Pathology Flashcards
What are the Transcription Factor Gene Mutations? What do they cause?
HOXD13- Brachydactyly syndrome
RUNX2- Cleidocranial dysphasia
FGFR3- Achondroplasia and thanatophoric dysphasia
What are Structural Protein disorders?
Osteogenesis imperfecta: skeletal fragility.
What are gene disorders influencing metabolic enzymes and transporters of the bone?
Osteopetrosis: Reduced resorption, no medullary canal
Treated with stem cell treatments.
Mucopolysaccharidoses: Lysomal storage, disorders. Can’t degrade some carbohydrates and it causes structural defects in cartilage by apoptosis.
Describe Osteoporosis. What is the difference between Osteoporosis and Osteopenia?
Osteopenia is bone loss from 1 to 2.5 standard deviations. Osteoporosis is more than 2.5 standard deviations.
Postmenopausal, senile, idiopathic are primary reasons. Osteoporosis is diagnosed by imaging only.
Paget Disease
Increased but disordered bone.
3 stages: osteolytic, mixed osteoclasts-osteoblastic, burned-out quiescent osteoscleric
Morphology: mosaic pattern of lamellae bone.
Usually radiologic diagnosis
Treated: calcitonin, bisphosphate.
Increased levels of serum alkaline phosphatase without an increase of Ca or Phosphate.*****
Rickets and Osteomalacia
Vitamin D and Calcium deficiency. Rickets: kids at growth plate
Osteomalacia: adult remodeling
Hyperparathyroidism
Increased osteoclast activity by PTH. Increase synthesis of vitamin D. Increase reopsorption of Ca in the kidneys.
Treated by reducing the PTH levels.
Renal Osteodystrophy
Increased resorption with not enough formation. (Too much clast, not enough blast)
Leads to renal failure, osteoporosis, osteomalacia, hyperparathyroidism (secondary), growth retardation.
What are the types of fractures
Simple Compound Comminuted-fragmented bone Displaced- ends aren’t aligned. Stress- slow developing Green stick- not all the way through Pathological- involving bone weakened by underlying disease.
Osteonecrosis
Infarction of the bone and marrow. Mostly happens in the medullary cavity.
Morphology: cortex usually not affected. Overlying cartilage lives. Usually wedge shaped.
Can heal if there isn’t disassociation from the cartilage.
Osteomyelitis. Differences between the two bacterial types?
Inflammation of bone and marrow
Pyogenic osteomyelitis: Hemagoenous spread or extension from a contiguous site (close by)
80-90% s. Aureous
Morphology: active neutrophil inflammation.
Mycobacteria Osteomyelitis: Most in underdeveloped countries. Can persist for years, is linked with tuberculosis and is very destructive.
Skeletal Syphilis
Syphilis and yaws
Can cause bone issues if syphilis isn’t treated. We may see more of these issues as syphilis is becoming more antibiotic resistant.
Cleidocranial Dysplasia
Birth defect that mostly affects bones and teeth. Collarbones are typically poorly developed or absent. Affected areas are shorter.
RUNX2 defect
Osterix or TF Sp7 causes what?
Osteogenesis imperfecta: blue tinge to white of eyes. Short height, loose joints, hearing loss, breathing problems.
Explain Osteogenesis Imperfecta
Mutation to COL1A1 and COL1A2
Causes deficiencies in the synthesis of type 1 collagen.
Most common inherited disorder of CT. Autosomal Dominant
Most mutations involve the substitution of glycine.
General: Too little bone, also blue sclerae, hearing loss, dental imperfections
4 types, but the most common is type 1 and is most mild. Most dangerous is type 2 and most people die in uterus.
Most dangerous types don’t allow helix to form. Most mild types are functional collagen with lower amounts
Explain Marian Syndrome
Mutations in FBN1 gene at chromosome 15q21. Very large gene, and all people with disease have mutations in this gene.
Defect in fibrillin-1 the scaffold for elastic CT.
Affects skeletal stature, long head, double joints, pectus excavatum or pigeon chest. Bilateral dislocation ocular change, Ectopia lentis
Most common cause of death is aortic rupture. No elastin.
Explain the secondary pathogens is of Marian syndrome
Loss of microfibrils leads to excess transforming growth factor-B TGF-B.
Usually gets stuck in the microfibrils, but the defect gives more free TGF-B to bind to receptors.
Explain Ehlers-Danilo’s Syndrome
Single gene disorders that are both autosomal dominant and recessive. 6 different variants
3 or more common variants:
- deficient type lll collagen from mutation in COL3A1 gene.
- Deficiency of enzyme lysyl hydroxylase
- Deficient synthesis of type 5 collagen
Defects in collagen synthesis and structure. Stretchy skin, fragile skin, hyper mobilize joint, poor wound healing, Serious large artery or colon ruptures.
Overall explain Systemic Sclerosis
Excessive fibrosis in multiple tissues, obliterating vascular disease with cutaneous involvement.
Visceral involvement of GI, lungs, kidneys, heart, and skeletal muscle are more fatal
Etiology is unknown
What are the two groups of systemic sclerosis?
Diffuse: characterized by widespread skin involvement, rapid progression, and early visceral involvement.
Limited: Mild skin involvement of fingers and face, late viscera involvement, CREST syndrome.
Calcinosis Raynaud phenomenon Esophageal dismotility Scelrodactyly Telangiectasia
Explain the pathogenesis of Systemic Sclerosis
Unknown etiology
3 paths
Autoimmune responses: of CD4 T cells responding to unidentified antigen and releasing cytokines. Presence of ANA anti-nuclear antibodies
Vascular Damage: Microvascular disease may be initial lesion leading to fibrosis.
Fibrosis: May be from activated macrophages, fibrogenic cytokines, or scarring floolowing ischemic damage by vascular lesions (hybrid)
Explain the morphology of systemic sclerosis
Skin fibrosis that begins in fingers. Increase in fibrosis of epidermis and dermis.
Fingers are tapered and clawed may develop cutaneous ulceration
Face becomes drawn mask
GI: lower 2/3 of esophagus is immobile leads to gastric reflux
Kidneys: Renal hypertension
Lungs: Pulmonary hypertension
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Heart: Myocardial fibrosis, and RV hypertrophy
Joint problems
