Path 2 - Osteo 2

drraythe's version from 2016-05-03 00:59

Metabolic Bone Dzs

Question Answer
Deficiency of mineralized bone can relate to what 4 conditions?Osteoporosis
Fibrous Osteodystrophy
Osteoporosis is bone ___Atrophy
Osteoporosis is characterized by...↓ in bone mass (osteopenia)
Enlargement of bone spaces
↑ fragility of affected bones
(Remaining bone is normally mineralized)
What is the GENERAL etiology/pathogenesis of Osteoporosis?Imbalance btwn bone formation & resorption in favor of resorption
Why is there reduced production of bone in Osteoporosis?Failure of normal osteoblastic activity
Combined w/ ↑ removal of previously formed bone
↑ REMOVAL is due to excess stimulation of osteoclasts by excess PTH production
(1°or 2° Hyperparathyroidism)
4 etiological czs (specific) of Osteoporosis?(1) ↓ Ca++
(2) Malnutrition
(3) Disuse
(4) Toxicity
Explain pathogenesis of Ca++ deficiency in OsteoporosisHypocalcemia → ↑ output of PTH → ↑ bone resorption
Explain pathogenesis of starvation & malnutrition in OsteoporosisReduced bone formation due to deficiencies of protein & mineral, as well as malabsorption of nutrients
Explain pathogenesis of physical inactivity (disuse Osteoporosis)↑ bone resorption & ↓ bone formation mediated through changes in piezoelectrical activity & stretch receptors
What are the 3 toxicities which can cz Osteoporosis? (explain how they cz the prob)(1) Vitamin A tox (↓ osteoblastic activity → ↓ bone formation)
(2) Adriamycin/Doxorubicin tox (chemo drug - ↓ osteoblastic activity)
(3) Fluoride tox (leads to abnormal osteocytes)
Postmenopausal Osteoporosis in women czs what 2 things?(1) Vertebral deformity or collapse
(2) Pathologic fractures of the femoral neck
How does administration of glucocorticoids & Osteoporosis relate? (Etiology)Administration of glucocorticoids ↓ rate at which bone is formed as well as the amount produced & it interferes w/ differentiation to osteoblasts
4 reasons senility leads to Osteoporosis↓ activity
↓ sex steroid hormones
↓ formation of Vitamin D metabolites
↓ responsiveness to Vitamin D metabolites
What are the lesions of CORTICAL bone in Osteoporosis?Reduced in thickness & ↑ in porosity (lack of normal density)
What are the lesions of TRABECULAR bone in Osteoporosis?Thinner w/ perforations & loss of trabeculae lost due to imbalance btwn formation & resorption
What are the lesions of the medullary cavity in Osteoporosis?Enlarged due to endosteal resorption & removal of metaphyseal cancellous bone
What are sequale to Osteoporosis?Fractures
Rickets is a dz of ____ boneImmature
Rickets it characterized by a failure of ____, bc it's a dz ofMineralization
Dz of bone & cartilage undergoing endochondral ossification
Does Rickets affect cartilage?YES
What are the etiological czs of Rickets ? (2, which is the main one)(1) Hypovitaminosis D ← main cz
(2) Could also be a deficiency of Calcium & Phosphorus (dietary, malabsorption, Renal Dz)
Rickets → basic fxn of vit D?Maintenance of serum levels of Calcium reqd for mineralization
Explain the pathogenesis of Rickets due to deficiency of Vitamin D↓ absorption. Tansport & deposition of Calcium & Phosphorus → Ca++ deficiency → failure of mineralization + 2º Fibrous Osteodystrophy
The basic lesions of Rickets are where?Epiphyseal cartilage & bone
What's “rachitic rosary” & what's it associated w/?RICKETS problem, enlarged costochondral junctions
Explain how Rickets affects the epiphyseal cartilageFailure of mineralization! Chondrocytes in the growth plates fail to degenerate > retention of cartilage matrix. Capillaries from the metaphysis are unable to penetrate the cartilage → growth plates: thickened & irregular
Explain how Rickets affects the bonesExcessive production of osteoid (matrix) which fails to mineralize → resistant to normal remodeling via osteoclasts. SOFT & DEFORMED
Which metabolic bone dz is YOUNG animals, which is OLDER?Young = Rickets
Old = Osteomalacia
Overall summary: lesions of RicketsFailure of endochondral ossification
Thickened physes
Flared metaphysis due to excess mineralized osteoid
Wide seams of osteoid on bone-forming surfaces
Hypocalcemia → 2°Fibrous Osteodystrophy
Bones: soft, deformed, fracture easily
Osteomalacia (softening of bones) → happens at what age? Characterized by failure of _ w/ subsequent DzOnly of bone in adults after endochondral bone growth has ceased. Failure of Mineralization → bone deformities & fractures
Osteomalacia czs an accumulation of excess___Mineralized osteoid
3 main etiological czs of Osteomalacia? (Which is most common)(1) Deficiency of Vitamin D or Phosphorus (most commonly)
(2) Chronic Renal Dz
(3) Chronic fluorosis
Pathogenesis of hypovitaminosis D in Osteomalacia↓ absorption of Ca & P
↓ transport of Ca & P
↓ deposition of Ca & P
Explain the pathogenesis of how hypophosphatemia can cz OsteomalaciaLack of P stimulates renal production of calcitriol (active D3), which ↑ intestinal absorption of Phosphorus by a PTH-independent mechanism & provokes osteoclastic resorption of bone. both bone resorption & hypophosphatemia tend to ↑ plasma ionized Ca2+ thus, suppressing PTH release & decreasing renal excretion of Phosphorus
How does chronic Renal Dz lead to Osteomalacia?↓ renal mass or phosphate retention czs altered vit D metabolism → ↓ synthesis of 1,25 (OH)2D3 (calcitriol) → diminished intestinal absorption of Calcium → ↓ calcemic response of the skeleton to PTH → impaired suppression of PTH secretion for any ↑ in serum Calcium level & altered collagen synthesis
Osteomalacia → Chronic Renal Dz leads to Osteomalacia & _ ?2° Hyperparathyroidism
What is the pathogenesis of chronic fluorosis czing Osteomalacia?Fluoride ions replace hydroxyl radicals in the apatite crystal resulting in abnormal osteoid. Bone is then defective & irregularly mineralized
What are lesions of Osteomalacia like?Similar to Rickets except that physeal cartilage & associated lesions are not present in the adult skeleton! You will see:
Wide seams of mineralized osteoid
Marrow cavity enlarged w/ extension into epiphysis
Cortex is thin
Spongy & soft
There is bone pain
Fractures & kyphosis, scoliosis, or both
What is Fibrous Osteodystrophy? What are some akas?Widespread ↑ osteoclastic resorption of bone & replacement by fibrous tissue
AKA: Osteitis Fibrosa Cystica
Von Recklinghausen's Dz
“Bighead” (Horses)
Simian Bone Dz
Osteogenesis Imperfecta
“Bran dz”
Renal Rickets
“Rubber jaw”
4 etiological czs of Fibrous Osteodystrophy?(1) Deficiency of Ca & Vitamin D
(2) ↑ dietary Ca:P ratio
(3) Severe Renal Dz
(4) Ingestion of ↑ oxalate plants (bind Ca)
What problem can eating ↑ oxalate plants cz?Fibrous Osteodystrophy (bc binds up all the Ca so PTH spikes)
Fibrous Osteodystrophy → why does ↑ P cz problems which lead to bone resorption?It ↓ intestinal absorption of Ca
Fibrous Osteodystrophy → examples of ↓-Calcium-↑-Phosphorus dietsAll-meat diets fed to dogs & cats
Unsupplemented cereal grain rations fed to swine
Horses on ↑-grain/poor quality roughage or all-bran diets
Lesions of Fibrous OsteodystrophyWeakening of bones:
Pathologic fractures
Collapse of articular surfaces of bones
Deformities (of ribs, vertebrae, etc.)
Renal Osteodystrophy is basically bcCant excrete P → P too ↑ & cant make Calcatriol → ↑ resorption of bone → ↓ Calcitriol & impaired mineralization
3 types of Hyperparathyroidism that lead to Fibrous Osteodystrophy(1) 1° (tumors)
(2) 2° (nutritional/renal)
(3) Paraneoplastic
Osteomalacia vs Fibrous Osteodystrophy?In Osteomalacia, the osteoid is being laid down but for some reason it can't be mineralized, so the osteoclasts can't remodel cartilage so it's just all soft
In Fibrous Osteodystrophy, the osteoclasts are remodeling too much & taking away mineralized bone