Day 8.2 MSK Flashcards
What are the layers of the epidermis?
From surface to base: Californians Like Girls in String Bikinis Stratum Corneum Stratum Lucidum Stratum Granulosum Stratum Spinosum Stratum Basalis
In psoriasis, how do the layers of the epidermis change?
Stratum spinosum thickness increases (this is what makes the plaques)
Stratum Granulosum thickness is decreased.
List the epithelial cell junctions
Zona occludens (tight jn) Zona adherens (intermediate jn) Macula adherens (desmosome) Gap jn Hemidesmosome
In which layer of skin are the blood vessels located?
in the dermis. nutrients get to the epidermis by diffusion.
Zona occludens
aka Tight Junction
At the top of the sides bt epithelial cells.
Prevents diffusion across the paracellular space
Made of claudins and occludins
Zona adherens
aka Intermediate Junction
bt the sides of the epithelial cells, just below the zona occludens (tight jn)
E-cadherens in the cell mbr connect to actin fillaments in the cell.
Cadherens are Ca2+dependent Adhesion molecules.
Macula adherens
aka Desmosome
On the sides bt 2 epithelial cells
sml, discrete sites of attachment, cadherins connect to intermediate filaments.
Desmoplakin connects to keratin in the cell.
Gap jn
Allows adjacent cells to communicate for electric and metabolic fns (heart cells, myocytes)
Md of connexon w central channel
Hemidesmosome
Connects epithelial cells to underlying basement mbr/extracellular matrix
Integrin maintains integrity of the BM, binds to the laminin in the BM.
Anti-hemidesmosome Ab
Bullus pemphigoid
Anti-desmosome Ab
Pemphigus vulgaris
Desmosome vs Hemidesmosome
Desmosome is on the side, bt epithelial cells
Hemidesmosome is on the bottom, bt one epithelial cell and the BM.
Anti-desmosome Ab = pemphigus vulgaris
Anti-hemidesmosome Ab = bullous pemphigoid
Unhappy triad
Knee injury
Hitting knee from lateral side (football)
Dmg to:
1. MCL (medial collateral ligament)
2. ACL (anterior cruciate ligament)
3. Lateral (56%) or Medial (44%) meniscus
Positive anterior drawer sign indicates tearing of the ACL (tibia comes anterior to the femur)
Abn passive abduction indicates a torn MCL (Lachman Test)
What are the 4 ligaments of the knee?
Anterior cruciate ligament
Posterior cruciate ligament
Lateral collateral ligament
Medial collateral ligament
Note: “anterior” and “posterior” refer to where the ligament is attached on the TIBIA. (so attached to ant tibia or attached to post tibia)
Where is the pudendal nerve blocked during delivery? (external landmark)
at the ischial spine (palpate thru vag)
Where is the appendix located? (external landmark)
McBurney’s point: 2/3 of the way from the umbilicus to the ASIS (anterior superior iliac spine)
External landmark for lumbar puncture
Level of iliac crest = L4
What are the rotator cuff muscles?
SItS: Supraspinatus Infraspinatus teres minor Subscapularis
Action of supraspinatus m
helps deltoid abduct arm- does first initial 10-15degrees of abduction
Action of infraspinatus m
laterally rotates arm
Action of teres minor m
adducts and laterally rotates arm
Action of subscapularis
adducts and medially rotates arm
Which is more anterior, the acromion or the coracoid?
coracoid
Impingement in rotator cuff
Supraspinatus (which is the rotator cuff muscle that is on top) is commonly impinged by the acromion d/t repetitive overhead activity (swimming/tennis) which causes hypertrophy of the muscle, or can also be congenital.
Dx by Empty Can Test- turn thumb downward (like emptying a can), and if it’s painful to abduct the first 10-15degrees, it’s impingement.
Repetitive elbow trauma
Degenerative injury d/t repeated use- leads to tiny tears in tendons and muscles. Can be inflammatory: Lateral epicondylitis (tennis elbow) Medial epicondylitis (golf elbow)
What structures can be dmgd in anterior shoulder dislocation?
Axillary Nerve
Posterior Circumflex Artery
Supraspinatus tendon
Bankhart lesion: anterior glenohumeral ligaments and glenoid labrum separate from articular surf of the anterior glenoid neck
Hill-Sack lesion: compression fracture- chip in posterolateral head of humerus d/t abrasion against anterior rim of the glenoid (hitting it against the rim during the dislocation)
Dislocated vs separated shoulder
Dislocated - head of humerus rotates out of glenoid cavity
Separated: clavicle separates from acromion and coracoid process of the scapula
What is leukocyte extravasation?
Neutrophils exit blood vessels at site of tsu injury/inflam.
4 steps- rolling, tight binding, diapedesis, migration.
Leukocyte extravasation: Rolling
first step.
PMLs express Sialyl Lewis-X
Endothelial cells express E-selectin on their surfaces.
E-selectin grabs the SL-X and causes the PML to “roll” along the surface.
Other adhering molcules include P-selectin, which is found 2 different places- expressed by endothelial cells, and also expressed on platelet surfaces. Also L-selectins are expressed on the surface of lymphocytes.
What enhances the synthesis/expression of endothelial adhesion molecules (E-selectin)
Acute phase cytokines: IL-1, IL-6, TNFa
Leukocyte extravasation: tight binding
2nd step.
Endothelial cells express ICAM-1
Leukocytes/PMNs express LFA-1, aka integrin.
ICAM binds integrin tightly, securing the PMN to the endothelial surface
(integrin integrates)
Leukocyte extravasation: Diapedesis
3rd step.
Leukocyte squeezes bt endothelial cells and exits the blood vessel into the interstitum.
PECAM-1 (aka CD31) on the endothelial cells and PECAM-1 (CD31) on the leukocyte mediate this.
Leukocyte extravasation: Migration
4th (last) step Leukocyte travels thru interstitum to the site of injury or infection, guided by chemotactic signals. Bacterial products in the interstitum/at the site of injury serve as chemotactic factors: CILK C5a IL-8 LTB4 Kallikrein
What factor enhances the process of binding, diapedesis, and migration?
Platelet Activating Factor (PAF)
What dz is caused by abnormal integrin?
Leukocyte adhesion syndrome
No integrin on leukocytes means they can’t tight bind with ICAM-1 on the endothelial cells.
Px: delayed separation of the umbilicus
How is muscle contraction initiated (how is Ca2+ released)?
First, an AP depolarization opens up the voltage-gated Ca2+ channels, causing NT rls. NTs bind to the post-synaptic cell and lead to muscle cell depolarization in the motor end plate. The depolarization travels along the muscle cell down T-tubules, and depolarizes voltage-sensitive dihydropyridine recetors, causing them to release Ca2+. That Ca2+ causes the ryanodine receptors on the SR to release Ca2+ (calcium-induced calcium rls). And, contraction can start.
How does muscle contraction take place, once Ca2+ has been rlsd from the SR?
The rlsd Ca2+ binds to troponin C, which is attached to the tropomyosin and moves it out of the way so that the myosin-binding groove on actin filaments is uncovered. Myosin (which is bound to ADP and Pi) attaches to the actin. Myosin rls’s the Pi and the ADP and does the power stroke (this is muscle contraction!)
After, ATP binds to the myosin, releasing it from the actin (relaxation).
Z line
end of the sarcomere unit (where 2 sarcomere units meet) (looks like ric-rac)
M line
middle of the sarcomere
middle of the thick myosin filament
A band
the length of the thick myosin filament (regardless of overlap of thick/thin fibers)- this always stays the same length (bc the myosin fiber itself can’t change lengths!)
H band
the part of the sarcomere that is only thick filament. (centered around the M line). When the sarcomere contracts toward the M line, the H band gets smaller as the thick and thin filaments overlap (because there is less length that is only thick filaments)
I band
the part of the sarcomere (and the one next to it) that is only think filaments. has the Z line (sarcomere boundary) in the middle. During muscle contraction, it gets shorter as the thick myosin and thin actin overlap.
Thick filaments, thin filaments
Thick filament - myosin
Thin filament - actin
Titin
long large molecule that anchors myosin to the z-line of the sarcomere.
How does muscle contraction affect the various bands of the sarcomere?
The H and I band shorten
The A band is Always the same length.
HIZ shrinkage.
What in initiation of muscle contraction, what blocks the rls of Ca2+ from dihydropyridine receptors?
Dihydropyridine CCBs:
Nifedipine, Amlodipine, etc
During initiation of muscle contraction, what blocks the rls of Ca2+ from the SR thru the Ryanodine receptors?
Ryanodine receptors are blocked by Dantrolene.
Dantrolene stops muscle contraction in NMS (neuroleptic malignant syndrome) and in malignant hypothermia
Type I muscle fibers
Slow twitch
Red fibers, bc incrsd mito and myogloblin concentrations (this means increased oxidative phosphorylation), which leads to
Sustained contraction.
“One slow red ox”: type 1, slow twitch, red fibers, ox-phos
Type II muscle fibers
Fast twitch White fibers (bc there is not much mito or myogloblin)- this means there is more anaerobic glycolysis. Weight training yields hypertrophy of fast-twitch (Type II) fibers.
What causes the myosin head to be cocked?
ATP –> ADP + Pi (both the ADP and Pi are still bound to the cocked myosin)
What allows the power stroke of myosin to take place?
Rls of Pi and ADP
If there is not ATP to bind the myosin heads, what pathology occurs?
Rigor mortis
What is the pathway for smooth muscle contraction and relaxation?
Contraction:
AP –> smooth musc mbr depolarizes –> voltage-gated Ca2+ chnls open –> increased Ca2+ in cytoplasm –> Ca2+ binds to calmodulin –> Ca2+/calmodulin activates MLCK (myosin light chain kinase) –> MLCK phosphorylates Myosin–> Myosin-P + actin form a cross-bridge and contract.
Relaxation: MLCP (myosin light chain phosphatase) dephosphorylates the Myosin-P, so there is just myosin (and actin, not linked), causing relaxation.
What drugs inhibit MLCK (myosin light chain kinase)? What effect does this have on the muscle?
Dihydropyridine CCBs,
Epi at the B2 receptor
Prostaglandin E2
These inhibit contraction.
Without MLCK, the myosin is not phosphorylated, so it can’t form a crossbridge w actin and cause contraction.
What drugs enhance the activity of MLCP (myosin light chain phosphatase)? What effect does this have on muscle?
Sildenafil
NO
LPS (gram-neg bacteria)
These promote relaxation.
MLCP removes the phosphate from myosin, causing relaxation of muscle. More MCLP effect means more relaxation.
What is endochondral ossification?
Longitudinal bone growth.
Cartilagenous model is first made by chondrocytes (endoCHRONDRAL ossification).
Later, osteoclasts and osteoblasts replace the cartilage with woven bone, and then remodel the woven bone to lamellar bone.
What is membranous ossification?
Flat bone growth (skull, facial bones, axial skeleton)
Woven bone is formed directly (w/o cartilage)
Later, the woven bone is remodeled to lamellar bone.
In endochondral ossification, the osteoblasts help replace the cartilage with woven bone. Where do the osteoblasts come from?
From mesenchymal stem cells in the periosteum.
List the bisphosphonates
-dronate etidronate pamidronate alendronate risedronate
Mechanism, use, toxicity of bisphosphonates
Mech: inhibit osteoclasts. reduce formation and resportion (both) of hydroxyapatite.
Use: post-menopausal osteoporosis, malignancy-assoc’d hypercalcemia, Paget’s dz of bone
Tox: corrosive esphg (don’t lay down after eating), naus/diarrhea
What is the FGF gene responsible for?
Limb lengthening.
(FGF - fibroblast growth factor)
In achondroplasia, constitutive activation of the FGF3 receptor actually inhib’s chondrocyte proliferation –> short limbs (dwarfism)
Achondroplasia
Dwarfism.
Longitudinal bone growth (endochondral ossification) does not occur –> short limbs.
Membranous ossification (flat bone growth) does occur tho, so normal head/trunk.
Normal life span and fertility.
Achondroplasia mutation pattern
> 85% of mutations occur sporadically. a/w advanced paternal age.
Can also be inherited - auto dom. inheritance.
But, homozyg dom (RR) is lethal in utero, so all pts w achondroplasia will be heterozyg (Rr).
Two pts w achondroplasia have a child. What are the chances the child has achondroplasia?
50%. All pts w achondroplasia are Rr, and it's auto-dominant. So Rr X Rr = 25% RR (these die in utero) 50% Rr (have achondroplasia) 25% rr (don't have achondroplasia)
One pt w achondroplasia and one normal pt have a child. What are the chances it will have achondroplasia?
50%. All pts w achondroplasia are Rr, and it's auto dom. Rr x rr = 50% Rr (have achondroplasia) 50% rr (don't have it)
T/F with autosomal dominant inheritance, there is no such thing as an unaffected/silent carrier.
True.
RR has it
Rr has it (since it’s dominant)
rr doesn’t have it (and doesn’t carry it)
What is osteoporosis? Risk factors?
Reduction of primary trabecular/spongy bone mass, even tho there is normal bone mineralization.
D/t: advanced age smoking thin white no weight-bearing exercise poor Ca2+ and Vit D intake hypogonadism (menopause, decreased testosterone, decreased estrogen) corticosteroid use (>3mo) heparin use (prolonged)
If a pt will be taking corticosteroids for >3mo, what other drug do they need to be taking?
A bisphosphonate (-dronate) to prevent osteoporosis.
What is Type I and Type II osteoporosis?
Type I: post-menopausal. increase bone resorption d/t decrsd estrogen lvls. estrogen replacement as prophylaxis controversial bc of side effects
Type II: Senile osteoporosis. Both M and F >70yo
What fractures are common in osteoporosis?
Vertebral crush fracture –> acute back pain, loss of height, kyphosis. Kyphosis is bc the loss of bone usu occurs in the anterior part of the vertebral body- so that part is crushed and spine curves in C shape)
Femoral neck fracture (femur fracture is life-threatening- hard to recover from)
Distal radius (Colles’) fracture- often px’g sign, esp if it was only d/t low impact.
Prophylaxis for osteoporosis
Exercise!
Eat Ca2+ before 30yo. Get Vit D
Don’t smoke or use corticosteroids.
Rx for osteoporosis
Estrogen and/or calcitonin
Bisphosphonates or PTH pulses (Teriparatide) for severe cases.
Don’t take glucocorticoids!
