12 - Bones, Joints, Muscle and Endocrine System Flashcards
Describe achondroplasia in terms of inheritance and what causes the disease
Autosomal dominant defect of long bone formation, caused by mutation in fibroblast growth factor 3 (FGFR3) which is expressed in cartilage and bone
Describe osteogenesis imperfecta in terms of inheritance and what causes the disease
autosomal recessive or dominant inheritance, caused by defective collagen type I and results in production of weak osteopenic bone
Describe osteopetrosis in terms of inheritance and what causes it.
Aka marble bone disease, it’s an autosomal or x-linked inherited disease resulting from defective osteoclast function. This results in bones growing but not remodeled, therefore resulting in thick but brittle bones
For DEXA, identify the ranges that indicate osteoporosis, osteopenia, and normal
Osteoporosis (< -2.5)
Osteopenia (-1 to -2.5)
Normal (-1 to +2)
Describe the two types of primary osteoporosis
Type I: postmenopausal osteoporosis
- loss of cancellous bone
- loss of estrogen
Type II: senile osteoporosis
- affects both men and women
- loss of cortical bone predominates
Describe secondary osteoporosis
Caused by hormonal imbalance, diet, immobilization, drugs, tumors
How is osteoporosis diagnosed?
- X-ray
- bone density studies
- no biochemical abnormalities
What are 7 risk factors for osteoporosis?
age, genetics, sex, hormones, nutrition, physical activity, environment
What are osteomalacia and rickets? What are the two major causes + pathogenesis?
Osteomalacia: inadequate mineralization resulting in softening of the bone
Rickets: osteomalacia in growing bones
Causes: vitamin D deficiency and hypophosphatemia (lack of phosphate)
Pathogenesis:
1. vit D def and hypophosphatemia leads to decreased absorption
2. causes increase in PTH which causes bone resorption
3. compensatory bone formation occurs to try and make up for lack of mineralization
What are 3 consequences of osteomalacia and rickets?
- bowlegs
- nodular and palpable costochondral junction -> rachitic rosary
- growth development problems
What is renal osteodystrophy and what does it result in?
Complex bone changes that occur in patients with chronic renal failure (CRF)
CRF results in decreased phosphate excretion -> secondary hyperphosphatemia -> secondary hyperparathyroidism -> increased osteoclast activity
What are three signs of renal osteodystrophy?
- osteomalacia
- osteofibrosis
- activation of osteoclast activity -> cystic changes
Describe the characteristics of Paget’s Bone Disease. What are the three phases?
- chronic disease of unknown etiology
- irregular restructuring results in thick and deformed bones (mosaic pattern in histology)
Three phases:
- osteolytic destructive phase
- mixed osteoclastic-osteoblastic phase
- burnt-out osteosclerotic phase
What are the 4 clinical features of Paget’s disease of bone
- pain of affected bone
- thickened cranial bones -> compression of cranial nerves -> dizziness, headache
- bowlegs
- may develope into osteosarcoma
What is osteomyelitis caused by? Treatment? Complications?
Inflammation of bone caused by hematogenous spread of bacteria (S. aureus, MB tuberculosis, T. pallidum)
Treatment: antibiotics +/- surgical drainage
Complications: bone deformities, fractures, squamous caricnoma, amyloidosis
Describe aseptic necrosis and give an example. What are 5 important causes?
AKA avascular necrosis or osteonecrosis, involves interruption of blood flow causing death to part of the bone
Example: Legge-Calve-Perthe disease
Important causes:
- trauma
- corticosteroids
- radiation therapy
- systemic disease
- emboli
Define the following types of #: simple, comminuted, complete, incomplete, closed, open/compound, pathological/spontaneous
Simple: single fracture line
Comminuted: multiple fracture lines/fragments
Complete: separated bone fragments
Incomplete: not complete discontinuity of bone
Closed: has intact overlying skin and soft tissue
Open/compound: communicawtes with external environment
Pathological/spontaneous: occurs in weakened bones without external trauma (e.g. Paget’s bone disease)
Describe the 4 stages of bone # healing
- Hematoma: fills # gap and creates framework for new vessels
- Granulation tissue: inflammatory mediators stimulate osteoblast and osteoclasts
- Bony callus: soft callus mineralizes to bony callus
- Remodelling: spongy/trabecular bone
Half of primary bone tumors and the other half are…?
Half are blood-forming cells of BM (multiple myeloma, leukemia)
Other half are…
benign: osteoma, chondroma, fibroma
Malignant: osteosarcoma, chondrosarcoma, Ewing’s sarcoma
what is the most common primary malignant bone tumor? Where does it normally start and what does it affect?How is it treated?
Osteosarcoma
Starts in the bone matrix, affects metaphysis of long bone
Treated with combined chemotherapy and surgery
what is the second most common primary malignant bone tumor? Where does it normally start and what does it affect?
Chondrosarcoma
- malignant neoplams that produces cartilage
- affects the axial skeleton (vertebrae, pelvis, femur, shoulder)
Describe Ewing’s sarcoma
- malignant neoplasm consisting of undifferentiated cells
- diaphysis of long bone, may arise in soft tissue
- metastases common
What is the name of the most common joint disease? What is it characterized by? Most common symptom? Diagnosis?
Osteoarthritis
characterized by asymmetric chronic degenerative disease of articular joints with loss of cartilage, sclerosis, eburnation, cysts, and osteophytes
most common symptom is pain
Diagnosis is based on clinical/radiology
Characteriziation of rheumatoid arthritis? What are the 4 extra-articular features?
- chronic system autoimmune disease of unknown etiology characterized by symmetric inflammation of joints
Extra-articular features:
- rheumatoid nodules
- lung disease
- eye disease
- vasculitis
Describe the pathogenesis of rheumatoid arthritis (5)
- synovitis (inflammation of synovial lining of joints)
- synovial cells proliferate
- transforms into granulation tissue (Pannus)
- destruction and immobilization of joint
- scar formation causing ankylosis (stiffening of joint)
Describe infectious arthritis. What is the most common cause?
Occurs via hematogenous spead (sepsis) or direct spread from bones
Most common bacterial arthritis is Lyme Disease caused by Borrelia burgdorferi which results in skin rashes and migratory arthritis eventually ending up in heart and CNS
Describe gout and differentiate btwn primary and secondary
Gout is characterized by hyperuricemia and deposition of uric acid crystals in joints, causing excruciating pain. Deposits in kidneys can lead to chronic renal failure.
Primary = consequence of either overproduction or underexcretion of uric acid
Secondary = consequence of either drugs or increased uric acid production
Describe ankylosing spondylitis
Disabling and asymmetric inflammatory arthritis preferentially affecting spine and sacrum
Involves destruction of joints with fusion of spine, limited chest expansion and back pain
Seronegative arthropathy, >90% positive for HLA-B27
Define the following terms: weakness, fatigability, spasm (myotonus/myotonia), fibrillation, myalgia, paralysis, quadriplegia, hemiplagia, paraplegia
- Weakness: inability to contract adequately
- Fatigability: inability to sustain contraction
- Spasm (myotonus/myotonia): continuous involuntary contraction
- Fibrillation: uncoordianted contraction of groups of fibers
- Myalgia: muscle pain
- Paralysis: loss of power or ability to move voluntarily
- Quadriplegia: paralysis of both upper and lower limbs
- Hemiplegia: paralysis of one side of the body
- Paraplegia: paralysis of only lower limbs
What is neutrogenic atrophy? Difference btwn upper and lower motor neuron injury?
Neutrogenic atrophy: muscle atrophy due to injury of nerve supplying the muscle
Upper motor neuron injury: injury to cerebral motor neurons or descending cerebrospinal tract (cortex lesion, cortical tract lesion, spinal tract injury)
Lower motor neuron injury: injury to motor neurons located in anterior horn of spinal cord (spinal nerve disease, nerve root compression, axonal injury)
Describe myasthenia gravis? How is it diagnosed
- autoimmune disease due to immune-mediated injury, causing decreased muscle acetylcholine receptors (antibodies bind and inhibit ACh)
- characterized by easy fatigability and weakness, most patients have enlarged thymus or neoplasm of thymus
- Diagnosed by clinical changes: anticholinesterase test, electromyographic testing
Describe Duchenne muscular dystrophy and its diagnosis
X-linked recessive inherited disease caused by deficiency of dystrophin, an integral protein in cell plasma membrane
Diagnosis: clinical findings, family history, lab tests
Describe Becker’s Muscular dystrophy
- same gene affected as Duchenne but milder disease
- also X-linked recessive
Describe inheritance, cause, symptoms of myotonic dystrophy
Inheritance: autosomal dominant
Cause: mutation of dystrophia myotonica protein kinase (DMPK)
Symptoms: muscle wasting, facial muscle weakness, eye drooping
Difference between congenital and acquired myopathies
Congenital:
FLOPPY BABY!! early onset slow progression. Proximal or generalized muscle wasting and hypotonia
Acquired: muscle weakness secondary to another disease. Diabetic myopathy = vascular, metabolic, neurogenic components. Cancer myopathy = paraneoplastic syndromes
What is myositis? Difference btwn infectious (3) and immune (4) myositis?
Inflammatory muscle diseaes
Infectious:
- caused by virus, bacteria, or parasite
- often associated with myalgia
- examples: tetanus, gas gangrene, trichinosis from trichinella spiralis
Immune:
- polymyositis
- dermatomyositis
- SLE-associated myositis
- sarcoidosis
Name 3 benign and 3 malignant muscle and soft tissue neoplasms
Benign:
- fibroma (fibroblasts)
- lipoma (fat)
- hemangioma (blood vessels)
Malignant:
- Rhabdomyosarcoma (skeletal muscle)
- Liposarcoma (adipocytes)
- Malignant fibrous histiocytoma (undifferentiated connective tissue)
Describe a pituitary adenoma. What causes symptoms? What is the most common pituitary adenoma and how to treat it?
Benign neoplasm of endocrine cells
Symptoms due to release of excess hormones
Most common: Prolactinoma which releases prolactin, can fix with surgery or medical therapy
Describe somatotrophic adenomas and characteristics
- neoplastic cells that produce growth hormones
- results in gigantism (enlarged body size and limbs) and acromegaly (enlargment of hands, feet, jaw, tongue, soft tissue)
Describe Corticotropic adenoma
- neoplastic cells produce adrenocorticotropin hormone (ACTH)
- Cushing’s disease: excess glucocorticoid released by adrenal cortex
- NOT the same as Cushing’s syndrome…it causes it
Describe 3 causes and 2 symptoms of pituritary hypofunction. Name and example and what causes it/results
Causes:
- defect in pituitary gland
- destructive tumor
- ischemia of gland
Symptoms:
- weakness, decreased appetite, decreased weight, hypotension
- secondary hypotension of target organs
Diabetes insipidus
- lack of ADH results in destructive lesion in hypothalamus
- unable to resorb water, large amts of hypotonic urine
What are the major causes, symptoms, and treatment of hyperthyroidism? What are two examples?
Major causes: agenesis, surgery, iodine deficiency, thyroiditis
Symptoms: cretinism/dwarfism, myxedema, sleepy/tire easily
Treatment: thyroid hormone replacement
Grave’s Disease: autoimmune disease where antibodies target TSH receptor on thyroid hormone and causes lots of it to be produced
Multinodular goiter: enlarged, nodular thyroid that produces an increased amt of thyroid hormone
Describe benign and malignant thyroid neoplasms. What are the two types of malignant neoplasms?
Adenoma:
- benign neoplasms of thyroid follicular cells
- may produce symptoms due to mass effect
- treated by surgery
Carcinoma:
- malignant neoplasms of thyroid follicular cells
- Two major types: papillary and follicular carcinoma
Difference btwn hyperparathyrodism and hypoparathyroidism (causes and symptoms)
Hyperthyroidism:
Causes: parathyroid adenoma and hyperplasia
Symptoms: bones, stones, moans, abdominal groans
Hypothyrodism:
Causes: surgery, congenital hypoplasia
Symptoms: hypocalcemia, muscle spasms, irregular heart beat, cardiac arrest
What is hypercortisolism? What syndrome does it correspond to? Common causes and findings?
Due to excess glucocorticoid hormone (cortisol)
Cushing’s Syndrome
Common cause: exogenous steroids, adrenal hyperplasia/neoplasia, Cushing’s disease, ectopic ACTH
Findings: central obesity, buffalo hump, moon face, striae
What is hyperaldosteronism? What syndrome does it correspond to? Common causes and findings?
due to excess mineralocorticoid hormone
Conn’s Syndrome
Cause: adrenocortical adenoma and adrenal hyperplasia
Findings: Present with HTN and hypoleukemia
What is adrenocortical hypofunction? What disease does it correspond to? Symptoms?
Autoimmune destruction of adrenals cuz TB
Addison’s Disease
Symptoms: fatigue, weight loss, nausea, low Na, high K
Name two adrenal gland tumors and their characteristics
Neuroblastoma:
- highly malignant neoplasm of neuroblasts (cuz metastasis)
- common in neonates and infants
- can arise anywhere throughout the sympathetic nervous system
Pheochromocytoma:
- involves adrenal medulla
- 10% malignant, bilateral, extra-adrenal, inherited
- diagnosed based on secretion of epinephrine and metabolites in urine
- clinical features: paroxysmal HTN, anxiety, sweating
What is diabetes mellitus? What are some symptoms? Classification?
- disease due to inadequate insulin activity, impaired glucose tolerance
- Symptoms: polyuria, polydypsia, weight loss
- Classification: Type I (insulin dependent, juvenile onset), Type II (non-insulin dependent, adult onset)
Pathogenesis of Diabetes Mellitus (4)
- insulin decreases blood glucose levels
- lack of insulin causes hyperglycemia
- striated muscle cells must use anaerobic glycolysis -> increased lactic acid
- increased free fatty acids
4 Complications and Treatments for the diff classifications of diabetes mellitus
Complications:
cardiovascular: increased atherosclerosis
Renal: glomerulosclerosis, pyelonephritis, papillary necrosis
Eyes: diabetic microangiopathy of retinal vessels
Nervous System
Treatments:
Type I: insulin
Type II: diet, oral hypoglycemics, insulin if uncontrollable
What is multiple endocrine neoplasia (MEN) Syndrome and what are the three main hereditary syndromes
MEN I
- pituitary adenoma
- parathyroid hyperplasia/adenoma
- pancreatic islet cell neoplasia
MEN IIa
- medullary thyroid carcinoma
- pheochromocytoma
- parathyroid
MEN IIb
- medullary thyroid carcinoma
- pheochromocytoma
- mucosal neuromas
