The CNS and normal neuromuscular and musculoskeletal function Week 1 Flashcards
What are activities of daily living ?
Roles of different health professionals ?
What is locomotion ?
- Locomotion is the ability to move from one place to another. In humans, walking upright, or bipedally, is the most common method of locomotion.
- Walking involves all the joints of the lower limb and is characterised by an ‘inverted pendulum’ motion, in which the body vaults over the non-moving limb.
What is the gait cycle ?
Stages of Walking
The typical walk consists of a repeated gait cycle. The cycle itself contains two phases – a stance phase and a swing phase:
-Stance phase: Accounts for 60% of the gait cycle. It can be divided into the heel strike, support, and toe-off phases.
-Swing phase: Accounts for 40% of the cycle. It can be divided into the leg lift and swing phases.
Describe heel strike ?
In the heel-strike stage, the foot hits the ground heel first. Three muscles/muscle sets are involved, each acting at a different joint:
Gluteus maximus – acts on the hip to decelerate the forward motion of the lower limb.
Quadriceps femoris – keeps the leg extended at the knee and the thigh flexed at the hip.
Anterior compartment of the leg – maintains the ankle dorsiflexion, positioning the heel for the strike.
Describe support ? (gait cycle )
After the heel strike stage, the rest of the leading foot hits the ground, and the muscles work to cope with the force passing through the leg. This is known as the support stage.
-Quadriceps femoris – stabilises the knee in extension, supporting the weight of the body.
-Foot inverters and evertors – contract in a balanced manner to stabilise the foot.
-Gluteus minimus, gluteus medius and tensor fascia lata – abduct the lower limb. Their contraction keeps the pelvis level by counteracting the imbalance created from having most of the body weight on one leg
Describe Toe - off ?
In the toe-off phase, the foot prepares the leave the ground – heel first, toes last.
-Hamstring muscles – extends the thigh at the hip.
-Quadriceps femoris – maintains the extended position of the knee.
-Posterior compartment of the leg – plantarflexes the ankle. The prime movers include gastrocnemius, soleus and tibialis posterior
Describe the leg lift ?
Once the foot has left the ground, the lower limb is raised in preparation for the swing stage.
-Iliopsoas and rectus femoris – flexes the thigh at the hip, driving the knee forwards.
-Hamstring muscles – flexes the leg at the knee joint.
-Anterior compartment of the leg – dorsiflexes the ankle.
Describe the swing ?
In the swing phase, the raised leg is propelled forward. This is where the forward motion of the walk occurs.
-Iliopsoas and rectus femoris – keep the thigh flexed at the hip, resisting gravity as it tries to pull the lower extremity down.
-Quadriceps femoris – extends the leg at the knee, positioning the foot for landing.
-Anterior compartment of the leg – maintains ankle dorsiflexion so that the heel is in place for landing.
Next, the heel hits the ground, and the whole cycle repeats.
Conditions that alter gait ?
Conditions that alter gait ?
Gait abnormality ?
Pathological gaits ?
-When thinking of the locomotor system we rightly focus on the lower limbs. The legs. But do not forget that our upper limbs are used both for balance, but also have a role in running.
-We have the femur, tibia and fibula, tarsals of the ankle, metatarsals of the food, and then the phalanges of the digits. These are the bones of the lower limb.
-On their own these bones do nothing. There are a series of joints that help the bones to move.
-There are ball on socket joints, pivot joints, hinge joints and ellipsoidal joints. The form and shape of the joints determines the movement of the bones and whether they move in one, two or all 3 directions.
Muscles attach to bones ?
- However it is worth remembering that bones and joints on their own don’t move. They need forces applied to them, and this is where muscles come in. Muscles connect two (or more) bones. When muscles contract they produce forces. Because the force is being applied to bones which have joints this creates movement.
-The rotational forces that muscles produce on bones around a joint is known as torque.
There are different descriptions of muscles depending on how they function:
-Agonists cause a movement through their own contraction.
-Antagonist muscles oppose those same movements.
Probably the most commonly used example is the biceps and triceps, biceps contraction causes flexion at the elbow, the triceps contracting causes extension of arm at the elbow.
Synergist Muscles:
-However we also have synergist muscles that help to perform the same motion as the agonist. In our arm example, we have the brachialis that also helps flexion of the elbow.
-Typically when talking about muscles contracting we think about muscles shortening, or concentric contractions. For example if you are weight lifting and doing biceps curls, to lift the weight up you contract your biceps, the muscles shortens and bulges and your arm moves up. However there is another form of contraction, where the muscle contracts as it lengthens. This is eccentric contraction.
Eccentric contraction: Usually this contraction is used to oppose a stronger force. If we go back to our biceps example, think about holding or carrying something. If you want to put it down carefully, you don’t just completely relax your biceps making your arms drop. You carefully control the extension of your arm and your biceps is contracting as it lengthens. Try it!
Position of muscle affects power and speed
Also appreciate that we can change how muscles function by just changing where the muscles originate and insert. If we move a muscle nearer or further from a joint you can change the moment arm of that muscle. The further away you move the muscle the larger the moment arm, the larger the moment, the more turning force or torque that muscle produces around that joint. But, this tends to make the limb movement relatively slower. Think of a seesaw. The longer the side that we are trying to move, the more force it takes to move it, but the further it will move when it does. It is a tradeoff between force and speed.
We see this if we look at the forelimbs of a cheetah and a badger for example. A badger is designed for force, but a cheetah for speed, and we can see that with the position of the teres major muscle.
In our bodies our muscles tend to be optimised for force or speed. We might find synergistic muscles optimised differently, so one might do force, whilst the other might be for speed. By playing around with activations of these muscles we can modify our movements as required.
Ligaments and Tendons
- Tendons join muscle to bone
- Ligaments join bone to bone
Lower Limb Muscles
- Gluteus Maximus
- Gluteus Medius
- Gluteus Minimums
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Gluteus Maximus
- The gluteus maximus is the largest of the gluteal muscles. It is also the most superficial, producing the shape of the buttocks.
Actions: It is the main extensor of the thigh, and assists with lateral rotation. However, it is only used when force is required, such as running or climbing.
Innervation: Inferior gluteal nerve.
Artery: superior and inferior gluteal artery
- Gluteus maximus: Main extension at hip
Gluteus Medius
- Actions: Abduction and medial rotation of the lower limb. It stabilises the pelvis during locomotion, preventing ‘dropping’ of the pelvis on the contralateral side.
Innervation: Superior gluteal nerve.
Artery: deep branch of the superior gluteal artery
- Gluteus medius and minimus: Abduction at hip
Gluteus Minimus
- The gluteus minimus is the deepest and smallest of the superficial gluteal muscles. It is similar in shape and function to the gluteus medius.
-Actions: Abduction and medial rotation of the lower limb. It stabilises the pelvis during locomotion, preventing ‘dropping’ of the pelvis on the contralateral side.
-Innervation: Superior gluteal nerve.
Artery: deep branch of the superior gluteal artery
Gluteus medius and minimus: Abduction at hip
Muscles of the anterior thigh ?
-The muscles of the anterior compartment of the thigh are a group of muscles that (mostly) act to extend the lower limb at the knee joint.
-They are collectively innervated by the femoral nerve (L2-L4), and recieve arterial supply from the femoral artery.
Describe the Iliopsoas ?
The iliopsoas is comprised of two separate muscles; the psoas major and iliacus. These muscles are in the pelvis area.
These muscles arise in the pelvis and pass under the inguinal ligament into the anterior compartment of the thigh – where they form a common tendon.
Unlike many of the anterior thigh muscles, the iliopsoas does not perform extension of the leg at the knee joint.
Insertion:
- Psoas major into the lesser trochanter of the femur
- Iliacus muscle: lesser trochanter of the femur via tendons of the psoas major
-Attachments: The psoas major originates from the lumbar vertebrae, and the iliacus originates from the iliac fossa of the pelvis. They insert together onto the lesser trochanter of the femur.
-Actions: Flexion of the the thigh at the hip joint.
-Innervation: The psoas major is innervated by anterior rami of L1-3, while the iliacus is innervated by the femoral nerve.
Describe the quadriceps femoris ?
-The quadriceps femoris consists of four individual muscles – the three vastus muscles and the rectus femoris. It forms the main bulk of the anterior thigh, and is one of the most powerful muscles in the body.
-The four muscles collectively insert onto the patella via the quadriceps tendon. The patella, in turn, is attached to the tibial tuberosity by the patella ligament.
Muscles in quadriceps femoris:
- Vastus Lateralis
- Vastus Intermedius
- Vastus Medialis
- Rectus Femoris
Describe Vastus Lateralis ?
-Actions: Extension of the knee joint. It has a secondary function of stabilising the patella.
-Innervation: Femoral nerve.
Describe the Vastus Intermedius ?
-Actions: Extension of the knee joint. It has a secondary function of stabilising the patella.
-Innervation: Femoral nerve
Describe the Vastus Medialis ?
- Actions: Extension of the knee joint. It has a secondary function of stabilising the patella.
-Innervation: Femoral nerve
Describe the Rectus Femoris ?
- Actions: Extension of the knee joint and flexion of the hip joint (it is the only muscle of the quadriceps group to cross both the hip and knee joints).
…………….
-Innervation: Femoral nerve
Describe the Sartorius ?
- Begins at the anterior superior iliac spine
The sartorius is the longest muscle in the body. It is long and thin, running across the thigh in a inferomedial direction. The sartorius is positioned more superficially than the other muscles in the leg.
-Actions: At the hip joint, it is a flexor, abductor and lateral rotator. At the knee joint, it is also a flexor.
-Innervation: Femoral nerve
Pectineus muscle ?
The pectineus is a flat, quadrangular-shaped muscle which contributes to the floor of the femoral triangle.
-Attachments: Originates from the pectineal line of the pubis bone. It inserts onto the pectineal line on the posterior aspect of the femur, immediately inferior to the lesser trochanter.
-Actions: Adduction and flexion at the hip joint.
-Innervation: Femoral nerve. May also receive a branch from the obturator nerve.
Prosecution of anterior thigh
Muscles of the medial compartment of the thigh ?
- The muscles in the medial compartment of the thigh are collectively known as the hip adductors.
There are five muscles in this group;
- gracilis
-obturator externus
-adductor brevis
- adductor longus
- adductor magnus.
All the medial thigh muscles are innervated by the obturator nerve, which arises from the lumbar plexus.
Arterial supply is through the obturator artery.
Actions:
-Adductor – Adduction and flexion of the thigh
-Hamstring – Adduction and extension of the thigh.
Innervation:
-Adductor – Obturator nerve (L2-L4)
-Hamstring part – Tibial component of the sciatic nerve (L4-S3).
3 Ducks Pecking Grass”
3 Ducks – Say it out loud “A-DUCK-TOR” = adductor. The three ducks are adductor longus, adductor brevis, adductor magnus
Pecking – Say it out loud, “PECK-ing” = “PECK-tin-e-us”. Pectineus is another adductor muscle of the thigh.
Grass – Say it out loud, “GRASS” = “GRASS-ill-us”. Gracilus is the last adductor muscle of the medial thigh.
Muscles of the posterior compartment of the thigh ?
-The muscles in the posterior compartment of the thigh are collectively known as the hamstrings.
They consist of the:
-biceps femoris
-semitendinosus
- semimembranosus
…….. which form prominent tendons medially and laterally at the back of the knee.
As group, these muscles act to extend at the hip, and flex at the knee. They are innervated by the sciatic nerve (L4-S3).
What are the muscles of the posterior compartment of the thigh ?
The muscles located within the posterior compartment of the thigh are:
- the biceps femoris
- semitendinosus
- semimembranosus.
Describe the function of the Biceps Femoris ?
- Main action is flexion at the knee. It also extends the thigh at the hip, and laterally rotates at the hip and knee.
-Innervation: Long head innervated by the tibial part of the sciatic nerve, whereas the short head is innervated by the common fibular part of the sciatic nerve.
Describe the function of the Semitendinosus ?
- Actions: Flexion of the leg at the knee joint. Extension of thigh at the hip. Medially rotates the thigh at the hip joint and the leg at the knee joint.
-Innervation: Tibial part of the sciatic nerve.
Describe the Semimembranosus ?
-Actions: Flexion of the leg at the knee joint. Extension of thigh at the hip. Medially rotates the thigh at the hip joint and the leg at the knee joint.
-Innervation: Tibial part of the sciatic nerve.
Muscles of the anterior leg ?
The muscles in the anterior compartment of the leg are a group of four muscles that act to dorsiflex and invert the foot.
These muscles are collectively innervated by the deep fibular nerve (L4-S1). The arterial supply is through the anterior tibial artery.
Muscles of teh anterior leg
Drug: Alendronic acid ?
Alendronic acid is a bisphosphonate medication used to treat osteoporosis and Paget’s disease of bone.
- It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes
- Drug class: Bisphosphonate
- After administration it distributes into soft tissue and bone or is excreted in the urineLabel. Alendronic acid does not undergo metabolism
- Mechanism: Inhibition of osteoclasts results in decreased bone resorption
Drug: Alendronic acid ?
Alendronic acid is a bisphosphonate medication used to treat osteoporosis and Paget’s disease of bone.
- It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes
- Drug class: Bisphosphonate
- After administration it distributes into soft tissue and bone or is excreted in the urineLabel. Alendronic acid does not undergo metabolism
Mechanism:
- Alendronic acid binds to bone hydroxyapatite
- Inhibition of osteoclasts results in decreased bone resorption
Drug: Calciferol
- aka as Vitamin D
- Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D₃ and vitamin D₂.
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Drug: HRT (Hormonal replacement therapy) ?
- Hormone replacement therapy (HRT) is a treatment to relieve symptoms of the menopause. It replaces hormones that are at a lower level as you approach the menopause.
The main benefit of HRT is that it can help relieve most of the menopausal symptoms, such as:
-hot flushes
-night sweats
-mood swings
-vaginal dryness
-reduced sex drive
-Many of these symptoms pass after a few years, but they can be unpleasant and taking HRT can offer relief for many women.
It can also help prevent weakening of the bones
Drug: Raloxifene ?
Drug Class: Selective estrogen receptor modulator (SERM)
Mechanim: On skeletal tissues, raloxifene stimulates bone-depositing osteoblasts and inhibits bone-resorbing osteoclasts
- is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids.
- For osteoporosis it is less preferred than bisphosphonates.
- It is also used to reduce the risk of breast cancer in those at high risk
The skeleton is split into the axial skeleton and appendicular skeleton ?
Axial skeleton:
-The axial skeleton forms the vertical central axis of the body and includes all bones of the head, neck, chest and back.
Appendicular skeleton:
- The appendicular skeleton includes all bones of the upper and lower limbs, including the shoulder and pelvic girdle – bones that attach each limb to the axial skeleton.
-Newborn skeleton – 300 bones approx
Mature adult skeleton- 206 bones
Bones of the skull classification ?
- We classify bones into 5 main groups according to their shape: Long bone, short bone, flat bone sesamoid bone and irregular bone.
The table below summarises the differences between these categories of bone. (Note that any single bone may belong to more than one category e.g. the frontal bone is both flat and pneumatic.)
Function of the skeleton ?
-Support
-Protection
-Movement
-Mineral storage
Haematopoiesis - is the formation of blood cellular components. Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues
Distinct features of long bones ?
Compact bone ( aka cortical bone):
-Dense
-Forms surface of bone
-Thickened in diaphysis (shaft)
Cancellous bone (aka soft bone):
-Spongy network of trabeculae
-Located on interior of bone
-Located at articular (joint) ends of long bones
Describe the epiphyses ?
Describe the diaphysis ?
Describe the medullar cavity ?
Epiphyseal plate ?
Describe short bones and flat bones ?
Describe sesamoid bones and irregular bones ?
Bone microstructure 1 ?
Bone microstructure 2 ?
Describe bone cells Osteoblasts ?
Describe bone cells Osteoclasts ?
Parathyroid hormone involvement in bones ?
Vitamin Ds involvement in bones ?
Calictonins involvement in bones ?
Homeostasis of bones ?
Embryonic ossification 1 ?
2 main steps:
- Intramembranous ossification
- Endochondral ossification
Embryonic ossification 2 ?
Embryonic ossification 3?
Summary embryonic ossification ?
Connective tissue and joint 1
Connective tissue and joints 2
Connective tissue and joints 3
Connective tissue and joints 4
Connective tissue and joints 5
Connective tissue and joints 6
Damage to the superior gluteal nerve will result in a Trendelenburg gait.
Where are the bones of the body skeleton derived from?
Where are the bones of the head derived from ?
- head: Neural Crest
- body: Mesoderm
Mesoderm layer
- In this lecture we will focus on the paraxial mesoderm
Somites ?
- Are paired structures on either side of the closing neural tubes
- somite’s can develop into a variety of structures but for todays lecture we will focus on the vertbrae, ribcage and parts of the occipital bone of the skull.
What do vertebrae develop from?
- Vertebrae develop from somites (mesoderm).
- The combination of Hox genes determining the shape (identity) of your vertebral bones
When do limb buds develop ?
-Moving from vertebral patterning, to the limbs. In embryos somewhere between weeks 4-5 you see the development of flipper-like limb buds. Again there are important patterning genes that help determine not just whether it is upper or lower limb, but whether we are looking at fingers, a hand, lower arm or humerus.
- There are an important set of cells at the apical ectodermal ridge, the distal most part of the limb bud, that are releasing chemical signals that help the in patterning. These signals also interact with signals from the zone of polarising activity which sits on the ulnar side of the hand. These two areas are responsible for determining segments and the appropriate cartilaginous precursors for the bones e.g. if it is a humerus, ulna, or metacarpal or phalange.
What are the two ways in which bones develop ?
-Bones develop within either a cartilaginous precursor (e.g. limb bones) or membranous precursor (e.g. dermal bones of skull).
- In both of these precursors the process of developing bones is known as ossification
What is another name for ossification from a cartilaginous precursor ?
- Endochondral ossification
- Ossification from a cartilaginous precursor, also known as endochrondral ossification looks like this. Cartilage grows and expands interstitially – it grows in all directions. This is particularly true of young cartilage, whilst older cartilage tends to grow from the outside. In early development, limbs grow by adding cartilage. Because the cells controlling cartilage growth (chondrocytes) need nutrients, when the cartilage gets to a certain size, blood vessels begin to invade it to ensure the nutrient and oxygen supply. As the blood vessels invade, the cartilage becomes calcified and eventually turns into bone. Much like the early stages of cartilage growth, this bone is initially deposited everywhere. Later, this bone is remodelled, with bone removal from the inside and bone added to the outside creating the marrow/medullary cavity.
-In long bones, we tend to find multiple ossification centres. The first is in the shaft (diaphysis). However we find secondary ossification centres in the ends of the bone near the joints (called the epiphysis). These two ossification centres are separated by a layer of cartilage. This layer of cartilage is known as the epiphyseal growth plate, and this is where the lengthening of growing bones occurs until skeletal maturity occurs and this cartilaginous plate ossifies as well. You can often see this plate and the in Xrays before and after skeletal maturity.
cartilage form how ?
Whilst we are going through bone development, we are going to have a quick look at cartilage too. Bone and cartilage are both connective tissues. All connective tissues comprise cells, and intercellular matrix consisting of fibres and ground substance. By varying the cells and intercellular matrix you vary the function of the connective tissues. For example mineralising the ground substance of cartilage, you can turn it into calcified cartilage, and eventually bone.
Cartilage is formed by the precursor cells called chondroblasts. These chondroblasts secrete the matrix, the substance around them. As they secrete the matrix they become entombed in the cartilage. When this happens, they become mature chondrocytes which maintain the cartilage around themselves. Chondrocytes are often arranged in stacks, and by doing so, as they secrete the matrix can act like a jack, forcing the ossification centres apart helping to lengthen the bones.
The typical cartilage you see is hyaline cartilage. This is found in the trachea, but also the cartilage that bone forms from. It forms the endochondral plate, and the joint surfaces. If you look at the images at the bottom you can see the diagram and actual images of chondrocytes within cartilage. The space in which the chondrocytes sit is called a lacuna (latin for lagoon)
Describe cartillage ?
Cartilage itself has no blood vessels. It gains its nutrition from diffusion, which is why developing long bones can only remain as cartilage for so long before they get too big to receive nutrition via diffusion. This is stage when blood vessels invade and ossification begins. What this means is cartilage is never very thick, particularly when you compare it to bone.
Cartilage grows both adding all around – interstitial growth. You can see this in the image on the right. When it matures, it tends to only add cartilage on the outside – appositional growth.
Because cartilage had no blood supply it heals very poorly. This has clinical implications for joint damage, as well as surgical interventions.
Epiphyseal growth plate ?
How do bones grow? We have talked a bit about the epiphyseal growth plate expanding and pushing apart the two ossification centres, particularly pushing the epiphysis from the shaft. But how about the bone increasing its thickness? Bone is laid down on the outside, whilst being removed on the inside. It’s a tube that expands as it grows.
Epiphyseal growth plate ?
On the left is a section through a long bone. In the centre, there is a pink line of cartilage, separating two regions of bone. On the right is a diagram of what we are seeing. The first zone, the zone of reserve cartilage. Then we have a zone of proliferation where you can see the cartilaginous cells in stacks. These stacks of cells are the ones driving the two ossification centres apart as if they were a car jack. As the cells proliferate, they leave behind mature and even old cells forming a whiter layer underneath. Here cartilage begins to degenerate as it is turned into bone. The cells expand the epiphysis, which ossifies behind it.
You can see growth plates on X-rays. It is important to be aware of them so there is no confusion between a break vs a normal growing bone. How can we tell the difference? There are very detailed accounts of bone ossification and growth that an expert would be able to use to tell the age of the individual. This has uses in forensics for aging skeletal remains, particularly for children. This is also useful for paediatricians for tracking growth of infants to see if there are growth issues.
If you were given this, how might you tell if this is a break or a growth plate? The first method is to look it up and see if this structure aligns with known growth plate positions.
The second, is to look closely at the X-ray. If you look at a normal bone, you see a white cortical exterior with a darker inside. In the X-ray you see the diaphysis or shaft looks like this, as does the ephiphysis. Having these two cortical regions next to each other shows it isn’t a break. If it was a fracture there just be a darker line through the grey region.
I’ve been using the terminology throughout the lecture, but just to make sure everything is clear. The ephiphysis is the part of the bone nearest the joint. In this case the distal most part of the bone. The physis or the epiphyseal growth plate is what we have been talking about. It separates the epiphysis from the shaft of the bone. The metaphysis is the bit of the shaft where the epiphysis is ossifiying, forming this wider part of the shaft. The diaphysis is the shaft itself.
Slipped epiphysis ?
Another thing that can go wrong with epiphyses is that they can slip. In fully fused bones, there isn’t a single weak spot, so bones tend to break. However, in young children, the weak point is the cartilage itself, so trauma disrupts the growth plate rather than breaking the bone. On the right it is fairly obvious. On the left we see an X-ray of a child with a sore pelvis. At first glance it looks fairly normal, but if you were to draw a line along the neck of the femur, where you’d see the line goes through epiphysis of the left femur, but does not on the right. You probably would never spot this, but this is why radiologists are specialists, and would be expected to spot this. This is why you should review X-rays with experts. A slipped epiphysis can happen in any of the endochondral bones and can be quite a serious issue for a child as they have damaged the growth centre of the bone. There is often a surgical intervention to help re-align the bones, and if unsuccessful may lead to a shortening of that bone.
Long bone morphology ?
Having talked a lot about bones, we are going to look at the anatomy/histology of a bone itself.
The first thing to notice, is the bone consists of a dense outer cortical shell. On the inside might be a space known as the medullary or marrow cavity. There might also be a honey comb structure of bone known as cancellous or trabecular bone. Think of a bone a bit like a crunchie chocolate bar, with the chocolate being cortical bone, and the honeycomb being the trabecular bone.
If we look at the cortical bone, we see that it is made of rings of bone kind of like a tree trunk. These circumferential lamellae have cells within these rings. If we work towards the middle of the bone we find smaller rings within the bone. That smaller ring of bone travels along the length of the bone and is known as an osteon. Within the central canal are blood vessels. This re-highlights how vascular bone is, compared to the avascular cartilage. If you damage cartilage you do not bleed, but if you damage bone you can bleed a lot.
Bone Histology
Bone like cartilage is a connective tissue. It contains cells, fibres, and ground substance. Unlike cartilage the ground substance is mineralised. There are 3 major cell types, the osteoblasts which build, the osteocytes which maintain, and the osteoclasts which remove/clear bone. In cartilage there are only two cell types, but again the blasts build, the cytes maintain
The osteoblasts, osteocytes and osteoclasts are therefore working together to maintain the bones, and when this goes awry you can get various diseases.
Osteoblasts
- OSTEOBLASTSare the cells that work in teams to form new bone. They have only one nucleus.They produce new bone called “osteoid” which is made of bone collagen and other proteins. Osteoblastsare specialized mesenchymal cells that synthesize bone matrix and coordinate the mineralization of the skeleton.
Bone is laid down by cells known as osteoblasts, which come from osteoblast precursors which are on the outside of the bone in the periosteum. Osteoblasts develop long processes that lay down the ground substance which becomes bone. As osteoblasts lay down the ground substance they become entombed, becoming osteocytes which are responsible for maintaining the bone
These osteocytes maintain the long cellular processes which connect to other cells allow communication throughout the bony tissues. Osteocytes also sit within lacuna within the bone, and the processes sit within canaliculi – small canal.
Osteoclasts
- Anosteoclastis a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodelling of bones of the vertebral skeleton. They are derived from precursors in the myeloid/monocyte lineage that circulate in the blood after their formation in the bone marrow.
Bone can be removed unlike cartilage. Bone is regularly renewing and repairing through a process of resorption and formation. Bone is resorbed by giant, multi-nucli cells called osteoclasts. Osteoclasts have ruffled borders, and secrete hydrochloric acid that dissolves the calcium in the bone, and the osteoclasts digest the collagen fibres in the bone. As they move over the surface of a bone, they scallop out big holes. This image shown here is famous one showing an osteoclast destroying a sperm whale bone.
Bone cells ?
Osteocytes have these long processes. If you remove all of the matrix, what you would see is the osteocytes with their networks of connections. These connections are likely important in helping to sense deformation or bending of the bone. If there is a lot of signal that the bone is bending, this will tell the osteocytes that they need to deposit more bone. If the bone is not being loaded very much and there isn’t much bending, then the osteoclasts will remove bone. This helps maintain the force and deformation that the bone undergoes during loading e.g. running.
Remodeling of bone form
When bone first forms it is laid down by the osteoblasts as woven bone with the collagen fibres being randomly oriented. This bone then is replaced by lamellar bone where the collage fibres are remodelled so that they are parallel and in layers.
Bone microstructure: Osteons
I highlighted these long thin tubular structures that extend along the length of the bone known as osteons. They are also called the haversian system. These osteons contain blood vessels, but also cells, and collagen fibres. The arrangement of the fibres and the mineral content is what gives the mechanical properties of the bone. If you look at the at the image on the left you might see in the osteon that extends above the others that the fibres are oriented in different directions in each layer. These different orientations make bones strong in all directions. The collagen helps allow bones to be flexible so that they can bend rather than just shattering like concrete does when overstressed. This helps prevent fractures.
This structure depends heavily on your activity levels in utero, as a child and throughout life. If you were to grow up in space you would likely find that your bones would not be suitable for life on earth.
Bone microstructure: Osteons
If you take a section through the osteon, we can see the central haversian canal surrounding this canal are concentric rings of bone called concentric lamella. You can see the entombed osteocytes in their lacunae.
On the right, you will see some osteons that are complete – primary osteons. Where the osteons themselves start being dug into by another osteon they are secondary osteons. This shows the continuing remodelling of the bones, and can be used to age individuals as well as tell activities levels. These systems can become disordered in certain diseases.
Surface remodeling
But it isn’t just the internal structure of bone that is remodelling through life. The surface can also remodel depending on developmental and functional drivers. The craniofacial skeleton grows by depositing bone everywhere. After the age of 5, the anterior margins of the face start resorbing to help keep the face vertical. In other primates which have longer or more prognathic faces, you do not see this same resorption.
We can see evidence of this using a scanning electron microscope looking at the bones of the face. Towards the top right we see nice smooth bone with organised collagen fibres and little holes for the osteoblasts which are becoming entombed to become osteocytes. On the top left of the image indicated by the arrows, we see a rough area where the bone is being hollowed out and removed by the osteoclasts.
Bone structure: Trabeculae
We’ve focussed heavily on the structure of the cortical bone. We are going to have a quick look at cancellous bone. It is also called trabecular or spongy bone. The individual bony spikes of bone are trabeculae. There are few trabeculae in the medullary cavity in the shaft, but are found commonly in the epiphyseal regions in particular, for example the neck of the femur.
These trabeculae form when osteoclasts remove bone from the middle of the bone. Where there are still lots of forces on the bone that don’t align with the primary cortical bone, such as in the epiphyses, trabeculae remain, and tend to have an orientation that aligns with the main forces on that joint. Where there are reduced forces such as the diaphysis or the shaft, the trabeculae are completely removed resulting in the medullary cavity.
Osteoporosis ?
As I’ve talked about regularly throughout the lecture, there is an important balance of deposition and resorption going on in bones throughout life to maintain the health of your skeleton. In early life, the formation of the trabecular network, and the formation of the bones, is determined by how you are loading it. Throughout life nutrition is important, for example, making sure you have enough vitamin D and calcium. Hormones play an important role, particularly in females. In menopause, the rate of deposition and absorption alters and a lot of bone is lost – several percent of skeletal mass is lost at menopause. It is vital that a lot of skeletal mass was put on early in life. Note that most of you can still add lots of bone mass by vigorous exercise, although this tends to reduce from your mid 20s.
Skeletal mass is also lost through breastfeeding, as the bones are raided for their calcium, but this tends to be reversible.
Trabeculae tend to be found in the bones near joints, such as the femoral neck. When the trabeculae are reduced as much as they are in osteoporotic bone there is a loss of mechanical integrity. This leads to breaks in the bone, and is particularly common in older women even without injury.
Joints ?
Now onto joints. A joint occurs between two bones. There are a lot more than you have probably ever considered. Those shown here are fibrous joints – synarthroses. The ones between the bones of the lower arm and leg are syndesmoses with the fibrous interosseous ligaments connecting them. The fibrous joints between bones of the skull are known as sutures
The difference between synarthroses joints and syndesmoses joints is how they move. Syndesmoses joints have very limited movement. They are only slightly movable. Synarthroses joints cannot be moved and have no cavity for the joint.
Joints ?
We have cartilaginous joints, some of which you will already have seen. For example the costochondral joints between the ribs and the sternum. You could argue that the epiphyseal plate is also a cartilaginous joint, as it joins two bones. There are also the fibrocartilage joints between vertebrae or in the pubic symphysis.
Joints?
The main joints we are concerned with are the synovial joints. These are what the joints you tend to think of, but are also the joints that a lot tends to go wrong with, particularly arthritis whether it is rheumatoid or osteoarthritis.
Onto the structure. We find that the two bones are connected by an external joint capsule. This is lined by a synovial membrane which produces synovial fluid which lubricates the joint. Where the two bones meet there is articular hyaline cartilage protecting the surface of the bone.
Synovial Joint histology ?
In the articular cartilage, we find several layers. The outer tangential layer, the cells align parallel to the surface of the cartilage. They are longitudinally aligned.
Below that we find the transitional layer where there is no orientation to the cells. We get to the radial layer, where we find cells in columns. This goes back to the cartilage acting like a jack and expanding upwards. Below this we find the cartilage calcifying and then bone.
In osteoarthritis you find tearing along the top of the cartilage and fibrillation as the cartilage turns into little fibres. This leads to bone changes due to the changes in loading with the loss of cartilage.
Arthritis ?
Arthritis is an incredibly common disease of the joints. It comes in these two main types – osteoarthritis and rheumatoid arthritis.
Where the articular cartilages break down through injury or disease or age you get osteoarthritis. This can happen in any of the joints, but particularly common in joints that have had high usage in life such has hands, knee and hip, neck and lower back.
If the synovial membrane becomes inflamed through autoimmune disease you get rheumatoid arthritis. It is believed to be a combination of genetic and environmental factors, and most commonly affects the small joints of the hand feet and cervical spine..
Mechanical adaption of bones ?
I’ve mentioned that bone adapts under loads. The osteocytes sense deformation, and trigger deposition or absorption depending on the stimuli. The result at a macro level is that bones vary tremendously depending on how bones have been loaded in life. Weight lifters are have more robust skeletons than non-weight lifters, but even professional tennis players have more robust bones in their dominant arm due to higher loading in that limb. Astronauts tend to have major reductions in bone mass even in short space flights. Certain palsies will develop skeletal elements with abnormal angles. This highlights just how important mechanical adaptation is to our skeletal shape.
Repair: fracture healing
But mechanical loading is also important when it comes to healing of a bone. When a bone fractures, you get a break with a large amount of bleeding. If the break isn’t major, this may be contained by the periosteum which is the membrane surrounding bones. The result is a bag of blood around the fracture. Fibrous cells proliferate under the periosteum, and lay down a fibrous tissue. This ossifies to form a rough woven bone known as a callous. This is the first attempt at fixing the bone as quickly as possible to provide some stability to it. Over time the woven bone is remodelled by the osteocytes and osteoclasts under the mechanical loading, so the bone regains structure and becomes lamellar bone. Eventually the marrow cavity reforms and the callous continues to reduce in size and may even disappear if given enough time and the fracture was set correctly.
What is the function of the calcitonin?
Secreted by the thyroid gland.
Calcitonin opposes pth and lowers blood calcium levels.
It decreases osteoclast activity and increases osteoblast activity.
Osteoblasts take calcium from the blood and into the bone
Osteoclasts get rid of calcium from bone.
Describe bone remodeling ?
Describe bone metabolism ?
Describe bone metabolism ?
Calcium and Phosphorus ?
Vitamin D ?
Parathyroid hormone ?
Calcitonin ?
Oestrogens ?
Androgens ?
The effects of hormones on bone metabolism ?
Metabolic bone disease?
Osteoporosis ?
Osteomalacia ?
Nervous system
Peripheral nervous system ?
The peripheral nervous system is itself classified into two systems: the somatic nervous system and the autonomic nervous system. Each system contains 2 components:
-The afferent arm consists of sensory (or afferent) neurones running from receptors to the CNS. Afferent nerves detect the external environment via receptors for external stimuli such as pressure or temperature etc. Afferent nerves exist in both the somatic and autonomic nervous systems as both can use sensory signals to alter their activity.
-The efferent arm consists of motor (or effector) neurones running from the CNS to the effector organ. Effector organs can either be muscles or glands.
Somatic and Autonomic Nervous Systems
The somatic nervous system of the PNS is responsible for voluntary, conscious control of skeletal muscles (effector organ). Its afferent arm links sensory receptors on the body surface or deeper within it with relevant processing circuits, whereas the efferent arm directly controls skeletal muscles using motor nerves.
The autonomic (visceral) nervous system control the visceral functions of the body and acts largely unconsciously. These visceral functions include the regulation of heart rate, digestion, salivation, urination, digestion, and many more. The afferent (sensory) arm of this system includes receptors that monitor the arterial pressure, levels of carbon dioxide and oxygen in the blood or the chemical composition of the content of the gastrointestinal tract. The efferent arm of this system can be further subdivided into the parasympathetic (PSNS) and sympathetic (SNS) components, which control numerous smooth muscles and glands.
The enteric nervous system is classified as a separate component of the autonomic nervous system and is sometimes even considered a third independent branch of the PNS.
The SNS and PSNS are sub-divisions of the autonomic nervous system. The autonomic nervous system has a unique structure as it employs a sequential two-neurone efferent pathway. Hence, the preganglionic neurone must first travel to and synapse upon a ganglion, a collection of neuronal cell bodies in the PNS. A ganglion then gives rise to a postganglionic neurone which innervates the target organ.
Sympathetic Nervous System
The SNS is responsible for the fight or flight response of the body and originates from the thoracolumbar segments of the spinal cord. It incorporates short preganglionic neurones and long postganglionic neurones.
The preganglionic neurones use acetylcholine as a neurotransmitter while the postganglionic neurones use noradrenaline. The exception to this rule is the innervation of the sweat glands and chromaffin cells of the adrenal medulla, which are cholinergic as they use acetylcholine as a neurotransmitter.
Another exception is the chromaffin cells of the adrenal medulla. They act as a modified sympathetic ganglion without the postganglionic neurones. Hence, the activation of chromaffin cells via preganglionic cells leads to the release of two neurotransmitters: adrenaline and to lesser extent noradrenaline, directly into the bloodstream.
The actions mediated by SNS are most apparent when the body is faced with stressful situations. It is designed to mobilise energy stores, allowing us to cope with the stress and increase our chances of survival.
Parasympathetic Nervous System
The PSNS is responsible for the rest and digest actions of the body. It originates from craniosacral segments of the spinal cord. This system consists of long preganglionic neurones and short postganglionic neurones. Both preganglionic and postganglionic neurones use the neurotransmitter acetylcholine.
Summary of SNS and PSNS:
The sympathetic and parasympathetic pathways have very similar structures but with a few key differences. The table below shows a comparison of these 2 systems.
Central nervous system ?
How neuroanatomical knowledge can locate a lesion:
Formation of the neural tube ?
The cells of the bilaminar disc (epiblast and hypoblast) undergo a highly specialised process called Gastrulation.
During Gastrulation two main things happen. One of them is the bilaminar disc becomes the trilaminar disc ( two germ layers become 3 germ layers) and the bodily axes observed in the mature adult are created.
Gastrulation involves the migration, invagination and differentiation of the epiblast. It is largely controlled and orchestrated by the primitive streak.
The epiblast cells migrate through the primitive groove and towards the hypoblast cells (invagination), they then replace these hypoblast cells. This layer is now called the Endoderm.
More epiblast cells migrate and move down and laterally (ventrally) through the primitive groove and form the mesoderm layer.
We now call the top layer of epiblast cells the Ectoderm
Epiblast – Ectoderm
New layer – Mesoderm
Hypoblast – Endoderm ( they are at the bottom the –end)
The three germ layers are called multipotent and can differentiate into any cell type, they are responsible for forming different tissues in the foetus.
Function of the notochord ?
The notochord forms from the mesoderm cells soon after gastrulation is complete.
Within the mesoderm there are three gaps where there is no mesoderm. The structures that lie in this area are the notochord, the prechordal plate and the cloacal plate.
Notochord releases growth factors that:
1. stimulate mesoderm differentiation
2. neurulation.
- nucleus pulposus is the central part of the vertebral column
Describe neurulation ?
Neurulation is the process by which ectoderm in the trilaminar embryo develops into the neural tube ( neuroectoderm tube) which is the basis for the nervous system.
Notochord: induces differentiation of overlying ectodermal cells above it to form neural plate
Neural plate ( made of ectoderm): thickening of ectoderm along the midline which causes a depression to form in the centre of neural plate. This is called the neural groove.
What do the neural folds become ?
What do the neural crest cells become ?
Neural folds:
Consists of cells forming lateral walls around neural groove, which elevate slightly above the rest of the ectoderm
The wave becomes the neural crest cells, which form a number of different peripheral nervous structures.
Neural crest cells = peripheral nervous structures
The neural folds circle upward and meet in the midline, forming a tube
This tube is pulled below the outer layer of ectoderm → now known as the neural tube
Neural crest cells separate and are located between the neural tube and the ectoderm.
Surface Ectoderm = Epidermis
Neural crest cells = peripheral nervous structures
Neural tube = CNS
At this point the primitive node and the primitive streak begin to fade.
What do the neural folds become ?
What do the neural crest cells become ?
Neural folds:
Consists of cells forming lateral walls around neural groove, which elevate slightly above the rest of the ectoderm
The wave becomes the neural crest cells, which form a number of different peripheral nervous structures.
Neural crest cells = peripheral nervous structures
The neural folds circle upward and meet in the midline, forming a tube
This tube is pulled below the outer layer of ectoderm → now known as the neural tube
Neural crest cells separate and are located between the neural tube and the ectoderm.
Surface Ectoderm = Epidermis
Neural crest cells = peripheral nervous structures
Neural tube = CNS
At this point the primitive node and the primitive streak begin to fade.
Closure of the neural tube ?
Folding occurs everything is zipped up and now we have a tube.
The neural tube becomes the CNS ( the brain and spinal chord). But first it needs to pinch off.
The top of the neural tube becomes the cranial/anterior neuropore - hole at the top of the tube.
The bottom of the neural tube becomes the caudal/posterior neuropore - hole at bottom end of the tube.
Cranial portion of neural tube: enlarges to become the brain
Caudal portion of neural tube: remains tubular, becomes the spinal cord
When the anterior/cranial neuropore closes on day 25. And the posterior/caudal neuropore closes on day 28 this is the end of neurulation.
The hole within the neurotube is the neural canal. It will fill with Cerebrus spinal fluid.
When is the cranial / rostral neuropore closed ?
When is the caudal neuropore closed ?
Rostral: day 25
lamina terminalis: The lamina terminalis forms the anterior wall of the third ventricle
Caudal: day 27
Upper and lower neural tube defects ?
- If we get upper neural tube defects it could mean the brain is not developed properly. An example of a congeital defect is Anencephaly
- If we get lower neural tube defects we can have not properly developed spinal tube. An example is Spina bifida occulata.
Spina Bifida:
-When either of the neuropore do not close correctly, or both do not close correctly it can cause complications in the brain.
-Spina bifida is when the posterior/caudal neuropore does not close. There are 3 types you need to know:
-Spina bifida occulta
-Meningocele ( closed spina bifida)
-Meningomyelocele ( open spina bifida)
The different types of spina bifida are distinguished by the level of tissue affected. The meningomyelocele is the most extreme type . The whole of the spinal cord is on the outside and is offered no protection by the bony vertebrae. It needs to be treated. It is possible to operate on spina bifida in utero where it is discovered in imaging.
Development of the brain ?
- The cranial / rostral end neurotube will dilate and become bigger the lumen will fill out and amass a lot of tissue and form the bits of the brain we are familiar with.
-Vesicalisation: This is what happens to the cranial portion of the neurotube. The brain differentiates into 3 primary primary brain vesicles. These are called the Prosencephalon, Mesencephalon and the Rhombencephalon.
Primary brain ?
Secondary brain ?
Bending (flexures) in the brain ?
- You can see the primary brain vesicles prosencephalon, mesencephalon and rhombencephalon.
- There are flexures or bends which you can see in the brain. There are:
- Pontine flexure
- Mesencephalic flexure
- Cervical flexure
- The telencephalon expands much more than any other part of the brain at this part of development.
- The dilation of the telencephalon becomes the cerebral hemispheres.
- The lamina terminalis is the outcome of the closure of the rostral neuropore closing.
Ventricles ?
-The adult outcome of the spaces within the brain are the ventricles.
- chambers of telencephalon become the lateral ventricles.
- the chambers of the diencephalon becomes the third ventricle.
- the chamber of the mid brain becomes the cerebral aqueduct.
- the chambers of the metencephalon becomes the fourth ventricle.
At 21 weeks you have the rough outline of the cerebral hemisphere.
Osteoarthritis ?
Total knee arthoplasty (TKA) - is surgery where you remove bone and put titanium plates on the ends of bones so that the bones are not rubbing against each other and so you feel less pain
Gout ?
- excessive uric acid levels, which causes crystallized uric acid (monosodium urate crystals ) to be deposited into tissues
-Gout is caused by the precipitation and deposition of monosodium urate crystals into the joint spaces and tissues, resulting in inflammatory arthritis.
-Precipitation of monosodium urate is due to increased uric acid production or decreased uric acid excretion.
- Purine-rich foods include red meats, liver, shellfish, and alcohol increase risk of gout
Which joint is most likely to be implicated in a gout attack ?
The first metatarsophalangeal (MTP) joint is most commonly implicated in a gout attack. Symptoms experienced during a gout attack include pain, erythema, edema, and decreased range of motion.
What is Pseudogout ?
- When we have too much calcium pyrophosphate dihydrtae crystals, which deposit into tissues and cause inflammation.
- often idiopathic
Septic arthiritis ?
- Caused by infection by pathogens which leads to inflammation of the joint
- typically monoarticular which means it affects one joint, often the knee
Osteoporosis ?
- Decrease in estrogen causes increased bone resorption
- hyperparathyroidism will increase osteoporosis
Which T-score on dual-energy x-ray absorptiometry is consistent with osteoporosis?
T-scores are used to define osteoporosis based on the average bone density of a healthy 30-year-old adult. Each integer change represents a standard deviation from this level. A T-score of ≤-2.5 defines osteoporosis and represents 2.5 deviations from the density of a 30-year-old adult.
Osteopenia: a medical condition in which the protein and mineral content of bone tissue is reduced, but less severely than in osteoporosis.
Osteopetrosis ?
Osteomalacia/Rickets ?
Rheumatoid arthritis ?
Lupus ?
Sjorgen Syndrome ?
Antiphospholipid Syndrome ?
Fibromyalgia ?
Scleroderma ?
Sarcoidosis ?
Symptoms of Sarcoidosis ?
Which stem cells give rise to osteoprogenitor cells ?
Which stem cells give rise to hematopoietic stem cells ?
- Mesenchymal stem cells give rise to osteoprogenitor cells
- Hematopoietic stem cells give rise to blood making cells
Achondroplasia
Pagets disease of the bone ?
- The pathophysiology of osteitis deformans is as follows: increased RANK-RANKL interaction → increased NF-κB activation → increased disorganized osteoblast and osteoclast activity → “woven bone” formation
- In the clinical setting, osteitis deformans often manifests as hearing loss that occurs as a result of vestibulocochlear nerve (CN VII) compression secondary to bone formation extending into the foramina of the skull.
Osteitis deformans also classically presents with an increased hat size due to increased bone deposition in the skull.
- incidence most common in central europe
- On blood tests calcium and phosphate levels are normal but there is high ALS levels
