Post-Mid Mod B2M3 Flashcards
(241 cards)
1
Q
What is the primary composition of mineralized bone
A
Calcium and phosphate > hydroxyapatite
Type I collagen, Type V collagen
Noncollagenous proteins
2
Q
Describe bone matrix structure
A
Osteocytes are housed within lacunae, which are pockets between rings of osteons (lamellae surrounding a central Haversian canal) that are connected by canaliculi
3
Q
What are the four general classifications of bones
A
Long (femur, metacarpals)
Short (carpals)
Flat (scapula)
Irregular (vertebra)
4
Q
What covers the articular surface of an epiphysis
A
Hyaline cartilage
5
Q
What is the general trend of spongy and compact bone in bony structures
A
More compact bone in diaphysis
More spongy bone in epiphysis
6
Q
Describe the composition of the periosteum
A
Fibrous connective tissue containing osteoprogenitor cells
7
Q
What is the difference between red and yellow bone marrow
A
Red- consists of blood cells in different stages of development (mostly in spongy bone)
Yellow- consists mostly of fat cells
8
Q
What connect the periosteum/endosteum to the Haversian canals
A
Perforating/Volkmann canals
9
Q
Openings in the bone through which blood vessels pass to reach the marrow
A
Nutrient foramina
10
Q
Where does most of the vascular supply to the bone come from (what canals)
A
Volkmann canals > Haversian canals > periosteal arteries
11
Q
Where is the lymphatic drainage for bones
A
Periosteum
12
Q
What are the major features of immature bone
A
No organized lamellated appearance (interlacing collagen fibers instead)
More affinity for hematoxylin stain
13
Q
What is the relationship between Haversian and Volkmann canals
A
Haversian canals run longitudinally parallel, and are connected via perpendicular Volkmann canals
In compact bone
14
Q
What is the origin of osteoprogenitor cells
A
Mesenchymal stem cells (expressing CBFA1)
15
Q
What stimulates osteoprogenitor differentiation into osteoblasts
A
IGF-1/IGF-2 signaling
16
Q
What compounds do osteoblasts secrete
A
Type I collagen
Bone matrix proteins (osteonectin, osteoponin, alkaline phosphatase)
17
Q
What are some notable markers of osteoblast activity
A
Alkaline Phosphatase
Osteocalcin
18
Q
Mature bone cell enclosed by bone matrix that was previously secreted as an osteoblast
A
Osteocyte
19
Q
What are the functions of osteocytes
A
Mechanotransduction- dec. mechanical stimuli causes bone loss, whereas inc. stimuli promotes bone formation
Happens via a transient electrical potential flowing through the interstitial fluid, acted upon by mechanical forces > results in inc. intracellular Ca2+
20
Q
What are the key histology characteristics of osteoclasts
A
Multinucleated
Acidophilic (especially TRAP staining)
21
Q
Describe the process of activating osteoclasts
A
RANK receptors on the osteoclasts bind to RANKL being secreted from T lymphocytes/osteoblasts > induces monocyte fusion into a giant multinucleated osteoclast
22
Q
What are the components of osteoclast lysosomes
A
Collagenase
Hydrochloric acid- dissolves hydroxyapatite
23
Q
How do osteoclasts resorb bone, functionally?
A
ATP-dependent proton pumps excrete carbonic acid > degenerates hydroxyapatite crystals
24
Q
What is the role of osteoprotegerin (OPG) in osteoclast functioning
A
OPG blocks RANKL from binding to RANK
Secreted by osteoblasts
25
Describe bone-lining cells
Flat cells overlying the bone surface (periosteal/endosteal); primary function is nutritional support of osteocytes
*Are derived from osteoblasts*
26
Describe the process of bone crystal nucleation and propagation in the matrix vesicles
Nucleation is the formation of hydroxyapatite crystals from intravesicular Ca2+ and PO4- > Propagation is the release of crystals from the matrix vesicle into the bone matrix (aided by osteocalcin and osteopontin proteins) and combined with collagen
27
What is the function of alkaline phosphatase in bone mineralization and what happens to it afterwards
ALP converts organophosphate (PPi) to Pi, which is then cotransported with Na+ inside the vesicle via SLC20; ALP is then liberated and goes to the plasma
*Thus, high EC concentrations of Ca2+ and Pi both inc. crystal formation*
*ALP also creates a more alkaline environment*
28
What are the consequences of osteopetrosis
Hypermineralized, chalk-like, brittle bones
29
A loss of bone integrity resulting from mechanical injury and/or diminished bone strength
Bone fracture
30
Bone fracture w/ the overlying skin intact
Simple facture
31
Bone fracture extending only partially through the bone
Greenstick fracture
*Common in infants*
32
Bone fracture where the ends of the bone at the fracture site are not aligned
Displaced fracture
*Requires open reduction and internal fixation*
33
Bone fracture in which the bone is fragmented into several pieces
Comminuted fracture
*Common in older patients with osteoporosis*
34
Bone fracture in which the bone communicates with the skin surface
Compound fracture
*High infection risk*
35
Bone fracture that is slowly developing, following a period of increased physical activity (repetitive loads)
Stress fracture
36
Bone fracture involving bone that has been weakened by an underlying disease process
Pathological fracture
37
Describe the healing process of a fracture
1) Rupture of blood vessels > hematoma (fills the fracture gap and surrounds the affected bone area)
2) Fibrin mesh deposition (blood clotting) and inflammatory cell infiltration
3) Activation of osteoprogenitor cells
4) Results in the production of a soft callus after the first week, and bony callus after two weeks*
5) As callus is subjected to mechanical forces, it undergoes endochondral ossification and is remodeled until it is lamellar bone
38
What is the typical timeline for bones to heal to weight-bearing loads
6-8 weeks
39
What are the effects of nicotine on bone repair
Inhibits fibroblast deposition of vascular tissue > decreased bone union rate
40
What is the typical timeline for a bone to regain original strength
3-6 months
41
What are frequent consequences of comminuted and displaced fractures
Bone deformity leads to pseudarthrosis (cystic degeneration of malformed bone callus, which becomes synovial-like cartilage- a false joint)
42
What causes osteonecrosis
Ischemia of bone/marrow cells caused by vascular injury, systemic disease, radiation, corticosteroids, thrombotic occlusion, compression, etc.
43
What is the mechanism of fat embolism syndrome
Soft tissue crush injury/rupture of vascular sinusoids (long bone fracture) > release microscopic fat globules into circulation
44
Symptoms of pulmonary insufficiency, neurologic symptoms, anemia, thrombocytopenia, and a diffuse petechial rash
Fat embolism syndrome
*Can occur after long bone injuries*
45
Which route of infection is most common for osteomyelitis in children and in adults
Children- Hematogenous spread
Adults- Direct contact (open fractures, surgery, diabetic foot)
46
What bacteria is usually responsible for osteomyelitis
Staph aureus
47
Symptoms of malaise, fever, chills, leukocytosis, and marked throbbing pain over a particular region
Osteomyelitis
*Requires radiological findings of bone inflammation; pos. bone culture*
48
What are some complications of chronic osteomyelitis
Recurrent, cyclical pain at area
Pathologic fractures
Secondary amyloidosis
Endocarditis
Sepsis
Squamous cell carcinoma
Sarcoma
49
Dead bone fragments
Sequestrum
50
What is a major risk of epiphyseal osteomyelitis in children
Infection of the articular cartilage can cause septic arthritis > permanent damage
51
What if a common causative agent of osteomyelitis in patients with sickle cell anemia
Salmonella spp.
*Unique for these patients*
52
Destructive infection of the vertebrae caused by Tuberculous Spondylitis > causes scoliosis/kyphosis and neuro deficits
Pott Disease
53
Know that mycobacterium tuberculosis commonly cause osteomyelitis (*)
*
54
What are some notable complications of Tertiary Syphilis
Cardiovascular syphilis
Neurosyphilis
Syphilitic osteomyelitis
*Can also cause complications with congenital syphilis in bones*
55
Which antibiotics are used to treat penicillin-resistant staph aureus osteomyelitis
Naficllin
Dicloxacillin
Oxacillin
Cefuroxime
*All are B-lactamase resistant penicillins*
Clindamycin
Rifampin
56
Which antibiotics are used to treat pseudomonas aeruginosa and serratia spp osteomyelitis
Piperacillin-tazobactam
Gentamicin
57
Which antibiotics are used to treat unknown/mixed osteomyelitis infections
Imipenem + Cilastatin
*Very broad spectrum B-lactamase resistant penicillin*
58
Which antibiotics are used against penicillin-sensitive staph aureus osteomyelitis
Cefazolin
Cefuroxime
Ceftriaxone
Clindamycin
59
Which antibiotics are used to treat anaerobe osteomyelitis
Clindamycin
60
What is the use of Vancomycin
-Methicillin-resistant staph a
-Penicillin-sensitive staph a
-Penicillin-resistant staph a
-Various strep
61
Which antibiotics are used to treat methicillin-resistant staph aureus osteomyelitis
Vancomycin
Teicoplanin
Dalbavancin
62
Which antibiotic is used to treat vancomycin-resistant enterococcus faecium osteomyelitis
Quinupristin-dalfopristin
63
What is the use of Linezolid antibiotics
-Vancomycin resistant
-Penicillin resistant
-Methicillin resistant
*Tedizolid is NOT for vanc-resistant*
64
Which antibiotic is used for methicillin/vancomycin/linezolid resistant osteomyelitis
Daptomycin
65
What is the use of ciprofloxacin
-Enteric G- rods
-Penicillin-resistant Staph a
-Neisseria gonorrhea septic arthritis
66
What is the most common presentation of community-acquired staph a
Soft tissue/skin abscesses
67
Which antibiotics are typically used for surgical antibiotic prophylaxis
Cephalosporins
Vancomycin
68
What are some good diet sources of calcium
Low-fat dairy products
Green leafy vegetables
Beans/legumes
Nuts/almonds
69
What are some good diet sources of vitamin D
Egg yolks
Saltwater fish
Liver
Milk
70
What is the recommended daily calcium intake for people 9-18 years olds
1300 mg daily
71
What is the recommended daily calcium intake for people 19-70 years olds
1000 mg daily
72
What is the recommended daily calcium intake for people 70+ years olds
1200 mg daily
73
What are some preventative measures to osteoporosis
-High calcium/vitamin D diet
-Exercise
-Maintaining healthy body weight
-Not smoking/drinking
-Not taking glucocorticoids
74
What is the clinical difference between osteoporosis and osteopenia
Bone density -1 to -2.5 is osteopenia, less than -2.5 is osteoporosis
75
What activates PTH and how does it affect the bones
PTH is released in response to low serum Ca2+, and stimulates osteoblasts to release RANKL > activates osteoclasts
76
What activates calcitonin and how does it affect the bones
Calcitonin is released in response to high serum Ca2+, and inhibits bone resorption
77
Explain Wolff's Law
Bones that bear more weight remodel faster
78
What is the function of vitamin D in relation to bone remodeling
Stimulates intestinal absorption of Ca2+ > increase calcitonin > inhibit bone resorption
79
What are some notable bone resorption activating factors
PTH
IL-1
Glucocorticoids
80
What are some notable bone formation activating factors
BMPs
Sex hormones
81
What are some differentials for elevated ALP
Paget's disease
Healing bone fracture
Bone tumor
Hyperthyroidism
82
Symptoms of extreme skeletal fragility, blue sclerae, sensorineural hearing loss, and misshapen blue/yellow teeth
Osteogenesis Imperfecta
83
What is the difference in prognosis between type I and II osteogenesis imperfecta
I- Normal life span, susceptible to fractures esp. in childhood
II- Always fatal in utero/perinatal
84
What is the mechanism of osteogenesis imperfecta
Auto dom mutation of a1 and a2 type I collagen chains > misshapen collagen I
85
Symptoms of congenital shortened proximal extremities w/ relatively normal trunk, macrocephaly; normal bone density and cognition
Achondroplasia
86
What is the mechanism of achondroplasia
Mutation of FGFR3 gene (gain of function) > inhibits proliferation of chondrocytes (cartilage-producing) and endochondral ossification
87
Symptoms of congenital disproportionately small limbs, frontal skull bossing, macrocephaly w/ a small chest cavity and bell-shaped abdomen
Thanatophoric Dysplasia
88
What is the mechanism of thanatophoric dysplasia
Mutation of the FGFR3 gene (gain of function) > diminished chondrocyte hyperplasia and disorganized zone of proliferation
89
Symptoms of abnormally brittle bones that fracture easily, and lack a medullary canal/the ends of bones are misshapen/bulbous; also leukopenia, anemia, mild cranial nerve deficits; diffuse symmetric skeletal sclerosis
Osteopetrosis
90
What is the mechanism of osteopetrosis
Auto rec mutation of carbonic anhydrase II > osteoclast failure to produce acid > defective bone resorption
91
Symptoms of genu varum, frontal bossing, overgrowth of epiphyseal cartilage, distorted/irregular cartilagenous masses. and other skeletal deformations
Rickets Disease
*Usually in children, and affects bone deposition in growth plates*
92
What is the mechanism of Rickets Disease
Vitamin D deficiency > dec. serum Ca2+ > PTH secretion > osteoclast activation
*Essentially, excess unmineralized bone matrix stemming from a lack of Ca2+ to make hydroxyapatite*
93
What is the difference between Rickets Disease and Osteomalacia
Rickets is in small children, osteomalacia is in adults and is associated with limited exposure to sunlight, vitamin D deficiency, or hypocalcemia
94
What bones are typically affected by osteomalacia
Vertebral bodies and femoral neck
95
Symptoms of easy bleeding in the gums/skin/joints, impaired wound healing, and growth restriction in children
Scurvy
96
What is the mechanism of scurvy
Vitamin C deficiency > impaired preprocollagen hydroxylation (collagen synthesis)
97
What is the mechanism of postmenopausal osteoporosis
Dec. in estrogen-mediated osteoclast apoptosis
Dec. in estrogen-mediate OPG production
98
What are some risk factors for osteoporosis
Old age
Post-menopausal women
Hyperthyroidism
Malnutrition/Malabsorption
Corticosteroid use
Smoking/drinking
Sedentary lifestyle
99
What bones are susceptible to pathogenic fractures via osteoporosis
Femur
Spine
Pelvis
100
What drugs are used to treat osteoporosis
Ca2+ and Vitamin D supplements
Bisphosphonates
Denosumab (anti-RANKL Ab)
Teriparatide (PTH analog)
101
Symptoms of bone pain (microfractures), lion face, femur and tibia bowing, secondary osteoarthritis, chalk stick-type fractures, spinal compression fractures, kyphosis
Paget's Disease
*Usually onset in late adulthood- will have normal Ca2+ and PO4-*
102
What is the classical histological finding for Paget's Disease
Mosaic pattern of lamellar bone
103
What is the mechanism of Paget's disease
SQSTM1 gene mutation > inc. NF-kB signaling > inc. RANKL (or also, OPG inactivating mutation)
104
What is the treatment for Paget's Disease
Calcitonin
Bisphosphonate
105
What are the effects of hyperparathyroidism on Ca2+ and PO4- concentrations
Increases both Ca2+ and PO4- concentration
*Also an inc. osteoclast activity > osteopenia*
106
Symptoms of kidney/gallstones, bone pain, abdominal pain, polyuria, and psychological disorders
Hyperparathyroidism
107
What are some common complications of hyperparathyroidism
Osteoporosis
Brown tumors- cause bone loss, secondary hemorrhages/microfractures
Osteitis fibrosa cystica- peritrabecular fibrosis (railroad track appearance on histology)
108
That is the use and mechanism of teriparatide
Used to treat osteoporosis- is a PTH analog that is taken at low doses
109
What is an antibiotic that can be used to treat hypercalcemia
Pilamycin
110
What is the mechanism of fluoride supplementation
Accumulates in bones and stabilizes hydroxyapatite crystals (also inc. osteoblast activity)
111
What are symptoms of fluoride intoxication
Nausea, vomiting
GI blood loss
Arthralgias, arthritis
112
What is the use and mechanism of denosumab
Used to treat osteoporosis and bone tumor metastases- anti-RANKL Ab (blocks osteoclast activation)
113
What is the use and mechanism of Romosozumab
Used to treat postmenopausal osteoporosis- anti-Sclerostin Ab (inc. bone formation and slows resorption)
*Avoid in patients with CVD risk*
114
What is the use of corticosteroids with respect to bone health and what is the mechanism
Used to treat hypercalcemia- antagonizes vitamin D-Ca2+ transport
*Can cause osteoporosis, and stunt skeletal development in kids*
115
What is the use and mechanism of Raloxifine
Used to treat post-menopausal osteoporosis- selective estrogen receptor modular (partial agonist)
116
What is the use and mechanism of bisphosphonates
Used to treat osteoporosis, Paget's disease, metastatic bone disease, and malignant hypercalcemia- PPi analog (dec. osteoclast activity)
117
What are the three types of cartilage and give an example of each
Hyaline- epiphyseal plates
Elastic- external ear
Fibrocartilage- IV discs
118
What is the major component of each of the three types of cartilage
Hyaline- Type II collagen
Elastic- elastic fibers w/ perichondrium
Fibrocartilage- Type I collagen
119
What are some of the important mechanical properties of cartilage
Compression and re-expansion, flexibility
120
What is the role of lysosomes with respect to cartilage maintenance
Intracellular lysosomes degrade proteoglycans, glycoproteins, and glycolipids (brought in via endocytosis)
121
Clusters of chondrocytes in hyaline cartilage- recently divided cells
Isogenous groups
122
What does the matrix of hyaline cartilage not stain homogenously
Matrix production results in cytoplasmic basophilia (the capsular matrix surrounds chondrocytes)
123
What is the vasculature of cartilage
It is avascular- nutrition is supplied via diffusion through the ECM
124
What directs internal remodeling processes of chondrocytes in cartilaginous tissues
Pressure loads on synovial joints create mechanical, electrical, and chemical signals that direct chondrocyte activity
125
What are the two types of cartilage growth
Appositional- forming new cartilage at surface of existing cartilage
Interstitial- forming new cartilage within an existing cartilage mass
126
What are the consequences of cartilage damage
Very difficult to self-heal; repair is centered around depositing type I collagen, not proliferation of more chondrocytes
127
What is the difference between normal hyaline cartilage and articular cartilage
Articular cartilage has no perichondrium
128
What is the sources of new chondrocytes, and surrounds cartilage structures
Perichondrium
129
What are the two types of original bone formation
Intramembranous
Endochondral
130
Explain the mechanism of intramembranous ossification
At ~8 wks gestation, mesenchymal cells migrate and aggregate, express CBFA1 TF, and differentiate into osteoprogenitor cells and begin secreting osteoid; there is no cartilage precursor to this bone
Irregular spicules > woven bone > compact/spongy bone
131
Explain the mechanism of endochondral ossification
Aggregation of mesenchymal cells are stimulated by FGF/BMPs to express Type II collagen and differentiate to chondroblasts > produce cartilage matrix (hyaline cartilage model bone is produced) > perichondral cells in the mid-region begin producing osteoblasts that produce the periosteum > cartilage matrix undergoes calcification (causes death of chondrocytes- produces a cavity) > mesenchymal stem cells migrate into the cavity and differentiate into osteoprogenitor cells (along with HSCs)
132
How do bones grow during development
Proliferation of cartilage at the epiphyseal growth plates of long bones, which then undergoes endochondral ossification (into spongy bone)- cartilage hypertrophy, calcification, resorption, and ossification
133
What is the role of VEGF and Type X collagen in endochondral bone formation
During bone formation, VEGF is secreted by the zone of hypertrophy of the epiphyseal growth plate, which initiates vascular invasion of the zone of resorption and production of Type X collagen
134
What components of bone formation are used to determine bone age
Sesamoid bones (like the patella) present as multiple, cartilaginous nodules in fetuses
Epiphyseal-diaphyseal fusion occurs by the age of 20 years
135
Benign cartilage-forming tumor
Osteochondroma
136
Malignant cartilage-forming tumor
Chondrosarcoma
137
Benign bone-forming tumor
Osteoid osteoma
Osteoblastoma
138
Malignant bone-forming tumor
Osteosarcoma
139
Bone tumor that is <2cm, in the metaphysis of long bones (femur, tibia), and have a thick rim of reactive cortical bone that is associated with severe nocturnal pain that is relieved by aspirin
Osteoid osteoma
140
Bone tumor that is characterized as a cartilage-capped tumor attached to the metaphysis near the growth plate via a bony stalk; usually in young men
Osteochondroma
141
Bone tumor that arises in the medullary cavity/cortical surface of the bone, associated with hyaline cartilage; have circumscribed lucency with central irregular calcifications and a sclerotic rim, intact cortex (usually in the small bones of hands/feet)
Enchondroma/Juxtacortical chondroma
142
Inherited disease characterized by multiple enchondromas
Maffucci syndrome, Ollier disease
143
Bone tumor characterized by multinucleated osteoclast-like giant cells on histology; usually in the epiphyses of long bones (distal femur, prox. tibia)- cause arthritis-like symptoms and pathologic fractures
Giant cell tumor of bone
*Benign*
144
Bone tumor characterized by multiloculated blood-filled cystic spaces; usually in children/young adults in the metaphysis of long bones and posterior vertebral bodies; lytic lesion with well-defined margins w/ fluid inside
Aneurysmal bone cysts
*Benign*
145
Bone tumor that produces osteoid matrix/mineralized bone; usually in younger patients in the metaphyseal dist. femur and prox. tibia; progressively painful, enlarging masses assoc. w/ mixed lytic and sclerotic mass, infiltrative margins, and breaks through the cortex/periosteum
Osteosarcoma
*Malignant*
146
What is the most common spot of bone tumor metastasis
Lungs
147
Bone tumors that produce cartilage (usually hyaline), in 40+ yo men in the axial skeleton and prox. bones; destroys the cortex and forms a soft tissue mass (progressively pain and enlarging mass)
Chondrosarcoma
*Malignant*
148
Bone tumor characterized by primitive round cells in the diaphysis of long bones; painful, enlarging masses that are tender, warm, and swollen; destructive lytic tumor with permeative margins into the surrounding soft tissue; usually in very young children (boys)
Ewing Sarcoma
*Malignant*
149
What is the pathogenesis of Ewing Sarcoma
Balanced 11;22 (q24;q12) translocation of the EWSR1 gene to the FLH1 gene
150
Know that metastatic bone tumors are more common than primary bone tumors (*)
*
*Usually involve the axial skeleton, esp. spine*
151
What is the treatment for osteosarcoma
Cyclophosphamide (alkylating agent) + MESNA
Ifofsamide (alkylating agent) + MESNA
Doxorubicin (topo II inhibitor)
Etoposide (topo II inhibitor)
Dacarbazine (methylating agent)
Cisplatin (DNA crosslinker)
Methotrexate (DHFR inhibitor)
Dactinomycin (DNA intercalator)
152
What are some major toxicities of osteosarcoma chemotherapy
Myelosuppression (cyclophosphamide, doxorubicin, etoposide, dactinomycin)
Ototoxicity (Cisplatin)
Nephrotoxicity (Cisplatin, methotrexate)
Cardiac toxicity (Doxorubicin)
153
Which NSAID is an equally potent analgesic as morphine
Ketorolac
*Highly COX-1 selective*
154
What disorder is contraindicated in acetaminophen use
congenital glutathione synthase deficiency
*Acetaminophen produces NAPQI*
155
What is a characteristic symptom of aspirin overdose
Tinnitus
156
What NSAID is used to close patent ductus arteriosus in newborns
Indomethacin
157
What NSAID is used to reduce the incidence of pre-eclampsia in high-risk pregnancies
Low-dose aspirin
158
Which NSAID is contraindicated to treat gouty arthritis pain
Aspirin
*Competes with uric acid for tubule secretion*
159
Why are synthetic glucocorticoids preferred over cortisol in the treatment of nonendocrine disorders
They are less prone to induce salt and water retention
160
What is the normal range of ionized calcium in serum
4.64-5.28 mg/dL
161
What are the symptoms of hypercalcemia
-Decreased excitability > lethargy > coma
-Abdominal cramps, constipation
-Polyuria/polydipsia
-Psychic disorders (anxiety, depression, dysfunction)
-Skeletal muscle weakness
162
What are the symptoms of hypocalcemia
-Tetany
-Seizures
-Perioral numbness
-Paresthesia of hand/feet
-Prolonged QT interval
-Extrapyramidal movement disorders
163
What are the effects of pH on Ca2+-albumin binding
Alkalosis inc. Ca2+-albumin binding (can create hypocalcemic symptoms, but will not be indicated by serum Ca2+ levels)
164
What is the diagnostic difference between primary and secondary hyperparathyroidism
Blood plasma Ca2+ is elevated in primary
Low/normal in secondary
*Reversed in hypoparathyroidism*
165
What are the effects of hyperparathyroidism on phosphate
Causes dec. phosphate reabsorption in the kidney > inc. excretion > low phosphate levels
166
What are possible causes of hypercalcemia without elevation in parathyroid hormone
Malignant neoplasia
Vitamin D toxicity
Milk alkali syndrome (Tums overdose)
167
What is the function of 1a-hydroxylase in the kidneys
Catalyzes synthesis of 1,25(OH)2D3 (Calcitriol) from 25-OHD3 (Calcidiol)
168
What induces 1a-hydroxylase expression, what decreases it?
Increase- PTH
Decrease- FGF23
169
What are the effects of PTH on Ca2+
Inc. Ca2+ reabsorption in the kidney
Inc. Ca2+ excretion (yes, that's right)
Overall: Inc. Ca2+ in serum
170
What are the effects of Mg2+ deficiency on PTH secretion
Dec. PTH secretion > hypocalcemia
171
How does hyperventilation predispose to reduction in serum Ca2+
Respiratory alkalosis can create hypocalcemia-like conditions
172
What are the two physical signs of hypocalcemia
Chvostek sign- quick contraction of ipsilateral facial muscle by tapping CN VII at the jaw
Trousseau sign- spasm of upper extremity muscles > flexion of wrist and thumb w/ extension of finger
173
What is the most common mechanism of paraneoplastic hypercalcemia
Elevated circulating PTHrP enhance PTH activity
174
The degeneration of cartilage that results in structural/functional failure of synovial joints
Osteoarthritis
175
What is the difference between primary and secondary osteoarthritis
Primary- Insidious/Idiopathic onset
Secondary- Caused by joint deformity/injury/underlying systemic disease
176
What percentage of people over age 70 have osteoarthritis
40%
177
What is the general mechanism of osteoarthritis
Chondrocyte degradation of type II collagen (via MMPs) eventually outweighs ECM synthesis > eventually, chondrocytes are lost
*MMPs induced by TGF-B via inflammation*
178
What joints are commonly involved in osteoarthritis
Hips
Knees
Lower lumbar/cervical vertebrae
PIP and DIP of fingers
First carpometacarpal
First tarsometatarsal
179
What is a characteristic physical sign of osteoarthritis
Heberden nodes- prominent osteophytes at the DIPs (more common in women)
180
What is the treatment for osteoarthritis (mostly management)
NSAIDs
Intra-articular corticosteroids
Activity modification
Arthroplasty
181
Chronic inflammatory disorder of autoimmune origin that attacks the joints- producing a nonsuppurative proliferative and inflammatory synovitis
Rheumatoid arthritis
*Can cause joint destruction and ankylosis*
182
What is the mechanism of rheumatoid arthritis
CD4+ T cells react with citrullinated proteins (self-antigens via modification of arginine)
RANKL expression is involved for the activation of osteoclasts
Macrophage activity stimulates (using TNF-a) synovial cells to secrete hyaline-destroying proteases
183
What is the pattern of joint involvement in rheumatoid arthritis
Symmetrical: hands, feet, ankles, elbows, knees
Involves MCP* and PIP joints
184
What is a major difference in stiffness between osteoarthritis and rheumatoid arthritis
RA is associated with morning stiffness/stiffness with inactivity
185
What is the characteristic radiograph finding for rheumatoid arthritis
Joint effusions and juxtaarticular osteopenia with erosions/narrowing of the joint space, loss of articular cartilage
*Ulnar deviation, flexion-hyperextension of the fingers*
186
What are the treatments for rheumatoid arthritis
Corticosteroids
Methotrexate
TNF antagonists
187
What are the characteristics of juvenile idiopathic arthritis
Oligoarthritis
Systemic disease (usually underlies the cause)
Mostly affects larger joints
Rheumatoid Factor(-), ANA(+)
188
What are the characteristics of seronegative spondyloarthropathies
Rheumatoid factor (-)
Involvement of sacroiliac joints (assymetrical peripheral arthritis of large joints)
Bony proliferation leading to ankylosis
Involve the vertebral column
189
Symptoms of lower back pain and spinal immobility during 20-30 yo, involvement of the peripheral joints; Anti-IL-17 Ab (+)
Ankylosing spondylitis
*Results in bony ankylosis fo the sacroiliac joints*
190
Symptoms of arthritis, urethritis/cervicitis, and conjunctivitis (usually men 20-30 yo); HLA-B27 (+); usually initiation by genitourinary infection
Reactive arthritis
191
Symptoms of oligoarthritis, spinal involvement, tenosynovitis, dactylitis (sausage fingers); rheumatoid factor (-)
Psoriatic arthritis
192
Which bacterial infections can cause arthritis
H. influenza in children < 2yo
S. aureus in >2yo
Gonococcus in young adults
*Mostly affect the knee joint*
193
What are the late persistent symptoms of Lyme disease
Arthritis (usually the knee, migratory)
Anti-borrelia Ab (+)
194
Symptoms of acute arthritis (usually the MIP joint, monoarticular) associated with hyperuricemia, a symptom-free interval, and then recurrent polyarticular attacks with decreasing intervals
Gout
195
What is the mechanism of Gout
Plasma Urate above 6.8 mg/dL (end product of purine catabolism, excreted by kidneys) > precipitate in the joints, which activate macrophages and neutrophils
196
About how long does it take for hyperuricemia to produce gout symptoms
20-30 years
197
What is the treatment for acute gout attacks
Colchicine- prevents tubulin polymerization, inhibits granulocytes
198
What is the treatment for chronic gout in uric acid overproducers
Allopurinol
Febuxostat
199
What are the toxicities of allopurinol
GI upset
Skin rash (SJS)
Hepatic toxicity
Myelosuppression, peripheral neuropathy are rare
200
What is the treatment for chronic gout in uric acid underexcreters
Probencid
Pegloticase
201
What are the contraindications for probenecid
Kidney failure
Kidney stones
202
What are the contraindications for pegloticase
G6PD deficiency
203
What are considered the first-line treatments for acute gout attacks
NSAIDs (not aspirin)
Glucocorticoids
204
What are common side effects of colchicine
Nausea
Vomiting
Abdominal pain
205
What are the effects of SLE on the joints
Nonerosive synovitis with little deformity
206
What cells composed synovial joints
Type A synoviocytes (specialized macrophages)
Type B synoviocytes (fibroblast that synthesize hyaluronic acid and proteins)
207
What is the difference between regular and articular hyaline cartilage
Articular does not have a perichondrium
208
List the layers of articular cartilage, from most superficial to deepest
Superficial/Tangential- flat chondrocytes
Intermediate/Transitional- round chondrocytes
Deep/Radial- small, round chondrocytes in short perpendicular columns
Calcified- small chondrocytes w/ calcified matrix
209
What layers of articular cartilage does the tidemark separate
Between the deep and calcified zones
210
What is fibrocartilage and where is it located
Combination of dense regular connective tissue and hyaline cartilage w/ no surrounding perichondrium- present in IV discs, pubic symphysis, SC joint, temporomandibular joint, and knee menisci
211
What is the function of fibrocartilage
Resist compression and shearing forces (shock absorber)
212
Attach muscle to bone
Tendons
213
Attach bone to bone
Ligament
214
Which have a more regularly arranged structure, tendons or ligaments
Tendons
215
Give an example of an elastic ligament
Ligamentum flavum
216
Note that septic arthritis is a medical emergency (*)
*
217
What viral infections can particularly cause transient arthritis
Rubella
Mumps
Hep B
Parvovirus B19
218
What is the presentation of parvovirus B19 arthritis
Adults with symmetrical, peripheral polyarthritis (usually remits in 2 weeks)
219
Granulation tissue at the edges of synovial lining associated with Rheumatoid arthritis
Pannus
220
What is the serum marker for rhematoid arthritis flares
Calprotectin inc.
221
What are the rheumatoid-specific serology tests
Anti-citrulline modified protein Ab
Rheumatoid factor (IgM Ab that binds aggregated IgG)
CRP
222
What is an important serology difference between RA and SLE
CRP is more elevated in RA
223
What is the genetic mutation associated with all seronegative spondylarthritis pathologies
HLA-B27
224
What is the most effective treatment for seronegative spondylarthritis pathologies
Anti-TNF agents
225
What is a major complication associated with juvenile idiopathic arthritis
Uveitis (potentially blinding)
226
What is the mechanism of azathioprine
Immunosuppressor (B cells, T cells, Ig, and IL-2)
Block purine synthesis
227
What is the mechanism of methotrexate
Blocks thymidylate synthase/dihydrofolate reductase > blocks purine synthesis
228
What is the mechanism of cyclophosphamide
DNA cross-linker that suppresses T and B cell function
229
What is the mechanism of cyclosporine
Peptide antibiotic than also inhibits IL-1 and IL-2 receptor production
230
What is the mechanism of mycophenolate mofetil
Inhibits purine synthesis > suppression of T and B cell proliferation
Interferes with leukocyte-endothelial cell adhesion
231
What is the mechanism of hydroxychloroquine
Suppression of T-lymphocyte response
Inhibit leukocyte chemotaxis
Traps free radicals
232
What is the mechanism of leflunomide
Inhibits dihydroorotate dehydrogenase > dec. ribonucleotide synthesis
Reduces B cell Ab production
233
What is the mechanism of sulfasalazine
Suppresses T cell response and B cell proliferation
234
What is the mechanism of abatacept
Binds to CD80 and CD86 on APCs and inhibits binding/activating T cells
235
What is the mechanism of Baricitinib
Inhibits JAK1 > JAK2
236
What is the mechanism of Belimumab
Inhibits B-lymphocyte stimulator (BLyS)
237
What is the mechanism of Rituximab
Kills CD20 B cells
238
What is the mechanism of Sarilumab
IL-6 receptor antagonist
239
What is the mechanism of Tocilizumab
IL-6 receptor antagonist
240
What is the mechanism of Tofacitinib
Selectively inhibits all JAKs (mostly JAK3 > JAK1)
241
Which RA drugs inhibit TNF
Infliximab
Etanercept
Adalimumab
Certolizumab
Golimumab
