Limbs and Back: Week Five Flashcards
What is the meaning of Amelia?
Total absence of limbs
What is the meaning of Meromelia?
Partial limb loss
What is the meaning of sirenomelia?
Fusion of limbs
What is mutated in Marfan’s syndrome?
FBNI gene. This is autosomal dominant.
What is the difference between dominate and recessive?
Dominant is one gene and recessive is two genes.
What is the meaning of ectrodactlyly?
Total absence of digits
What is the meaning of syndactyly?
Failure of differentiation
What is the meaning of brachydactyly?
Shortened digits
What is the meaning of macrodactyly?
Enlarged digits
What does the Sclerotome form?
Vertebrae and ribs
What is the function of Neurotrophin-3?
Directs the dermatome to become the dermis.
Which two protien combine to activate MYOD?
Wnt (activating) and BMP (inhibitory)
What is the function of sonic hedgehog and noggin?
Induce Sclerotome function
What does the lateral somitic frontier separate?
The somites and the lateral plate mesoderm. It separates the two domains: primaxial and abaxial.
Where is are the primaxial and abaxial domains located?
The primaxial is the region around the neural tube. The abaxial is the parietal layers of the lateral plate.
Name some muscles that are derived from the primaxial layer
Scalene, Geniohyoid, paravertebral, intercostal, rhomboids, levator scapular, latissimus dorsi
Name some muscles that are derived from the abaxial layer
Infrahyoid, pectoralis major and minor, external and internal oblique, transverse abdominus, sternalis, rectus abdominus, pelvic diaphragm, distal limb muscles
Where does the latissimus dorsi derive from?
Primaxial layer
Where do the rhomboids derive from?
Primaxial layer
Were does the levator scapula derive from?
Primaxial layer
Where do the intercostal derive from?
Primaxial layer
Where does the pectoralis major and minor derive from?
Abaxial layer
Where does the external and internal oblique derive from?
Abaxial layer
The primaxial area has somite derived cells. What does the Abaxial area contain?
Parietal layer of the lateral plate and somites that have migrated across.
What is the difference between epaxial and hypaxial?
Abaxial is innervated by the dorsal primary rami. Hypaxial is innervated by ventral primary rami.
What does the hypaxial area form?
Diaphragm, abdomen, and limbs
What does the epaxial area form?
Vertebra, ribs and skull
What are limb buds and when do they become visible?
They are undifferentiated mesoderm which is covered in ectoderm. Appear at day 24.
When does limb morphogenesis occur?
Week 4-8
Where does the upper limb buds originate from?
Ventrolateral body wall
The appearance of mesenchyme is the first sign of condensation. Where does mesenchyme differentiate from?
Dorsolateral mesoderm of somites. It is also from parietal layer of lateral plate.
What shape is the ectoderm that surrounds the mesenchyme core of limb buds?
Cuboidal
What is the undifferentiated ectoderm at the dorsal border called?
The apical ectodermal ridge
What is the function of FGF10?
Limb outgrowth.
What does the dorsal ectoderm express?
Signalling molecule called radical fringe.
What does the ventral ectoderm express?
Transcription factor called engrailed-1
What is the function of FGF4 and FGF8?
Maintenance of undifferentiated zone
Which end does retonic acid start differentiation?
Proximal
What does the AER promote and prevent?
Promotes mitosis and prevents differentiation.
What is polydactyly a mutation of?
HOX genes
The terminal portion of buds will become flattened to hand-plates and footplates. They are separated by proximal segments by constriction. A second constriction will divide them into digits. At which week does this usually occur at?
6
The development of the limb proceeds proximodistally into three parts. What are the three parts and what do they compose of?
Stylopod: humerus and femur
Zeugopod: Radius, Ulna, Tibia, Fibula
Autopod: carpals, metacarpals, digits, tarsals, metatarsals
What is the positioning of limbs regulated by?
HOX genes is a craiocaudal sequence (9-13)
What transcription factor is produced in forelimb?
TBX-5
What transcription factor is produced in hindlimb?
TBX-4 and PITX1
By what day is digit separation complete?
Day 56
The limbs rotate during week seven. Which way do the upper and lower limbs rotate?
Lower limb: medially
Upper limb: laterally
At what week do cartilage models form?
6
when does ossification begin?
Week 8
Where is BMP4 secreted and what is its function?
Secreted by ectoderm and induces production of WNT by dorsal neural tube.
Where is sonic hedgehog derived from?
Notochord and floor or neural tube
Which mesoderm are voluntary head Muslces derived from?
Paraxial mesoderm
What is Sarcopenia?
The loos of skeletal mass and strength due to aging.
What is Cachexia?
Severe muslce wasting due to disease
What is indirect fracture healing?
This is the formation of bone via a process of differential tissue formation until skeletal continuity is restored.
What is the first stage of indirect fracture healing?
Fracture Hematoma and Inflammation: Broken vessels form a clot and there is swelling and inflammation. Platelets and immune cells are involved and this process occurs 6-8 hours after injury.
What is the second stage of indirect fracture healing?
Fibrocartilage Callus: new capillaries organise the hematoma into granulation tissue, forming a procallus. Fibroblasts and oestrogenic cells invade. Chondrocytes make fibrocartilage and collagen is produced. Collagen helps bind bone together. This last 3 weeks.
What is the third stage of indirect fracture healing?
Bone hard callus: osteoblasts make woven bone and this occurs around 3 weeks after injury. This lasts around 3-4 months.
What is the fourth stage of indirect fracture healing?
Bone remodelling: osteoclasts remodel wove bone into compact bone and trabecular bone. This lasts up to 6 months.
What is direct fracture healing?
This is the direct formation of bone, without the process of callus formation, to restore skeletal continuity. There is no movement and this is a unique surgical situation.
What are some factors that inhibit fracture healing?
Age, diabetes, anaemia, malnutrition, smoking, alcohol, NSAIDs, bisphosphates, peripheral vascualr disease, hypothyroidism
Why do NSAIDs inhibit fracture healing?
They recue local vascularity
What is involved during interphase?
Chromosomes duplicate and remain attached
What is involved during prophase?
Chromosomes condense and the spindle forms
What is involved during prometaphase?
Nuclear membrane breaks and spindle interacts
What is involved during metaphase?
Chromosomes align
What is involved during anaphase?
Chromosomes separate
What is involved during telophase?
Nuclear membrane forms and spindle breaks
Give some examples of lipid-soluble molecules, i.e molecules that are hydrophobic and can diffuse straight through the cell membrane
Steroids, Thyroid hormones
What is the difference between primary and secondary messengers?
Primary: extracellular messengers that reach the cell
Secondary: diffuse straight through cell
How do ions flow through a ligand-gated channel?
The ion binds to the specific receptor and causes shape change. This allows the ions to diffuse through down their concentration gradient,
Give an example of a Ligand-gated channel
Acetylcholine receptor in nerve cells
How many transmembrane spans does a G-protein coupled receptor have?
7
Describe the process of G-protein coupled receptors
- A ligand will bind to a GPCR
- GPCR undergoes conformational shape change
- The alpha-unit (attached to beta and gamma) exchanges its GDP to GTP
- The alpha unit dissociates and regulates a target protien
- The target protein will relay signals via a secondary messenger
- GTP is hydrolysed to GDP
What happens when Adrenaline binds to its receptor?
Adrenaline binds to its GPCR (adrenergic receptor). The alpha unit activates adenylyl cyclase which converts ATP to cAMP. cAMP is the secondary messenger that causes increased hear rate, pupil dilation and the conversion of glycogen to glucose etc.
G-protein coupled receptor have no intrinsic enzyme activity. True of False?
True
What happens when a ligand behinds to a receptor tyrosine kinase?
- Ligand binds onto the ligand binding site
- Extracellular ligand causes dimerization of the RTK monomers
- The dimer undergoes autophosporylation whereby each monomer phosphorylates the other
- This creates a phosphor-tyrosine residue on cytoplasmic domain of the RTK
- These are then binding sites for extracellular proteins
Give some examples of G-protien that activate RAS
PDGF, EGF, M-CSF
What type of protien kinases does the RAS pathway involve?
Serine/threonine
What happens in a mutation of the RAS pathway?
GTPase is inactivated which means that the protien cant shut itself down and there is uncontrolled cell division
Explain the first stage of Endochondral Ossification - Development of cartilage model
Development of cartilage model: mesenchyme cells aggregate together in the general shape of the bone and develop into chondroblasts. The chondroblasts secrete cartilage ECM, producing a cartilage model consisting of hyaline cartilage.
Explain the second stage of Endochondral Ossification - Growth of cartilage model
Growth of cartilage model: once the chondroblasts are surrounded by cartilage matrix, they are called chondrocytes. Chondrocytes continues to divide and secrete cartilage resulting in the matrix growing.
Explain the third stage of Endochondral Ossification - Development of primary ossification centres
Development of primary ossification centre: a nutrient artery penetrates the perichondrium towards the centre of the calcifying cartilage model, stimulating oestrogenic cells to differentiate into osteoblasts. As the perichondrium forms bones, it is known as the periosteum (periosteal bone collar). In the middle of the model, bone tissue will replace most of the cartilage and becomes primary ossification centres. Osteoblasts secrete bone ECM over remnants of calcified cartilage. forming spongy bone.
Explain the fourth stage of Endochondral Ossification - Development of medullary cavity
Development of medullary cavity: as primary ossification centres grows towards the end of the bone, osteoclasts break down some newly formed spongy bone. This leaves the medullary cavity in the diaphysis. The wall of the diaphysis is eventually replaced with compact bone.
Explain the fifth stage of Endochondral Ossification - Development of secondary ossification centres
When developing arteries reach the epiphysis, secondary ossification centres develop. This is usually the time around birth. The spongy bone that is formed remains and has no cavity. In contrast to primary ossification centres, the secondary centres proceed outwards.
Explain the sixth stage of Endochondral Ossification - Formation of articular cartilage and epiphyseal growth
Hyaline cartilage covering epiphysis becomes articular cartilage. The hyaline cartilage remains between the diaphysis and epiphysis. These areas are known as epiphyseal growth plate.
What is the difference between primary and secondary ossification centres?
Primary centres: First part of the bone to ossify, typically occurs about the 8th foetal week for most bones. Located in the middle of the shaft
Secondary Centres: Develop after birth 2 months–> 18 years. At proximal and distal epiphyses
What is growth in length called?
Interstitial growth
What are the layers of the epiphyseal growth plate, top to bottom?
- Zone of resting cartilage
- Zone of proliferating cartilage
- Zone of hypertrophic cartilage
- Zone of calcified cartilage
Explain interstitial growth.
There is a layer of stem cells immediately below the epiphyses and this gives rise to chondrocytes. The layers closest to the diaphysis are disintegrating. The osteoclasts are degrading this bone to allow the medullary cavity to form.
Explain Appositional growth
This is growth in width. The osteoblasts beneath the periosteum of the bone from new osteons on the external surface. Bone becomes thicker and stronger.
Explain the process of intramembranous ossification
1) centrally located mesenchymal cells with the embryonic fibrous connective tissue begins to condense. Some cells form capillaries while other form osteoblasts. These condensation form ossification centres.
2) Osteoblasts secret osteoid and mineralization occurs in several days. Following mineralization, osteoblasts from osteocytes.
3) Bone spicules of trabecula start to radiate out ways from ossification centres in random patterns between developing blood vessels to from woven bone, which is then converted into lamellar bone. Bone spicules become surrounded by mesenchymal cells and this forms the periosteum. Osteoblasts continue to secret osteoid, which become calcified.
4) Layers of bone are built beneath periosteum. As they become thicker, they form compact bone. Deeper, trabeculae persists and gives rise to spongy bone.
What is the mutation in achondroplasia?
This is autosomal dominant. There is a mutation of the 380th amino acid where glycine is switched by arginine. This is one the FGFR3 gene located on chromosome 4.
What is the developing treatment for achondroplasia called?
This is vasoritide. This is a CNP-analogue that causes crates the production of cAMP then cGKII. This leads to the inactivation of MEK1 and ERK1.
During limb development, what does the dorsal mass of the mesoderm develop into?
Extensors, pronators and adductors
What are the attachments of the inguinal ligaments?
The anterior superior iliac spine and pubic tubercle
What is mesenchyme derived from?
Mesoderm of somites and somatic lateral plate.
What nerve is damaged when there is no foot dorsiflexion possible?
The common peroneal nerve
What is Valgus?
The distal part is more lateral. In the case of knees, the knees are together an the feet are pushed outwards.
What is Varus?
The distal part is more medial. In the case of the knees, the knees are apart from each other and the feet are together.
Which ligaments creates a popping sound when it becomes damaged?
The anterior cruciate ligament
Which foramen does the pudendal nerve go through?
The lesser sciatic foremen
What are the borders and contents of the popliteal fossa?
Serve And Volley Next Ball (medial to lateral)
- semimembranosus and semitendinosus are the superior medial border
- popliteal artery
- popliteal vein
- tibial nerve
- biceps fibrosis is lateral superior border
The heads of the gastrocnemius forms the inferior lateral and medial border.
Which muscles forms the inferior medial and lateral border of the popliteal fossa?
Heads of the Gastrocnemius
The abdominal aorta becomes the common iliac artery. The common iliac artery then becomes the external and internal iliac arteries. When does the external iliac become the common femoral and what branch does it immediately give off?
After crossing the inguinal ligament. It gives of the profundus artery.
The femoral artery will then become the popliteal artery. What does this artery split to?
The anterior tibial and tibio-peroneal trunk.
What does the tibio-peroneal trunk divide into?
The posterior tibia and peroneal arteries.
which artery becomes the dorsalis Pedis artery?
The anterior tibial
What are some of the branches of the internal iliac artery?
iliolumbar, lateral sacral, gluteals, pudendal and obturator
What does the profundus artery spilt into?
The medial and lateral circumflex arteries
What supplies the anterior thigh muslce and where does it originate?
The femoral nerve. This is from L2-L4
What supplies the adductor thigh compartment and where does it originate?
Obturator nerve. This is from the L2-L4 ventral rami
What supplies the posterior thigh compartment and where does it originate?
The sciatic nerve. This is form L4-S3 ventral rami.
What does the sciatic nerve split into when it reaches the top of the popliteal fossa?
The tibial and common peroneal nerves
what does the common peroneal nerve split into?
The superficial and deep peroneal nerves.
What does the superficial and deep peroneal nerves innervate?
The superficial innervates the lateral leg and the deep supplies the anterior leg.
Some of the muscles of the gluteal region can be expressed with mnemonic P-GO-GO-Q. What are these muslce?
The mnemonic P-GO-GO-Q gives the muscles in order of top to bottom.
- Piriformis
- Gemullus superior
- Obturators internus
- Gemullus inferior
- Obturator externus
- Quadratus femoris
What are the four Muslces that are not in the mnemonic P-GO-GO-Q, part are part of the gluteal region?
The tensor fascia latae, the gluteus Maximus, gluteus Medius and gluteus Minimus.
What are the functions of the deep gluteal Muslces (ie the mnemonic P-GO-GO-Q)
Lateral rotation
Where do all of the Muslces from the mnemonic P-GO-GO-Q insert, expect the Quadratus femoris?
The greater trochanter. The Quadratus femoris inserts into Quadrate tubercle on the femur.
What is the function of the Tensor fascia latae?
Stabilises knee during extension
What is the difference in nerve supply of the Gluts?
The Maximus is supplied by the inferior gluteal nerve whereas the Medius and Minimus is supplied by the superior gluteal nerve.
Where does the Gluteus Minimus and Medius insert?
Greater trochanter
What is the function of the Gluteus Maximus?
Extension and lateral rotation.
What is the function of the Gluteus Minimus and Medius?
Abduction and medially rotation
What nerve supplies the anterior thigh Muslces?
Femoral nerve
Name all the Muslces of the anterior compartment of the thigh. ( I Saw a Pretty Queen )
Iliopsoas: iliacus and psoas major
Sartorius
Pectinues
Quadriceps: rectus femoris, vastus lateralis, vastus intermedius and vastus medialis
Name the Quadriceps
The Rectus femoris, Vastus Lateralis, Vastus Medialis and Vastus Intermedius
Which Quadriceps is the most superficial?
Rectus femoris
What is the blood supply to the Quadriceps?
Lateral circumflex artery
What is the function of the Quadriceps?
Knee extension
What is the function of the Muslces of the anterior thigh (not including the Quadriceps)?
Thigh flexion
What two muscles are grouped to the term Iliopsoas?
Iliacus and Psoas Major
Where do the Quadriceps insert?
Quadriceps tendon
What are the five muscles of the medial thigh compartment? ( Obama Gave 3 Apples )
Obturator externus Gracilis Adductor longus Adductor brevis Adductor magus
What is the function of the medial thigh compartment?
Adduction
What is the blood and nerve supply to the medial thigh compartment?
Obturator artery and Obturator nerve
The adductor Magnus has a adductor and hamstring part. Which one is medial and which one is lateral?
Adductor is lateral and Hamstring is medial
What are the posterior thigh muscles collectively known as?
The hamstrings.
What is the function of the hamstrings?
Extend at the hip, and flex at the knee
What is the innervated of the hamstrings?
Sciatic nerve
What are the three hamstrings? ( Semi has Super Bag)
Semi-membranous
Semi-tendinous
Biceps femoris
What is the blood supply to the hamstrings?
The profundus femoris artery
What is the most lateral Muslces of the hamstrings?
Biceps femoris
What is the arrangement of the semi-membranous and semi-tendinous?
The Semi-tendinous lies media to the biceps and the semi-membranous lies deep to it.
What is the superior border of the femoral triangle?
Inguinal ligament
What is the medial and lateral border of the femoral triangle?
Medial: Medial Sartorius
Lateral: Medial adductor longus
What is the function of the anterior thigh muscles?
Extend leg at knee joint