Musculo/Derm 2 Flashcards
What is Spondylolisthesis?
Forward displacement of one vertebra over another
What is Spondylosis?
Degeneration of the spinal column
Spinal Stenosis occurs mainly due to?
Increasing age
What 3 processes occur in Spinal Stenosis?
- Intervertebral discs shrink → narrows foramen
- Facet joints rub against each other → arthritis → bone spurs
- Ligamentum flavum hypertrophies
What posture narrows the lumbar canal?
Standing straight
Spinal stenosis causes what symptom?
Neurogenic Claudication
What is Neurogenic Claudication? What are 2 clinical features?
- Leg pain with walking in spinal stenosis
- Persists with standing, improves with stooped/flexed posture
What are the motor and sensory innervations of the Sciatic nerve (not including branches)?
Motor: Muscles of posterior thigh + Hamstring portion of adductor magnus
Sensory: No direct sensory functions
What are the 3 Hamstring muscles?
Biceps femoris (lateral), Semimembranosus, Semitendinosus
What are the 3 main functions of the Hamstring muscles?
Knee flexion, hip extension, hip rotation (minor)
What is Sciatica?
Clinical syndrome used to describe low back pain radiating along the path of the sciatic nerve (lumbar radiculopathy)
What is a common cause of Sciatica?
Herniated disk
What are 3 causes of Complete Sciatic neuropathy?
- Hip fracture or dislocation
- Hip replacement therapy
- Prolonged compression (coma/bed rest)
Posterior hip dislocations commonly cause?
Sciatic neuropathy
Severe Sciatic neuropathy can lead to what symptoms?
- Hamstring muscle weakness
- Foot drop (common peroneal nerve)
- Sensory loss in lower leg/foot
Herniated disc at L4/L5 lead to compression of which nerve?
Bottom, L5
What is the most common Radiculopathy Syndrome? This is usually due to?
L5, herniated disc at L4/L5
L5 nerve compression will cause what symptoms?
- Back pain down lateral leg
- Weak foot dorsiflexion, toe extension → Difficult walking on heels
What is the 2nd most common Radiculopathy Syndrome?
S1 nerve root
S1 Nerve compression leads to what symptoms?
- Pain down back of leg
- Weakness plantar flexion → Difficulty standing on toes
- Ankle reflex lost
L5 nerve root compression mainly involves what nerve?
Common peroneal
S1 nerve root compression mainly involves what nerve?
Tibial nerve
L2/L3/L4 nerve roots compression mostly involves what nerve?
Femoral
L2/L3/L4 nerve roots compression lead to what symptoms?
- Pain to anterior thigh and knee
- Weak hip flexion and knee extension
- Reduced knee (patellar) reflex
What is Lasègue’s sign?
Worsening back pain with straight leg raise
What are Major flexors of the hip joint?
- Iliopsoas
- Sartorius
- Pectinius
- Tensor fasciae latae
What are Major Extensors of the hip joint?
Gluteus maximus, Hamstrings: Semimembranosus, semitendinosus, Biceps femoris
What are Major Abductors of the hip joint?
Gluteus medius, Gluteus minimus
What are Major Adductors of the hip joint?
- Adductor magnus
- Adductor longus
- Adductor brevis
- Pectineus, gracilis
What are 4 muscles involved in External rotation of the hip joint?
- Gluteus maximus
- Obturator internus
- Gemellus superior/inferior
- Quadratus femoris
What are 7 muscles involved in Internal rotation of the hip joint?
Gluteus medius/minimus, Tensor fasciae latae, Adductor longus/brevis, Posterior head of adductor magnus, Pectineus
Superior Gluteal Nerve is derived from?
Sacral plexus (L4-S1)
Superior Gluteal Nerve supplies what 3 muscles?
- Gluteus minimus/medius (abductors)
- Tensor fasciae latae (flexor)
Superior Gluteal Nerve is sometimes injured by _____. What can be done to prevent this?
- IM injection to buttocks
- Inject in upper, outer quadrant to avoid injury
What is a classic finding of Superior Gluteal Nerve injury?
Trendelenburg sign
What is the Trendelenburg sign?
Weight bearing leg cannot maintain balance → Pelvis tilts with walking
What does the Inferior Gluteal Nerve supply?
Gluteus maximus
Inferior Gluteal Nerve injury presents with difficulty?
Standing from sitting position
Inferior Gluteal Nerve is rarely injured by?
Pelvic masses
Avascular Necrosis is common at the?
Femoral head
What is the most common complaint of Avascular Necrosis? What other symptoms are present?
- Groin pain
- Leg and thigh pain, difficulty bearing weight
Avascular Necrosis is often caused by?
Trauma (femoral head fracture)
What is the major blood supply to the Femoral head? What artery is it from?
- Medial circumflex femoral artery
- Femoral profunda artery
Damage to Medial circumflex femoral artery leads to?
Avascular necrosis
What are non-traumatic causes of Avascular necrosis?
- Steroid therapy
- SLE
- Heavy alcohol consumption
- Sickle cell anemia
- Gaucher disease (lysosomal storage disease)
What is the most common hip disorder in adolescence?
Slipped Capital Femoral Epiphysis
What is Slipped Capital Femoral Epiphysis?
Fracture through growth plate → Slippage of overlying end of femur
Slipped Capital Femoral Epiphysis can lead to?
Avascular necrosis
What is Legg-Calvé-Perthes Disease? What is it caused by?
- Idiopathic avascular necrosis in children
- Abnormal blood flow
A muscle cell is also called?
Muscle fiber
Sacrolemma is the?
Plasma membrane of muscle cell
Sarcoplasmic reticulum is similar to what other structure?
Endoplasmic reticulum
Sarcoplasmic reticulum is important for?
Calcium storage
What is a T-tubule?
Invaginations of plasma membrane
What is a terminal cisternae?
Sarcoplasmic Reticulum near T-tubule
Muscle fibers are made up of?
Myofibrils (contractile structure)
What are sarcomeres?
Contractile structures within myofibrils
Sacromeres contains what 2 filaments?
Actin and myosin filaments
What forms the thick and thin filaments of sacromeres?
Thin: mostly actin, troponin, tropomyosin
Thick: Myosin
What are Z disks? What is the function?
Ends of sarcomeres, mechanical stability
Z disks contain what 2 filaments?
Vimentin and desmin
What tethers myosin to Z disks?
Titin
What is the I, A, and H band in a sarcomere contain? What is the M line?
- I Band: Light band near Z disks, mostly actin
- A Band: Between I bands, where actin and myosin overlap
- H Band: Center of sarcomere, Myosin only
- M line: Central proteins for alignment
What band in the sarcomere does not change with contraction?
A band
What are the 3 subunits of troponin? What is the function of each?
Troponin C: binds calcium
Troponin T: binds tropomyosin
Troponin I: inhibits myosin binding to actin
Muscle contraction is initiated via?
Calcium binding troponin
What blocks ‘binding groove’ for myosin?
Tropomyosin
What happens when Calcium binds troponin?
Conformational change in tropomyosin → exposes actin to myosin
Myosin bind ____ at rest?
ATP
What happens after myosin binds ATP in muscle contraction?
ATP hydrolyzed to ADP and Pi → assumes ‘cocked’ position → can bind to actin if Tropomyosin block is removed → ‘power stroke’ → myosin binds new ATP and detaches from actin
What is Excitation-Contraction Coupling?
Contraction occurs when cell depolarizes (action potential)
Neuron depolarization leads to what events in skeletal muscle contraction?
Presynaptic calcium entry into neuron → release of ACh → bind Nicotinic Acetylcholine Receptors on muscle cells → Na+ receptor opens → depolarization of muscle
What leads to the release of Calcium from SR after the sarcolemma is depolarized?
T tubules depolarize → conformational change of Dihydropyridine receptors → opens Ryanodine receptors on terminal cisternae (SR near T-tubule) → releases calcium → initiates contractions
What is the role of Dihydropyridine Receptors in skeletal muscle?
Proteins that span gap between T-tubule and SR, depolarization leads to conformational change which opens ryanodine receptors
What is SERCA? What is the function?
- Sarco/endoplasmic reticulum Ca2+-ATPase
- Transfers Ca2+ from cytosol back into SR using ATP
What are 2 drugs associated with Malignant Hyperthermia?
Succinylcholine, Halothane
What is Malignant Hyperthermia? What is the underlying mechanism?
- Rare, dangerous reaction to anesthetics
- Abnormal ryanodine receptors causes excessive calcium release → consumption of ATP by SERCA → heat, muscle damage → ↑CK/K+ → Fever, muscle rigidity after surgery
What is used to treat Malignant Hyperthermia?
Dantrolene
What is the mechanism of Dantrolene?
Ryanodine receptor antagonist, block Ca2+ release from SR → relaxes muscle
Slow twitch fibers are also called?
Red fibers
What are 4 characteristics of Slow twitch fibers?
- Have extra myoglobin (Resists fatigue)
- More mitochondria = more oxidative phosphorylation
- More fatty acid metabolism
- Moderate glycolysis activity
What muscles consist of more Slow twitch fibers?
Postural muscles (spine)
Fast twitch fibers are also called?
White fibers
Fast twitch fibers primarily metabolize?
Glucose and glycogen
What muscles are mostly Fast twitch fibers?
Eye muscles
What are 3 characteristics of Fast twitch fibers?
- Increased activity of glycolysis enzymes
- More glycogen storage
- Less mitochondria
What are differences between Cardiac muscle and Skeletal muscle?
- Dyads vs Triads
- Cardiac muscle is depolarized by pacemaker cells (SA node) and contain Gap junctions
- Different action potential
How is the Cardiac muscle action potential different from skeletal muscle?
Calcium influx via L-type calcium channels causes a plateau (Phase 2)
Dihydropyridine receptors are what type of receptors?
L-type Ca+ Channels
What are examples of dihydropyridine/non-dihydropyridine Ca+ channel blockers? Which are low/high affinity for dihydropyridine receptors?
Low affinity: Amlodipine, nifedipine
High affinity: Diltiazem, verapamil
What is the importance of Dihydropyridine receptors in cardiac muscle?
Allows influx of calcium → triggers SR calcium release via ryanodine receptor (‘Calcium-triggered calcium release’)
How do Cardiac muscle cells increase contractility?
Increase calcium entry into cell via L-type Ca channels
What is the mechanism of Diltiazem and verapamil? What does this lead to?
Block L type calcium channels in cardiac myocytes → decreases contractility, slows conduction and lowers heart rate
How does the Sympathetic Nervous system increase cardiac contractility?
β1 Receptors linked Gs proteins → activate adenylyl cyclase → increase cAMP/PKA → increase Ca into cell → increase contractility
What is Lusitropy?
Myocardial relaxation
Increase in Lusitropy always accompanies increase in?
Contractility (Faster contraction → faster relaxation)
What mediates Lusitropy?
SERCA
What is a key regulatory protein of Lusitropy? What is the role in regulation?
- Phospholamban
- Inhibits SERCA unless it is phosphorylated by beta adrenergic stimulation/PKA
What is Phospholamban?
Key regulator protein of Lusitropy
What are differences between smooth muscle cells and striated muscle?
- Do not depend on action potential
- Do not require membrane depolarization to contract
- Slow, sustained contraction
- Utilize Ca2+ differently
Skeletal muscle is [thin/thick] filament regulated and Smooth muscle is [thin/thick] filament regulated.
Thin, thick
What is modified to control contraction in Smooth muscle? What regulates contraction/tone?
- Myosin light chain
- MLC Phosphorylation
MLC phosphorylation is regulated by what 2 proteins?
Myosin light chain kinase, Myosin light chain phosphatase
Only [non-phosphorylated/phosphorylated] MLC interacts with actin.
Phosphorylated
What is Calmodulin? What is the function?
Ubiquitous smooth muscle cell protein, binds calcium and activates MLC Kinase
What are the 2 sources of Calcium for Smooth muscle cells?
SR and L-type Calcium channels that bind dihydropyridine (‘Dihydropyridine receptors’)
What interacts with actin?
Only non-phosphorylated MLC interacts with actin.
What is Calmodulin? What is its function?
Ubiquitous smooth muscle cell protein that binds calcium and activates MLC Kinase.
What are the 2 sources of Calcium for Smooth muscle cells?
SR and L-type Calcium channels that bind dihydropyridine.
What is the mechanism of Amlodipine, Felodipine, and Nicardipine? What is it used for?
L-type calcium channel blockers → less Ca → Vascular smooth muscle relaxation. Used in hypertension.
What are the 2 major regulators of smooth muscle tone?
Calcium in cell and Myosin light chain phosphorylation.
What are the 3 major 2nd messengers in smooth muscle?
cAMP, cGMP, IP3.
What does cAMP in smooth muscle lead to?
MLK kinase inhibition → relaxation.
What does cGMP in smooth muscle lead to?
MLC phosphatase activation → relaxation.
What does IP3 in smooth muscle lead to?
Calcium release from SR → contraction.
What is Nitric Oxide also called?
Endothelial derived relaxing factor.
Nitric Oxide is synthesized from what amino acid? What cell?
L-arginine, Endothelial cells.
What are 4 stimuli for increased production of Nitric Oxide?
Blood flow/shear stress, Acetylcholine, Bradykinin, Substance-P.
What action does Nitric Oxide do in smooth muscle?
Activates guanylyl cyclase → increase cGMP → activates MLC phosphatase → smooth muscle relaxation.
Acetylcholine and bradykinin work indirectly through what to cause smooth muscle relaxation?
Endothelial cells.
What is the mechanism of Nitroglycerine? Uses?
Converted to NO in smooth muscle. Used for Angina and heart failure.
Nitroprusside is a vasodilator used for?
Hypertensive emergency.
What is the effect of G proteins (Gs, Gi, Gq) on smooth muscle? What is the mechanism?
Gs: increase cAMP → relaxation. Gi: decrease cAMP → contraction. Gq: increase IP3 → contraction.
What does the periosteum contain?
Blood vessels and sensory nerves.
Where is Trabecular bone found?
At the ends of long bones.
What are Osteoclasts?
Specialized macrophages.
What do Osteoclasts secrete?
Acid (H+) and proteases.
What do Osteoblasts buried in bone matrix become?
Osteocytes.
What does Bone Matrix contain?
Type I collagen and Hydroxyapatite (contains calcium and phosphorus).
Bone Matrix is synthesized from?
Osteoblasts.
Bone matrix is first synthesized as?
Osteoid: Non-mineralized bone matrix laid down by osteoblasts followed by mineralization.
What modulates Bone turnover?
Signals from osteoblasts.
What is RANK? What is its function?
Receptor expressed on surface of osteoclasts. Ligand binding leads to receptor synthesis of NF-kB → Osteoclast stimulation.
What is RANK-L? What is its function?
Receptor expressed by osteoblasts, binds RANK → osteoclast stimulation.
What is Osteoprotegerin (OPG)? What is its function?
Decoy receptor made by osteoblasts that binds RANK-L → prevents RANK binding.
What is the role of M-CSF in bone turnover? It is secreted by what cells?
Stimulates osteoclasts. Secreted by osteoblasts.
What are the 2 types of bone formation?
Endochondral ossification and Membranous ossification.
When does Endochondral Ossification occur?
During embryogenesis.
How do Long bones develop?
Via Endochondral Ossification.
What begins Endochondral Ossification?
Hyaline cartilage ‘model’ → primary and secondary ossification centers grow toward each other → leaves area of cartilage that becomes the Epiphyseal plate (‘growth plate’).
Where is the growth plate found?
Between Metaphysis and epiphysis.
What occurs at the growth plate?
Chondrocytes grow toward epiphysis. Osteoblasts lay down matrix toward diaphysis.
What is Woven and Lamellar bone?
Woven bone: first type of bone formed by osteoblasts, disorganized collagen fibers/weaker → later remodeled into lamellar bone. Lamellar bone: layered bone, organized, and stronger.
When is woven bone seen in adults?
After injury.
What does Membranous Ossification form?
Most flat bones (skull, facial bones).
How does Membranous Ossification occur?
Matrix formed directly, osteoblasts lay down woven bone → remodeled to lamellar bone.
What is the most common cause of dwarfism?
Achondroplasia.
What gene mutation is associated with Achondroplasia?
FGFR3 gene mutation.
What percentage of Achondroplasia cases are due to spontaneous mutation?
80%.
What happens to babies with homozygous gene mutation for Achondroplasia?
They will die.
What is the inheritance pattern of Achondroplasia?
Autosomal dominant.
Achondroplasia occurs due to defective?
Endochondral ossification.
What are Mucopolysaccharidoses? What are 2 examples?
Lysosomal storage disease. Hurler’s and Hunter’s syndrome.
What do Hurler’s and Hunter’s syndrome lead to?
Inability to metabolize Heparan and dermatan sulfate.
What happens to chondrocytes in Hurler’s and Hunter’s syndrome? What does this lead to?
Mucopolysaccharides accumulate in Chondrocytes → cell death. Leads to short stature and malformed bones.
What are 3 osteoblast activity markers?
Alkaline phosphatase, Osteocalcin, Type I procollagen.
What is Osteocalcin?
Major non-collagen protein in bone matrix.
Type I procollagen is synthesized by what cells? What is it made of?
Osteoblasts. Made of 3 pro alpha chains.
What is the function of Alkaline Phosphatase in bone?
Creates alkaline environment for calcium deposition.
Where is Alkaline Phosphatase found?
In bone and liver.
What stimulates osteoclasts?
Acidosis.
What does continuous administration of PTH lead to?
Cortical bone resorption → ↑ serum calcium.
What does low dose once daily bolus administration of PTH lead to?
Increase in Trabecular bone formation.
What is the mechanism of Teriparatide? What is it used for?
Artificial PTH, used for Osteoporosis.
Which cells contain PTH receptors?
Osteoblasts.
What are 2 effects of estrogen on bone?
Increase bone density and close growth plate at puberty.
What does estrogen induce?
Apoptosis of osteoclasts.
What does estrogen increase/decrease in terms of bone related proteins?
Stimulates OPG synthesis, decreases M-CSF and RANK production.
What occurs due to defective osteoclast activity?
Osteopetrosis.
What are the 2 main forms of Osteopetrosis? Which is most severe?
Autosomal recessive (infantile) form: more severe. Autosomal dominant form: milder form, present in adolescence.
What results from a mutation in carbonic anhydrase type II gene?
Infantile form of Osteopetrosis.
What condition may a patient with Infantile form of Osteopetrosis also have?
Renal tubular acidosis.
What is the autosomal dominant form of Osteopetrosis also called?
Albers Schönberg disease.
What is the clinical presentation of Osteopetrosis?
Bones prone to fracture, excess bone → loss of bone marrow → Pancytopenia, enlarged liver and spleen (extramedullary hematopoiesis), excess bone in skull → cranial nerve compression (Vision loss, Deafness, Facial paralysis), Hydrocephalus.
What is Osteopetrosis potentially curable with?
Bone marrow transplant.
What is Rickets and Osteomalacia caused by? This leads to?
Low calcium or vitamin D intake leads to poor mineralization of osteoid.
Where is osteoid found?
Area of new bone growth: Children = growth plates, Adults = bone turnover.
What occurs to the bone in Rickets?
Growth plate thickens from osteoid accumulation, distorted bone growth, epiphyseal widening.
What are clinical features seen in Rickets?
Genu Varum, Rachitic rosary: swelling at costochondral junctions, Craniotabes (soft skull).
Where does Osteomalacia occur?
In areas of bone turnover (most often spine, pelvis, legs).
What are 2 clinical features of Osteomalacia?
Bone pain/tenderness and fractures.
What are 2 classic X-ray findings of Osteomalacia? What is it caused by?
Pseudofractures, Looser Zones. Caused by repaired stress fractures that are inadequately mineralized.
What are common causes for Vitamin D deficiency?
Maternal deficiency during pregnancy, reduced sun exposure, fat malabsorption, liver and renal failure.
What are 5 lab findings seen in Rickets and Osteomalacia?
Low Calcium, Low Vit D.
