Pathology Flashcards
Achondroplasia
Autosomal Dominant Gain of function mutation in FGFR3 leads to improper endochondral bone growth
90% of mutations are new; associated with paternal age
Short extremities; normal head and chest
Mental function, lifespan, fertility unaffected
Osteogenesis Imperfecta
Autosomal Dominant Loss of Function mutation in COLIA1 resulting in an amino acid substitution for glycine.
Improper formation of collagen ultrastructures
Multiple fractures of bone; blue sclera (choroidal veins); hearing loss (inner ear fracture)
Osteopetrosis
Poor osteoclast function results in abnormally dense, wide bone formation, lack of medulla
Mutations common in CA; May also have mutation of LRP5 increasing osteoblast activity.
Acellularity due to lack of medulla and lack of hematopoeisis, fractures common, hepatosplenomegaly, cranial nerve deficits common
Treatment is bone marrow transplant (monocytes are hematopoetic)
Rickets/Osteomalacia
Abnormal mineralization of osteoid due to decreased Vitamin D
Associated with decreased sun exposure; poor diet; malabsorption; liver or kidney failure
Rickets: Children (Pigeon Deformity, Richitic Rosary, Leg bowing)
Adults: Low Calcium, Low Phosphate, High PTH, High Alkaline Phosphatase (osteoblast activity)
Activation of Vitamin D
25 hydroxylation in the liver followed by 1 alpha hydroxylation in the PCT of the kidney
Actions of Vitamin D for calcium levels
Increases intestinal absorption of calcium and phosphate
Increases kidney resorption of calcium and phosphate
Increases bone resorption of calcium and phosphate
Osteoporosis
Loss of bone mineral density as a consequence of osteoblast/clast imbalance
Peak bone density reached between 30-40
Influenced by diet, exercise, sex hormones, and genetics
Labs are normal; treat with exercise, vitamin D, bisphosphonates, derivatives of estrogen,
IL-1, IL-6 and TNF increase osteoclast activity
Paget Disease of Bone
Characterized by mosaic pattern of bone; three stages (osteoclasts, mixed, osteoblasts)
Mutation in SQSTM1 increases RANK signaling increasing osteoclastic activity; paramyxovirus may be associated with osteoclast infection and deactivation
Increasing hat size, lion like facies, elevated alkaline phosphatase, bone pain, hearing loss
Treat with calcitonin or bisphosphonates
Increased likelihood of osteosarcoma
Osteomyelitis
Infection of bone resulting in characteristic sequestrum and involucrum from reactive bone
Seeding occurs via hemotogenous spread (metaphysis in kids, epiphysis in adults) or direct seeding
Most common (S. Aureus), Sickle cell (Salmonella), Sex Active (Gonorrhea), IV Druggies (Pseudomonas)
If affecting spine like tuberculosis (Potts)
Avascular Necrosis
Ischemic Necrosis of Bone and Marrow (Wedge shaped lysis)
Common in femoral head (glucocorticoid use, fracture, trauma, sickle cell, and caisson disease)
Can cause secondary osteoarthritis and fracture
Causes 10% of all joint replacements
Type IV delayed hypersensitivity
Often associated with nickel
Also associated with poison ivy
Spongiosis, intradermal vesicles (non-communicating), hyperkeratosis, acanthosis
Contact Dermatitis
Vesicles lead to spongiosis
Vesicles and bullae that rupture easily
Lesions of oral mucosa, scalp, face, chest, axillae, groin, and umbilicus
Intraepidermal bullae which split the epidermis above the basal layer
Positive Nikolsky sign
Linear deposits of IgG in the stratum spinosum
Pemphigus Vulgaris
Bullous pemphigus is when the layers separate from the basement membrane.
Sudden onset of targetoid lesions on palms and soles
HSV associated
Perivascular lymphocytic infiltrate, accumulation of lymphocytes along the dermoepidermal junction, necrosis of keratinocytes with subepidermal vesicle or bullous formation
Erythema multiforme
Stevens-Johnsons syndrome (when mucosa is affected)
Toxic Epidermal Necrolysis (serious condition affecting the skin resulting from adverse drug interaction)
Bilaterally symmetric pruritic eruption on extensor surfaces
Red papules and plaques covered by white adherent scales
Positive Auspitz sign
Perakaratosis, Acanthosis, Elongation of Rete ridges, Neutrophils and munro abscesses
Psoriasis
Can lead to psoriatic arthritis
Dark brown papules and plaques on the face and back with a “stuck on” appearance
Oval or round in shape, uniform in color
Hyperkeratosis, acanthosis, papillomatosis, melanocytic hyperplasia, horn cysts
Seborrheic keratosis
