Vignettes

Question 1

Von Hippel Lindau:

• Most common manifestations? (4)
• Inheritance pattern?
• VHL and HIF-1-alpha mechanism normal?
• With hypoxia?
• With mutated or absent VHL?
• Leads to? (2)

Answer 1

• Vascular tumors, renal cell carcinoma, hemangioblastoma, pheochromoctytoma (adrenals), often multiple in single organ
• AD
• VHL targets HIF-a which is destroyed after ubiquitization
• HIF-B binds HIF-a and enters nucleus as a TF
• No regulation of HIF-a so it keeps acting as TF
• VEGF and PDGF

Question 2

Von Hippel Lindau:
- Practical implications?
- Leads to?
- 60-70% of clear cell kidney cancer have inactivation of what? How?
- New treatments target what? Not what?
- Two therapies typically used?
2 New Treatment agents:
1.) Sorafenib: Type of drug? Target what? (2) Complete response? Side effects? (2)
2.) Sunitinib: Type of drug? Type of response? Side effects?

Answer 2

• VHL is often sporadically mutated
• Renal cell carcinomas
• VHL alleles; hypermethylation
• Downstream stuff; HIF which hasn’t worked
• mTOR inhibitors and monoclonal antibodies against VEGF

1. ) Oral kinase inhibitor; RAS and VEGFR; rarely; skin disease and diahrea
2. ) Oral tyrosine kinase inhibitor; rarely; skin disease and diahrea

Question 3

Multiple Sclerosis:

• What is nerve conduction?
• Consequences of demylenation? (3)
• Symptoms of MS? (6)
• Therapies? (2) How they work? Names of drugs? (3)
• Why target B cells instead of T cells?

Answer 3

• Electric transmission of messages from brain to muscles via action potentials
• 1.) Neuron damage 2.) Decreased conduction speed 3.) Proliferation of Na+ channels along axon
• Walking impairment, spascicity, cognitive impairment, bladder dysfunction, pain, brain lesions
• 1.) Na+ Channel blockers preserve axons = phenytoin, flecainide, dalframpadine
  2. ) K+ channel blockade increase conduction of AP by inhibiting K+
• Bigger effect by blocking the immune response

Question 4

DKA:
- 8 steps of insulin release?

• Clinical symptoms? (5)
• 4 things to test for?
• Action of insulin in liver?
• Action of insulin in muscle?
• Action of insulin in adipose tissue?

Answer 4

1. ) Beta cells produce insulin 2.) Glucose enters via Glut2 transporter 3.) Glucose metabolized via glycolysis (inc. ATP) 4.) Incr. ATP inhibits K+ channels 5.) Incr. K+ depolar. cell 6.) This activates Ca2+ channels to open 7.) Increased Ca2+ in cell leads to ER release of more Ca2+ 8.) Leads to exocytosis of insulin
   - Polyuria, polydipsia (drink a lot), rapid breathing, nausea, vomiting
   - Blood glucose, venous PH, Bicarbonate, K+
   - Increase glucose uptake; increase lipogenesis
   - Increase glucose uptake; increase protein synthesis
   - Increase glucose uptake; increase triglyceride uptake; increase lipid synthesis

Question 5

DKA:

• New sources of energy with insulin deficiency? (3)
• Equation being affected?
• Deep respirations called?
• How to treat? (3)
• Major concern? Tested for how? Therapy that may help?
• Why might blood K+ appear normal?

Answer 5

• lipolysis, fatty acid oxid., ketoacids
• H+ + HCO3- –> H2CO3 –> H2O + CO2
  Increased H+ due to ketoacids; H+ is also exchanged with K+ which leaves in urine
• Kausmaul respirations
• Insulin, IV fluids, K+
• Cerebral Edema; dilated pupils via occ. n.; mannitol therapy
• Being release in urine

Question 6

Cholera:

• Clinical features? (4)
• Molecule composition of cholera toxin?
• Molecular progression? (3)
• How does oral rehydration therapy work?
• One CFTR mutation?
• Prevention? (3)

Answer 6

• watery feces, vomiting, severe dehydration, skin turgor w/ pinch test
• a subunit = active unit; b subunit = transport unit
• 1.) B subunit binds to eneterocyte 2.) a subunit causes increase in cAMP which activates CFTR channel 3.) Cl- flows into intestines with water
• 1.4:1 glucose: Na+ work with solute coupled receptors in lumen
• May protect against cholera
• hand washing; clean water; food safety

Question 7

Li-Fraumeni:

• Increases what? Inheritance pattern?
• About 70% affect? Types of tumors? (4)
• About 40% p53 affected for what?
• Benefits of IDing it early? (3)
• Criteria for LFS? (3)
• Cirteria for LFL? (3)
• Follows what theory?
• Functions of p53? (3)

Answer 7

• cancer suseptibility, AD
• p53; Solid tumors = sarcomas, lymphomas, leukemias, adreno cortisol
• Li Fraumeni like syndrome
• avoid delay with second tumor, avoid radiation, prenatal advice
• 1.) proband with sarcoma before 45 AND
  2. ) 1 deg relative with any cancer under 45 AND
  3. ) 1 or 2 deg with any cancer under 45 or sarcoma at any age
• 1.) proband with childhood cancer or sarcoma before 45 AND
  2. ) 1 deg relative with any cancer under 45 AND
  3. ) 1 or 2 deg with any cancer under 60
• 2 hit theory
• protects against carcinogens and uv radiation; regulates expression of many genes, regulates miRNA’s