GEP (Life Structure) Week 1 Flashcards
What are the different types of bones
What is the structure of the long bone and how its catogarised
The periosteum is a highly vascularised and innervated membrane that covers the bone.
There are 2 types:
-Cortical
-Spongy (cancellous - trabecular bone)
Yellow and red marrow are the functions of haematopoiesis and bone metabolism
Epiphysis – end of the bone, contains red bone marrow
Metaphysis – shaft flares and meets epiphysis to form ‘growth plate’
Diaphysis – hollow tubular shaft connecting proximal and distal ends, contains yellow bone marrow
Physis is the boundry inbetween the metaphysis and epiphysis in kids, close around 14-15 in kids. Its where the bone grows
You’ll hear ‘-physis’ a lot = “to grow)
Symphysis = to grow together
Epi = upon, in addition to (like epinephrin)
Diaphysis = grow through
Metaphysis = change – like
What are the 3 types of joints
Fibrous
Cartilagenous
Synovial
Give an overview of fibrous joint and some examples
Sutures
Immovable between flat bones of the skull
Gomphoses
Immovable between teeth and jaw
Syndesmoses
Slightly moveable between bones held together by interosseus membranes (for example like tibia and fibia to ankle)
Give an overview of Cartilagenous Joint
Synchondrosis
Immovable joints connected by hyaline cartilage e.g. joint between diaphysis and metaphysis of growing bone.
Symphyses
Bones connected by fibrocartilage e.g pubic symphyses.
Give an overview of synovial joints
Pivot - Allows for rotation only. Formed by a central bony pivot, which is surrounded by a bony-ligamentous ring
E.g. proximal and distal radioulnar joints, atlantoaxial joint.
Hinge - Permits movement in one plane – usually flexion and extension.
E.g. elbow joint, knee joint.
Plane - The articular surfaces are relatively flat, Allowing the bones to glide over one another.
E.g. acromioclavicular joint, subtalar joint.
Saddle - Characterised by opposing articular surfaces with a reciprocal concave-convex shape. Allows for flexion, extension, adduction, abduction, and circumduction
E.g. carpometacarpal joints.
Condyloid - Contains a convex surface which articulates with a concave elliptical cavity. Allows for flexion, extension, abduction, and adduction movements
E.g. wrist joint, metacarpophalangeal joint, metatarsophalangeal joint.
Ball and Socket - The ball-shaped surface of one rounded bone fits into the cup-like depression of another bone. Permits free movement in numerous axes. E.g. hip joint, shoulder joint.
Hip joint have acetabulum
Shoulder joint is called glenoid
What is the function of cartilage
Functions:
Supportive framework for walls of airways preventing collapse
Forms articular surfaces of bones
A template for majority of the skeleton
-Hyaline cartilage
-Elastic cartilage
-Fibrocartilage
Give examples of the different types of cartilage
Hyaline - Most common and weakest - Mostly collagen (type II)
Fibro - Strongest type, Found in joint capsules, tendon insertions, ligaments and intervertebral disks
Elastic - Articular cartilage is a subtype which is found on the surfaces of bones in synovial joints -> Articular cartilage is a subtype which is found on the surfaces of bones in synovial joints
Precursor of bone and found in epiphyseal growth
Cartilage has superficial (fibres parallel to the surface, horizontal), transitional (random fibres), deep zone (Fibres perpendicular to the surface), tidemark, subchondral bone and cancellous bone.
Overview of the anatomy of the bones of the pelvic girdle
The left and right hip bones (innominate bones, pelvic bones) are two irregularly shaped bones that form part of the pelvic girdle – the bony structure that attaches the axial skeleton to the lower limbs.
The hip bones have three main articulations:
Sacroiliac joint – articulation with the sacrum.
Pubic symphysis – articulation between the left and right hip bones.
Hip joint – articulation with the head of femur.
What are the main ligaments in the hips
The ligaments of the hip are named nicely - they always are a mash up of the two bones that they are connecting!
Bowed leg is varus
valvus is locked knees.
Give a brief overview of tendons
Tendons attach muscle to bone.
Bone tendon junction, goes from tendon to fibrocartilage to bone.
The area in-between the tendon and fibrocartilage has the least amount of blood supply.
Epitendon is the outer layer of the tendon, endotendon is the inside of the tendon. They are made of collagen fibrils.
Patella tendon is actually a ligament
Muscle outer later is epimysin and inner is endomysin. Inner most is myofibril.
What are the different types of MSK injuries
Fracture
Dislocation
Sprian
Give an overview of fracture injury
oblique and spiral is the most common type of fractures. Comminuted is high energy impact, avulsion is where the bone is pulled out.
Primary: natural healing where you align the bone and new canals form, callus doesn’t form
Secondary: if you leave it a big ball of callus will form and this can reduce range of motion, this occurs through a haemotoma.
Give an overview on dislocation injury
Epileptic have posterior shoulder dislocation but majority of all shoulder dislocation is anterior.
Dislocation have a risk for potential vascular and nerve damage.
Axillary sends sensation to the regimental patch, this is used for shoulder dislocation.
Medina, ok sign
Ulnar, cross finger
Radial, wrist extension.
Give an overview of sprain/tear injury
Grade 1-3: small tear, large tear and complete tear.
Simmonds test is used for Achilles tendon tear, when the calves needs to be squished and see if the feet move, if it doesn’t it’s a positive test for tear.
What are the common rheumatological conditions
Osteoarthritis
Rheumatoid arthritis
Lupus
Gout
Scleroderma
Characterized by inflammatory process, often involves more than 1 joint, genetic marker and systemic.
Osteo will have areas where in the joint some area will still have cartilage but with rheumatoid arthritis this wont be the case and you can see bone degrading as well on the whole areas of the joint. Treatment is replacement.
What are the surrounding structure of the femoral triangle
What are the borders and content of the femoral traingle
NAVEL - femoral Nerve, femoral Artery, femoral Vein, empty (femoral canal), Lymphatics
Lateral to medial
what compartments is the thigh divided into
Anterior
Posterior
Medial
What are the compartments of the lower leg
What are the ligaments of the Knee
Tibiofemoral ligament
Medial and lateral condyles of the femur articulate with the tibial condyles. It is the weight-bearing component of the knee joint.
Patellofemoral - Anterior aspect of the distal femur articulates with the patella. It allows the tendon of the quadriceps femoris to be inserted directly over the knee – increasing the efficiency of the muscle
Define Meniscus and Bursae
The meniscus acts as a smooth surface for motion and absorbs the load of the body above the knee when standing.
The knee joint is surrounded by fluid-filled sacs called bursae, which serve as gliding surfaces that reduce friction of the tendons.
Menisci
The medial and lateral menisci are fibrocartilage structures in the knee that serve two functions:
To deepen the articular surface of the tibia, thus increasing stability of the joint.
To act as shock absorbers by increasing surface area to further dissipate forces.
They are C shaped and attached at both ends to the intercondylar area of the tibia.
Bursae
Suprapatellar bursa
Extension of the synovial cavity of the knee, located between the quadriceps femoris and the femur.
Prepatellar bursa
Infrapatellar bursa
Deep bursa lies between the tibia and the patella ligament.
Superficial lies between the patella ligament and the skin.
Semimembranosus bursa - Located posteriorly in the knee joint, between the semimembranosus muscle and the medial head of the gastrocnemius.
What are the functions and distribution of calcium
Bone growth and remodeling
Secretion
Muscle contraction
Blood clotting
Co-enzye
Stabilization of membrane potential
2nd messenger/ stimulus response coupling.
What is the function and distribution of phosphate (H2PO4-, HPO4-2)
Element in:
High energy compounds e.g. ATP
Second messengers e.g. cAMP
Constituent of:
DNA/RNA,
phospholipid membranes
bone
Intracellular anion
Phosphorylation (activation) of enzymes
What is corrected calcium
corrected” calcium is an estimate of the total calcium concentration, had serum protein (albumin) concentration been normal
Acid levels in the blood can influence corrected calcium levels
What is the process of daily turnover of calcium and phosphate
The proximal tubule is responsible for the
reabsorption of phosphate filtered at the glomerulus
and is the primary regulator of phosphate balance in
the body. Transportation in the proximal tubule is driven
primarily by sodium–potassium ATPase, which is located
in the baso-lateral membrane of the cell (8-11). Under
normal conditions, about 85% of the filtered phosphate
is reabsorbed via the sodium–phosphate co-transporter
(NaPi2a and NaPi2c) in the proximal tubule
What other hormones are involved in the bone turnover and bone absorption
What is the anatomy of the parathyroid
2 Pairs (4 Glands )
3-5 mm
30-50mg
Closely related to thyroid
May be ectopic
Chief cells and oxyphill cells
Supplied by blood from the inferior thyroid arteries (thyroid surgery)
What are calcium sensing receptors (CaSR) and their role in parathyroid hormone
Circulating calcium levels sensed by Ca2+ receptor
When calcium levels are high:
2) Gαi inhibits constitutive activity of AC cyclase: cAMP and PKA production reduced.
3) Gαq increases IP3 pathway. Intracellular concentrations of Ca2+ rise, PKA falls and PTH secretion is inhibited.
Low levels of calcium decrease IP3, increase PKA and increase PTH secretion
What is the relationship between serum Ca2+ and PTH secretion
What are the actions of PTH
Stimulate osteoblasts to produce M-CSF and RANK ligand-> increased bone resorption
Increase Ca2+ reabsorption in the distal convoluted tubule
Increase phosphate excretion
Increases 1-α hydroxylase in the proximal tubule
What is the role of Vitamin D in Calcium Homeostatis
Increases Ca2+ absorption in the gut
Requires CaBP’s - synthesis stimulated by Vitamin D
Synergises with PTH on bone
Inhibits PTH synthesis
Inhibits 1a-hydroxylase
What is the synthesis of active form of vitamin D3
They have type 2 nuclear receptor
(1 alpha-hydroxylase) plays an important role in calcium homeostasis by catalyzing synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D(3), in the kidney
What is the transport of calcium across the epithelial cells of the intestines
Paracellular transport – diffusion through tight junctions dependent on concentration gradient; does not require energy
Transcellular – at apical region calcium enters cell through a selective calcium transporter (TRPV), binds to calbindin, transported across cell and extruded at the basolateral membrane by a sodium-calcium exchanger and a Ca2+/ ATPase transporter.
What is the action of 1,25 Dihydroxyvitamin D
What is the role of FGF23
Fibroblast growth factor 23 is a protein and member of the fibroblast growth factor family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the FGF23 gene. FGF23 decreases reabsorption of phosphate in the kidney.
Regulation
Increased FGF 23
high Phosphate
High 1,25(OH)2 Vitamin D
Action
increases phosphate excretion
inhibits 1-hydroxylase (CYP27B1)
Inhibits PTH Secretion
What are the cells involved in bone remodelling
The four main types of cells:
Osteocytes → mature cells that maintain the bone tissue
Osteogenic/osteoprogenitor cells → stem cells that differentiate into osteoblasts
Osteoclasts → multinucleated cells that secrete acids and enzymes to resorb bone
Osteoblasts → cells that form bone
How does bone remodelling occur part 1
Vitamin D and PTH stimulate osteoblasts to secrete factors (e.g. M-CSF) → osteoclast precursors proliferate and differentiate.
With further stimulation by RANK ligand (RANKL) → mononuclear osteoclasts fuse to become multinucleated osteoclasts
-OPG blocks the action of RANKL → negative feedback
Osteoclasts resorb bone in discrete areas in contact with the “ruffled border”
Osteoclast secrete acid and proteases into a confined resorption space (the lacuna) → dissolve bone mineral and hydrolyse matrix proteins
Osteoblasts replace the osteoclast and build new bone matrix → promote mineralization
MCS-F stands for macrophage colony stimulating factor
How does bone modelling occur part 2
The final step in bone remodelling is bone mineralisation → need Ca2+ and PO43- for that
Regulatory hormones of calcium metabolism:
PTH (parathyroid hormone) → works on the bone and kidney, complex actions
Vitamin D → ↑Ca2+ levels
FGF23 → ↓PO43- levels
Calcitonin → its role is not fully understood, potentially ↓Ca2+ levels
How is PTH secreted
PTH is secreted by the chief cells of the parathyroid glands
Circulating Ca2+ levels are sensed by the calcium sensing receptor (CaSR)
CaSR binds Ca2+ → if there is too much Ca2+ in the blood → CaSR blocks the secretion of PTH (Gi-coupled GPCR)
Low levels of Ca2+ → CaSR is not signalling → PTH is secreted
Some cancers can also secrete a PTH-homologue (PTHrP)
Small cell lung cancer, certain lymphomas etc.
What is the action of PTH
Bone:
Stimulation of osteoblasts →→ bone resorption → ↑Ca2+ and ↑phosphate
Kidney:
Increased Ca2+ reabsorption in the DCT → ↑Ca2+
Reduced phosphate reabsorption in the PCT → ↓phosphate
Increased activity of 1ɑ-hydroxylase → ↑vitamin D conversion
This will have a negative feedback on PTH secretion (i.e. vitamin D blocks PTH secretion)
What is the production of Vitamin D
Multi-step synthesis:
UV light in the skin converts 7-dehydrocholesterol → cholecalciferol (D3)
Diet (animal products) provides with vitamin D3
Vitamin D2 comes from plant sources
25-hydroxylase in the liver converts it to 25-hydroxyvitamin D3 (i.e. calcidiol)
1α-hydroxylase in the kidney converts calcidiol → calcitriol D3 (1,25-dihydroxyvitamin D3)
What are the actions of Vitamin D
Increased Ca2+ and phosphate reabsorption in the gut (duodenum, jejunum) → ↑Ca2+ and ↑phosphate
Increased bone resorption → ↑Ca2+ and ↑phosphate
Inhibition of PTH synthesis
Inhibition of 1α-hydroxylase function → negative feedback
Causes of Vitamin D difficiency
Liver/kidney disease (synthesis)
Resistance to hormone (receptor)
Mal-absorption
Dietary insufficiency
Poor exposure to sunlight
Sun block
Obesity
Latitude
Skin pigmentation (melanocytes)
Treatment for Vitamin D defficiency
Calcium and vitamin D tablets 800-1000IU daily
Vitamin D injection 300 000U im every 6 months
Alpha calcidol (1alpha hydroxy vitamin D) 0.25-1mg daily
What is the role of FGF23
FGF23 is a hormone released by bones in response to high phosphate levels
Acts on the the FGF23 receptor and its obligate co-receptor Klotho
Actions of FGF23:
Inhibition of phosphate reabsorption in the PCT (at the same site are PTH)
Inhibition of 1α-hydroxylase function → ↓vitamin D
Inhibition of PTH secretion
Osteocytes produce fibroblast growth factor 23 (FGF23)
FGF23 acts on the kidney to decrease synthesis of active vitamin D and to increase excretion of inorganic phosphate (Pi)
What are the different types of hyperparathyroidism
Primary= increase in Ca2+
Secondary= Equal or lower Ca2+
Tertiary= increase in Ca2+
What is primary hyperparathyroidism
Commonest cause of elevated PTH and calcium levels
0.5-5 per 1000
older than 40 years
female-to-male ratio of 3:1
85% of cases are single adenoma
15% caused by diffuse hyperplasia
< 1% by parathyroid carcinoma
May be related to multiple endocrine neoplasia (MEN)
What is secondary hyperparaythyroidism
Secondary HPT
compensatory hyperfunctioning of the parathyroid glands caused by hypocalcaemia or peripheral resistance to PTH.
chronic renal insufficiency,
calcium malabsorption,
vitamin D deficiency,
deranged vitamin D metabolism.
What is Tertiary hyperparathyroism
Tertiary HPT
occurs following previous secondary HPT in which the glandular hyperfunction continue despite correction of the underlying abnormality,
renal transplantation.
What are the treatment for hyperparathyroidism
Surgery
Medical - Observation - Bisphosponates
Calcimimetics
Cinacalcet
Give an overview of hypercalemia
Symptoms:
Bones → bone pain
Stones → renal stones
Abdominal groans → abdo pain, N/V, constipation etc.
Psychic moans → depression, confusion
Causes:
Malignancy
Hyperparathyroidism
Primary → adenomas
Secondary → ↓vitamin D (mostly present in hypocalcaemia)
Tertiary → ESRD
ESRD - end-stage renal disease
You get tertiary hyperparathyroidism in ESRD because the patient was in secondary hyperparathyroidism for a long time beforehand (due to lack of activated vitamin D and thus low levels of blood calcium in chronic kidney disease). So when they get a kidney transplant, even if their new kidney can activate vitamin D now, their parathyroid gland has become hyperplastic and secretes PTH even in the presence of calcium.
Treatment of Hypercalcamia
Saline Rehydration 3-6L
Frusemide
Pamidronate Infusion 15-90mg
Calcitonin 400iU im qds
Prednisolone 40mg
Dialysis
Give an overview of Hypocalcaemia
Clinical signs:
Trousseau’s sign
Chvostek’s sign
Causes:
Vitamin D deficiency → malnutrition, malabsorption (coeliac), liver disease, renal disease (CKD)
Hypoparathyroidism → primary or secondary (after thyroid surgery)
Chelation of calcium (massive blood transfusion, pancreatitis, rhabdomyolysis, ethylene glycol etc.)
Treatment for Hypocalcamia
Treat underlying cause
Discontinue offending drugs
Correct other electrolyte disorders
Oral (enteral): Up to 2g per day
Vitamin D supplementation
Severe Hypocalcamia:
Iv 10ml 10% Calcium gluconate diluted in 200ml N saline over 10 minutes
Carpopedal spasm
Fitting
Arrhythmia
Calcium < 1.7mmol/l
What are the main differences between Ricekets, Osteomalacia, Osteoporosis
Bone Softening
- due to faulty process of bone mineralisation
-Deficient or impaired metabolsim of Vitamin D Phosphate and calcium
This can lead to rickets in kids and the adult version is Osteomalacia
Give an Risk factors and clincial signs of Rickets and osteomalacia
**Risk factors: **
Deficient diet → malnutrition
Malabsorption conditions → Crohn’s, coeliac disease
Lack of exposure to sunlight
Temperate regions → keep large parts of the skin covered
Dark skin
Regions of little sunlight (closer to poles)
Liver disease → reduced fat absorption, vitamin D synthesis pathway affected
Renal disease → vitamin D synthesis pathway affected
**Clinical signs and symptoms: **
**Osteomalacia: **
Muscle weakness → due to proximal myopathy (not enough PO43- for energy)
Waddling gait
Difficulty climbing stairs and getting out of chair
Widespread bone pain → hydration of the demineralised matrix → periosteal distension
Dull, worse on weight-bearing and walking
Can be reproduced by pressure on the sternum or tibia
Insufficiency fractures → femoral neck
**Rickets: **
Craniotabes → thin, deformed skull
Widened epiphyses at the wrists and ankles
Lower limb deformities → bow-legged, knock-kneed
Myopathy, hypotonia
What are the investigations and management for osteomalacia and rickets
**Investigations: **
Bloods
Ca2+ → low
Phosphate → low
PTH → high (no block from vitamin D)
Serum vitamin D → low
ALP → high (present in bone)
Radiographs
Decreased bone mineralisation → loss of cortical bone
Looser’s pseudo-fractures (mostly in scapula, inferior femoral neck and medial femoral shaft) → narrow radiolucent lines with sclerotic borders perpendicular to the cortex
Cupped, ragged metaphyseal surfaces (Rickets)
**Management: **
Vitamin D replacement
Calcium supplementation
Define osteoartheritis, risk factors and clinical signs
Osteoarthritis is a degenerative joint disease, in which the tissues in the joint break down over time. It is the most common type of arthritis and is more common in older people. People with osteoarthritis usually have joint pain and, after rest or inactivity, stiffness for a short period of time.
Risk factors - Age, Female, Obesity, Trauma, Joint malalignment, Occupational
Clinical features- Pain, Function impairment, Bony deformity, Reduced ROM, Malalignment, Crepitus
What are the investigations for osteoartheristis
Clinical Hx:
Risk factors and CFs
1st line test:
Xray, CRP, ESR
2nd line:
RF
Anti CCP
Most test will be -ve to rule out other forms of arthritis which you’ll cover later in the module
What is the management for osteoartheritis
Management:
No cure for OA it is about managing pain control and symptoms for patients
What are the different types of pain
Pain for >6 months - exists beyond physiological healing time
Summary
Calcium levels are closely controlled.
Parathyroid hormone and Vitamin D are the main regulators of plasma Calcium levels
Hypercalcaemia is Caused by
Hyperparathyroidism
Malignancy
Hypocalcaemia is Caused by
Vitamin D deficiency
Parathyroid destruction
