Systems Pathology exam 1

compact bone

densely packed, tightly organized osteons

spongy (trabecular) bone

sparsely packed, seemingly random but arranged along lines of stress

components of bone

organic- cellular (osteoblasts, osteocytes, osteoclasts, osteoprogenitor cells) and protein (collagen, osteoid); inorganic- mineral (hydroxyapatite, calcium, phosphorus)

woven bone

immature osteoid, highly cellular, disorganized, abnormal in adults

lamellar bone

mature, less cellular (more matrix), organized along stress lines, normal in adults

osteoprogenitor cells

stem cells, differentiate into osteoblasts

osteoblasts

bone forming cells, mature into osteocytes after surrounded by bone

osteocytes

mature bone cells, maintain bony matrix

osteoclasts

bone resorbing cells, mature from same stem cells as macrophages

bone remodelling

normally at equilibrium in adulthood, no net increase or decrease in bone mass, slight shift towards bone loss after age 30 (lose 1/2 a % every year), thrown off during pathology of after injury

osteoclast activity

osteoclast precursor has RANK receptor, requires binding of RANK ligand (RANKL) from osteoblast, interaction is needed to sustain osteoclast viability, interaction may be inhibited by osteoprotegerin from osteoblast

musculoskeletal (MSK) physiology

from, function, protection, hematopoiesis and mineral storage

pathologies can be

local (structural, protective) or generalized (hematopoiesis and mineral storage)

dysostosis

developmental anomaly of bone or cartilage

localized congenital disorders

abnormality, abnormal mesenchymal migration, abnormal ossification of fetal cartilage, aplasia, supernumerary digit, klippel-feil syndrome, congenital kyphosis, congenital and idiopathic etiology

congenital kyphosis type I

failed development, severe deformity, possible/likely cord compression, surgical fusion needed- early gives better outcomes while late has complications

congenital kyphosis type II

failed segmentation, mild deformity compared to type I, segments fused together and never separated

entire skeleton congenital disorders

not pre-cancerous, achondroplasia, cleidocranial dysplasia, osteogenesis imperfecta, osteoporosis, osteodysplasia (type I spondylolisthesis, genetic etiology)

cleidocranial dysplasia

absent/under-developed clavicles, dental abnormalities, delayed closure of cranial sutures, short stature, genetic abnormality in RUNX2 gene, RUNX2 has important function during skeletal formation and bone maintenance

achondroplasia

most common cause of dwarfism and skeletal dysplasia, leads to shortened long bones, increases odds of having stenosis of foramen magnum and spinal stenosis

features of achondroplasia

height of 4’10 or less, bullet vertebrae- hyperlordosis/hyperkyphosis/scoliosis, stenosis of foramen magnum (brain stem, may be lethal) and/or lumbar spinal canal (radiculopathy), trident hand

pathogenesis of achondroplasia

inhibited endochondral growth, decreased cartilage synthesis, short/bowed long bones, frontal bossing, midface hypoplasia, caused by mutated inherited FGFR3 gene- 90% are spontaneous

osteogenesis imperfecta

brittle bone disease, type I collagen disease, inherited condition that results in brittle bones and weak connective tissue due to altered type 1 collagen- weak foundation for hydroxyapatite deposition, 2 types- I (normal lifespan) and II (lethal in utero)

osteogenesis imperfecta pathogenesis

mutated type I collagen- alpha 1/2 chains, premature breakdown, autosomal dominant, 1 in 20,000, inherited pathology, zebra stripe sign, blue/transparent sclera, childhood signs- fractures/bowing/scoliosis, hearing loss, dwarfism

radiolucent

areas appearing darker on x-ray due to lower density of structure- cartilage, foramen, gas in GI tract, bone destroying tumor, osteoporotic bone (with reduced density)

radiopaque/radiodensity

areas appearing brighter/whiter on x-ray, due to higher density of structure- bone, metal

osteopetrosis

marble bone disease, group of genetic disorders- skeletal sclerosis (high bone density), bony stenosis (cranial nerve palsies), deranged hematopoiesis (fatigue and infections), erlenmeyer flask syndrome

osteopetrosis pathology

inherited decreased osteoclast activity causes inability to remodel/reabsorb bone and dense and thick but brittle bones, loss of hematopoietic bone marrow- reduced production of red & white blood cells; treatment- decreased calcium intake and/or stem cell transplant

osteoporosis

acquired severe loss of bone density and mass, bone mineral density (BMD) measured by DEXA scan, increased risk of bone fracture, asymptomatic, affects trabecular bone in vertebral bodies, femoral neck, and calcaneus; advanced thins cortex; x-rays are non-diagnostic- not sensitive enough for screening (only finds it when it’s well-developed and 30-40% of bone mass is lost)

osteopenia

milder loss of bone density and mass

osteopenia and osteoporosis similarities

decreased bone mass, increased porosity, asymptomatic until skeletal fragility

DEXA scan

dual energy x-ray absorptiometry- measures bone mineral density, determines risks for fracture; osteoporosis shows greater than 2/5 standard deviations; osteopenia shows between 1-2.5 standard deviations below

T-score

DEXA compared to peak bone mineral density

Z-score

DEXA compared to age & gender matched BMD

osteoporosis pathology

localized or entire skeleton; primary- senile, postmenopausal; secondary- neoplasia, body-wide immobilization, hyperparathyroidism, nutrient deficiencies, corticosteroids, alcohol, smoking

primary osteoporosis

senile- elderly/age-related, normal phenomenon, decreased GFs cause decreased osteoblast activity, starting mid 20s 0.7% bone mass lost each year; menopausal- women averaging age 51, decreased estrogen causes increased osteoclast activity, 50% of postmenopausal females

osteoporosis risk factors/consequences

risk factors- increased age, females, sedentary lifestyle, family history; consequences- vertebral body compression (dowager’s hump & kyphoscoliosis- causes short height and risks pneumonia), femoral neck fracture- disabling & risk for pulmonary emboli

osteoporosis prevention

1- physical activity- regular exercise, best prior to age 30 to maximize bone density; 2- dietary calcium and vitamin D; 3- antiresorptive pharmacologic agents- biphosphonates

Rickets

undermineralized bone, weak & bowing bones, poor growth plates, failed osteoid formation and failed deposition of bone in growth plates; affects all ages but is more severe in children; caused by a UV or dietary deficiency, malabsorption, chronic renal disorder

osteomalacia

undermineralized bone that is weak and prone to fracture; caused by failed remodeling and undermineralized matrix accumulation via a UV/dietary deficiency, malabsorption, and/or chronic renal disorder; affects adults more severely than children

hyperparathyroidism

most common cause of hypercalcemia; parathyroidism glands secrete PTH & maintains increased serum calcium, primary- autonomous PTH production most commonly from an adenoma, increased osteoclast activity, increased renal tubule resorption of calcium; secondary- renal failure → hypopcalcemia → increased PTH; “painful bones, renal stones, abdominal groans, & psychic moans”

primary hyperparathyroidism

usually asymptomatic, symptoms when present- kidney stones are most common, unique skeletal changes and radiographic features, ruger-jersey spine, subperiosteal resorption, salt & pepper skull, bone pain, fractures, anorexia, decreased cognition; treatment depends on cause- drinking water, physical activity, avoiding diuretics, reversible when PTH levels are normalized

primary hyperparathyroidism how/why/who

how- parathyroid adenoma causes an increase in- parathyroid hormone (PTH), osteoclast activity, and Ca2+ in blood, resorbs cortical and trabecular bone and replaces it with connective tissue/’brown tumor’; why- idiopathic via parathyroid adenoma; who- most commonly affects post-menopausal females

secondary hyperparathyridism

caused by kidney failure

paget disease of bone (osteitis deformans)

disordered bone remodeling of axial skeleton, thick but weak bone, ‘shaggy’ appearance, most commonly (80%) is asymptomatic, bone pain and bowing, nerve compression, increase risk of fracture; diagnosed via increased alkaline phosphatase in serum; chalkstick fractures, mosaic pattern of tissue, ivory vertebrae sign

paget disease of bone how/why/who

how- disordered bone remodeling causes excessive osteoclast activity and reactionary increased activity of osteoblasts, occurs in stages; why- idiopathic (genetic, geographic); who- most common in older caucasian males

stages of paget disease of bone

1- regional osteoclastic activity, 2- osteoblastic activity= excessive bone → disorganized, greater mass, poor quality, ‘shaggy’, 3- sclerotic phase (osteosclerotic)

paget disease

most (85%) have multiple sites, MC in axial skeleton/femur- pelvis, sacrum, skull, MC diagnosis at age 70- 2x in males

closed fracture

intact overlying tissue

compound/open fracture

skin is ruptured, infection almost expected and could be life-threatening

comminuted fracture

bone is fragmented/splintered

displaced fracture

distal segment is misaligned

pathological fracture

at site of any pathology, generic name

stress fracture

microfractures, from repetitive use, develops slowly, common on lower leg/foot

optimal healing time for tissues

soft tissue callus (noncalcified)- 1 week; woven bone- 2-3 weeks; endochondral ossification → bony callus- 6-8 weeks; remodeling- lifetime

week 0-1 of fracture healing process

hematoma with fibrin clot and fibroblast= formation of soft callus

week 1-2 of fracture healing process

weka and irregular woven bone= formation of hard callus

week 2-8 of fracture healing process

endochondral ossification and remodeling= formation of mature lamellar bone

reasons for delayed fracture healing

nonunion= large callus, comminution= fragments must be reabsorbs, inadequate immobilization disrupts callus, infection causes inflammation- most common with compound fracture, nutritional deficiencies (Ca++, vit D, phosphorus), advanced age

who does salter-harris fractures (SHF) affect?

only children because it affects open growth plates

type I SHF

a fracture that goes straight through growth plate (epiphyseal plate), may appear as normal on x-ray id there’s no displacement, diagnosis often made clinically via severe tenderness, favorable prognosis

type II SHF

occurs when there is a fracture that extends through the growth plate and metaphysis, most common type- 75% of fractures, favorable prognosis

type III SHF

occurs when a fracture goes through plate and epiphysis, articular fracture, 10% of fractures, confirmed radiographically via epiphyseal fragment

type IV SHF

occurs when a fracture goes through the metaphysis and growth plate and epiphysis, articular fracture, 10% of fractures, poor prognosis due to severity

type V SHF

occurs when there is a crush injury to the growth plate, worst prognosis of all SHF fractures- damages growth plate, arrests bone growth, last common type

SALTR mnemonic

S- slipped = type I; A- above= type II; L- lower= type III; T- through= type IV; R- rammed= type V

osteonecrosis

avascular necrosis/ischemic necrosis of bone, caused by mechanical trauma to vasculature or thrombotic occlusion (blood clot), highly irregular joint surface, either asymptomatic or painful, may preserve cortex or collapse, most common in 30-50 year-olds (widely variable), 25% idiopathic (never identified)

alternate name for osteonecrosis

osteochondritis dissecans

legg-calve-perthes disease

pediatric avascular necrosis of the hip, commonly results in misshapen femoral head, reduced hip ROM and pain, may self resolve

osteomyelitis

bone-marrow inflammation from an infection, acute (MC) or chronic, wbcs → destruction, subacute= brodie abscess, fever/chills big indicators for infection, 3 infection types- hematogenous, adjacent infection, implantation, 2 types

most common cause of osteolmyelitis in children

hematogenous infections

most common causes of osteomyelitis in adults

adjacent infections, implantations (surgical procedures, open fractures)

2 types of osteomyelitis

pyogenic osteomyelitis, mycobacterial osteomyelitis

pyogenic osteomyelitis

overall most common from staphylocossus aureus; serious acute condition, diagnosed via radiography/biopsy- possible microbes in blood culture, involucrum, sequestrum, draining sinus

involucrum, sequestrum, draining sinus of pyogenic osteomyelitis

involucrum- reactive woven/lamellar bone surrounds infected bone; sequestrum- entrapped necrotic bone; draining sinus- pus drains into surrounding soft tissues

mycobacterial osteomyelitis/ Tuberculosis

not common in developed countries, TB is cause of bone-marrow infection (3%), risk increases with immunodeficiencies, most commonly spreads via hematogenous, affects long bones/vertebrae

arthritis definition

inflammation of a joint

types of arthritis

degenerative (MC)- OA, DJD, DDD; immune-mediated- RA, AS; metabolic (crystal induced)- gout, pseudogout/CPPD; infectious; neoplastic

osteoarthritis (OA, DJD)

MC joint disorder, wear-and-tear, major source of morbidity, articular cartilage breakdown- fibrillations/cracks leads to softening, possible inflammation & subchondral changes, primary and secondary types; location- L4/L5 MC degenerative site, cervical/lumbar spine, knees/hips, DIP/ 1st MCP/1st TMT joints,; identifiable features- osteophytosis (bone spurs) and sclerosis, advanced- subchondral cyst, joint mice; treatment is palliative

primary osteoarthritis

insidious, oligoarticular, most common form- adults, no significant trauma

secondary osteoarthritis

develops from previous injury or deformity- trauma/obesity/disease, only type that affects children (5%)

joint mice

pieces of bone/cartilage that break free and calcify, cause painful locking of joints

osteoarthritis what/how/who/why

what- asymmetrical degeneration of articular cartilage, symptoms- pain worse in AM, decreased ROM, worse in weight bearing joints, imaging shows osteophytes/bone spurs; how- age related wear and tear, accelerated by many factors including decreased chondrocyte activity; who- MC age related in older individuals, patients with history of trauma (obesity secondary); why- primarily wear and tear, genetic components not well understood but linked to chondrocyte activity, history of trauma/obesity

degenerative disc disease (DDD)

spinal OA and DDD often occur together, facet degeneration stresses discs, degenerating discs stresses facets, spondylosis (spinal pain from degenerative changes), genetics are 30-75% of risk (collagen/immune activity), osteophytes, synovial cysts

rheumatoid arthritis (RA)

type II hypersensitivity (T cell mediated), inflammatory, autoimmune disease, chronic, systemic, rheumatoid factor (RF) positive in 80% of cases, HLA-DRB1 is genetic predisposition, anti-cyclic citrullinated peptides positive in 70% of cases, CD4+ T cells & macrophages (TNF), increased collagenase & osteoclast activity near joints can result in fusion, smoking is #1 environmental factor for developing this

rheumatoid arthritis signs/symptoms

MC affects small joints- hands/wrist/feet/ankles/elbows, insidious onset of pain, aching and stiffness, atlantoaxial instability- 65% patients, Pannus- inflammatory tissue within a joint (destruction over 10-15 years), ulnar deviation, swan-neck deformity, eventual ankylosis, decreased ROM, MC in women 30-50, 3-5x in females, idiopathic, high risk genes- HLA DRB1

felty syndrome

combination of RA, neutropenia (lack of neutrophils), and splenomegaly; classic features of RA, neutropenia leads to recurrent infections (fever, weight loss, fatigue), MC among older female (50-70), poorly understood

caplan syndrome

combination of RA and pneumoconiosis, classic features of RA, may mimic asthma (cough, shortness of breath, wheezing), presence of RA alters immune status (risk for pneumoconiosis)

juvenile rheumatoid arthritis (JRA, JIA)

autoimmunity of multiple tissues, pain/dysfunction (knees/hips), not a childhood onset of RA- negative for RF, girls have 2-3x increased risk; oligoarticular (few joints), polyarticular (many joints), still’s disease (arthritis + spiking fever, rash, pericarditis); diagnosis- onset before age 16 and symptoms last for 6 weeks or more, MC age 1-3 and 6-12

osteochondrosis

group of disorders affecting growing bones and apophyses, causes vary- injury, abnormal stress during growth, vascular abnormalities, genetic, hormonal irregularities; results in irregular bone & joint surfaces- dysfunction and pain common; ex- scheurmann’s disease, osgoood-schlatter, legg-calve-perthes

scheurmann’s disease (juvenile kyphosis)

vertebral endplate abnormality (osteochondritis), increased kyphosis, achy pain, schmorl’s nodes, wedging of vertebral bodies; cause poorly understood, likely associated with trauma/injury to vertebral endplate during growth; more likely in adolescent males that present with history of dull/chronic mid-back pain, in up to 8% of population; diagnosed via signs/symptoms and radiography

seronegative spondyloarthropathies

autoimmune attack of spinal joints, Rheumatoid factor negative, HLA-B27 positive in majority of cases, spinal ligaments have syndesmophytes; PEAR- Psoriatic arthritis, Enteropathic arthritis, Ankylosing spondylitis, Reactive arthritis

reactive arthritis/Reiter’s disease

autoimmune cross reactivity with GI/GU pathogen, lower extremity arthritis in lower (large joints), cross reactivity following recent GI or GU infection- Campylobacter jejuni (MC), salmonella, chlamydia; affects those with history of high risk infections and high risk HLA-B27

Reactive Arthritis phrase

can’t see- conjunctivitis, uveitis; can’t pee- urethritis; can’t climb a tree- oligoarthritis

ankylosing spondylitis (AS)

chronic inflammation, pain, ankylosis, axial skeleton (SI joints) and sites of ligament attachment, syndesmophytes decrease lordosis and flexion; affects men prior to age 40; high risk HLA-B27 gene, genetic risk; morning stiffness for 30+ mins, nocturnal LBP, decreased chest expansion, diagnosis via clinical appearance and radiography

psoriatic arthritis

seronegative arthritis (RF-), high risk HLA-B27 gene, history of psoriasis of skin (20-30% will develop this condition), often starts with fingers/hands (sausage fingers) and almost always progresses to SI joints

enteropathic arthritis

seronegative arthritis (RF-), high risk HLA-B27 gene, history of GI inflammatory disorder, SI joint & axial skeleton pain and arthritis

Polymyalgia Rheumatica (PMR)

acute shoulder pain and myalgia (muscle pain), responds so well to corticosteroids it sometimes is used to diagnose, seen 2x in older women with history of temporal arteritis (GCA, inflamed temporal artery)

gout

abnormal uric acid/crystals depositied into synovial joints, leads to inflammation, joint damage, pain, monoarticular, MC in big toe 1st MTP joint(podagra), tophus present, primarily caused by abnormal purine metabolism/excretion, seen in older males with poor diet (lots of sugar, alcohol, and organ meats- why it’s called “king’s disease”), primary and secondary forms

tophus

a buildup of chalky crystalline substance that leads to breakdown, seen in gout