochondrial enzyme in the de novo pyrimidine synthesis pathway.
➡️ This inhibition reduces uridine monophosphate (UMP) synthesis, leading to:
Decreased proliferation of activated T and B lymphocytes
Reduced production of autoantibodies and inflammatory cytokines
➡️ Overall, this results in immunomodulatory and anti-inflammatory effects in autoimmune diseases like rheumatoid arthritis.
first-line treatment for SLE (systemic lupus erythematosus)
1) Hydroxychloroquine (anti-malarial) safe in pregnancy
others: prednisolone, MTX, azathioprine (steroid-sparing), Belimumab (NICE only fund if pregnant, kidney or liver damaged)
What is the mechanism of action and clinical use of Abatacept?
Mechanism of Action:
🔹 Abatacept is a fusion protein (CTLA-4 linked to IgG1 Fc region)
🔹 Binds to CD80/86 on APCs, blocking interaction with CD28 on T-cells
🔹 Inhibits the second co-stimulatory signal required for full T-cell activation
🔹 Result: Decreased T-cell activation, reduced autoimmune inflammation
Dosage:
💉 IV infusion (30 min–1 hr), once monthly; weight-based
⏱ Onset of effect: ~3 months
Clinical Use:
🦠 Moderate to severe rheumatoid arthritis (RA)
🧒 Juvenile idiopathic arthritis (JIA)/ oligoarthritis
➡️ Used in patients with inadequate response to DMARDs
Related Drug:
🔹 Belatacept – similar structure, used in transplant rejection; blocks T-cell costimulation
Why is cartilage repair limited in OA?
Avascular tissue, few reserve chondrocytes, poor nutrient supply
How does RA cause anemia?
Anemia of chronic disease: blunted EPO, iron dysregulation, shortened RBC lifespan (normocytic → microcytic in severe cases)
How do OA and RA differ in joint distribution?
OA: asymmetric, weight-bearing joints (knees/hips).
RA: symmetric, small joints (PIPs/MCPs).
What is “pannus” in RA?
Pannus= (CD4+) Inflamed synovial tissue invading cartilage/bone , driven by cytokines (TNF, IL-17, RANKL)
Why might RA patients develop OA?
Chronic joint damage from inflammation accelerates degenerative changes
Name a cytokine targeted in RA treatment
TNF (adalimumab), IL-6 (tocilizumab), IL-17 (secukinumab)
which HLA is the main genetic risk factor for developing rheumatoid arthritis (RA)
The HLA-DRB1 gene, specifically alleles containing the “shared epitope” (SE), is the strongest known genetic risk factor for rheumatoid arthritis (RA)
What class of biological is the only one that can be taken orally?
Janus kinase (JAK) inhibitors can be taken orally
In polymyositis, what are the majority of the cells found between the muscle fibers?
Lymphocytes (CD8⁺)
where is the epiphyseal plate located between in children
Growth Plate (Epiphyseal Plate)
Located between the metaphysis and epiphysis in children
Responsible for longitudinal bone growth
Closes after puberty → becomes the epiphyseal lin
Is a bursa the same as a synovial joint?
No!
Bursa:
A tiny, fluid-filled sac; acts like a cushion between bones, tendons, and muscles.
Purpose: Reduces friction (e.g., stops your shoulder from grinding when you lift your arm).
Problem: Bursitis = swollen/painful bursa.
Synovial Joint:
The actual joint where bones meet (e.g., knee, shoulder).
Contains synovial fluid for smooth movement.
Problem: Arthritis = joint inflammation.
Analogy:
Bursa = Grease packet near a hinge (prevents rubbing).
Synovial joint = Hinge itself (allows movement).
Why It Matters:
Bursitis hurts the cushion (bursa), while arthritis hurts the joint (synovial membrane).
Example:
Shoulder Bursitis: Pain when raising your arm (bursa inflamed).
Shoulder Arthritis: Pain even at rest (joint cartilage worn out)
