General to know

Question 1

Down syndrome comorbidities (neuro, cardio, GI, endocrine, oncologic, orthopedic)

Answer 1

Question 2

What are stress-related mucosal diseases, and how do Curling and Cushing ulcers differ in cause and location?

Answer 2

• Definition: Acute gastric mucosal damage due to severe physiologic stress (e.g., shock, burns, sepsis, trauma, intracranial injury).
  
  • Pathogenesis: Impaired mucosal protection from local ischemia due to hypotension and vasoconstriction.
  • Curling ulcers: Proximal duodenum ulcers from severe trauma/burns.
  • Cushing ulcers: Esophagus/stomach/duodenum ulcers from intracranial injury, caused by vagus nerve stimulation → ↑ ACh → ↑ acid secretion.

Question 3

Label this image

Answer 3

Question 4

Label this image

Answer 4

Question 5

How do additive, synergistic, and permissive effects differ in pharmacology or physiology?

Answer 5

• Additive effect: Combined response equals the sum of individual effects (e.g., 1 + 1 = 2).
  
  • Synergistic effect: Combined response exceeds the sum of individual effects (e.g., 1 + 1 > 2).
  • Permissive effect: One agent has no direct effect but allows another to exert its maximal effect (e.g., 1 + 0 > 1).

Question 6

Main culprits of drug induced lupus erythematous

Answer 6

Question 7

Symptoms of anticholinergic toxicity

Answer 7

Question 8

What is germline mosaicism?

Answer 8

Germline mosaicism means that a parent has a genetic mutation in some of their egg or sperm cells, but not in the rest of their body. This means:

The mutation is not detectable in the parent’s blood or somatic cells, so routine testing will show no mutation.

However, the parent can still pass on the mutation to their children if affected germ cells are used during fertilization.

Question 9

When should germline mosaicism be suspected in genetic diseases?

Answer 9

When multiple offspring are affected by the same genetic mutation, but the parents are unaffected and testing of their somatic cells is negative, suggesting the mutation is confined to germ cells.

Question 10

What is somatic mosaicism?

Answer 10

Somatic mosaicism refers to the presence of two or more genetically distinct cell lines within the same individual, arising from a mutation that occurs after fertilization during embryonic development. Unlike germline mosaicism, these mutations affect only somatic (non-reproductive) cells and are not passed on to offspring.

The earlier in development the mutation occurs, the more tissues and organs will carry the altered genetic material. Somatic mosaicism can lead to localized disease or segmental expression of a disorder, and its clinical presentation depends on the distribution and proportion of mutant cells in the body.

Question 11

MoA of tyrosine kinase receptors

Answer 11

Dimerization of 2 identical receptor subunits = self-phosphorylation = downstream activation

Question 12

Difference between receptor vs non-receptor tyrosine kinase

Answer 12

*Receptor tyrosine kinase: The receptor itself has intrinsic tyrosine kinase activity in its intracellular domain.

*Non-receptor: require another molecule (e.g. JAK) for phosphorylation: Ligand binding still causes dimerization, which activates JAK, which then phosphorylates tyrosines on the receptor. This allows STAT proteins to bind, become phosphorylated, and then translocate to the nucleus to alter gene expression.

Question 13

Examples of receptor tyrosine kinases vs non-receptor tyrosine kinases

Answer 13

Receptor: epidermal growth factor receptors, insulin
NR: EPO receptor