Musculoskeletal, skin, and connective tissue Flashcards
1
Q
Anterior drawer sign
A
With the patient supine, bend the knee at a 90 degree angle. If there is an increase in anterior gliding of tibia, there is an ACL injury. Anterior refers to ACL
2
Q
Posterior drawer sign
A
With the patient supine, bend the knee at a 90 degree angle. If there is an increase in posterior gliding of tibia, there is an PCL injury. Posterior refers to PCL
3
Q
Abnormal passive abduction
A
with the patient supine and knee either extended or at 30 degree angle, if a lateral (valgus) force leads to a medial space widening of tibia, than there is a MCL injury
4
Q
Abnormal passive adduction
A
with the patient supine and knee either extended or at 30 degree angle, if a medial (varus) force leads to a lateral space widening of tibia, than there is a LCL injury
5
Q
McMurray test
A
With patient supine and knee internally and externally rotated during range of motion: pain and popping on external rotation is indicative of a medial meniscal tear, pain and popping on internal rotation is indicative of a lateral meniscal tear.
6
Q
Knee injuries due to lateral force to planted leg
A
A common injury in contact sports is due to lateral force applied to a planted leg. Classically, damage consists of ACL, MCL, and medial meniscus (attached to MCL). However, the lateral meniscus injury is more common. It presents with acute knee pain and sign of joint injury/ instability.
7
Q
Prepatellar bursitis
A
Also called housemaid’s knee. It can be caused by repeated trauma or pressure from extensive kneeling. On x-ray, there is prepatellar bursitis and Baker cyst.
8
Q
Baker cyst
A
A popliteal fluid collection commonly related to chronic joint disease.
9
Q
Rotator cuff muscles
A
Shoulder muscles that form the rotator cuff from most anterior to posterior the subscapularis, supraspinatus, infraspinatus, and teres minor. They are innervated by primarily C5-C6. SItS (small t is for teres minor)
10
Q
Subscapularis
A
It is innervated by the upper and lower subscapular nerves. It medially rotates and adducts arm.
11
Q
Supraspinatus
A
It is innervated by the suprascapular nerve. It abducts the arm initially (before action from the deltoid) and is the most commonly injured rotator cuff muscle. It is assesed by the empty/ full can test.
12
Q
Infraspinatus
A
It is innervated by the suprascapular nerve. It laterally rotates arm and is often injured due to pitching.
13
Q
Medial epicondylitis (golfer’s elbow)
A
It occurs due to repetitive flexion (forehand shots) or idiopathic. It causes pain near the medial epicondyle.
14
Q
Lateral epicondylitis (tennis elbow)
A
It occurs due to repetitive extension (backhand shots) or idiopathic, causing pain near the lateral epicondyle.
15
Q
Wrist bones
A
Starting from proximal radial side. Some Lovers Try Positions That They Cannot Handle: Scaphoid, Lunate, Triquetrum , Pisiform, Trapezium, Trapezoid, Capitate, and Hamate.
16
Q
Scaphoid injury
A
It can be palpated in the anatomical snuff box and is the most commonly fractured carpal bone and is prone to avascular necrosis owing to retrograde blood supply.
17
Q
Lunate injury
A
Dislocation of the lunate may cause acute carpal tunnel syndrome.
18
Q
Hamate injury
A
Fall on an outstretched hand can damage the hook of the hamate can cause ulnar nerve injury.
19
Q
Carpal tunnel syndrome
A
Due to entrapment of median nerve in carpal tunnel; nerve compression leads to paresthesia, pain, and numbness in the distribution of the median nerve. It is associated with pregnancy, rheumatoid arthritis, hypothyroidism, and may be associated with repetitive use.
20
Q
Guyon canal syndrome
A
It occurs due to compression of the ulnar nerve at wrist or hand. It is classically seen in cyclists due to pressure from handlebars. Symptoms usually begin with a feeling of pins and needles in the ring and little fingers before progressing to a loss of sensation and/or impaired motor function of the intrinsic muscles of the hand.
21
Q
Axillary nerve
A
C5-C6. It is derived from the posterior cord. It innervates the teres minor and deltoid muscles. It can get injured with fracture of the surgical neck of the humerus and anterior dislocation of the humerus. Injury presents with a flattened deltoid, loss of arm abduction at shoulder greater than 15 degrees, and loss of sensation over deltoid muscle and lateral arm.
22
Q
Musculocutaneous nerve
A
C5-C7. It is derived from the lateral cord. It innervates the anterior compartment of the arm. Cause of injury includes upper trunk compression. It presents as loss of forearm flexion and supination and loss of sensation over the lateral forearm.
23
Q
Radial nerve
A
C5-T1. It is derived from the posterior cord. It innervates the posterior compartment of the forearm (extensor and supinator muscles) and the radial dorsal side of the hand. Injury can occur due to midshaft fracture of the humerus; compression of the axilla, eg due to crutches or sleeping with your arm over the chair (Saturday night palsy). Presentation includes wrist drop (loss of elbow, wrist and finger extension), a decrease in grip strength (wrist extension is necessary for the maximal action of flexors), and loss of sensation over the posterior arm/forearm and dorsal side of the hand.
24
Q
Median nerve
A
C5-T1. It is derived from the lateral and medial cords. It innervates flexor and pronator muscles of the forearm, thenar muscles, and the flexor muscle of digits 2 and 3. It innervates the cutaneous aspect of the radial side of the palm and the palmer side of digits 1-4. Injury can occur with a supracondylar fracture of the humerus (proximal lesion) or carpal tunnel syndrome and wrist laceration (distal lesion). Injury presents as ape hand and pope’s blessing (can’t flex fingers 2 and 3); loss of wrist flexion of lateral fingers, thumb opposition, lumbricals (flex the metacarpophalangeal joints and extend the interphalangeal joints) of 2nd and 3rd digits. There is loss of sensation over the thenar eminence and the dorsal and palmar aspects of the lateral 3.5 fingers with a proximal lesion. Tinel sign (tingling on percussion) will be positive with carpal tunnel syndrome.
25
Ulnar nerve
C8-T1. It is derived from the medial cord. It innervates flexor muscles of the forearm, flexor muscle of metacarpophalangeal and interphalangeal joints of digits 4 and 5, and the intermediate and hypothenar muscles. It also innervates the cutaneous palm of the ulnar side and the palmar side of digits 4 and 5. Injury can occur with a fracture of the medial epicondyle of the humerous "funny bone" or with a fractured hook of hamate (distal lesion). Injury presents with a Ulnar claw (can't extend fingers 4 and 5), radial deviation of wrist upon flexion (proximal lesion). There is also a loss of wrist flexion, flexion of medial fingers, abduction and adduction of fingers (interossei), action of medial 2 lumbrical (flex the metacarpophalangeal joints and extend the interphalangeal joints) muscles. There is also a loss of sensation over the medial 1.5 fingers including hypothenar eminence.
26
Recurrent branch of median nerve
C5-T1. It is derived from the median nerve. It innervates the thenar muscles. Injury can occur with superficial laceration of palm. It presents as ape hand. The loss of the thenar muscle group (opposition, abduction, and flexion of thumb). There is no loss of sensation.
27
Erb palsy
It is also called waiter's tip. It occurs due to traction or tear of upper (Erb-er) trunk: C5-C6 roots. In infants it occurs due to lateral traction on the neck during delivery. In adults it occurs with trauma. Muscles effected include deltoid and supraspinatus, which abducts the arm so the arm hangs by the side; infraspinatus, which laterally rotates the arm so it is medially rotated, and biceps brachii, which flexes and supinates the forearm so that the arm is extended and pronated.
28
Brachial plexus lesions
Composed of roots, trunks, divisions, cords, and branches. Randy Travis Drinks Cold Beer.
29
Klumpke palsy
It occurs to traction or tear of the lower trunk: C8-T1 root. In infants injury can occur with an upward force on the arm during delivery. In adults, it occurs due to trauma (eg grabbing a tree branch to break a fall). Muscle defects include intrinsic hand muscles (lumbricals, interossei, thenar, hypothenar). It presents as a total claw hand; the lumbricals normally flex MCP joints and extend DIP and PIP joints.
30
Thoracic outlet syndrome
It occurs due to compression of the lower trunk (C8 and T1) and subclavian vessels. Causes include a cervical rib (a supernumerary rib which arises from the seventh cervical vertebra) or a pancoast tumor. Muscle defects include intrinsic hand muscles (lumbricals, interossei, thenar, hypothenar). It presents as atrophy of intrinsic hand muscles; ischemia, pain, and edema due to vascular compression.
31
Winged scapula
It occurs due to a lesion of the long thoracic nerve (C5-C7). Causes include axillary node dissection after a mastectomy or a stab wound. The muscle defect is in the serratus anterior causing there to be the inability to anchor the scapula to thoracic cage, leading to inability to abduct the arm above the horizontal position.
32
Upper trunk
C5 and C6. It contributes to the lateral and posterior cords. It is damaged in Erb palsy (waiter's tip)
33
Middle trunk
C7. It contributes to the lateral and posterior cords.
34
Lower trunk
C8 and T1. It contributes to the posterior and medial cords. It is damaged in Klumpke palsy (claw hand)
35
Lateral cord
Made up of upper and middle trunk (C5-C7). It contributes to the musculocutaneous and median (flexor) nerves.
36
Posterior cord
Made up of the upper, middle, and lower trunks (C5-T1). It contributes to the axillary and radial nerves (extensor).
37
Medial cord
Made up of the lower trunk (C8-T1). It contributes to the median (flexor) and ulnar nerve.
38
Long thoracic
C5-C7. It innervates the serratus anterior and injury results in a winged scapula.
39
Deltoid paralysis
injury to the axillary nerve
40
Saturday nigh palsy (wrist drop)
injury to the radial nerve
41
Difficulty flexing elbow with sensory loss
injury to the musculocutaneous nerve
42
Decreased thumb function and Pope's blessing
injury to the median nerve
43
Injury to the intrinsic muscles of the hand, a claw hand
injury to the ulnar nerve
44
Distortions of the hand
At rest, a balance exists between the extrinsic flexors and extensors of the hand, as well as the intrinsic muscles of the hand- particularly the lumbrical muscles (flexion of the MCP, extension of DIP and PIP joints). Clawing is best seen with distal lesions of the median or ulnar nerves. The remaining extrinsic flexors of the digits exaggerate the loss of the lumbricals, so that fingers are extended at the MCP and flexion at the DIP and PIP. Deficits are less pronounced in proximal lesions and they present during voluntary flexion of the digits.
45
Ulnar claw
Digits 4 and 5 remain flexed. occurs due to a distal ulnar nerve lesion and is seen during extension of fingers or at rest
46
Popes blessing
Digits 1 and 2 remain extended. Occurs due to a proximal lesion of the median nerve and is seen while trying to make a fist.
47
Median claw
Digits 1 and 2 remain flexed. Occurs due to distal median nerve lesion and is seen while extending fingers or at rest.
48
OK gesture
5th digit remains extended. Occurs due to a proximal ulnar nerve and is seen while trying to make a fist.
49
Thenar muscles
Innervated by the median nerve, atrophy will cause an unopposable thumb (ape hand). Muscles include Opponens pollicis, Abductor pollicis brevis, superficial head (deep head is innervated by the ulnar nerve) (Opposem Abduct, Flex: OAF).
50
Hypothenar muscle
innervated by the ulnar nerve. Muscles include Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi brevis. (Opposem Abduct, Flex: OAF).
51
Dorsal interossei muscles
abduct the fingers DAB= Dorsals ABduct
52
Palmar interossei
adduct the fingers PAD= Palmars ADDuct.
53
Lumbricals
Flex at the MCP joint, extend PIP and DIP joints.
54
Obturator nerve
L2-L4. Injury can occur during pelvic surgery and results in reduced medial thigh sensation and reduced thigh adduction.
55
Femoral nerve
L2-L4. Injury can occur with a pelvic fracture. Injury results in reduced thigh flexion and leg extension.
56
Common peroneal nerve
L4-S2. Injury can occur due to trauma or compression of the lateral aspect of the leg, and fibular neck fracture. It presents as foot drop (inverted and plantarflexed at rest), occurs due to loss of eversion and dorsiflexion. Steppage gait (high stepping). Loss of sensation on the dorsum of foot. PED= Peroneal Everts and Dorsiflexes; if injured foot dropPED.
57
Tibial nerve
L4-S3. Injury may occur due to knee trauma, Baker cyst (proximal lesion); tarsal tunnel syndrome (distal lesion). Results in an inability to curl toes and loss of sensation on the sole of foot. In a proximal lesions, foot everted at rest with a loss of inversion and plantarflexion. TIP=Tibial Inverts and Plantarflexes; if injured, can't stand on TIPtoes.
58
Superior gluteal nerve
L4-S1. It innervates the medius and minimus gluteal muscles. Injury can be iatrogenic during an intramuscular injection to upper medial gluteal region. It would present as trendelenburg sign/gait (pelvis tilts because the weight bearing leg cannot maintain alignment of pelvis through hip abduction). Lesion is on the contralateral side to the side of the hip that drops, ipsilateral to the extremity on which the patient stands.
59
Inferior gluteal nerve
L5-S2. It innervates the gluteal maximus. Injury can occur with a posterior hip dislocation. It will present as difficulty climbing stairs, rising from seated position and loss of hip extension.
60
Sciatic nerve
L4-S3. It innervates the posterior thing, splits into common peroneal and tibial nerves.
61
Pudendal nerve
S2-S4. It innervates perineum. It can be blocked with local anesthetic during childbirth using the ischial spin as a landmark for injection.
62
Signs of lumbrosacral radiculopathy
There will be paresthesias and weakness in the distribution of specific lumbar or sacral spinal nerves. It is often due to intervertebral disc herniation in which the nerve association with the inferior vertebral body is impinged (eg herniation of L3-L4 disc affects the L4 spinal nerve). Intervertebral discs generally herniate posterolaterally, due to the thin posterior longitudinal ligament and thicker anterior longitudinal ligament along the midline of the vertebral bodies.
63
Level of vertebral injury with weakness of knee extension, and a decrease in patellar reflex
L3-L4
64
Level of vertebral injury with weakness of dorsiflexion and difficulty in heel-walking
L4-L5
65
Level of vertebral injury with weakness of plantarflexion and difficulty in toe walking with a decrease in achilles reflex
L5-S1
66
Artery traveling with the long thoracic nerve
Lateral thoracic
67
Artery traveling with the axillary nerve
Posterior circumflex
68
Artery traveling with the radial nerve
Deep brachial
69
Artery traveling with the median nerve
brachial
70
Artery traveling with the tibial nerve
Popliteal, which turns into the posterior tibial.
71
Striated muscle excitation from nerve
Action potential depolarization opens presynaptic voltage-gated Ca channels, inducing neurotransmitter release. Postsynaptic ligand binding leads to muscle cell depolarization in the motor end plate.
72
Striated muscle conduction
Depolarization travels along the muscle cell and down the T-tubule. Depolarization of the voltage-sensitive dihydropyridine receptor, with is mechanically coupled to the ryanodine receptor on the sarcoplasmic reticulum, inducing a conformational change and causing Ca release from the sacroplasmic reticulum.
73
Striated muscle contraction
Released Ca binds to troponin C, causing a conformational change that moves tropomyosin out of the myosin-binding groove on actin filaments. Myosin releases bound ADP and inorganic PO4, leading to displacement of myosin on the actin filament (power stroke). Contraction results in shortening of H and I bands and between Z lines (HIZ shrinkage), but the A band remains the same length (A band is Always the same length). Binding of a new ATP molecule causes the detachment of myosin head from actin filament. Hydrolysis of bound ATP, converting it to ADP, myosin head adopts a high-energy position (cooked) for the next contraction cycle.
74
T-tubules
It is an extension of plasma membrane juxtaposed with terminal cisternae and are a part of the sarcoplasmic reticulum. In skeleton muscle, there are 1 T-tubule and 2 terminal cisternae= triad. In cardiac muscle, 1 T-tubule and 1 terminal cisternae=diad.
75
H band
the zone of the thick filaments that is not superimposed by the thin filaments.
76
Z band
marks the boarders of sacromere
77
A band
contains the entire length of a single thick filament
78
Type 1 muscle fiber
A slow twitch; red fibers resulting from an increase in mitochondria and myoglobin concentration (an increase in oxidative phosphorylation), which causes a sustained contraction. Think "1 slow red ox"
79
Type 2 muscle fiber
A fast twitch; white fibers resulting from a decrease in mitochondria and myoglobin concentration (an increase in anaerobic glycolysis); weight training results in hypertrophy of fast-twitch muscle fibers.
80
Smooth muscle contraction
With increased intracellular concentrations in the smooth muscle cell, the Ca2+ ions can combine and form a complex with the acidic protein calmodulin. The Ca2+-calmodulin complex activates myosin light chain kinase (MLCK), which allows it to phosphorylate the light chain of myosin. In addition to the Ca2+-dependent activation of myosin light chain kinase, the state of myosin light chain phosphorylation is further regulated by myosin light chain phosphatase. This enzyme removes the high-energy phosphate from the light chain of myosin to promote smooth muscle relaxation.
81
Smooth muscle relaxation
Smooth muscle relaxation can also occur through nitric oxide-mediated stimulation of guanylate cyclase activity, which leads to increased cGMP-induced smooth muscle relaxation. Increased levels of cGMP promote myosin light chain phosphatase activity. (Remember: “Nitric oXide -> RelaXation”)
82
Endochondral ossification
bones of the axial and appendicular skeleton and base of the skull. Cartilaginous model for bone is first made by chondrocytes. Osteoclasts and ostesoblasts later replace with woven bone and then remodel to lamellar bone. In adults, woven bone occurs after fractures and in Paget disease.
83
Membranous ossification
Includes bones of calvarium and facial bones. Woven bone formed directly without cartilage. Later remodeled to lamellar bone.
84
Osteoblasts
Builds bone by secreting collagen and catalyzing mineralization. Differentiate from mesenchymal stem cells in periosteum.
85
Osteoclasts
Multinucleated cells that dissolve by secreting acid and collagenases. Differentiate from monocytes.
86
Parathyroid hormone
At low, intermittent levels, exerts anabolic effects (building bone) on osteoblasts and osteoclasts (indirect). Chronically increased PTH levels (due to primary hyperparathyroidism) cause catabolic effects (osteitis fibrosa cystica).
87
Estrogen and bone biology
Estrogen inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing osteoclasts. Estrogen deficiency (surgical or postmenopausal), excess cycles of remolding, and bone resorption lead to osteoporosis.
88
Achondroplasia
Failure of longitudinal bone growth (endochondral ossification), causing shortening of limbs. Membranous ossification is not affected leading to a large head relative to limbs. Constitutive activation of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation. Over 85% of mutations occur sporadically; autosomal dominant with full penetrance (homozygosity is lethal). It is the most common cause of dwarfism.
89
Primary osteoporosis
Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (serum Ca and PO4). Diagnosed by a bone mineralization and lab values (serum Ca and PO4). Diagnosed by a bone mineral density test (DEXA) with a T-score less than -2.5. Can be caused by long term exogenous steroid use, anticonvulsants, anticoagulants, thyroid replacement therapy. It can lead to vertebral compression fractures, acute back pain, loss of height, kyphosis. Also can present with fractures of femoral neck, distal radius (Colles fracture).
90
Type I osteoporosis
Post-menopausal. There is a increase in bone resorption due to a decrease in estrogen levels.
91
Type II osteoporosis
Senile. Affects men and women over 70.
92
Prevention and treatment of osteoporosis
Prophylaxis includes regular weight bearing exercise and adequate Ca and vitamin D intake throughout adulthood. Treatment includes bisphosphonates, PTH analogs, SERMs, rarely calcitonin; Donosumab (monoclonal antibody against RANKL).
93
Osteopetrosis
Marble bone disease. Failure of normal bone resorption due to defective osteoblasts, creating thickened, dense bones that are prone to fracture. Bone fills marrow space, creating pancytopenia, extramedullary hematopoiesis. Mutations (eg carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption. X-rays show bone in bone appearance (diffusely dense). Can result in cranial nerve impingement and palsies as a result of narrowed foramina. Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes.
94
Osteomalacia/ rickets
Vitamin D deficiency leads to osteomalacia in adults and rickets in children. Due to defective mineralization/ calcification of osteoid, there are soft bones that bow out. A decrease in vitamin D causes there to be a decrease in serum Ca, increasing PTH secretion, decreasing serum PO4. Hyperactivity of osteoblasts increases ALP (osteoblasts require alkaline environment).
95
Paget disease of the bone
Also called osteitis dormans. It is a common, localized disorder of bone remodeling caused by an increase in both osteoblastic and osteoclastic activity. Serum Ca, phosphorus and PTH levels are normal. Alkaline phosphatase (ALP) is increased. The bone has a mosaic pattern of woven and lamellar bone. Long bones will have chalk stick fracture. There is an increase in blood flow from an increase is arteriovenous shunts may cause high output heart failure. There is an increase risk of osteogenic sarcoma. Hat size can be increased; hearing loss is common due to auditory foramen narrowing. The stages of Paget disease include: Lytic (osteoclasts), Mixed (osteoclasts plus osteoblasts), Sclerotic (osteoblasts), Quiescent (minimal osteoclasts/ osteoblast activity). H&E stain will show osteocytes within lacunae (scattered small white dots) and chaotic mosaic pattern (lacy purple lines) of bone remodeling.
96
Osteonecrosis
Avascular necrosis. Infarction of bone and marrow, which is usually very painful. The most common site is the femoral head (due to insufficiency of the medial circumflex femoral artery). Causes include Alcoholism, Sickle cell disease, Storage disorders, Exogenous/ Endogenous corticosteroids, Pancreatitis, Trauma, Idiopathic (Legg-Calve-Perthes disease), Caisson (the bends): ASEPTIC. X-ray will show irregular lucencies with adjacent sclerosis. MRI will show dark serpiginous necrotic bone.
97
Lab values with osteoporosis
Serum Ca, PO4, ALP, and PTH are normal. There is a decrease in bone mass.
98
Lab values with osteopetrosis
Serum Ca is decreased or normal. PO4, ALP, and PTH are normal. There are dense, brittle bones, Ca is decreased in severe, malignant disease.
99
Lab values with Paget disease of the bone
Serum Ca, PO4, and PTH are normal. ALP is increased. There is a mosaic bone architecture.
100
Lab values with osteomalacia/ rickets
Serum Ca and PO4 is decreased. ALP and PTH are increased. The bones are soft.
101
Lab values with hypervitaminosis D
Serum Ca and PO4 is increased. ALP is normal. PTH is decreased. It can be caused by oversupplementation or granulomatous disease (eg sarcoidosis).
102
Lab values with osteitis fibrosa cystica (primary hyperparathyroidism)
Serum Ca, ALP, PTH are increased. PO4 is decreased. There are brown tumors due to fibrous replacement of bone, subperiosteal thinning. Causes include idiopathic or parathyroid hyperplasia, adenoma, carcinoma.
103
Lab values with osteitis fibrosa cystica (secondary hyperparathyroidism)
Serum Ca is decreased. PO4, ALP, and PTH are increased. It is often compensation for end-stage renal disease (ESRD). There are a decreased in PO4 excretion and production of activated vitamin D.
104
Giant cell tumor
Benign primary bone tumor. Occurs in 20-40 year olds. Tumor location is in the epiphyseal end of the long bone. It is also called osteoclastoma. It is a locally aggressive benign tumor often around the knee. It has a soap bubble appearance of X-ray. Histology shows a multinucleated giant cell.
105
Osteochondroma
Benign primary bone tumor. It is the most common benign tumor of the bone. It is an exostosis of the bone (a benign outgrowth of cartilaginous tissue on a bone). It occurs in males under the age of 25. It is a mature bone with cartilaginous (chondroid) cap. It rarely transforms to chondrosarcoma.
106
Osteosarcoma (osteogenic sarcoma)
Malignant primary bone tumor. It is the 2nd most common primary bone tumor (after multiple myeloma). Bimodal distribution: 10-20 year old (primary) and over the age of 65 (secondary). Predisposing factors include Paget disease of the bone, bone infarcts, radiation, familial retinoblastoma, and Li-Fraumeni syndrome (germline p53 mutation). Occurs in the metaphysis of long bones, often around the knee. Codman triangle occurs with aggressive lesions, the periosteum does not have time to ossify with shells of new bone, so only the edge of the raised periosteum will ossify. It can also occur as a sunburst pattern on X-ray. It is aggressive. Treated with surgical en bloc resection (with limb salvage) and chemotherapy.
107
Ewing sarcoma
Malignant primary bone tumor. It occurs in boy under the age of 15. It commonly appears in diaphysis of long bones, pelvis, scapula, and ribs. Histology shows anaplastic small blue cell of a malignant tumor. It is extremely aggressive with early metastases, but responsive to chemotherapy. They usually present as moth-eaten destructive permeative lucent lesions in the shaft of long bones with large soft tissue component without osteoid matrix, and typical onion skin periostitis. It is associated with t(11;22) translocation causing fusion protein of EWS-FLI1.
108
Osteoarthritis vs rheumatoid arthritis etiology
Osteoarthritis occurs do to mechanical joint wear and tear, which destroys articular cartilage. Rheumatoid arthritis occurs due to an autoimmune reaction that causes inflammatory destruction of synovial joints. It is mediated by cytokine and type III and type IV hypersensitivity reactions.
109
Osteoarthritis joint findings
Osteoarthritis findings include subchondral cysts, sclerosis (stiffened), osteophytes (bone spurs), eburnation (polished, ivory-like appearance of bone), synovitis, Heberden nodes (DIP), Bouchard nodes (PIP). No MCP involvement. Joint space narrowing, osteophyte (a bony outgrowth associated with the degeneration of cartilage at joints).
110
Osteoarthritis predisposing factors
Osteoarthritis risk factors include age, obesity, and joint trauma.
111
Osteoarthritis vs rheumatoid arthritis classic presentation
Osteoarthritis presents as pain in weight bearing joints after use (eg at the end of the day), improving with rest. Knee cartilage loss begins medially (bowlegged). Rheumatoid arthritis has morning stiffness lasting more than 30 min and improving with use, symmetric joint involvement, systemic symptoms (fever, fatigue, weight loss, pleuritis, and pericarditis).
112
Osteoarthritis treatment
Osteoarthritis treatment includes acetaminophen, NSAIDs, intra-articular glucocorticoids.
113
Rheumatoid arthritis joint findings
Rheumatoid arthritis findings include pannus (inflammatory granulation tissue) formation in joints (MCP and PIP), subcutaneous rheumatoid nodules (fribrinoid necrosis), ulnar deviation of fingers, subluxation (slight misalignment). Rarely there are swan neck and Boitonniere deformities the joint nearest the knuckle (PIP) is permanently bent toward the palm). Rarely there is DIP involvement. Increased synovial fluid. Bone and cartilage erosion.
114
Rheumatoid arthritis predisposing factors
Rheumatoid arthritis affects females more than males. Over 80% have a positive rheumatoid factor (anti-IgG antibody); anti-cyclic citrullinated peptide antibody is more specific. There is also a strong association with HLA-DR4.
115
Rheumatoid arthritis treatment
Rheumatoid arthritis treatment includes NSAIDs, glucocorticoids, disease modifying agents (methotrexate, sulfasalazine), biologics (TNF-alpha inhibitors).
116
Sjogren syndrome
An autoimmune disorder characterized by destruction of exocrine glands (especially lacrimal and salivary) by lymphocytic infiltrates. It predominantly affects females 40-60 years old. Findings includes inflammatory join pain, xarophthalmia (a decrease in tear production and subsequent corneal damage), xerostomia (a decrease in saliva production). There is also the presence of antinuclear antibodies including SS-A (anti-Ro) and/or SS-B (anti-La). Bilateral parotid enlargement is also present. It is a common primary disorder or a secondary syndrome associated with other autoimmune disorders (eg rheumatoid arthritis). Complications include dental caries; mucosa-associated lymphoid tissue (MALT) lymphoma (may present as parotid enlargement).
117
Findings with gout
Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints. It is more common in males. It is associated with hyperuricemia, which can be caused by underexcretion of uric acid (90% of patient), which is largely idiopathic and can be exacerbated by certain medications (eg thiazide diuretics) or due to overproduction of uric acid (10% of patients), due to Lesch-Nyhan syndrome, PRPP excess, increase cell turnover (eg tumor lysis syndrome), or von Gierke disease. Crystals are needle shaped and negative birefringent under polarized light (yeLLow under paraLLel light, blue under perpendicular light).
118
Symptoms of gout
Asymmetric joint distribution. Joint is swollen, red, and painful. Classic manifestation is painful MTP joint of big toes (podagra). Tophus formation (often on external ear, olecranon bursa, or Achilles tendon). Acute attack tends to occur after a large meal or alcohol consumption (alcohol metabolites compete for some excretion sites in kidney as uric acid, which decreases uric acid secretion and subsequent buildup in blood).
119
Treatment of gout
Acute treatment includes NSAIDs (eg indomethacin), glucocorticoids, colchicine. Chronic treatment (preventive) includes xanthine oxidase inhibitors (eg allopurinol, febuxostat).
120
Pseudogout
It presents with pain and effusion in a joint, caused by deposition of calcium pyrophosphate crystals within the joint space (chondrocalcinosis on x-ray). Forms basophilic, rhomboid crystals that are weakly birefringent under polarized light. It usually affects large joints (classically the knee). Occurs in those over the age of 50; both sexes are affected equally. Diseases are associated with pseudogout include hemochromatosis, hyperparathyroidism, osteoarthritis. Treatment includes NSAIDs for sudden, severe attacks; glucocorticoids; colchicine for prophylaxis.
121
Gout vs pseudogout
Gout crystals are yellow when parallel to the light. Pseudogout crystals are blue when parallel to light.
122
Infectious arthritis
S aureus, Streptococcus, and Neisseria gonorrhoease are common causes. Gonococcal arthritis is an STD that presents as a migratory arthritis with an asymmetric pattern. Affected joint is swollen, red, and painful. STD= Synovitis (eg knee), Tenosynovitis (eg hand), and Dermatitis (eg pustules).
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Seronegative spondyloarthropathies
Arthritis without rheumatoid factor (no anti-IgG antibody). There is a strong association with HLA-B27 (gene that codes for MHC class I). It occurs more often in males. PAIR: Psoriatic arthritis, Ankylosing spondylitis, Inflammatory bowel disease, Reactive arthritis (Reiter syndrome).
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Psoriatic arthritis
A seronegative spondyloarthropathies. Joint pain and stiffness associated with psoriasis. Asymmetric and patchy involvement. Dactylitis (sausage fingers), pencil in cup deformity on x-ray. It is seen in fewer than 1/3 of patients with psoriasis.
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Ankylosing spondylitis
A seronegative spondyloarthropathies. Chronic inflammatory disease of the spine and sacroiliac joints causing ankylosis (stiff spine due to fusion of joints), uveitis, aortic regurgitation. Bamboo spine (vertebral fusion).
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Arthritis in inflammatory bowel disease
A seronegative spondyloarthropathies. Crohn disease and ulcerative colitis are often accompanied by ankylosing spondylitis or peripheral arthritis.
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Reactive arthritis
A seronegative spondyloarthropathies. It has the classic triad of conjunctivitis and anterior uveitis, urethritis, and arthritis. Can't see, can't pee, can't bend my knee. Often due to post-GI (Shigella, Salmonella, Yersinia, Campylobacter) or Chlamydia infections.
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Presentation of systemic lupus erythematous
The classic presentation includes rash, joint pain, and fever, most commonly in a female of reproductive age and African descent. However, presentation can include any of the following (RASH OR PAIN): Rash (malar or discoid), Arthritis, Soft tissues/ serositis, Hematologic disorders (cytopenia), Oral/ Nasopharyngeal ulcers, Renal disease, Raynaud phenomenon, Photosensitivity, Positive VDRL/RPR (screening for syphilis), Antinuclear antibodies, Immunosuppressants, Neurologic disorders (eg seizures, psychosis). Common causes of death in SLE: Cardiovascular disease, infection, renal disease.
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Libman Sacks endocarditis
Occurs with SLE. It is a non-bacterial, wart-like vegetations on both sides of the value.
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Lupus nephritis
A type III hypersensitivity reaction. Nephritic manifests as diffuse proliferative glomerulonephritis. Nephrotic syndrome presents as membranous glomerulnephritis.
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Findings of SLE
Antinuclear antibodies (ANA) is sensitive but not specific. Anti-dsDNA antibodies is specific and has a poor prognosis for renal disease. Anti-Smith antibodies is specific, but not prognostic (its directed against snRNPs). Antihistone antibodies is sensitive for drug-induced lupus. A decrease in Cs, C4, and CH50 due to immune complex formation.
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Treatment of SLE
NSAIDs, steroids, immunosuppressants, and hydroxychloroquine.
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Antiphospholipid syndrome
It is primary or secondary autoimmune disorder (most commonly in SLE). Diagnose based on clinical criteria including history of thrombosis (arterial or venous) or spontaneous abortion along with laboratory findings of lupus anticoagulant, anti-cardiolipin, anti-beta2 glycoprotein antibodies. Treat with systemic anticoagulation. Anti-cardiolipin antibodies and lupus anticoagulant can cause a false positive VDRL and prolonged PTT.
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Sarcoidosis
It is characterized by immune-mediated, widespread noncaseating granulomas, elevated serum ACE levels, and elevated CD4+/ CD8+ ratio. It is common in black females. Often is asymptomatic except for enlarged lymph nodes. Findings on CXR of bilateral adenopathy and coarse reticular opacities, CT of the chest better demonstrates the extensive hilar and mediastinal adenopathy. Associated with restrictive lung disease (interstitial fibrosis), erythema nodosum, lupus pernio, Bell palsy, epithelioid granulomas containing microscopic Schaumann and asteroid bodies, uveitis, hypercalcemia (due to an increase 1-alpha hydroxylase mediated vitamin D activation in macrophages). Treatment is steroids.
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Polymyalgia rheumatica
Symptoms include pain and stiffness in soulders and hips, often with fever, malaise, weighted loss. It does not cause muscular weakness. It is more common in women for the age of 50. It is associated with temporal (giant cell)arteritis. Findings include an increase ESR and CRP and normal CK. Treatment is rapid response to low dose corticosteroids.
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Fibromyalgia
Most commonly seen in females between 20-50 years old. Presents as chronic, widespread musculoskeletal pain associated with stiffness, paresthesias, poor sleep, fatigue. Treat with regular exercise, antidepressants (TCAs, SNRIs), anticonvulsants.
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Polymyositis/ dermatomyositis
There will be an increase in CK. Positive ANA, anti-Jo-1, anti-SRP, anti-Mi-2 antibodies. Treatment is steroids followed by long term immunosuppressant therapy (eg methotrexate).
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Polymyositis
Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with CD8+ T cells. Most often involves shoulders.
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Dermatomyositis
Similar to polymyositis, but also involves malar rash (similar to SLE), Gottron papules, heliotrope (erythematous periorbital) rash, shawl and face rash, mechanic's hands. There is an increase risk of occult malignancy. Perimysial inflammation and atrophy with CD4+ T cells.
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Myasthenia gravis
It is the most common NMJ disorder. It is due to autoantibodies to postsynaptic ACh receptor. Clinical presentation includes ptosis, diplopia, weakness, which worsens with muscle use. It is associated with thymoma and thymic hyperplasia. AChE inhibitors will reverse symptoms.
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Lambert-Eaton myasthenic syndrome
It is pretty uncommon. Autobodies to presynaptic Ca channel, which decrease ACh release. It presents as proximal muscle weakness, autonomic symptoms (dry mouth, impotence). It is associated with small cell lung cancer. AChE inhibitor has a minimal effect of symptoms.
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Myositis ossificans
Metaplasia of skeletal muscle into bone following muscular trauma. It is most often seen in upper or lower extremity. May present as suspicious mass at site of known trauma or as incidental finding on radiography.
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Scleroderma (systemic sclerosis)
It is a triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis. It commonly sclerosis of skin, manifesting as puffy, taut skin without wrinkles, fingertip pitting. Also sclerosis of renal, pulmonary (is the most common cause of death), cardiovascular, GI systems. 75% are female. There are two major types: diffuse and limited scleroderma.
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Diffuse scleroderma
Widespread skin involvement, rapid progression, early visceral involvement. Associated with anti-Scl-70 antibody (anti-DNA topoisomerase I antibody).
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Limited scleroderma
There is limited skin involvement confined to fingers and face. It is also associated with CREST: Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. It has a more benign clinical coarse than diffuse scleroderma. It is associated with anti-centromere antibody.
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Layers of the epidermis
Skin has three layers: epidermis, dermis, subcutaneous fat (hypodermis, subcutaneous fat). From surface to base: Stratum Corneum (keratin), Stratum Lucidum, Stratum Granulosum, Stratum Spinosum (desmosomes), Stratum Basale (stem cell site). (Californians Like Girls in String Bikinis).
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Tight junction
Also called zonula occludens, prevents paracellular movement of solutes; composed of claudins and occludins.
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Adherens junction
Also called zonula adherins, It is located below the tight junction, forms belt connecting actin cytoskeletons of adjacent cells with CADherins (Ca dependent ADhesion proteins). Loss of E-cadherin promotes metastasis.
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Desmosome
Also called macula adherens. It provides structural support via keratin interactions. Autoantibodies to desmosome causes pemphigus vulgaris.
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Gap junction
It contains channel proteins called connexons permit electrical and chemical communication between cells.
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Hemidesmosome
Connects keratin in basal cells to underlying basement membrane. Autoantibodies to hemidesmosome leads to bullous pemphigoid. (Hemidesmosome are down below).
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Integrins
Membrane proteins that maintain integrity of basolateral membrane by binding to collagen and laminin in basement membrane.
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Macule
Flat lesion with well-circomscribed change in skin color less than 1 cm. Examples include freckle and labial macule.
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Patch
Macules over 1 cm in size. For example, large birthmark (congenital nevus).
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Papule
Elevated solid skin lesion under 1 cm in size. eg, mole (nevus), acne.
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Plaque
A papule over 1 cm. Eg psoriasis.
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Vesicle
Small fluid containing blister under 1 cm. eg chickenpox, shingles.
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Bulla
Large fluid-containing blister over 1 cm. eg bullous pemphigoid.
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Pustule
Vesicle containing pus. eg pustular psoriasis.
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Wheal
Transient smooth papule or plaque. eg hives (urticaria)
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Scale
Flaking off of stratum corneum. eg eczema, psoriasis, SCC
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Crust
Dry exudate. Impetigo.
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Hyperkeratosis
An increase thickness of stratum corneum, eg psoriasis, calluses.
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Parakeratosis
Hyperkeratosis with retention of nuclei in stratum corneum. eg psoriasis.
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Spongiosis
Epidermal accumulation of edematous fluid in intercellular spaces. Eczematous dermatitis.
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Acantholysis
Separation of epidermal cells. eg pemphigus vulgaris.
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Acanthosis
Epidermal hyperplasia (an increase spinosum). eg acanthosis nigricans.
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Albinism
Normal melanocyte number with normal melanin production due to a decrease tyrosinase activity or defective tyrosine transport. It can also be caused by failure of neural crest cell migration during development. There is an increase risk of cancer.
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Melasma (chloasma)
Hyperpigmentation associated with pregnancy (mark of pregnancy) or OCP use.
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Vitiligo
Irregular areas of complete depigmentation. Caused by autoimmune destruction of melanocytes.
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Acne
Obstructive and inflammatory disease of the pilosebacceous unit predominantly found on the face and trunk. It is most common in adolescents but can occur at any age.
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Atopic dermatitis (eczema)
Pruritic eruption, commonly on skin flexures. Often associated with other atopic diseases (asthma, allergic rhinitis). It usually starts on the face in infancy and often appears in the antecubital fossae thereafter.
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Allergic contact dermatitis
Type IV hypersensitivity reaction that follows exposure to allergen. Lesions occur at site of contact (eg nickel, poison ivy, neomycin).
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Melanocytic nevus
A common mole. Benign, but melanoma can arise in congenital or atypical moles. Intredermal nevi are papular. Junctional nevi are flat macules.
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Psoriasis
Papules and plaques with silvery scaling, especially on knees and elbows. Acanthosis with parakeratotic scaling (nuclei still in stratum corneum). There is an increase in stratum spinosum a decrease in stratum granulosum. Auspitz sign is pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off. It can be associated with nail pitting and psoriatic arthritis.
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Rosacea
Inflammatory facial skin disorder characterized by erythematous papules and pustules, but no comedones. It may be associated with facial flushing to external stumuli (eg alcohol, heat). Chronic inflammatory changes may result in rhinophyma (bulbous deformation of the nose).
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Seborrheic keratosis
Flat, greasy, pigmented squamous epithelial proliferation with keratin-filled cysts (horn cysts). It looks stuck on. Lesions occur on head, trunk, and extremities. Common benign neoplasm of older persons. Leser-Trelat sign is the sudden appearance of multiple seborrheic keratoses, indicating an underlying malignancy (eg GI, lymphoid).
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Verrucae
Warts; caused by HPV. They are soft, tan colored, cauliflower-like papules. Epidermal hyperplasia, hyperkeratosis, koilocytosis. Condyloma acuminatum on genitals.
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Urticaria
Hives. Pruritic wheals that form after mast cell degranulation. Characterized by superficial dermal edema and lymphatic channel dilation.
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Impetigo
It is very superficial skin infection. Usually from S. aureus or S. pyogenes. Highly contagious. Honey-colored crusting. Bullous impetigo has bullae and is usually caused by S. aureus.
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Cellulitis
Acute, painful, spreading infection of deeper dermis and subcutaneous tissues. It usually occurs from S. pyogenes or S. aureus. It often starts with a break in skin from trauma or another infection.
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Erysipelas
Infection involving upper dermis and superficial lymphatics, usually from S pyogenes. Presents with well defined demarcation between infected and normal skin.
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Abscess
A collection of pus from a walled off infection within deeper layers of skin. Offending organism is almost always S. aureus, which is frequently methicillin resistant.
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Necrotizing fasciitis
Deeper tissue injury, usually from anaerobic bacteria or S pyogenes. Results in crepitus from methane and CO2 production. Flesh eating bacteria. Causes bullae and a purple color to the skin.
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Staphylococcal scalded skin syndrome
Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which destroys epidermal-dermal junction). Characterized by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis that heals completely. Seen in newborns and children, adults with renal insufficiency.
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herpes
Herpes virus infections (HSV1 and HSV2) of skin can occur anywhere from mucosal surfaces to normal skin. These include herpes labialis, herpes genitalis, herpetic whitlow (finger).
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Molluscom contagiosum
Umbilicated papules caused by a poxvirus. While frequently seen in children, it may be sexually transmitted in adults.
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Varicella zoster virus
It causes varicella (chickenpox) and zoster (shingles). Varicella presents with multiple crops of lesions in various stages from vesicles to crusts. Zoster is a reactivation of the virus in dermatomal distribution (unless it is disseminated).
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Hairy leukoplakia
Irregular, white, painless plaques on tongue that cannot be scarped off. EBV mediated. Occurs in HIV-positive patients, organ transplant recipients. Contrast with thrush (scrapable) and leukoplakia (precancerous).
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Pemphigus vulgaris
Potentially fatal autoimmune skin disorder with IgG antibody against desmoglein (component of desmosomes). Flaccid intraepidermal bullae are caused by acantholysis (keratinocytes in stratum spinosum are connected by desmosomes); oral mucosa is also involved. Immunofluorescence reveals antibodies around epidermal cells in a reticular (net like) pattern. Nikolsky sign positive (separation of epidermis upon mannual stroking of skin).
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Bullous pemphigoid
Less severe than pemphigus vulgaris. It involves IgG antibody against hemidesmosomes (epidermal basement membrane; antibodies are BULLOw the epidermis). Tense blisters containing eosinophils that affect skin but spare oral mucosa. Immunofluorescence reveals linear pattern at epidermal-dermal junction. Nikolsky sign negative (unlike pemphigus vulgaris).
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Dermatitis herpetiformis
Pruritic papules, vesicles, and bullae (often found on elbows). Deposits of IgA at tips of dermal papillae. Associated with celiac disease.
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Erythema multiforme
It is associated with infections (eg Mycoplasma pneumoniae, HSV), drugs (eg sulfa drugs, beta-lactams, phenytoin), cancers, autoimmune disease. It presents with multiple rings and dusky center showing epithelial disruption).
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Stevens-johnson syndrome
It is characterized by fever, bullae formation and necrosis, sloughing of skin, high mortality rate. There are typically 2 mucous membranes are involved, and targetoid skin lesions may appear, as seen in erythema multiforme. Usually associated with adverse drug reaction. A more severe form of Stevens-Johnson syndrome (SJS) with over 30% of the body surface area involved is toxic epidermal necrolysis (TEN). 10-30% involvement denotes SJS-TEN.
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Acanthosis nigricans
Epidermal hyperplasia causing symmetric, hyperpigmented thickening of skin, especially in axilla or on neck. It is associated with hyperinsulinemia (eg diabetes, obesity, cushing syndrome), visceral malignancy (eg gastric adenocarinoma).
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Actinic keratosis
Premalignant lesions caused by sun exposure. Small, rough, erythematous or brownish papules or plaques. Risk of squamous cell carcinoma is proportional to degree of epithelial dysplasia.
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Erythema nodosum
Painful inflammatory lesions of subcutaneous fat, usually on anterior shins. Often idiopathic, but can be associated with sarcoidosis, coccidoidomycosis, histoplasmosis, TB, streptococcal infections, leprosy, and Crohn disease
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Lichen Planus
Pruitic, purple, polygonal planar papules, and plaques are the 6 P's of lichen Planus. Mucosal involvement manifests as Wickham striae (reticular white lines). Sawtooth infiltrate of lymphocytes at dermal epidermal junction. It is associated with hepatitis C.
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Pityriasis rosea
The rash often begins with a single, round or oval, pink patch that is scaly with a raised border (herald patch). This is followed days later by other scaly erthematous plaques, often seen in a Christmas tree distribution. Multiple plaques with collarette scale. Self-resolving in 6-8 weeks.
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Sunburn
Acute cutneous infammatory reaction due to excessive UV irradiation. Causes DNA mutations, inducing apoptosis of keratinocytes. UVA is dominant in tanning and photoaging,, UVB in sunburn. Can lead to impetigo, skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma).
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Basal cell carcinoma
It the most common skin cancer. Found in sun-exposed areas of body. Locally invasive, but rarely metastasizes. Pink, pearly nodules, commonly with telangiectasias, rolled borders, central crusting or ulceration. BCCs also appear as nonhealing ulcers with infiltrating growth or as scaling plaque (superficial BCC). Basal cell tumors have a palisading nuclei.
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Squamous cell carcinoma
Second most common skin cancer. Associated with excessive exposure to sunlight, immunosuppresion, and occasionally arsenic exposure. Commonly appears on face, lower lip, ears, and hands. Locally invasive, may spread to lymph nodes, and will rarely metastasize. Ulverative red lesions with frequent scale. Associated with chronic draining sinuses. Histology is marked by keratin pearls.
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Actinic keratosis
A scaly plaque, is a precursor to squamous cell carcinoma.
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Keratoacanthoma
A variant of squamous cell carcinoma that grows rapidly (4-6 weeks) and may regress spontaneously over months.
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Melanoma
A common tumor with significant risk of metastasis. S-100 tumor marker. It is associated with sunlight exposure; fair skinned persons are at an increased risk. The depth of tumor correlates with a risk of metastasis. Look for ABCDE: Asymmetry, Border irregularity, Color variation, Diameter over 6mm, and Evolution over time. At least 4 different types of melanoma, including superficial spreading, nodular, lentigo maligna, and acral lentiginous. It is often driven by an activating mutation in BRAF kinase. Primary treatment is excision with appropriately wide margins. Metastatic or un-resectable melanoma melanoma inpatients with BRAF V600E mutation may benefit from vemurafenib, a BRAF kinase inhibitor.
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Inhibitor of phospholipase A2
Cortisone/ hydrocortisone, predinisone/ prednisolone, triamcinolone/ methylprednisone, dexamethasone/ betamethasone.
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Phospholipase A2
converts membrane phospholipids into arachidonic acid
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Lipoxygenase
converts arachidonic acid into 5-HPETE, which gets converted into leukotrienes (LTC4, LTD4, LTE4, LTB4)
209
Cox 1 and cox 2
Converts arachidonic acid to cyclic endoperoxides, which gets converted into prostacyclin (PGI2), prostaglandins (PGE1, PGE2, PGF2), and thromboxane (TXA2).
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LTC4
Increases bronchial tone
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LTD4
Increases bronchial tone
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LTE4
Increases bronchial tone
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LTB4
Increases neutrophil chemotaxis. Neutrophils B4 the others.
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PGI2
Decreases platelet aggregation. Decreases vascular tone. Platelet Gathering Inhibitor.
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PGE1
It decreases vascular tone.
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PGE2
Increases uterine tone.
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PGF2
Increases uterine tone.
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TXA2
Increases platelet aggregation. Increases vascular tone.
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Drug that inhibit lipoxygenase inhibitor
Zileuton
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Drugs that inhibit leukotrienes
Montelukast and zafirlukast.
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Dugs that inhibit COX-1 and COX-2
NSAIDs (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen)
222
Cyclooxygenase 2 inhibitors
Celecoxib
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Drugs mimicking PGI2
Epoprostenol. Decreases platelet aggregation. Decreases vascular tone.
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Drugs mimicking PGE1
Alprostadil. It decreases vascular tone.
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Drugs mimicking PGE2
Dinoprostone. Increases uterine tone.
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Drugs mimicking PGF2
Carboprost. Increases uterine tone.
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Acetaminophen
It reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally. Antipyretic, analgesic, but not anti-inflammatory. It is used instead of aspirin to avoid Reye syndrome in children with viral infection. An overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver. N-acteylcysteine is antidote, which regenerates glutathione.
228
Aspirin
Irreversibly inhibits cyclooxygenase (both Cox-1 and COX-2) via acetylation, which decreases synthesis of TXA2 and prostaglandins. Increases bleeding time. No effect on PT, PTT. A type of NSAID. A low dose (less then 300 mg/day) for a decrease in platelet aggregation. Intermediate dose (300-2400 mg/day) for antipyretic and analgesic. A high dose (2400-4000 mg/day) is an anti-inflammatory.
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Celecoxib
Reversibly inhibits specifaclly the cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares cox-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on cox-1. Used for rheumatoid arthritis and osteoarthritis. There is an increase risk of thrombosis. There is also a sulfa allergy.
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NSAIDs
Includes ibuprofen, naproxen, indomethacin, ketorolae, diclofenac. It reversibly inhibits cyclooxygenase (both cox-1 and cox-2). Block prostaglandin synthesis. It is used for antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA. It can cause interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia (prostaglandins vasodilator afferent arteriole).
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Bisphosphonates
Includes alendronate or other -dronates. It is a pyrophosphate analogs; binds hydroxyapatite in bone, inhibiting osteoclast activity. Clinical uses include osteoporosis, hypercalcemia, Paget disease of bone. It can cause corrosive esophagitis (patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of jaw.
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Teriparatide
It is a recombinant PTH analog given subcutaneously daily. There is an increase in osteoblastic activity. It is used for osteoporosis. It causes an increase bone growth compared to anti-resoptive therapies (eg bisphosphonates). It can transient hypercalemia. It may increase the risk of osteosarcoma (seen in rodent studies).
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Allopurinol
Chronic gout drugs. It inhibits xanthine oxidase after being converted to alloxanthine, decreases conversion of xanthine to uric acid. It is also used in lymphoma and leukemia to prevent tumor lysis, which is associated with urate nephropathy. An increase in concentrations of azathioprine and 6-mp (both normally metabolized by xanthine oxidase).
234
Febuxostat
Chronic gout drugs. Inhibits xanthine oxidase.
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Pegloticase
Chronic gout drugs. Recombinant uricase that catalyze metabolism of uric acid to allantoin (a more water-soluble product).
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Probenecid
Chronic gout drugs. Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin). Can precipitate uric acid calculi.
237
Acute gout drugs
NSAIDs, glucocorticoids, cholchicine. Do not give salicylates; all but the highest doses depress uric acid clearance. Even high doses (5-6 dg/day) have only minor uricosuric activity.
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Colchicine
Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation. Acute and prophylactic value. GI side effects.
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TNF-alpha inhibitors
All TNF-alpha inhibitors predispose to infection, including reactivation of latent TB, since TNF a important in granuloma formation and stabilization.
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Etanercept
Fusion protein (receptor for TNF-alpha plus IgG1 Fc), produced by recombinant DNA. Etanercept is a TNF decoy reCEPTor. It is used for rheumatoid arthritis, psoriasis, ankylosing spondylitis.
241
Infliximab
Anti-TNF-alpha monoclonal antibody. It is used for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, and psoriases.
242
Adalimimab
Anti-TNF-alpha monoclonal antibody. It is used for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, and psoriases.
