Pathoma Flashcards
Achondroplasia
AD - impaired cartilage proliferation in the growth plate; common cause due to an activating mutation in fibroblast growth factor receptor 3 (FGFR3);
Most mutations are sporadic and related to increased paternal age.
poor endochondral bone formation; intramembranous bone formation is not affected = flat bones = normal head size
Osteogenesis imperfecta
autosomal dominant defect in collagen type 1 synthesis
Clinical features: Multiple fractures, hearing loss, blue sclera—thinning of scleral collagen reveals underlying choroidal veins.
Osteopetrosis
Abnormally thick heavy bone that fractures easily - defect of bone resorption
Carbonic anhydrase II mutation - acid required to remove calcium from bone –> can’t resorb bone
Bone fractures, anemia, thrombocytopenia, leukopenia, vision/hearding impairment (foramen thickening), hydrocephalus, renal tubular acidosis (w/ carbonic anhydrase deficiency).
Treat w/ bone marrow transplant - osteoclasts derived from monocytes
Rickets/osteomalacia
Defective osteoid mineralization - osteoid deposits
Low Vit D levels (resorb Ca and PO4 from intestine)
Rickets - kids <1 year bowing of leg in kids >1
Osteomalacia - weak bone w/ increased risk for fracture
Ca and phosphate decreased, PTH increased, All pos increased
Osteoperosis
Reduced trabecular bone mass –> porous bone w/ increased fracture risk
calcium, phosphate, and PTH are NORMAL vs. osteomalacia
Tx: Exercise, vit D, bisphosphanates - induce osteoclast apoptosis
Osteoblast activation
Increased alkaline phosphatase - need alkaline to lay down calcium.
Paget Dz of bone
Imbalance between osteoblast and osteoclast - localized process 1-2 bones
Osteoclast resorbs excess bone
Results in thick sclerotic bone - osteoblasts try to overcompensate - cement lines between bones - mosaic pattern of lamellar bone
Bone pain (micro fractures), increased hat size, hearing loss, lion-like facies
Isolated alk phos
Tx: Calcitonin (inhibit osteoclasts, opposite of PTH) and bisphosphanates
Complications: osteosarcoma and high-output cardiac output failure
Osteomyelitis
Bacteria in bone - mostly children (seed metaphysis) Adults (seed epiphysis)
S. aureus (most common), pseudomonas (IVDU), TB< pasteurella, N. Gonorrhea, Salmonella (sickle cell)
Bone pain w/ fever + leukocytosis, lytic focus surrounded by sclerosis on X-ray, Dx w/ blood culture
Osteoma
Benign
Surface of facial bones
a/w gardner (familial polyposis, fibromatosis, osteoma)
Osteid osteoma
Benign tumor of osteoblasts - rim of reactive bone
Young adults < 25 years in Cortex of long bones
Bone pain resolves w/ aspirin - bony mass w/ radiolucent core
Osteoblastoma
Benign tumor of osteoblasts
vs. osteoid osteopath - Larger, arises in vertebrae, presents are bone pain that isn’t ASA responsive
Osteochondroma
Benign - Tumor of bone w/ overlying cartilage cap
Cartilage can transform to chondrosarcoma
Osteosarcoma
Malignant osteoblast proliferation - teenagers most common
Risk factors: familial RB
Elederly - paget Dz of bone and radiation increase risk
Metaphysis of long boneDistal femur or proximal tibia
Presents as pathologic fracture, or bone pain and swelling
BX: large pleomorphic cells producing osteoid
Giant cell tumor
Giant cells w/ stroll cells - young adults
In epiphysis - ONLY ONE - Soap bubble on X-ray
Locally aggressive
Ewing sarcoma
Poorlydifferentiated - derived from neuroectoderm
In diaphysis of long bone in young males
Onion skin appearance on X-ray
Easily confused w/ osteomyelitis - fever
(11:22) translocation - chemorpsponsive
Chondroma
Benign - cartilage tumor
Occur in small bones - hands/feet
arises in medulla
Chondrosarcoma
Malignant cartilage tumor
Occur in pelvis/ central skeleton
arises in medulla
Bony metastasis
Most common bone malignancy- mostly osteolytic (punched out)
Prostate cancer is osteoblastic
HLA DR4
Rheumatoid arthritis - synovitis + pannus (inflamed granulation tissue) - DIP spared
Rheumatoid factor - IgM ab against Fc portion of IgG
HLA-B27
seronegative spondyloarthropathies: Psoriatic arthritis, ankylosing spondylitis, and Reiter syndrome
Ankylosing spondylarthritis
sacroiliac joints and spine - male young adults
involvement of vertebral bodies eventually arises, leading to fusion of the vertebrae (‘bamboo spine ).
uveitis and aortitis (leading to aortic regurgitation).
Reiter syndrome
arthritis, urethritis, and conjunctivitis after GI or chlamydia infection (can’t see, can’t pee, can’t climb a tree)
Psoriatic arthritis
In 10% of cases of psoriasis.
Involves axial and peripheral joints; DIP joints of the hands and feet are most commonly affected, leading to “sausage” fingers or toes.
Infectious arthritis
Causes include: N. Gonorrhea— most common, sexually active young adult, S aureus—older children and adults;
single joint, usually the knee, warm with limited range of motion; fever, increased white count, and elevated ESR are often present.
Treat immediately
Secondary gout
Lesch-nyhan
Leukemia/myeloproliferative disorders
renal insufficiency (decreased uric acid excretion)
Chronic gout
Tophi
Renal failure—Urate crystals may deposit in kidney tubules (urate nephropathy)
Pseudogout
deposition of calcium pyrophosphate dihydrate (CPPD);
synovial fluid shows rhomboid-shaped crystals with weakly positive birefringence under polarized light.
Dermatomyositis
Inflammatory disorder of the skin and skeletal muscle, some cases are associated with carcinoma (e.g., gastric) consider underlying carcinoma
Bilateral proximal muscle weakness; distal involvement can develop late in disease. Rash of the upper eyelids (heliotrope rash); malar rash. Red papules on the elbows, knuckles, and knees (Grotton lesion)
Laboratory findings: Increased creatinine kinase, Positive ANA and anti-jo-l antibody
Bx: Perimysial inflammation (CD4+ T cells) with perifascicular atrophy on biopsy
Tx: corticosteroids.
Polymyositis
Inflammatory disorder of skeletal muscle
Resembles dermatomyositis clinically, but skin is not involved
Bx: endomysial inflammation (CD4+ T cells) with necrotic muscle fibers
X-linked (duchenne) Muscular dystrophy
Replacement of muscle with adipose
Deletions of dystrophin (linker molecule) - mostly spontaneous
Elevated creatinine kinase
death from cardiac or respiratory failure
Becker muscular dystrophy
Mutation of dystrophin vs. deletion in duchenne
Milder disease than duchenne, appears later in childhood
Lambert eaton
Proximal muscular weakness
Autoantibodies against pre-synaptic calcium channels
Paraneoplastic - small cell lung cancer
Thymoma/thymic hyperplasia
a/w myasthenia gravis
Lipoma
Benign tumor of adipose tissue
Most common benign soft tissue tumor in adults
Liposarcoma
Malignant tumor of adipose tissue
Most common malignant soft tissue tumor in adults
Lipoblast is the characteristic cell.
Rhabdomyoma
Benign tumor of skeletal muscle
Cardiac rhabdomyoma is associated with tuberous sclerosis.
Rhabdomyosarcoma
Malignant tumor of skeletal muscle
Most common malignant soft tissue tumor in children
Rhabdomyoblast is the characteristic cell; desmin positive
Mos tcommon site is the head and neck; vagina is the classic site in young girls.
Layers of the skin
Epidermis is comprised of keratioocytes and has four layers
- Stratum basalis—regenerative (stem cell) layer
- Stratum spinosum—characterized by desmosomes between keratinocytes
- Stratum granulosum—characterized by granules in keratinocytes
- Stratum corneum—characterized by keratin in anucleate cells
Dermis
connective tissue, nerve endings, blood and lymphatic vessels, and adnexal structures (e.g., hair shafts, sweat glands, and sebaceous glands).
Psoriasis
Excessive keratinocyte proliferation
Acanthosis - epidermal hyperplasia
Parakeratosis - hyperkeratosis with retention of keratinocyte nuclei in the stratum comeum) –> silvery scale
Thinning of the epidermis above elongated dermal papillae; results in bleeding when scale is picked off (Auspitz sign)
Lichen planus
Pruritic, planar, polygonal, purple papules, often with reticular white
lines on their surface (Wickham striae); commonly involves wrists, elbows, and oral mucosa
I, Oral involvement manifests as Wickham striae,
Histology shows inflammation of the dermal-epidermal junction with a ‘saw-tooth’ appearance
a/wchronic hepatitis C virus infection
Pemphigus vulgaris
IgG antibody against desmoglein (type II hypersensitivity)
Acantholysis (separation) of stratum spinosum keratinocytes (normally
connected by desmosomes) results in suprabasal blisters.
Basal layer cells remain attached to basement membrane via hemidesmosomes
(‘tombstone’ appearance)
NIkolsky sign: Thin-walled bullae rupture easily, leading to shallow erosions
with dried crust.
Immunofluorescence highlights IgG surrounding keratinocytes in a ‘fish net’ pattern.
Bullous pemphigoid
Autoimmune destruction of hem idesmo somes between basal cells and basement membrane
IgG antibody against basement membrane collagen (type 4)
Oral mucosa is spared.
Basal cell layer is detached from the basement membrane
clinically milder than pemphigus vulgaris
Immunofluorescence highlights IgG along basement membrane (linear pattern).
Dermatitis herpetiformis
Autoimmune deposition of IgA at the tips of dermal papillae
pruritic vesicles and bullae that are grouped (herpetiform)
Strong association with celiac disease; resolves with gluten-free diet
Erythema multiforme
Hypersensitivity reaction characterized by targeloid rash and bullae (central epidermal necrosis)
HSV infection
SJS when there is oral mucosa/lip involvement and fever.
Toxic epidermal necrolysis: severe form of SJS characterized by diffuse sloughing of skin, d/t adverse drug reaction
Lesser treat sign
sudden onset of multiple seborrheic keratoses and suggests underlying carcinoma of the GI tract
Basal cell carcinoma
Presents as an elevated nodule with a central, ulcerated crater surrounded by dilated (telangiectatic) vessels, ‘pink, pearl-like papule’
Classic location is the upper lip.
Histology shows nodules of basal cells with peripheral palisading
Surgically excise, metastasis rare
Squamous cell carcinoma
Presents as an ulcerated, nodular mass, usually on the face (lower lip)
Excise, metastasis is uncommon.
Actinic keratosis is a precursor lesion of squamous cell carcinoma and presents as a
hyperkeratotic, scaly plaque, often on the face, back, or neck.
Keratoacanthoma is well-differentiated squamous cell carcinoma that develops
rapidly and regresses spontaneously; presents as a cup-shaped tumor filled with keratin debris
Melanocytes
Responsible for pigmentation - present in the basal layer
Derived from neural crest
Synthesize melanin in melanosomes using tyrosine as a precursor molecule
Vitiligo
Localized loss of skin pigmentation due to autoimmune destruction of melanocytes
Albinism
Enzyme deficiency (usually tyrosinase) that impaired melanin PRODUCTION
Increased risk of squamous cell carcinoma, basal cell carcinoma, and melanoma due
to reduced protection against UVB
Freckle (ephesus)
Due to increased number of melanosomes (melanocytes are not increased)
Melasma
Mask-like hyperpig mentation of the cheeks
Associated with pregnancy and oral contraceptives
Staphylococcal scalded skin syndrome
Sloughing of skin with erythematous rash and fever; leads to significant skin loss
Due to S aureus infection; exfoliative A and B toxins result in epidermolysis of the stratum granulosum.
Distinguished histologically from toxic epidermal necrolysis by level of skin
separation; separation in TEN occurs at the dermal-epidermal junction.
Transthyretin
Senile cardiac amyloidosis
CD14
TLR on macrophages that recognizes LPS
