sbj - test 2

stromal cells: support matrix, fat cells, fibroblasts, macrophages, monocytes, and lymphocytes

hematopoetic elements:erythroid precursors adjacent to venous sinuses, granulocytic precursors deep in cords, and megakaryocytes adjacent to venous sinuses

granulocytic precursors

erythroid precursors and megakaryocytes

neutrophils, eosinophils, and basophils

Auer rods (accumulation of primary granules)

primary granules (strongly + for MPO)

secondary granules

myelocyte, promyelocyte, myeloblast, CFU-GM, CFU-GEMM

PMN leukocyte (neutrophil)

phagocytosis and elimation of injured tissue or invading organisms

1) migrate
2) bind and eat
3) digest or kill

(marginate to outside of blood vessel and adhere to endothelial cells, diapedesis, phagocytosis, lysosomal enzymes kill)

peripheral blood

in the tissue

1) phagocytosis
2) production of cytokines
3) production of inflammatory accessory molecules
4) antigen presentation
5) storage of iron
6) removal of senescent cells
7) participation of anti-tumor responses

eosinophil

-eosinophils, early megas

myeloblasts

CFU-GEMM, CFU-GM, myeloblast, promyelocyte, myelocyte, metamyelocyte, neutrophil

promyelocyte

myeloblast, promyelocyte

myeloblast

myeloblast

myelocyte

lysozyme, plasminogen activators

metamyelocyte

band

neutrophils

megakaryocytes

production of platelet

megakaryocyte

early have single or bilobed nuclei and euchromatin; late have multisegmented nucleus with heterochromatin and cytoplasm containes granules

numerous large, round granules containing a crystallois compound made up of major basic protein (MBP)

eosinophils

basophils

histamine, heparin, and chemotactic factor

basophils

tissues

anaphylactic and piecemeal

monocytic

mature monocytes

mature monocytes

bone marrow, thymus

lymphatic vessels, lymph nodes, spleen, lymphoid nodules

larger into left subclavian vein and smaller right thoracic duct drains lymph into right subclavian vein

left upper quadrant of abdominal cavity, under the diaphragm

lymphoid nodules associated with the GI tract; include palatine, pharyngeal, and lingual tonsils, and peyer's patches

lymphocytes distributed along the segmental bronchioles and bronchi

T cells (part of the lymph node)

B cells (part of the lymph node)

they become secondary follicles with germinal centers

medullary cords and medullary sinuses

Afferent lymphatics or high endothelial venules

periarteriolar lymphocytic sheath (PALS); these cells are predominantly T cells

secondary lymphoid organ

filter for the blood

macrophages at the splenic cord-splenic sinus interface

densely packed immature pre-T lymphocytes, irregular epithelial cells

mature T cells

fused remnants of epithelial cells found in medulla of the thymus

1. lymphocytes
2. plasma cells
3. dendritic cells
4. natural killer cells

small with a compact nucleus composed of heterochromatin and cytoplasm populated by few organelles

larger with a large nucleus composed of euchromatin

pluripotent stem cell, lymphoid progenitor cell, T or B cell or NK cell

terminally differentiated B cells; therefore non-dividing

secrete large quantities of immunoglobin

abundant rough ER

area of clearing near the nucleus that consists of the golgi apparatus

eccentric and looks like a soccer ball

abundant cytoplasm, numerous lysosomes, long cytoplasmic projections

specialied lymphoid cells that mediate non-specific cytotoxicity

large, abundant cytoplasm with numerous large cytoplasmic granules

begins at the end of the 6th week of embryogenesis and at 8 weeks there are 6 primary lymph sacs

only T cells (after birth, B cells migrate to the nodes and form B cell follicles)

during 5th week

dorsal mesogastrium

3rd (thymus and inferior parathyroid gland) and 4th (superior parathyroid) pharyngeal pouches

digeorge syndrome

leukocytosis (normal or low), anemia, thrombocytopenia

obstruction or destruction of small capillaries, primarily in CNS and lungs

-low platelets
-prolonged PTT
-low fibrinogen
-+ fibrin monomers
-increased D-dimers

1) morphologic
2) cytogenetics and FISH
3) flow cytometry
4) DNA based analysis

hypercellularity and lack of heterogeneity

nearly all hematopoietic cells

immaturity without lineage specificity

lymphoid immaturity (ALL)

T cell marker (T-ALL)

B cells marker (B-ALL)

most specific B cell marker (B-ALL)

myeloid lineage markers

most specific marker for myeloid lineage and AML

monocytic differentiation

translocation 15 and 17, inversion 16, translocation 8 and 21

normal karyotype

>3 abnormalities, deletions involving 5 and 7

translocation 9 and 22, translocation 4 and 11, hypodiploidy, near triploidy, complex abnormalities

CEPBA mutation, FLT3 wild type

NPM mutation, FLT3 wild type

FLT3 mutated

c-kit mutated

c-kit wild type

myeloid differentiation of leukemic blasts

presence of auer rods or presence of certain proteins on the cell surface

cytarabine (7 days), idarubicin (3 days)

translocation 15 and 17, promyeloblasts with abundant auer rods or large purple granules

DIC, and targeted agents such as ATRA and arsenic are able to reverse the abnormal physiology

abnormal fusion protein binds and blocks transcription so blasts can't differentiate

dissociate the abnormal protein, which allows transcription and subsequent differentiation of the promyeloblasts to mature neutrophils

surface CD3 negative, CD1a negative

surface CD3 variable, CD1a positive

surface CD3 positive, CD1a negative

age

L-asparagine, vincristine, corticosteroids, daunorubicin, imatinib, dasatinib

intratehcal chemotherapy: methotrexate/Ara-C

disorder of blood cell formation, akin to dysplasia characterized by abnormal maturation of any blood cell lineage and can be observed morphologically in BM or peripheral blood

hypogranular neutrophils and bands, hyposegmented neutrophil

hypolobulated, multi-nucleated, small

trinucleated, mitosis, ringed sideroblasts

dyspoiesis of one or more cell lineages, hypercellularity, and < 20% blasts

elevated percentage of blast cells between 5-19%, ringed sideroblasts, cytogenetic or FISH abnormality, loss of a chromosome (5 or 7)

MDS do not have hyperleukocytosis, tumor lysis, or present with organ infiltration of blasts

normal, negative y, deletion of 5q, deletion of 20q

complex (>3 abnormalities), chromosome 7 abnormality

growth factor (EPO, G-CSF), immunomodulation agents (lenaliomide)

allogenic stem cell transfer, methyltransferase inhibitors (azacytidine, decitabine)

transcription factor can't bind, can't make proteins necessary to mature the blast cell normally

DNA methyltransferase

total bone marrow aplasia; autoimmune condition in which T cells attack hematopoietic precursor cells, resulting in marrow failure

lack of hematopoietic cells which are replaced by fat cells,

ANC < 500, ARC < 40,000, platelets < 20,000

ANC < 200

bone marrow transplant

immunosuppressive therapy (horse ATG and cyclosporin)

-CML
-polycythemia vera
-essential thrombocythemia
-myelofibrosis

BCR-ABL (9;22) translocation

dimerizes and phosphorylates itself, creates abnormal protein, enhances cell signaling, causes myeloblasts to proliferate abnormally and create more WBC

full complement of white cell series: bands, neutrophils, metamyelocytes, myelocytes, promyelocytes, blasts, basophils, and eosinophils, basophilia, eosinophilia

fatigue, weakness, pallor, left upper quadrant fullness, early satiety, splenomegaly, hepatomegaly, purpura

<10% blasts

10-19% blasts

>20% blasts

occupies the ATP binding pocket of the Abl kinase domain which prevents substrate phosphorylation and signlaing

antagonist developed specifically to inhibit the mutant tyrosine kinase

nilotinib and dasatinib

1. hemoglobin >18 men >16 women
2. JAK2 mutation

1. hypercellularity with pan myelosis, erythroid, granulocytic, and megakaryocytic proliferation
2. serum EPO below normal
3. endogenous erythroid colony formation in vitro

asymptomatic, fatigue, headache, pruritis, dyspnea, dizziness, visual change, splenomegaly, thrombosis

hypercellularity, clustering of megakaryocytes, and panmyelosis

phlebotomy, daily aspirin and if patient is at high risk of thrombosis cytoreductive therapy with hydroxyurea

megakaryocyte hyperplasia in bone marrow and sustained thrombocytosis in the peripheral blood

persistent thrombocytosis, absence of iron deficiency, JAK2, rule out others

increased number of large mature megakaryocytes in clusters

leukoerythroblastic blood smear: immature white blood cells, tear drop red blood cells, and nucleated red blood cells

-leukoerythroblastic, increased marrow reticulum, splenomegaly, JAK2, CD34 cells, rule out others

fibrosis and bizarre, dysplastic megakaryocytes

bone marrow cavity is replaced by fibrosis

ruxolitinib (JAK2 inhibitor): splenomegaly and constitutional symptoms, radiation: bone pain, darbopoietin: anemia

1. drug toxicity (damage to stem cells decrease production of WBCs)
2. severe infection (increased movement of neutrophils into tissues)

GM-CSF or G-CSF

1. immunodeficiency
2. high cortisol state (induces apoptosis of lymphocytes
3. autoimmune destruction
4. whole body radiation

1. bacterial infection
2. tissue necrosis
3. high cortisol state (knocks the neutro off the endothelial wall therefore enters circulation)

decrease in Fc receptors and therefore CD16

chronic inflammatory states and malignancy

allergic reactions, parasitic infection, and hodgkin lymphoma (IL5 production)

CML

1. viral infections
2. bordetella pertussis infection (lymphocytosis-promoting factor blocks lymphocytes from leaving blood to enter lymph node)

1. oropharynx
2. liver
3. B cells

1. generalized lymphadenopathy (paracortex)
2. splenomegaly (PALS)
3. high WBC count

lymphocytic leukocytosis comprised of reactive CD8+ t cells

EBV viral capsid antigen

1. risk of splenic rupture
2. rash
3. dormancy leading to risk of recurrence and B-cell lymphoma

large, immature, punched out nucleoli

DNA polymerase

TdT, CD10, CD19, CD20

translocation 12,21 and translocation 9, 22

good usually seen in children

poor usually seen in adults

TdT, CD2 through CD8 NOT CD10

teenagers, thymic mass (so actually is called a lymphoma)

MPO

crystal aggregates of MPO

translocation 15, 17: translocation of retinoic acid blocks maturation and promyelocytes accumulate

abnormal promyelocytes contain numerous primary granules and auer rods which can activate coAg cascade and therefore DIC

ATRA which will bind the altered receptor and cause blasts to mature and eventually die

1. proliferation of monoblasts
2. lack MPO
3. infiltrate gums

1. proliferationg of megas
2. lack MPO
3. associated with Downs before the age of 5

cytopenias, hypercellular bone marrow, abnormal maturation of cells, and increased blasts (less than 20%)

naive B cells that co-express CD5 and CD20

increased lymphocytes and smudge cell

1. hypogammaglobinemia
2. autoimmune hemolytic anemia
3. diffuse large B-cell lymphoma with enlarging lymph node or spleen

mature B cells characterized by hairy cytoplasmic processes

TRAP positive, splenomegaly, dry tap on bone marrow aspiration

2-CDA (an adenosine deaminase inhibitor)

mature CD4 T cells associated with HTLV-1

rash, LAD, hepatosplenomegaly, lytic bone lesions with hypercalcemia

mature CD4 T cells that infiltrate the skin leading to rash, plaques, and nodules

aggregates of neoplastic cells in the epidermis

lymphocytes with cerebriform nuclei

high WBC count with hypercellular bone marrow - cells of all myeloid lineages are increased but are classified based on dominant myeloid cell produces

1. hyperuricemia and gout
2. marrow fibrosis and transformation to acute leukemia

myeloid cells especially granulocytes and basophils

translocation 9,22 which creates fusion protein with increased tyrosine kinase actitivy

pluripotent stem cell therefore than go to AML or ALL

1. negative leukocyte alkaline phosphatase stain (grans in leukemoid reaction are LAS positive)
2. increased basophils
3. translocation 9,22

myeloid cells especially RBCs, grans, and platelets

JAK2

1. blurry vision and headache
2. increased risk of venous thrombosis
3. flushed face
4. itching

phlebotomy and hydroxyurea

1. EPO levels decreased
2. RP: high EPO low O2 in high altitude or lung disease and high O2 in renal cell carcinoma

myeloid cells especially platelets

JAK2 kinase

increased risk of bleeding and/or thrombosis

myeloid cells especially megakaryocytes

JAK2 kinase

megakaryocytes producing excess platelet-derived growth factor

1. splenomegaly
2. leukoerythroblastic smear (tear drop RBCs, nucleated RBCs, and immature granulocytes)

single lymph node group

multiple lymph node groups on same side of diaphragm

multiple lymph node groups on both sides of diaphragm

multiple extranodal sites or lymph nodes and extranodal disease (i.e. lung, liver, bone)

with constitutional symptoms - weight loss, fever, drenching night sweats

CLL/SLL

diffuse large B-cell lymphoma

mantle cell lymphoma

burkitt lymphoma (also TdT and BCL2 negative and CD20 positive)

stage I and II: R Chop for 3 cycles

stage III and IV R Chop for 6 cycles

CLL

abnormal complete blood count in asymptomatic individual

FCR in younger patients
(Fludarabine, Cytoxan, rituximab)

required only for 3-4 stages

lymphocytosis only

lymphadenopathy

splenomegaly

anemia

thrombocytopenia

CLL/SLL

follicle center (germinal center) B cells with a partially follicular pattern

B cells are centrocytes and centroblasts

asymptomatic, enlarged peripheral lymph node

translocation 14, 18

palliative
younger: R chop or R bendamustin followed by consolidation and maintenance with rituximab

small monomorphic B cells with irrgeular nuclear contents in an expanding mantle layer

translocation 11, 14 which involves cyclin D gene which moves cells through the cell cycle from G1 to S phase much more rapidly than normal causes increased proliferation

incurable but very responsive to initial immunochemotherapy using R-hyperCVAD

translocation 8, 14

abrupt abdominal symptoms associated with advanced, bulky, adenopathy

bone marrow involvement, elevated LAD and uric acid, high risk of tumor lysis syndrome, uric acid, phosphorous, calcium, and potassium levels must be monitored

curable:
R hyperCVAD immunochemotherapy

-splenic
-extranodal/mucosa associated
-nodal

translocation 11, 18

nodal

R bendamustine or R Chop

hep C treatment or if no hep C, splenectomy or rituximab

caused by h pylori therefore treat the h pylori

small B cells, plasamctoid cells, and plasma cells in bone marrow, spleen, and lymph nodes associated with IgM monoclonoal gammopathy

hyperviscosity syndrome with dilated retinal veins, visual blurring, epistaxis, and confusion due to elevated IgM, neuropathies, or cryoglobinemia (rash, renal insufficiency)

plasmapheresis to remove IgM, rituximab + bendamustine, or rituximab, boretozomib, dexamethasone

small mature B cells with oval nuclei, hairy projections in bone marrow and splenic red pulp

CD 103 positive
CD 25 positive
CD 123 positive
annexin 1 positive
CD 5 negative
CD 10 negative

splenomegaly, cytopenias

remission for majority of patients

anaplastic large-cell lymphoma ALK positive

its a CD 20 antibody and CD20 is not on the surface of T cells

HL: better prognosis, younger age, less common, orderly lymph node spread, classic disease distribution

mononucleated and multinucleated (hodgkins and reed sternburg) tumor cells with admixture of nonneoplastic inflammatory cells

CD 15 positive
CD 30 positive

1) nodular sclerosis
2) mixed cellularity
3) lymphocyte predominant
4) lymphocyte depleted

popcorn cell: large with irregular nuclear membrane

CHL

NLPHL

1) B symptoms
2) bulky disease ( greater than 10 cm)
3) 2 or more nodal sites
4) extranodal sites
5) 40 years old and up
6) mixed cellularity or lymphocyte depleted
7) ESR greater than 50 if withouth B symptoms

2 cycles of ABVD plus 20-30 gy of radiotherapy

radiation only

4 cycles of ABVD plus 30 gy of radiotherapy (or 6 ABVD cycles)

6 to 8 cycles of ABVD or escalated BEACOPP

rituximab and chemotherapy

3 cycles of salvage chemotherapy followed by autologous hematopoietic stem cell transplantation

expansion of a clone of immunoglobulin secreting, heavy chain class switched, terminally differentiated B cells that typically secretes a single monoclonal immunoglobulin called M-protein (monoclonal gammopathy)

CD 138
CD 19

MGUS: less than 3 M-protein and less than 10 percent bone marrow plasma cells

smoldering: greater than 3 and greater than 10

asymptomatic and finds abnormal protein on blood test

1. serum free light chain (kappa:lambda vs normal)
2. type of immunoglobulin (IGA worse)
3. size of M protein (the bigger the worse)

deletion 17
translocation 4, 14
translocation 14, 16

CD 19 negative
CD 56 positive
CD 138 positive

only for multiple myeloma

Calcium
Renal insufficiency
Anemia
Bone lesions

1) low albumin
2) gap between total protein and albumin of greater than 4
3) high calcium
4) high creatinine

young: bortezomib, lenalidomide, dexamethasone

elderly: bort and dex or lena and dex

lenalidomide

albumin greater than 3.5 and beta 2 microglobulin less than 3.5

beta 2 microglobulin greater than 5.5

zoledronic acid

collection of plasma cells in a single bony site or a single extramedullary site (upper respiratory tract)

no bone marrow involvement

focal external beam radiation

neoplastic plasma cells that secrete light chains which deposit in various tissues and form beta pleated sheets that binds congo red and displays apple green birefringence

heart, peripheral nerve, kidney, GI tract, fat, or liver

deposition disease does not bind to congo red and does not show apple green birefringence

localized absence of skin, usually on scalp, often part of another syndrome

dry, fish skin like scales, hyperkeratosis, involving entire body surface, increased cell-cell adhesion, causes abnormal desquamation, leading to retention of abnormal scale

rare, autosomal recessive, thick-ridged cracked skin

form of icthyosis

covered by thick, taut membrane, cracks with respiration, may shed membrane leaving behind normal or abnormal skin

benign tumor of lymphatics (aka lymphangioma)

most common neoplasm in infants, children, B9 endothelial cell tumor (aka strawberry nevus)

melanocytes fail to produce melanin because of lack of enzyme tyrosinase

AD, localized albinism, white forelock, lack of melanin in patch of skin or hair; caused by mutation in KIT protooncogene

KIT proto-oncogene encodes cell surface receptor transmembrane tyrosine kinase for embryonic growth factor, steel factor, which regulates melanocyte proliferation

failure of normal muscle development, widespread joint contractures, all associated with decreased fetal movement

"wry neck" injury to SCM muscle with fixed rotation, tilting of head, because of fibrosis of SCM muscle

-can't flex the neck (bring to midline)

innervation of muscle (neurogenic), myopathic (primary defect - congenital muscular dystrophy), or lack of normal growth of the muscle (amyoplasia)

upper extremity (75%)

chromosomal anomalies - Trisomy 18

brachydactyly

thalidomide between d 24-36

multifactorial

amniotic band sequence

complete absence of limb; suppression of limb bud development in week 4

week 4

partial absence of limb; arrest/disturbance of differentiation/growth in week 5

week 5

cleft hand or foot, lobster-claw deformity; absent of central digits, developmental failure of one or more digital ray

usually also has a missing thumb with lateral deviation and contraction abnormalities

supernumerary digit (greater than 5); can be autosomal dominant, extra digit is not normal, lacks normal muscle, usually lateral

webbing of digit, most common limb anomaly, due to imcomplete programmed cell death (apoptosis) of the tissue between the digital rays. in severe cases there is fusion of bones

abnormal positioning, restricted limb movement in utero due to reduction of amount of amniotic fluid

talipe (club foot), deformity of talus (ankle), abnormal foot position prevents normal weight bearing, walk on ankle

amnion tear results in constriction or amputation of a developing limb or body part (accident - most likely will not occur in next pregnancies)

deficient bone matrix deficient bone matrix calcification due to inadequate calcium intake, vit D deficiency, impairs intestinal Ca absoprtion

altered endochondral bone growth

short, deformed, bowed long bones, frontal bossing, squared head, hypertrophic epiphyseal cartilage (thickened growth plate) at costochondral junction results in rachitic rosary

congenital (maternal vit D deficiency), hereditary (defect in Vit D activation of renal tubule phosphate reabsorption), no Vitamin D supplementation, calcium nutrition, inadequate exposure to sunlight

premature closure of cranial sutures

long narrow wedge-shaped skull
-scaphocephaly

oxycephaly (turricephaly) : high tower like skull

X-rays!! get baby gram! if baby dies, autopsy to classify

Autosomal dominant

usually paternal chromosome de novo mutation, risk increases with increased paternal age,

25% chance if two dwarfs; homozygous

due to activating mutation in fibroblast growth factor receptor 3 (FGFR3); overexpression of FGFR2 inhibits growth

1) short extremities with normal sized head and chest (endochondral bone formation defect not intramembranous bone formation - normal bone width), frontal bossing, flattened nasal bridge,

lethal, die with respiratory insufficiecny/lung hypoplasia, frontal bossing, small rib cage, relative macrocephaly FGFR3 mutation

congenital defect of bone resorption resultin in structurally weak bone
-defect in type I collagen synthesis (autosomal dominant)

1. multiple fractures of bone(osteopenia)
2. blue sclera - thinning of scleral collagen reveals underlying choroidal veins
3. hearing loss - bones of middle ear fracture easily

decreases synthesis of normal collagen - mild phenotype

abnormal collagen chains that don't form collagen triple helix - lethal phenotype

bone. joint, eye, ear, skin and teeth

marble bone disease of albers-schonberg

inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily; osteoclast dysfunction causes diffuse symmetrical skeletal sclerosis

benign, in adolescence with repeated fractures, mild anemia

malignant; fractures, anemia, hydrocephaly, extramedullary hematopoiesis, hepatosplenomegaly and entrapped cranial nerves (optic atrophy, deafness, facial parlysis)
entrapped cranial nerves (optic atrophy, deafness, facial parlysis)

carbonic anhydrase II mutation leads to loss of acidic microenvironment required for bone resorption

1. bone fractures
2. anemia, thrombocytopenia, and leukopenia with extramedullary hematopoiesis due to myelophthisic process - bony replacement of marrow)
3. vision and hearing impairment
4. hydrocephalus - narrowing of foramen magnum
5. renal tubular acidosis: lack of CAII results in decreased tubular reabsorption of bicarb leading to metabolic acidosis
6. radiopaque bones lackin medullary cavity with erlenmeyer flask deformity on Xray

osteoclasts are derived from marrow monocyte precursors

the enzyme urate oxidase

alcohol intake, g6pd deficiency, sickle cell anemia, myeloproliferative disorder, renal insufficiency, drugs such as thiazide or loop diuretics, cyclosporine A, or low dose aspirin

PRPP and HPRT both are X-linked

asymptomatic hyperuricemia, acute intermittent gout, intercritical gout, chronic tophaceous gout

first attacks are monoarticular with first metatarsophalangeal joint with rapid development of warmth, swelling, erythema, severe pain

awakens them from sleep when asymptomatic before sleep

time period between acute attacks

intercritical periods are no longer free of pain; persistently swollen, uncomfortable, polyarticular, painful background

irregularly shaped firm nodules with a shiny yellow appearance of underlying skin; found in tendon, joint, extensor forearm, olecrenon bursa, achilles, helix of ear; peripheral nerve root compression

arthrocentesis; aspiration of monosodium urate crystals seen as negatively birefringent needle-shaped crystals within and outside neutrophils

erosions have overhanging edge creating a "rat bite", joint space preserved, absence of juxta-articular osteopenia

acute inflammatory episode

prevention of recurrent attacks by modifying risk factors and reducing serum urate

colchicine, Nsaids, corticosteroids

indomethacin

diarrhea

xanthine oxidase inhibitors, uricosuric agents, uricase agents

hypersensitivity

xanthine oxidase inhibitor - blocks synthesis of uric acid

xanthine oxidase inhibitor

renal impairment, nephrolithiasis

modified porcine recombinant uricase for chronic gout that is refractory to conventional therapies

hyperparathyroidism, hemochromatosis, hypophosphatasia, and hypomagnesemia

articular and periarticular tissue usually near the surface of the chondral sites

square/rectangular/rhomboid/rod intracellular inclusions with a weakly positive (blue) birefringence under polarized microscopy

punctate and linear densities in articular hylaine or fibrocartilage

tendon, IV disc, joint capsule, synovium, cartilage

soft tissue deposition of basic calcium phosphate crystals

polarized light cannot detect, aggregate and can be seen by light microscopy as shiny red coins (alizarin red)

osteoarthritis: their presence correlates with severity of radiologic osteoarthritis

milwaukee shoulder - destructive arthropathy - pain on shoulder use and at night

rotator cuff is most common location; BCP crystal elicit a major inflammatory response,

overt renal failure

crystal identificiation in joint fluid or tissue - bipyramidal and/or envelope shape; brightly birefringent on polarized microscopy (yellow)

fatigue, sleep, cognitive dysfunction, anxiety, depression, central pain, IBS, cysitis, chronic pelvic pain, TMJ

lyme, EBV, parvovirus

centrally mediated augmentation of pain and sensory processes (increased body pain, increased responsiveness to any stimuli)

unpleasant abnormal sensation such as burning, wetness, itching, electric shock, pins and needles (neuropathic)

pain where low intensity stimulation is felt as painful

extreme sensitivity to noxious stimuli

acute sensation and perception of mechanical, thermal, or chemical noxious stimuli that acts as alert to imminent danger

directly from action on nerves (severing or crushing)

tissue damage, signaling tissue repair is needed

abnormalities in pain systems: hypoperfusion of thalamus, changes in structure of cingulate gyrus and thalamus

5htt, comt, sodium channels, abnormal levels of neurotransmitters, increased baseline of opiate receptors

SIG E CAPS
sleep, interest loss, guilt, energy loss, cognition impairment, appetite change, anxiety, suicide

feeling helpless about their pain, ruminate about pain, poor coping, worse outcomes

meet thresholds for widespread pain index, symptom severity scale, greater than 3 months, no other disorder that might be causing pain, labs are normal

amitriptyline, cyclobenzaprine, SSRIs, pregabalin/gabapentin

NOT steroids, NSAIDS, and opiates

affect norepi transporter and moderate effect on 5HT

venlafaxine, duloxetine, milnacipram

exercise - water aerobics, education, cognitive behavioral therapy

polymyalgia rheumatica, multiple myeloma, lupus, sjogrens

proximal muscle weakness, elevated serum levels of skeletal muscle enzymes, myopathic changes on EMG and muscle biospy evidence of inflammation, skin rash (dermatomyositis)

chronic inflammation of striated muscle and skin

IIM

ocular or facial muscles are not typically affected

-stairs
-getting up from a chair
-rise from sitting on the floor
-falls
-combing hair

-heliotrope rash
-gottrons papules or sign
-macular erythema
-dystrophic cuticles and periungual telangiectasias
-peeling dryness at tips of fingers

dermatomyositis

lung

basilar crackles, intersitial fibrosis, pulmonary function is restrictive, secondary pulmonary hypertension

electrical disturbances, cardiomyopathy, myocarditis

upper dysphagia,

mucosal ulceration and hemorrhage

cricopharyngeal muscle dysfunction - blocking sensation on swallowing or retrosternal sticking of food

elevated CK, aldolase, LDH, AST, ALT

trauma, exercise, seizures

cardiac isoform troponin I

inclusion body

anti-jo, anti mi2, anti-signal recognition particle Antibody

anti PM scl, u1 RNP, Ku, Ro/SSA

sensitive but nonspecific

fibrillation potentials, complex repetative discharges, and positive sharp waves on needle insertion

unilateral EMG but use that location to then take a contralateral biopsy to avoid inflammatory artifact

muscle biopsy

degeneration and regeneration of muscle fibers and CD8s invading non-necrotic fibers.

CD4s and Bs predominate in perivascular areas and perifascicular atrophy related to capillary depletion and dropout

presence of lined or rimed vacuoles

cutaneous manifestations for 6 months or longer, but without proximal muscle weakness

autoantibodies against aminoacyl tRNA synthetase enzymes; muscle involvement, interstitial lung disease, raynaud's phenomenon, mechanics hands, inflammatory arthritis, fevers

distal and proximal asymmetrical weakness and atrophy of anterior thigh; no GI, no pulmonary, no autoantibodies

dermatomyositis > polymyositis

ovary, lung, pancreas, stomach, colorectal, non-hodgkins lymphoma

anti-T155/140

1. glucocorticoids
2. immunosuppressive medications
3. IV gamma globulin
4. topical treatments
5. physical therapy

if infection is a concern when using immunosuppressive medications

hydroxychloroquine, quinacrine, isotretinoin, topical tacrolimus

myalgias, muscle tenderness, or weakness, cramp or ache in trunk or proximal muscles, tendon pain, night cramps, increase with exercise, difficulty with fine motor movement

mcardles, myoadenylate deaminase, cpmtII deficiency

thyroid abnormality, electrolyte abnormality

alteration to membranes and mitochondria, inhibit coenzyme production, exacerbate underlying undiagnoses mitochondrial or metabolic myopathy, higher serum drug levels more frequently associated with myotoxicity

age, glucocorticoid use, gender, secondary osteoporosis, history of fracture, parental history of hop fracture, femoral neck BMD, smoking, low BMI, slcohol

systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with an increase in bone fragility and susceptibility to fractures

20 out of 100, 40 out of 100, 70 out of 100

1. nutritional problems
2. lack of menstrual periods
3. anorexia

addressing pediatric diseases, addressing menopause, addressing age related bone loss

disturbance of resorption and formation ratio

normal bone mass starts to decrease and absorption exceeds formation

normal bone mass starts to decrease and resporption exceeds formation

metabolic functions, bone health, neuromuscular functions

UVB rays come in and change cholesterol precursors to vitamin D which goes to the liver where it become 25 hydroxylated then goes to the kidney, intestine, bone to increase calcium and phosphorous absorption and mobilize calcium stores

standard deviations compared to young adult mean

used to define category of osteoporosis

standard deviations compared to age matched adults

may be a clue to presence of secondary osteoarthritis

-2 or less without any risk factors, -1.5 or less with risk factors

0 normal
negative 1 osteopenia
negative 2.5 osteoporosis

+2 above age
0 same as age
-2 below age

age independent, gender and race dependent

women >65, men >70
ages 50-70 with risk factors
fracture after 50 years old
disease or medication with low BM or bone loss
taking or being considered for treatment
women discontinuing estrogen
not for healthy young adults or children

alk phos, osteocalcin, PICP, PINP

10 year probability of a hip fracture. treat those with >35% hip risk or >20% other

calcium daily intake (1500 mg), vit D daily intake (600-800 IU)

poison osteoclasts and prevent them from resorbing bone; induce apoptosis or osteoclasts

corrosive esophagitis, nausea, diarrhea, osteonecrosis of jaw

verterbral fracture in women, can also protect against breast cancer, hot flashes, venous thrombosis, leg cramps

receptor antagonists in breast and agonists in bone; block the binding of estrogen to estrogen-receptor positive cells

osteoblasts which are repairing bone are signaling (with RANK) to monocytes to become osteoclasts so if you increase rank you increase osteoclasts and increase resporption; osteopegrin which is lost at menopause tones down resporption by binding up RANK; denosumab is an analog for osteopegrin therefore can decrease resoroption

increase rate of new bone formation

dexa for menopausal women and men >65 years old, exercise, daily calcium and vitamin D,

estrogen replacement and maybe bisphosphonates

bisphosphonates and maybe estrogen replacement

risedronate and calcitonin

workup for secondary causes (hyperthyroid, hypergonad, alcoholism)