Rheumatology, Dermatology, MSK Flashcards
What is essential for the formation and differentiation of osteoclasts?
The RANK receptor/ RANK ligand interaction
What results from overexpression of RANK receptors in hypoestrogenic states?
Increased bone resorption due to increased osteoclastic activity.
What is heteroplasmy?
The condition of having different mitochondrial organellar genomes (mutated and wild type) within a single cell.
Name the three classes of drugs used to treat acute gouty arthritis and which of these treatments is first line.
Colchicine, NSAIDs, glucocorticoids. NSAIDs are first line.
What is the mechanism of action of colchicine?
Treats acute gouty arthritis by binding the intracellular protein tubulin and inhibiting its polymerization into microtubules (cytoskeletal elements).
What toxicites are associated with colchicine use?
GI toxicity (diarrhea), nausea, abdominal pain. Should be avoided in patients who are elderly or who have renal dysfunction.
What is the function of MMP (matrix metalloproteinases) in wound healing?
Encourages myofibroblast accumulation at the wound edges and scar tissue remodelling. Myofibroblasts then initiate wound contraction during healing by second intention.
When do contractures occur in wound healing?
When unusually pronounced MMP activity results in excessive wound contraction. Contractures cause wound deformities.
What type of bone is most commonly affected in postmenopausal osteoperosis and where is this bone present?
Cancellous bone; predominantely present in the vertebral column, distal radius, hip, and neck of the femur.
What effect does primary osteoperosis have on serum calcium, phosphorous, and PTH levels?
Normal calcium, phosphorus, and PTH
What is the first line treatment for disease modification in patients with moderate to severe RA?
Methotrexate (can be combined with Leflunomide and TNF1 inhibitors if no response with MTX alone)
What are the side effects of methotrexate?
Stomatitis (mouth ulcers), hepatotoxicity (abnormal LFTs), myelosuppression. Folic acid supplementation reduces stomatitis.
What is hydroxychloroquine used to treat?
SLE or early mild seronegative rheumatoid arthritis.
What is a potentially serious effect of hydroxychloroquine use?
Permanent retinal damage.
Where does the Posterior Cruciate ligamant originate and insert?
Originates from the anterolateral surface of the medial femoral condyle and inserts into the posterior intercondylar area of the tibia.
How are osteocytes connected to each other?
By gap junctions.
How do osteocytes exchange nutrients/ waste products and send signals to each other?
Through gap junctions.
What is the function of osteocytes?
To maintain the structure of mineralized matrix and to control the short term release and deposition of calcium (calcium homeostasis).
What osteocyte cell structures are used to send signals/ exchange information between osteocytes?
Long intracanalicular processes that extend through the ossified bone matrix.
What comorbid condition is present in the majority of patients with myasthenia gravis?
Thymoma or thymic hyperplasia
From what embryologic structure is the thymus derived?
Third pharyngeal pouch
From what embryologic structure are the inferior parathyroid glands derived?
Third pharyngeal pouch.
What is derived from the first pharyngeal pouch?
Epithelium of middle ear and auditory tube
What is derived from the second pharyngeal pouch?
The epithelium of the palatine tonsil crypts
What is derived from the third pharyngeal pouch?
Thymus, inferior parathyroid glands.
What is derived from the fourth pharyngeal pouch?
Superior parathyroid glands, ultimobranchial body.
What is derived from the first pharyngeal membrane?
Tympanic membrane
What is derived from the first pharyngeal groove?
Epithelium of the external ear canal.
What symptoms are associated with damage to the musculocutaneous nerve?
Loss of innervation of the upper arm flexors (biceps brachii, coracobrachialis, brachialis) and lack of sensory information to the skin of the lateral forearm
From what nerve roots does the musculocutaneous nerve arise?
C5-C7 rami; upper trunk of the brachial plexus.
What types of injuries may cause musculocutaneous nerve damage?
Forceful injuries that cause separation of the neck and shoulder.
What is the most common presentation of tinea corporis?
An annular scaling plaque with well demarcated, raised erythematous borders and central clearing.
What drug is commonly used to treat dermatophytosis and what drug class is it in?
Terbinafine, allylamines class
What is the mechanism of action of Terbinafine?
Inhibition of synthesis of ergosterol of the fungal membrane by inhibiting the enzyme squalene epoxidase.
What are bacterioid species?
Gram negative anaerobic rods that produce beta lactamase
What is Piperacillin-tazobactam used to treat?
Combination of extended spectrum penicillin with a beta lactamase inhibitor. Effective against gram negative enteric rods including Pseudomonas a. and Bacteroides fragilis.
Pending lab results for septic arthritis, what drug should be prophylactically given and what condition is it used to treat?
Ceftriaxone to treat gonococcal arthritis.
What symptoms are characterized by the term Eczematous dermatitis?
Erythematous, papulovesicular, weeping, encrusted lesions that may evolve into thickened scaly plaques.
What five conditions are characterized by the term Eczematous dermatits?
Allergic contact dermatitis, atopic dermatitis, drug related eczematous dermatitis, photo eczematous dermatitis, primary irritant dermatitis.
Describe the immunologic process associated with allergic contact dermatitis.
Antigens at the epidermal surface are selected by Langerhans cells and carried to draining lymph nodes where they are presented by Langerhans cells to CD4 T cells. The T cells migrate to the skin and incite an inflammatory response within 24 hours of antigen re-exposure.
What is spongiosis histologically?
Epidermal accumulation of edematous fluid in the intercellular spaces.
What condition is characterized by spongiosis?
Acute eczematous dermatitis (contact dermatitis).
What factor is responsible for up to 80% of the variation in peak bone mass among individuals?
Genetic factors.
Name five side effects of thiazide diuretics.
Increased urinary excretion of K+ and H+ (hypokalemia and metabolic alkalosis), hyponatremia, hyperuricemia (uric acid reabsorption), hyperlipidemia, decreased insulin secretion and glucose uptake- hyperglycemia
What findings are characteristic of hypokalemia?
Muscle weakness/ paralysis, Prominent U waves on EKG
Name a drug that both decreases bone fracture and breast cancer risk.
Raloxifene
What type of drug is Raloxifene?
Selective estrogen receptor modulator (SERM); binds to estrogen receptors and exhibits tissue specific behaviour that either imitates or antagonizes the natural effects of estrogen.
How does Raloxifene act on bone?
As an estrogen agonist to inhibit osteoperosis
How does Raloxifene act on mammary tissue?
As an estrogen receptor antagonist to provide protection against estrogen receptor positive breast cancer.
What type of injury typically characterizes a lunate dislocation?
Fall on an outstretched, dorsiflexed hand.
What is the relationship of the lunate bone to the scaphoid bone?
Lunate bone is directly medial (i.e. towards the pinky) to the scaphoid bone.
What three structures pass through the popliteal fossa?
Tibial nerve, popliteal vein, popliteal artery.
What muscles are innervated by the tibial nerve?
Gastrocnemius, soleus, plantaris muscles; all responsible for plantar flexion of the foot; flexor digitorum and hallucis longus- responsible for toe flexion, and tibialias posterior muscle responsible for inversion of foot.
In a patient with a tibial nerve injury, what is the position of their lower extremity?
Dorsiflexed and everted foot.
What sensory innervation is lost in tibial nerve injury?
Sensory loss to the distal plantar surface of the foot (skin of the sole of the foot).
What histologically characterizes urticaria?
Superficial dermal edema and lymphatic channel dilation. No epidermal changes are present.
Describe Lichen planus.
Polygonal, planar, pruritic, purplish plaques on the wrists, hands, trunk, and legs.
Describe the muscular changes occuring in the eye during acommodation.
When the eye focuses on a near object, contraction of the cilliary muscles causes relaxation of the zonular fibers allowing the lens to relax and assume a more convex shape.
What happens to the ciliary muscle when looking at a distant object?
It relaxes and the lens flattens due to outward radial tension exerted by the zonular fibers.
What physiological changes cause presbyopia?
Decreased lens elasticity, changes in lens curvature, diminished strength of the ciliary muscle.
What characterizes aging of the skin?
Thinning of the dermis and epidermis with flattening of the dermoepidermal junction, decreased numbers of fibroblasts, reduced synthesis and breakdown of collagen and elastin fibers.
What type of crystals are diagnostic for acute gouty arthritis?
Negatively bifringent crystals.
What is the mechanism of action of colchicine?
An anti-inflammatory drug that acts by binding to the intracellular protein tubulin and preventing tubulin polymerization into microtubules. This leads to impaired leukocyte migration and phagocytosis.
What is the most common defect associated with achondroplasia?
Activating mutation of the fibroblast growth factor receptor-3 at the epiphyseal growth plate which inhibits growth of the plate.
What is characteristic of bone length in patients with achondroplasia?
Short, thick tubular long bones in the appendicular skeleton and normal axial (spine length)
What are the layers in order from middle to end of young long bones?
Diaphysis, metaphysis, epiphyseal cartilage, epiphysis.
What is the typical presentation of a patient with Paget’s disease of the bone?
An older patient with increased alkaline phosphatase levels
Describe the disease process of Paget’s disease of the bone.
Marked osteoclastic activation is followed by an increase in osteoblasts. This causes increased bone resorption and formation of abnormal bone. New collagen is laid down haphazardly causing a mosaic pattern of lamellar bone with irregular sections linked by cement lines (representing previous areas of bone resorption).
What symptoms are consistent with congenital hypothyroidism?
Neonates that appear lethargic, that feed poorly, that exhibit prolonged jaundice, and that demonstrate constipation, muscle hypotonia, and a hoarse cry. Patient has pale, cole, dry skin, mysedema, and macroglossia. Coarse facial features and umbillical hernia are also commonly present.
What comorbid conditions do infants with congenital hypothyroidism have increased risk for?
Congenital heart defects such as ASDs and VSDs.
How does Malassezia furfur appear on light microscopy?
Spaghetti and meatballs appearance with spores and hyphae (with short cigar butt appearance)
What inflammatory mediators are produced in psoriasis?
Th1 and Th17 cytokines, TNFa, IFNy, IL-23, IL-17 and keratinocyte growth factors leading to keratinocyte proliferation, inflammation, and angiogenesis.
How do topical vitamin D analogs work in the treatment of psoriasis?
By binding to and activating the vitamin D receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation. It also inhibits T cell proliferation and other inflammatory mediators.
Name three topical vitamin D analogs used in the treatment of psoriasis.
Calcipotriene, calcitrol, tacalcitol.
What is the mechanism of action of etanercept?
Recombinant form of the TNF receptor that binds TNFa; it is used to treat moderate to severe plaque type psoriasis.
What organism causes over 95% of gas gangrene?
Clostridum perfringens.
What conditions are caused by clostridum perfringens?
Gas gangrene and toxin mediated, late onset food posioning characterized by transient watery diarrhea
During what type of surgical procedure is the long thoracic nerve often injured?
During axillary lymph node dissections as may occur during radical mastectomy.
To what drug class does nafcillin belong?
Penicillinase-resistant penicillins
What is nafcillin most commonly used to treat?
Empirical treatment of skin and soft tissue infections due to S. aureus
What is caudal regression syndrome?
A rare condition where patients are born with agenesis of the sacrum and occasionally the lumbar spine. They experience flaccid paralysis of the legs, dorsiflexed contractures of the feet, and urinary incontinence.
What condition is related to caudal regression syndrome?
Poorly controlled maternal diabetes.
What is necessary for nucleoside analog antiviral drugs to function?
They must be phosphorylated into nucleotides to function and require viral phosphorylating enzymes.
Name four nucleoside analog drugs.
Acyclovir, valacyclovir, famciclovir, ganciclovir.
The absence of viral thymidine kinase in a herpesvirus strain confers resistance to what class of drugs?
Nucleoside analog antiviral drugs.
Thymidine kinase deficient (and acyclovir-resistant) varicella zoster virus isolates are obtained from what type of patient?
AIDS patients exclusively.
In an AIDS patient with herpes zoster, what drugs are used to treat the condition?
Foscarnet or cidofovir
How is cidofovir activated?
It is a nucleoside monophosphate (nucleotide) that requires only cellular kinases for activation
What part of the sarcomere is composed exclusively of myosin thick filaments?
The H band (part of the A band on either side of the M line)
What happens when a tRNA is mischarged with the incorrect amino acid (and is not corrected by proofreading)?
It will be incorporated into the growing polypeptide chain.
Chronic corticosteroid therapy for atopic eczematous dermatitis causes what condition?
Decreased production of extracellular matrix collagen and glycosaminoglycans causing atrophy of the dermis with loss of dermal collagen, cracking, drying, and or tightening of the skin. Telangiectasias, ecchymoses, and atrophic striae may also be found.
What is the most common complication associated with a varicella zoster virus infection?
Post herpetic neuralgia lasting for more than one month after an erruption.
What conditions may be caused by Bartonella henselae?
Cat scratch disease, bacillary angiomatosis in immunocompromised patients, culture negative endocarditis.
How does bacillary angiomatosis present?
As red-purple papular skin lesions
What is the virulence factor of staph a.?
Protein A; it forms part of the outer peptidoglycan layer of S. aureus and binds with the Fc portion of IgG antibodies at the complement binding site, preventing complement activation. This causes decreased production of C3b, leading to impaired opsonization and phagocytosis.
What causes gout?
Deposition of monosodium urate crystals
What is the function of Phosphoribosyl pyrophosphate (PRPP) synthetase?
Enzyme responsible for production of the activated ribose necessary for de novo synthesis of purine and pyrimidine nucleotides.
Describe the inflammatory process associated with gout.
Phagocytosis of urate crystals by neutrophils causes release of cytokines and inflammatory mediators which leads to further neutrophil activation and chemotaxis. This causes a positive feedback loop which amplifies the inflammatory response.
Where is procollagen synthesized?
Within the endoplasmic reticulum
Where is procollagen converted to tropocollagen?
The extracellular space.
What is the typical presentation of a patient with Lambert-Eaton myasthenic syndrome?
Proximal muscle weakness, gait alteration, difficulty arising from a chair, difficulty climbing stairs. Often patients have cranial nerve involvement (diplopia, ptosis, dysarthria, dysphagia, etc)
What is the pathophysiology of Lambert Eaton myasthenic syndrome?
Antibodies directed against voltage gated calcium channels that participate in Ach release. Half of all patients with this condition also have a malignancy (small cell lung cancer classically).
Children with what condition benefit from administration of vitamin A?
Children with measles
What symptoms are associated with CREST syndrome?
Calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, teleangiectasias
What antibodies are specific for CREST syndrome?
Anti-centromere antibodies.
What antibodies are specific for systemic sclerosis (diffuse scleroderma)?
Anti-DNA topoisomerase I (Scl-70) antibodies.
In what condition are anti-histone antibodies found?
Drug induced SLE.
