Week 3 Flashcards
What genetic and environmental risk factors are associated with the development of rheumatoid arthritis?
Genetically, the most potent risk factor is the shared epitope, a particular sequence of amino acids that is found on certain class II HLA DR receptor variants (specifically, the HLA-DR4 and HLA-DR1 variants). Presence of a particular isoform of peptidylarginine deiminase (PADI4) is also associated with rheumatoid arthritis.
Cigarette smoking is the most clearly established environmental risk factor for RA. Exposure to certain infectious agents and inhalation of dust are also thought to be possible environmental triggers.
How do the treatment options available for gout compare to those available for calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystal disorders?
Medications for treatment of acute attacks exist for all three conditions and include NSAIDs and glucocorticoids.
In contrast, no medications are currently available for the prevention of CPPD and BCP attacks. Preventative medications do exist for the prevention of acute gout attacks and include xanthine oxidase inhibitors (allopurinol, fexobustat), uricosurics (probenecid, lesinurad), and uricases (pegloticase).
What are potential side effects associated with the use of opioids?
- Respiratory depression – the most common cause of death in opioid overdose
- Constipation/Nausea/Vomiting
- Miosis (constricted pupils) – useful for diagnosing an opioid overdose (miosis, respiratory depression, and extreme sedation are a classic triad indicative of opioid overdose)
- Feelings of euphoria
- Urinary retention
- Itching
- Neonatal tolerance and dependence when taken by pregnant women
How do buprenorphine and methadone differ in their mechanism of action for treating opioid dependence?
Buprenorphine is a partial mu-opioid receptor agonist; consequently, it is able to ward off cravings and withdrawal symptoms while having a lower risk of adverse effects compared to full agonists.
In contrast, methadone is a full mu-opioid receptor agonist, but it has a long half-life (about 24 hours), allowing it to control cravings and withdrawal symptoms with less frequent dosing.
What is a possible differential diagnosis for a patient presenting with low back pain?
- Intervertebral Disc Conditions (e.g., disc degeneration, disc rupture/herniation)
- Intervertebral Facet Joint Disease (e.g., osteoarthritis of the facet joints)
- Bone Fractures (e.g., vertebral body compression fracture)
- Muscle Injury (e.g., paraspinal muscle strain/spasm)
- Sacroiliac Joint Disease (e.g., sacroiliitis, ankylosing spondylitis)
- Referred Pain (e.g., from kidney stones, abdominal aortic aneurysms, etc.)
What gait abnormality would be expected if a patient suffers an injury to the superior gluteal nerve? What about to the common fibular (peroneal) nerve?
Superior Gluteal Nerve:
Injury leads to loss of innervation to the gluteus medius and gluteus minimus muscles; these muscles are responsible for stabilizing the pelvis when the contralateral leg is lifted during the swing phase of the gait. Thus, as a consequence of superior gluteal nerve injury, the pelvis will tilt away from the affected side as the contralateral leg is lifted - this is known as a Trendelenburg gait.
Common Fibular (Peroneal) Nerve: The common fibular nerve bifurcates into the deep and superficial fibular nerves in the leg – the deep fibular nerve then innervates the muscles of the anterior leg compartment, which are responsible for dorsiflexing the foot. The resultant weakness of the ankle dorsiflexors causes a drop foot, slapping foot, and/or a steppage gait.
What are common visceral organs/organ systems affected by systemic sclerosis (scleroderma)?
Lungs – interstitial lung disease
Cardiovascular System – vasospasm (Raynaud phenomenon), pulmonary arterial hypertension
Kidneys – scleroderma renal crisis (malignant hypertension/hyperreninemia/microangiopathic hemolytic anemia/renal failure)
GI tract – reduced motility (esophageal dysmotility, impaired gastric emptying, small bowel/colonic pseudo-obstruction)
How do the rashes of systemic-onset juvenile idiopathic arthritis, Kawasaki Disease, IgA vasculitis, and juvenile dermatomyositis appear?
Systemic-Onset Juvenile Idiopathic Arthritis: Transient salmon-pink maculopapular rash
Kawasaki Disease: Truncal non-vesicular polymorphous rash
IgA Vasculitis: Palpable purpura (raised rash that does not blanch with pressure)
Juvenile Dermatomyositis: red/violet papules on the back of the hand (Gottron papules) and red/violet rash around the eyes (heliotrope rash)
What are the major side effects associated with NSAID use?
Side effects are generally related to reduced prostaglandin/prostacyclin/thromboxane formation from COX-1 inhibition:
- Gastrointestinal Ulcers (prostaglandins are important in mucosal protection from gastric acid)
- Renal Toxicity (prostaglandins are important for increasing renal blood flow/maintaining GFR in low-flow conditions)
- Increased Bleeding Risk (thromboxane is important for platelet activity/appropriate blood coagulation)
- Impaired Bone Healing (prostaglandins are important in bone metabolism)
What is the associated gene, mode of inheritance, and mechanism of mutation effect for each of the following conditions?
- Achondroplasia
- Marfan Syndrome
- Osteogenesis Imperfecta Type I
- Ehlers-Danlos Syndrome Classical Type
Achondroplasia:
Associate Gene: FGFR3
Mode of Inheritance: Autosomal Dominant
Mechanism of Mutation Effect: Gain-of-Function Effect
Marfan Syndrome:
Associated Gene: Fibrillin-1
Mode of Inheritance: Autosomal Dominant
Mechanism of Mutation Effect: Haploinsufficiency
Osteogenesis Imperfecta Type I
Associated Gene: Type I Collagen
Mode of Inheritance: Autosomal Dominant
Mechanism of Mutation Effect: Dominant Negative
Ehlers-Danlos Syndrome Classical Type
Associated Gene: Type 5 Collagen
Mode of Inheritance: Autosomal Dominant
Mechanism of Mutation Effect: Haploinsufficiency
