Clinical Correlates Flashcards
Chondroma vs Chondrosarcoma
Benign and malignant tumors in cartilage respectively
Do not metastasis often due to avascular it’s of cartilage, must get into perichondrium to have a chance of metastasis
Calcification of cartilage
Occurs via deposition of CaPO4 crystals in the ECM during aging and repairing
- most common in hyaline cartilage repairs especially in costal cartilages
Osteosarcoma
Cancer from osteoprogenitor cells.
Very rare
Metastatic bone tumors
Skeleton is very common site of metastasis since small blood and lymphatic vessels from the entire body move through bones.
Osteopetrosis
Dense heavy bones caused by osteoclast deficiencies in ruffled borders
- dont possess ruffled borders and cannot resorb bone well at all.
- thickening of bones causes obliteration of marrow cavity, ultimately causing depressed blood cell formation and overall anemia
- most patients that experience osteopetrosis have mutations in cell proton-ATPase pumps and/or chloride channels.
Osteoporosis
Excessive bone formation causes calcium loss in bones and overall reduced density.
- not caused by calcium deficiencies but excess osteoclast activity.
DEXA scans are used to screen for osteoporosis.
Osteomalacia
Mineralization of ECM is impaired causing increased spongy bone and decreased compact bone. Soft bones develops and causes easy breaking.
- use of tetracycline as a fluorescent label can be used to screen for this.
Osteitis fibrosis cystica
Increased osteoclast activity removes bone matrix and replaces it with fibroids tissue
- caused by hyperparathroidism increasing activity of osteoclasts.
- appear moth eaten bones in xrays
Osteogenesis imperfecta
Osteoblasts produce deficient type 1 collagen due to mutations
- usually mutation is replacement of “Gly” amino acid with another amino acid.
- marked by significant fragility of bones. “Brittle bone disease”
- four specific types of osteogenesis imperfecta
Bone fracture repair
Damaged blood vessels from bone fractures create a hematoma.
Clotted blood, tissue debris and cell-free bone are moved by macrophages and osteoclasts
Periosteum and endosteum form a soft callus of fibrocartilage tissue around the fracture site.
Callus is gradually replaced by woven bone
Woven bone is eventually resorted and replaced with lamellar bone.
Pituitary dwarfism vs gigantism
Lack of growth hormone and IGF-1 causes little growth of epiphyseal cartilage
Excess of growth hormone or IGF-1 causes excessive epiphyseal cartilage growth.
Acromegaly
Similar to gigantism and crawfish in that excess GH and IGF-1 are present.
However this is in adults, where epiphyseal plates dont exist. Instead bones become THICKER rather than longer.
Rheumatoid arthritis
Autoimmune disorder that causes Chronic inflammation of synovial membrane causes thickening of CT and stimulates releases of collagenases and hydrolysis enzymes from macrophages
- causes destruction of articular cartilage and direct contact of bone into the joint.
Rickets
Osteomalacia in children essentially
Bone matrix does not calcify normally along the primary ossification enter (sometimes distorts the epiphyseal plate).
Causes bones to grow more slowly and often become deformed.
- deficiency is caused usually by insufficient calcium in diet or insufficient steroid pro hormone Vitamin D
Osteoarthritis
Gradual loss of articular cartilage due to physical or pathological damage or old age.
Scurvy
Vitamin C (ascorbate) deficiency
- greatly decreases tension strength of collagen fibers due to lack of intrachain H-bond formation between collagen.
- causes easy bruising, loose teeth and poor gums
- poor wound healing and bone development
Menkes syndrome
mutations in ATP7A (a cu2+ transporter) causes lack of intraceuular Cu2+.
Causes improper cross-linking of collagen.
- most notable characteristics are weak muscle tone, sagging facial features and “kinky hair” disease (brittle hair).
X-linked recessive disease (70%)
De-novo (30%)
Wilson’s disease
Caused by copper toxicity.
Type 1 osteogenesis imperfecta
mild bone fragility, hearing loss and blue sclera in eyes
- MOST COMMON w/ BEST PROGNOSIS*
- usually survive and is an autosomal dominant inheritance
Type 2 osteogenesis imperfecta
Almost always lethal in perinatal period
- almost always lethal and is usually inherited in autosomal recessive pattern
- can be a de novo mutation
- MOST SEVERE*
Type 3 osteogenesis imperfecta
Multiple fractures at birth, short stature, and increased spinal curvatures.
severe but not as bad as type 2
Ehlers-Danlos syndrome (EDS)
Defective collagens of processing enzymes.
Two forms
- classic form = collagen 5 defect
- vascular form = collagen 3 defect
Clinical symptoms = hyperextensible skin, hypermobile joints and increased fragility of skin tissue. (Also may have blue sclara in eyes)
can be severe since arteries become defective
Marfan syndrome
Mutations in fibrilin-1 group
Autosomal dominant, pleiotropic disorder.
Clinical signs =
-arachnodactyly (unusually long spidery fingers and tall overall)
- ectopic lens (lens dislocation) and abnormally weak arteries
- weak arteries can cause sudden death in midlife due to rupture of aorta
- ALWAYS positive sign = thumb and little finger overlap the wrist and can touch each other
Williams-Beuren syndrome
Chromosomal deletion of #7, which encodes for elastin
Affects multiple genes
Occurs due to random events and is unlikely to be inherited
Clinical signs:
- developmental disorders
- distinctive “long” facial features and cardiovascular problems
LAMA2-related muscular dystrophy
Mutations in LAMA2 gene (specifically (a)-2 subunit in lamina 2 and 4 groups)
Autosomal recessive disorder
Clinical signs:
- general muscle weakness and atrophy
- can be severe early onset or mild late onset
Hypertrophy vs hyperplasia
Increased muscle mass typically occurs due to sustained increase load.
Individual size of myofibers or the number of myofibers can increase
Atrophy and hypotrophy
Decrease muscle mass typically due to decrease load on muscles, loss of Innervation or pathological reasons
Leiomyomas
Benign tumors in smooth muscle myofibers
Typically dont cause problems
In uterine = fibroids
Cardiac ischemia
Loss of oxygenated blood to cardiac cells leads to myocardial infarction.
Duchenne muscular dystrophy
Mutation of dystrophin gene leads to defective dystrophin linkage between cytoskeleton and ECM
Presents 3-5 years old
Causes muscle wasting and muscle cell damage. Muscle biopsy is required to confirm presence
X-linked recessive disorder.
Becker muscular dystrophy
Mutation in dystrophin gene similar to duchenne except with a later presentation in life
Presents 17-20 years old.
Myasthenia gravid
Autoimmune disorder where antibodies target acetylcholine receptors
Spinal muscular atrophy
Gene mutation that encodes for survival motor neuron (SMN) protein required for survival of somatic spinal motor neurons
Wernicke-Korsakoff Syndrome
Thiamine deficiency causes decreased thiamine pyrophosphate coenzyme
Disrupts proper use of ATP in all systems, especially in central nervous system
Leigh syndrome
Caused by mutation to the PDH complex or ATP-synthase
Rare progressive neurodegenerative disorder
Chronic lactic acidosis
Deficiency in the activity of the (a)-subunit of the PDH complex
- is an X-linked dominant disorder
Arsenic Poisoning
Arsenide forms thiolase bonds with lipoid acid making it unavailable.
Causes neurological disturbances and death
CPT-2 deficiencies
Caused by 70 different mutations
Affects cardiac and skeletal muscle specifically and disables fatty acid oxidation
-autosomal recessive and usually is fatal.
