Block 38

Question 1

Systemic mastocytosis

Answer 1

Clonal mast cell proliferation occurs in the bone marrow, skin, and other organs. Mast cell proliferation often is associated with mutation in the KIT receptor tyrosine kinase.
-these cells are characterized by prominenet expression of mast cell tryptase.
-excessive histamine release from degranulation of mast cells mediates many of symptoms of the disease such as syncope, flushing, hypotension, pruritus and urticaria. In addition, histamine induces gastric acid secretion, which can lead to gastric ulceration. The excess acid also inactivates pancreatic and intestinal enzymes, causing diarrhea. Other GI symptoms include nausea, vomiting and abdominal cramps.
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Question 2

PV

Answer 2

Presents with increased RBC mass, increased plasma volume, and low EPO levels with normal O2 saturation(only altered in seconday polycythemia due to lung injury).

• additional manifestation include elevated platelet and/or WBC count, thrombotic events, peptic ulceration and pruritus(histamine release from basophils), and gouty arthritis (increased cells turnover).
• plethora, ruddy face and splenomegaly is common.
• the mutation replace valine with phenylalanie at 617 gene position in JAK2 gene rendering the hematopoietic cells —> “sensetive to growth factors”

Question 3

L.monocytogenes

Answer 3

Its a facultative intracellular organism that can cause signficant disease in patients with cell mediated immunodeficiency, including infants, HIV patients, organ transplant recipient and certain malignancy patients.

• clinical syndrome include febrile gastroenteritis, septicemia and meningoencephalitis. Infection in pregnant women can lead to amnionitis with neonatal sepsis or fetal demise.
• its a common organism in the intestinal tract of cattle and can be transmitted via milk. Outbreak are associated with dairy products(soft cheese, milk , ice cream) also raw fruit or meat.

Question 4

Tay sachs disease

Answer 4

Is autosomal recessive neurodegenerative disease commonly seen in ashkenazi jewish population. Tay sachs is caused by ß-hexosaminidase A deficiency which results in accumulation of the cell membrane GM2 ganglioside within lysosomes.

• affected nfants typically have normal development in first few months followed by progressive neurologic deterioration.
• weaknes, hypotonia, seizures, spasticity and blindness.
• the center of fovea appears bright red (cherry red macula spot)
• patients have no hepatosplenomegaly

Question 5

Hypermethioninemia due to homocysteinuria , which amino acid is essential for these patients

Answer 5

Cysteine

Question 6

Mefipristone

Answer 6

Progesterone and glucocorticods antagonist

• can be used to terminate pregnancy—> apoptosis and necrosis of uterine decidua.
• when misoprostol (PG E1 agonist) is used along mefipristone there is increased success rate.

Question 7

Minute ventilation
Alveolar ventilation
Dead space

Answer 7

Minute ventilation= tidal volume X breath/min
Alveolar ventilation is volume of new air reaching the gas exchange areas per minute. Therefore it doesnt include dead space volume. (Alveolar ventilation = minute ventilation -deadpace volume.
Physiologic dead space is total dead space in lung. It consist of anatomic dead space of conducting system (approximately 150 ml) and alveolar dead space due to well ventilated but poorly perfused alveoli.

Question 8

Prolonged cortiocsteroids therapy

Answer 8

Chronic glucocorticod use is charactrized by low CRH, ACTH and cortisol levels that cannot rise in response to stressful stimuli.
This lack of stress response can result in relative glucocorticod deficiency even when the patients baseline glucocorticod regimen is maintained.

Question 9

Fibrotic focus in lower love of lung in conjunction with calcified lymph node

Answer 9

It can occur in primary TB.
Lower lung lesion (ghon focus) accompanied by ipsilateral hilar adenopathy is described as ghon complex.
The ghon complex occurs during initial infection with M. Tuberculosis.

Question 10

Obstructive sleep apnea stimulation therapy

Answer 10

Stimulation of hypoglossal nerve using an implantable nerve stimulator causes the tongue to move forward slightly, increasing the anteroposterior diameter of airways

Question 11

Vascular access during cardiac catheterization from common femoral artery can predispose to

Answer 11

-arterial puncture above the inguinal ligament increases the risk of retroperitoneal hemorrhage.

Question 12

Highly charged drugs

Answer 12

The volume of distribution refers to the hypothetical volume of fluid into which administred drug would need to be uniformly distributed to produce the observed plasma concentration.
- low volume of distribution indicates that the drug have high molecular weight, high plasma protein binding, high charge and hydrophilicity tend to trap the drug in plasma compartment rather than intracellularly

Question 13

RNA dependent DNA polymerase activity is seen in DS DNA circular virus

Answer 13

Hepatitis B

Question 14

Maternal serum AFP screening

Answer 14

High MSAFP:
1. Open neural tube defects
2. Ventral wall defects
3. Multiple gestation
Low MSAFP:
1. Trisomy 18 , 21 (aneuploidies in general)
2. Dating error( search for history of irregular menses)

Question 15

Combination of nicotinic and muscarinic blockade is highly suggestive of

Answer 15

• clostridium botulinium toxin.
• the toxin inhibit Ach release from presynaptic nerve terminals at the neuromuscular junction, thereby preventing muscular contraction.
• this effect can be seen on EMG as decrease in the compound muscle action potential following stimulation of motor nerve.
• high rate, repetitive nerve stimulation improves the deficit as the rapid depolarization rate increases calcium concentration in the presynaptic nerve terminal.
• classic 3d’s occur —> diplopia , dysphagia and dysphonia within 12-36 hours of consumption.

Question 16

AChE increase in amniotic fluid is present in

Answer 16

Neural tube defects

Question 17

Lacunar infarcts -syndrome result example

Answer 17

1. Pure motor hemiparesis —> posterior limb of internal capsule or basal pons
2. Pure sensory stroke —> VPL or VPM thalmus nuclei
3. Ataxia-hemiplegia syndrome —> posterior limb of internal capsule
4. Dysarthria clumsy hand syndrome -> genu of the internal capsule or basal pons.

Question 18

Sertraline

Phenelzine

Answer 18

SSRI and MAO inhibitor respectively . Combination of the 2 can cause serotonin syndrome. 2 weeks should be free of drugs after MAO inhibitor drug in order to establish monamine oxidase enzyme.

Question 19

Potency of inhalation drug is determined by

Answer 19

The minimum concentration of a drug in the brain necessary to achieve an adequate level of anesthesia. When an inhaled anesthetic is administered at a constant rate over prolonged time , its partial pressure in the brain equals its partial pressure in other compartment.

• potency is inversly proportional to MAC.
• MAC depends on body temperature and age of the patient

Question 20

Panic attack treatment in emergency

Answer 20

Benzodiazepines which is a drug that binds allosterically to the GABA receptor. —> increased frequency of chloride ion channel opening —> neuronal hyperpolarization and inhibition of Action potential.
-barbiturates on high doses have same effect, on lower doses prolongs the channel opening in response to GABA.

Question 21

Spasticity due to MS

Answer 21

Spasticity is defined as an increase in resistance to passive muscle movement or a velocity dependent increase in tonic strech reflexes. Its a common problem in MS patients and manifests clinically as muscle stiffness, painful muscle spasm, scissoring gait and lack of dexterity. The loss of descending inhibitor control form the upper motor neuron results in lower motor neuron overactivity leading to increased tone and hyperreflexia.

• baclofen, an agonist of GABA-B receptor is effective for the treatment.
• tizanidine (a2 agonist) is also useful.

Question 22

Hypocalcemia sings

Answer 22

• tingling, numbness
• trosseaus
• chevostek sign
• muscle spasm
• seizures

Question 23

CREST syndrome

Answer 23

• presence of anti centromere antibodies
• Calcinosis
• Raynauds phenomenon
• Esophageal dysmotility
• Sacrodactyly
• Telengectasia

Question 24

Angiogenesis is predominantly driven by 2 substances

Answer 24

1. vascular endothelial factor : VEGF stimulates angiogenesis in a variety of tissues. As VEGF increases endothelial cell motility and proliferation, new capillaries begin to sprout.
2. Fibroblast growth factor: FGF-2 is produced by a wide range of cells and is involved in endothelial cell proliferation, migration and differentiation. It appears to play important role in embryogenesis by stimulating angioblast production.

Question 25

Previously infected infleunza virus individuals are protected from further infection due to antibodies against

Answer 25

Hemaglutinin.

Question 26

PSGN is seen as ? In EM

Answer 26

- subepithelial deposits, - IgG and C3 - lumpy bumpy appearance on IF

Question 27

Myocardial hibernation

Answer 27

Refers to a state of chronic myocardial ischemia in which both metabolism and function are reduced to match concomitant reduction in coronary blood flow. This new equilibrium prevent myocardial necrosis. The changes include decreased expression and disorganization of contractile and cytoskletal proteins, altred adrenergic control and reduced Ca+ responsiveness. -these changes lead to decreased contractility and LV systolic dysfunction. However coronary revascularization improves contractility and LV function.

Question 28

Cytokeratin and HER2

Answer 28

Is found in epithelial cells Its commonly used immunohistochemical marker for epithelial dervied tumors such as breast cancer. -HER2 oncogene codes for human epidermal growth factor receptor with tyrosine kinase activity in the intracellular domain. -epithelial carcinoma that overexpress HER2 demonstrate increased proliferation and resistance to apoptosis.