Block 30

Question 1

Multiple myeloma effect on Ca+ metabolism

Answer 1

Hypercalcemia in MM is the result of osteolysis induced by tumor cells, which release osteoclast activating factor.

• elevation of Ca+ leads to decreased PTH —> low levels of PTH -> increased Ca+ in urine.
• hypercalcemia and light chain nephropathy in MM causes progressive renal failure. This leads to depletion of 1a hydroxylase, the activity of which is already supressed by hyperphosphatemia and low PTH —> low 1,25 dihydroxyvitamin D levels

Question 2

PTH related protein

Answer 2

Its the most common cause of hypercalcemia in malignancy.

Question 3

Nitrates side effects

Answer 3

Main adverse effects seen are

• headache
• cutaneous flushing
• lightheadedness
• hypotension
• reflex tachcardia.

Question 4

Anaphylaxis

Answer 4

Triggers:
-food
-medication
-insect stings
Clinical manifestation:
-cardiovascular -> hypotension and edema with tachcarida
-respiratory -> stridor hoarsness and wheezing
-cutaneous -> urticarial rash, pruritus, flushing
-GI -> nausea,vomiting, and abdominal pain.
Tx:
-intramuscular epinephrine
-airway management
-adjuvent therapy such as antihistaminic and steroids.

Question 5

Anaphylaxis pathophysiology

Answer 5

It result from widespread mast cell and basophil degranulation and resultant histamine and tryptase release.

• tryptase is an enzyme that is relatively specific to mast cells and elevated serum levels support diagnosis of anaphylaxis.
• anaphylaxis occurs usually within minutes or seconds after intravascular exposure to an inciting factor, but can take up to 2 hours in oral trigger.

Question 6

Fructose 2,6 bisphospate and glucose metabolism

Answer 6

It helps to control the balance between gluconeogenesis and glycolysis, through inverse regulation of PFK-1, and 1,6 bisphosphatase. Fructose 2,6 bis activates PFK-1 the main ergulatory enzyme involved in glycolysis, which converts fructose 6 phosphate into fructose 1,6 bisP.
-this substrate is inolved in increasing glycolysis thus decreasing gluconenogenesis.( inhibit conversion of alanine to glucose )

Question 7

Thyroid cancer - nests of polyglonal cells with congo red positive deposits

Answer 7

Medullary cancer

Question 8

Thyroid cancer - branching structure with interspersed calcified bodies (psammoma bodies)

Answer 8

Also follicular hyperplasia with tall cells forming interfollicular projections is found in papillary thyroid cancer

Question 9

High affinity IgE receptor is

Answer 9

Found on most mast cells and basophils and plays a primary role in mediating the allergic response. The receptor normally binds the Fc portion of circulating IgE , coating the cell with various antigen specific IgE molecule

• when a multivalent antigen comes in contact with the cell, multiple IgE antibodies become cross linked resulting in aggregation of the FcERI receptors on mast cell surface.
• this clumping of receptor leads to activation of non-receptor tyrosine kinases triggering an intracellular cascade that ultimately results in mast cell and basophil degranulation.

Question 10

Insulin acts on which receptors

Answer 10

• the surface receptor for insulin is transmembrane receptor protein with intrinsic tyrosine kinase activity in its cytoplasmic domain.
• insulin binding activates tyrosine kinase, leading to phosphorylation of insulin receptor substrate 1(IRS-1).
• activation of PI3K stimulates metabolic functions such as translocation of GLUT-4 to cell membrane, glycogen synthesis and fat synthesis.

Question 11

How insulin stimulate glycogen synthesis

Answer 11

PI3K stimulation promotes glycogen synthesis by activating protein phosphatase, enzyme that dephosphorylates glycogen synthase leading to its activation, and inhibit glycogen phosphorylase.

Question 12

Adenosine mechanism of action

Answer 12

It affect phase 4 of the action potential of pacemaker, reducing the rate of spontaneous depolarization in cardiac pacemaker cells.

• adenosine interacts with A1 receptors on the surface of cardiac cells, activating K+ channels and increasing K+ conductance, causing membrane hyperpolarization.
• it also inhibits L-type Ca+2 further prolonging depolrization time.
• this result in slowing the Sinus rhythm and increase AV conduction delay.

Question 13

Risk factor for nephrolithiasis

Answer 13

Dietery intake:
-low fluid
- low calcium
-high oxalate
-high protein
-high sodium
- high fructose 
Diseases: 
1. increased PTH 
2. Chrons disease 
3. Distal renal tubular acidosis (hypo-citrate-uria)
4. Gout

Question 14

S.aureus normally present in

Answer 14

-commonly found in the nares.(epidimiologist usually check the nares for colonization)

Question 15

Meckles diverticulum - mucosa of other organs present in it is a termed

Answer 15

Ectopy (not metaplasia), normally functioning cells in abnormal location

Question 16

C.perferingis toxin

Answer 16

-lecithinase is the main toxin for c.perferingis, (also known as phospholipase C ) catalyzes the splitting of phospholipid molecules. It hydrolyzes leciithin containing lipoprotein complexes in the cell membranes causing cell lysis including erythrocyte hemolysis, tissue necrosis and edema.

Question 17

Respiratory acidosis - heroin abuse

Answer 17

Acidosis can be acute or chronic, increased pCO2 leads to increase in hydrogen ion concentration in the body. The kidney attempt to compensate for this by increasing renal excertion of hydrogen ions.

• the process of compensation requires 3-5 days to have maximal effect, therefore it typically isnt seen in cases of acute respiratory acidosis.
• heroin overdose is an acute event, it suppresses respiratory centers and cause hypoventillation with CO2 retention.
• in case of high HCO3 with high PCO2 the case is of chronic respiratory acidosis and heroin abuse is unlikely to be the cause.

Question 18

Wilson disease

Answer 18

Autsomal receesive mutation of ATP7B- > hepatic copper accumulation -> leak from damged hepatocytes -> deposits in tissues (basal ganglia, cerbellum)
- clinically : 1. Hepatic (cirhosis, failure etc…)
2. Neurologic (parkinsonism, gait disturbances and dysarthria)
3. Psychiatric (depression, personality changes ..)
-diagnosis : - decreased ceruoloplasmin, and urinary copper excertion
-kayser fliescher rings
-increased copper in biopsy
Treatment :
- zinc and chelators ( d-pencillamine, trientine)

Question 19

Canagliflozin

Answer 19

New class of oral antidiabetic, that inhibits SGLT2 (leads to urinary loss of glucose)

• side effects include UTI and genital mycotic infection due to glucosuria, increased osmotic diuresis can also cause osmotic diureseis seen as hypotension.
• it should be avoided in patients with moderate to severe renal impairment due to lack of efficacy and increased risk of adverse effect.

Question 20

Zinc finger is present in

Answer 20

The zinc finger structure represent the most commonly identified DNA binding domain in humans.

• many transription factors use multiple zinc finger motifs to recognize specific genes and alter their activity.
• although most hormones alter transcription regulation to some degree, only intracellular receptors located in the cytoplasm or nucleus can act directly as transcription factor.
• these intracellular receptors typically bind lipid soluble hormones because the ligand has to diffuse across the cell membrane to reach the receptor. Once bound to their ligand these receptors bind directly to target DNA sequences via zinc fingers to regulate gene expression.
• examples include steroids, thyroid hormones and fat soluble vitamin receptors.

Question 21

Termination of protein synthesis uses >

Answer 21

-stop codon, stop codon doesn’t code for any amino acid or bind tRNA rather when the ribosome encounters stop codon, releasing factor proteins bind to the ribosome and stimulate release of the formed polypeptide chain and dissolution of the ribosome mRNA complex.

Question 22

Clomiphene use in PCOS

Answer 22

Is a selective estrogen receptor modulator that prevents negative feedback inhibition on the hypothalamus and pituitary by circuating estrogen , resulting in increased gonadotropin production and ovulation.
-used for pregnancy induction in PCOS

Question 23

Glucagon action on reversing beta blockers

Answer 23

Glucagon acts on G-protein coupled receptors, increasing intracellular cAMP and thus increasing release of intracellular calcium during muscle contraction. This increases HR and cardaiac contractility.

Question 24

Folinic acid (drug)

Answer 24

(Also called Leucovorin) can reverse Methotrexate toxicity if given early, it serves as a reduced form of folic acid though not to require DHFR to become THF and is therefore unaffected by Methotrexate.
-in addition when used in combination with 5-fluouracil, it poteintiates the cytotoxic effect of 5-fluouracil (by binding thymidylate synthease)
And is frequently included in colorectal cancer chemotherapy regimins.

Question 25

SSRI most important side effects

Answer 25

- it can cause sexual dysfunction in up to 50% of patients which include decreased libido, arousal ,anorgasmia in women and increased ejaculation latency in men. - if a patient develop sexual dysfunction and wishes to change the drug the first drug of choice is bupropion, its also causes less weight gain than other antidepressants.

Question 26

Vascular and immunologic manifestation of infective endocarditis.

Answer 26

Vascular phenomenoa: -systemic embloi (cerberal, pulmonary, or splenic infarcts) -mycotic aneurysm -janeway lesions - macular, erythmatous, non-tender lesion on the palms and soles Immunologic phenomenon: -osler nodes : painful, violaceous nodules seen on fingertips and toes. - roth spots : edematous and hemorrhagic lesion of the retina.

Question 27

Pioglitazone side effect

Answer 27

Weight gain and edema

Question 28

Substance used in hypotension that can increase PVR, increase SBP, decrease pulse pressure and decrease HR

Answer 28

Phenylephrine.

Question 29

M.pneumoniae can lead to (beside pneumonia)

Answer 29

-anemia, due to the complement mediated intravascualr hemolytic anemia due to the similarity between antigens in the cell membrane of M.pneumoniae and the cell membrane of erythrocytes (I-antigen). Elevated levels of the cross reacting IfM antibodies called cold agglutinins due to their ability to agglutinate erythrocytes in vitro at low temperature can help diagnose mycoplasma infection. -evidence of hemolytic anemia, positive coombs and elevated reticulocytes can also be seen. After a immune response have faded the concentration of cold aglutinins decrease an anemia resolves. -M.pneumoniae can also lead to SJS, joint pain, encephalitis, cardiac rhythm disturbances and bullous myringitis

Question 30

Tinel signs and phalen signs

Answer 30

Seen in carppel tunnle syndrome Tinel sign : tapping over the flexor surface of the wrist reproduces symptoms Phalen sign: flexion of wrist reproduces symptoms.

Question 31

Heriditary non polyposis colon cancer (lynch) is associated with what mutation

Answer 31

MSH 2, MLH 1 , MSH 6, and PMS2 (Not APC as that is associated with familial polyposis). -the mutation is present in gene responsible for DNA mismatch repair (MSH2) . The product of these genes proofread DNA during replication. Patients usually have mutation in allele and mutation of the second allele occurs during adult life.

Question 32

Drugs associated with acute pancreatitis

Answer 32

Azathioprine ,sulfasalazine, furosemide , valproic acid

Question 33

Major dopaminergic pathways

Answer 33

1. Mesocortical 2. Mesolimbic 3. Nigrostriatal 4. Tuberoinfundibular

Question 34

Poor prognostic factors in liver cirrhosis patients

Answer 34

- hypoalbuminemia | - prolonged prothrombin time

Question 35

Hypoxic vasoconstriction phemomenon

Answer 35

Vascular resistnace in pulmonary vasculature, is decreased in well aerated alveoli compared to undervetilated alveoli. - this occur so that blood flow is diverted away from under-ventilated regions of the lung and toward better ventilated areas where gas exchange occur more efficiently, thereby decreasing physiological shunting. - the relationship between tissue hypoxia and vascular resistance is reversed in the systemic circulation where it ensures that hypoxic tissue receives increased blood flow.

Question 36

Myopia and presbyopia

Answer 36

- when a patient with a history of myopia(image focus in front of the retina) gets older he might develop presbiopia in which image focuses behind the retina. - these cases combined together can lead to image focusing on the retina due to 2 opposite alteration. And patient will report of better vision.

Question 37

Pulmonary abscess

Answer 37

Local suppurative collection within lung parenchyma that result in necrosis of surrounding lung tissue. - if the abscess cavity communicates with an air passage the semiliquid exudate within will partially drain, creating and air containing cavity that can be identified on chest radiograph. - destruction of lung parenchyma within the abscess cavity is seen , this is due to release of lysosomal enzymes by neutrophils and macrophages. - the lyzozomal enzymes serve to digest the offending pathogens and tissue debris.