HY lecture notes:
Tx of community-acquired sepsis –> if USMLE asks you for one drug, the answer = third-generation cephalosporin –> ceftriaxone is almost always the answer; if the presentation is a young kid, the answer will be cefotaxime.
Cefotaxime is preferred over ceftriaxone because it doesn’t displace bilirubin from albumin as much as ceftriaxone.
One of the 2CK peds forms gives a 12-month-old girl with sickle cell who missed a dose of penicillin prophylaxis (for S. pneumo) + had septic shock –> answer is cefotaxime, not penicillin or ceftriaxone –> consideration is: “yes, penicillin is given for prophylaxis, but once the kid already has sepsis, we must give the third-generation cephalosporin instead for broader coverage.”
One of the Qs on NBME 8 for 2CK gives sepsis in a 6-year-old; answer was ceftriaxone; they didn’t list cefotaxime –> consideration is: “if they list both ceftriaxone and cefotaxime as answers for sepsis in a kid, choose cefotaxime; if they only list ceftriaxone, just go with that.”
For quick refresh: sepsis = SIRS (systemic inflammatory response syndrome) + source of infection.
SIRS = 2 or more of the following:
- Temperature <36 or >38 C.
- WBCs <4,000 or >16,000.
- RR 20+.
- HR 90+.
Septic shock then just = sepsis + low BP.
Asplenia / sickle cell vaccines = Neisseria meningitides, Haemophilus influenzae type B, Strep pneumoniae.
When peds shelf / 2CK asks “which organism are we most trying to protect against when we give cefriaxone/cefotaxime?” the student thinks, “Um can’t it just be all three; I don’t understand.” –> USMLE wants S. pneumo.
Third-generation cephalosporins are good for community-acquired sepsis, but they’re also notably good against S. pneumo. The reason we don’t give them, however, for empiric Tx in community-acquired pneumonia (CAP) is because they’re too broad-spectrum and are overkill; azithromycin is standard CAP empiric Tx (in peds, roxithromycin is often used clinically, although this won’t specifically show up on NBME forms).
Myotonic dystrophy
Caused by CTG repeat expansion
- Myotonic dystrophy is an AD disease on chromosome 19, with an expansion of CTG (MyoTonic dystrophy).
- This leads to abnormal expression of a myotonin-protein kinase, a type of serine-threonine kinase.
Presentation is generally easy on the USMLE
- Characterized by sustained muscle contraction, muscle wasting, baldness, cataracts, and testicular atrophy.
- The key feature is the sustained muscle contraction, where the individual will demonstrate an inability to relax his or her muscles.
- This shows up in questions as an extra-long handshake or not being able to let go of the golf club or doorknob.
Friedreich ataxia
Caused by GAA repeat expansion
- Friedreich ataxia is an AR disorder on chromosome 9, with an expansion of GAA (Friedreich AtaxiA).
- USMLE wants you to know the gene is called frataxin. Do NOT confuse this with Fragile X, which is the FMR1 gene.
HY findings
- May present with cardiomyopathy. Sources differ as to whether hypertrophic or dilated is more common. But the USMLE will give you a clear presentation as to which one they’re referring to.
- If hypertrophic, the patient will have a severely thickened LV and (often) an S4 heart sound; there will be diastolic dysfunction (↑ diastolic filling pressure + preserved ejection fraction). If dilated, there will be a lateralized apex beat / apical impulse, a dilated cardiac silhouette, and an S3 heart sound.
- Early-onset T2DM is a notable feature.
- Kyphoscoliosis and pes cavus (high-arched foot) are HY.
- The disorder is characterized by (obviously) ataxia, Babinski reflexes, dysarthria, and hammer toes (contraction deformity of toes).
Inheritance pattern and molecular understanding are really HY for USMLE
- Both Duchenne and Becker are X-linked recessive.
- Caused by mutations in the dystrophin gene (DMD).
- Dystrophin is a large cytoskeletal protein inside skeletal muscle that stabilizes the cytoskeleton with the extracellular matrix.
- Dystrophin binds to a transmembrane protein called beta-dystroglycan.
- The dystroglycan-dystrophan complex is necessary for normal skeletal muscle cell integrity.
| USMLE wants you to know that Duchenne is usually caused by a frameshift mutation (i.e., 1 or 2 bp deleted or inserted).
In contrast, Becker is usually not caused by a frameshift (i.e., a missense mutation, or deletion/insertion in repeats of 3 bp, etc.). |
Age of onset and the Gower maneuver
- You need to know that Duchenne is worse than Becker.
- Questions on Duchenne will almost always mention a young boy, whereas for Becker they’ll almost always mention a teenager or adult.
- Boys who have Duchenne classically exhibit the Gower maneuver. This is described as walking backwards with the arms in order to stand up. You will not see the Gower maneuver being described in a patient with Becker; on the Step1, this is Duchenne only.
Psuedohypertrophy and affected muscles
- All hypertrophy that occurs is followed by pseudohypertrophy, which is fibroadipose deposition in the muscle.
- Despite the seemingly enlarged muscle size, patients progress to profound weakness.
- Asymmetrical weakening of paraspinal muscles leads to kyphoscoliosis.
- The USMLE-tested cause of death from both diseases is cardiomyopathy/heart failure.
| Pseudohypertrophy = fibroadipose replacement of the muscle.
Biopsy shows fibrous and fatty tissue; it also shows variation in fiber diameter and ↑ # of internalized nuclei + fiber regeneration / degeneration. |
- The muscular dystrophies tend to affect pelvic girdle muscles and calves first.
- If they ever ask you which location the weakness starts first, and calves and hips are both answers, hips are correct over calves.
- Most students get this wrong because these patients are classically photographed for having massively hypertrophied calves, but the calves are typically not the first place affected.
Miscellaneous
- One last point about the DMD gene is that it is the longest human gene. This means if they ever ask you which gene would be most likely to undergo a spontaneous mutation, the answer is DMD.
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Infants of diabetic moms –> five classic disturbances are possible in the neonate:
- Hypoglycemia
- Hypocalcemia
- Hypomagnesemia
- Hyperbilirubinemia
- Polycythemia
Calcium derangement is associated with QT prolongation in the neonate.
Hypoglycemia in the neonate is the answer when he/she has jittery movements.
