MSK-Pathology

*Because Chondrocyte proliferation inhibition due to Overactive FGFR3 leads to Defective ENDOCHONDRAL OSSIFICATION -Long bone growth=Longitudinal bone (Limbs) needs this type of ossification at epiphyseal growth plates,so they have short,thick,tubular long bones in appendicular skeleton(Limbs), while head,chest,flat bones of wrist,AXIAL skeleton(SPINE)don't need endochondrial ossification/cartilage mediator as they undergo Membranous ossification, thus their length can be normal.*Achondroplasia is MCC of Short-limbed dwarfism*Note PTH,GH,IGF1 are usually normal.*Boards also freakin WANT you to know that risk of Achondroplasia in progeny increases with Increased PATERNAL age(Contrast this with maternal age in down's)-achondroPPlasia-PPaternal.*Mental function, life span, and fertility not affected(Questions love to describe guy who has short limbs but becomes scientist or some cool guy with bunch of children lol)*Once again LINEAR growth at epiphyseal growth plate is inhibited.*+UW wants u to know that they can have some craniofacial abnormalities like depression of the nose root,forehead bulging.u should also contrast this short stature that preferentially affects Appendicular skeleton to Short stature caused by GH/IGF1 deficiency where appendicular skeleton(limbs) and Axial skeleton(Spine) are proportionate.

*Cancellous bone is found in VERTEBRAL BODIES,Ends of Long bones.*Compact bone(Cortical Bone) is found in Most of the appendicular skeleton, provides support and MUSCLE ATTACHMENT sites.*Hyperparathyroidism(High PTH) usually results in SUBPeriosteal thinning as bone resorption takes place in Cortical(Compact bone)*Osteoporosis on the other hand mainly involves Spongy(Trabecullar,cancellous) bone>VERTEBRAL FRACTURES(MC),Fractures at the neck of the femur(50% is trabecular).Note that Osteoporosis does also affect Compact(Cortical bone) withOUT altering mineralization process, but yet spongy bone(More metabolically active) is preferentially affected.*know that LABS will be all normal in osteoporosis(Calcium,phosphate,PTH,ALP) but Calcium/ALP will be increased and Phosphate will be decreased in primary hyperparathyroidism.*If they make u choose lab abnormal in osteoporosis it is likely cortisosl(Hypercortisolism-like in cushing's syndrome can cause/potentiate osteooporosis)

*Remember in osteopetrosis OsteoCLASTS can't do their job of bone resorption and unmineralized spongiosa can't be broken down/Replaced.*Thickened, dense bones can't adopt to stress properly and are prone to FRACTURE.*Hepatosplenomegaly is common finding due to extramedullary hematopoiesis(Instead of bone marrow which would normally give us blood cells,we have "Bone in Bone" leading to myelophthisic process), but compensation is not enough and often patients can have anemia,thrombocytopenia,leukpenia(RISK OF INFECTION).*Remember that defect at molecular level is Defective Carbonic Anhydrase2(Which would normally promote Creation of Acidic environment by OsteoCLASTS)*Thickened bone>Narrowing of foramina>Patients often present with Cranial nerve palsies(Can manifest as VISION or HEARING changes)*Treatment is Bone marrow transplant as you give new osteoclasts(Come from Bone marrow monocytes) which don't have that defect and can break down bone when needed.**Mutation in Carbonic anhydrase can lead to Renal tubular acidosis as this enzyme is needed for HCO3 reabsorbtion.*Patient can have Hydrocephalus due to narrowing of Foramen magnum.(Hydrocephalus can manifest with urinary incontinence,Cognitive impairment,Ataxia)

*In damage of DEEP branch of Brachial artery.*In damage of RADIAL nerve.(WRIST drop due to paralysis of extensors)*Supracondylar fracture can also cause damage to brachial artery.(Supracondylar fracture mostly results in median nerve damage<Proximal lesion)

*OsteoBLASTS(Can lay down bone)

*Till horizontal you need supraspinatus(First 15 degress) and from there to horizontal you need deltoid, after horizontal position you need serratus anterior.

*in OI you have Autosomal Dominant defect in formation Type ONE collagen as there is defect in formation of Triple Helix(3alpha chains), which makes up PROcollagen(needs disulfide and hydrogen bonds in triple alpha helix) could be due to defect in glycosylation of pro-a-chain hydroxylysine residues.*BLUE SCLERA is ver characteristic finding(defect in type 1 collagen>Choroidal veins are visible) and this blue sclera will help you to differ from Child abuse (characterized by SPIRAL fractures), child with OI may be deaf(fracture of middle ear bones)and with Blue/Brown teeth that easily rots(due to lack of dentin).*uw wants you to know that bone matrix is made up of Type1 collagen+Hydroxyapetite and thus Bone matrix FORMAITON is defective in OI(Contrast this with defect in Mineralizaiton in Vit.D deficiency)*In EDS you have defective cross linking between tropocollagen molecules(insoluble molecule in Extracellular space, these guys should aggreagate together by COVALENT lysine-hydroxylysine cross-linkage to create stable collagen fibrils), typically patient would have Hyperextensible skin,Joints(can present with Excessive hip rotation) and tendency to bleed(Classic type which affects Joints,Skin involves type 5collagen(5letters in CLASS) defect while Vascular type involves defect in Type 3 found in vessels/organs>Organ rupture,berry/aortic aneurysm.)

*back pain which is NOT relieved by rest,changin position, should make you think of neoplastic bone disease esp. in older male POSSIBLE signs of prostate cancer(Loves to metastasize to bone, note that Breast is overall most common metastases to bone, so obv. vignette could give you patient with breast cancer metastases to bone.)

1)Most likely Spleen(Overlied by 9-11 ribs)2)Most likely liver.3)Most likely left kidney

*Low body fat(Less estrogen) increases your risk of osteoporosis.*everyone knows about smoking,corticosteroids and alcohol and lack of physical activity, so don't forget the weird one.*Note:Patient would most likely be Caucasian(more common than in blacks)*Peak bone mass (reached at 30 years of age)depends on genetics (Vit D receptor variation), diet and determines the risk of developing osteoporosis(It is higher in Males and thus they have lower risk, same is true for black vs white females, white females have higher risk of osteoporosis as black females have more bone mass to start with)*HISTOLOGICALLY osteoporosis is characterized by TRABECULAR THINNING+FEVER INTERCONNECTIONS(DISRUPTION OF NORMAL BONE ARCHITECTURE)

*Defective mineralization of the matrix/Cartilogenous growth plates occurs in growing bones causing weight-bearing bones to bow laterally (genu varus-medial angulation),Epiphysial widening and metaphyseal cupping/fraying are commonly observed on xray of RICKETS(Result of vitamin D def in children)other common findings include bony prominence at the costochondral junction (rachitic rosary=due to Osteoid deposition in costochondral junction), indentations in the lower ribs (Harrison’s sulci), softening of the skull= (craniotabes), hypocalcemia, hypophosphatemia hypertonia, and growth retardation , don't forget Pectus craniatum (pigeon breast=inward benging of the ribs with anterior protrusion of the ribs).*Some characteristic findings of Osteomalacia which is result of Vit.D def in adults are "Pseudofractures"-visulaized as looser zones+Xray would show osteopenia.

*The are Uniformly-distributed invaginations of the sarcolemma (muscle cell membrane) extending into each muscle fiber.*They allow Uniform contraction of all muscle fibrils, due to their uniform distribution*T-tubule depolarization-induced SR Ca2+ release is controlled by dihydropyridine receptors.*Ryanodine receptors are located on Sarcoplasmic reticulum.

*GASTRIC carcinoma,Generally any cancer.*Dermatomyositis has been associated with increased risk of occult malignancy(Cancer detected at advanced stage)*Rash will help you to differ DERMAtomyositis from Polymyositis but Important testable fact is that in contrast to Perimysial atrophy with CD4Tcell infitrate, in Polymyositis we have CD8+Tcells and ENDomysial inflammation.(Call me at 8 P.M and we END this relationship.*ANA is often + but it is not specific, Anti-Jo1 is way more specific finding for dermatomyositis.(uw wants u to know that)

*She could have vertebral compression fractures, Colles fracture(Distal radius effected), Fracture of femoral NECK.*T score EQUAL to or Less than- 2,5 SD is daignostic for osteoprosis, fragility fracture of hip/vertebra is also diagnostic.***Her Calcium and Phosphate levels would be NORMAL(They love to test this)*Bisphosphonates(inhibitors of osteoclast activity by binding hydroxyapetite) are DOC.*Teriparatide(recombinant PTH that increases osteoblast activity)*SERM(Like Raloxifene)*Calcitonin(Normally released from C cells of thyroid in response to high levels of calcium in blood and promotes buidling of the bone,while decreasing calcium levels in blood.)*Denosumab(antibody not against RANK but against LIGAND of RANK, thus mimics osteoprotegerin and inhibits maturation of OsteoCLASTS)*Remember that Weight-bearing exercises(NOT SWIMMING) with proper intake of Calcium and Vitamin D are prophylactic measures.*If patient is smoker he needs to stop smoking(Inhibits OsteoBLAST activity)

*Anticonvulsants and thyroid replacement therapy have been associated with Osteoporosis(Our patient presents with classic symptoms and Colles fracture)*Poppie wants you to know that heparin can also cause osteoporosis by decreasing bone formation and increasing resorption.*He also wants you to know that Space travel(lack of bone stress) and Anorexia nervosa(due to malnutrion), Hypogonadism(Hypopituitarism),hypercortisolism can cause osteoporosis too.*HIGHEST YIELD for osteoporosis is that there are NO ABNORMAL lab findings(PTH,Calcium,Phopshate,ALP are all NORMAL)<Separates it from osteomalacia(where calcium/phosphate are low but ALP and PTH are increased)