Block 34

Question 1

Erythromycin effect on P450

Answer 1

Its a C-P450 inhibitor

Question 2

Trastuzumab

Answer 2

Is a monoclonal antibody used in the managment of breast cancer with HER2 positive.

• it binds to a portion of extracellular domain of HER2 and prevents activation of a transmembrane tyrosine kinase.
• this downregulates cellular proliferation and promotes apoptosis.
• approximately 20% of all invasive breast cancers overexpress HER2, this can also be found in other solid tumors.

Question 3

Colchecine side effects

Answer 3

Due to the fact that it inhibits microtubule formation it leads to diarrhea many times, less commonly nausea, vomiting and abdominal pain.

Question 4

Secondary lactose intolerance

Answer 4

• it due to secondary lactase deficiency, an aquired condition resulting from inflammation/infection, overgrowth and infectious enteritis that causes injury to the mucosal brush border of the small bowell where lactase is expressed.
• the fermentation of undigested lactose by gut bacteria leads to increased production of short chain fatty acids that acidify the stool(decrease PH).
• during this process hydrogen gas is also produced leading to increased breath hydrogen content.
• in addition the high amounts of undigested lactose in the bowel lead to elevated stool osmolarity which attracts excess water in the bowel lumen causing osmotic diarrhea.

Question 5

What is the most common type of kidney stones

Answer 5

Calcium stones represent 75-80% of all renal caliculi.

-the most common cause of kidney stones are hypercalciuria with normal calcemia in blood.

Question 6

Cancer cell cycle

Answer 6

M- cell division - vinca alkaloids and taxanes (vincristine)
G1- organele duplication
S- synthesis - antimetabolites
G2- DNA damage and repair - bleomycin and doxurubicin

Question 7

Infective endocarditis renal involvment

Answer 7

• elevated creatine and hematuria and proteinuria suggest renal insufficiency due to nephritic syndrome.
• in some patients of infective endocarditis may be complicated by depositibo of circulating immune complexes in the glomelular capillary wall resulting in glomerulonephritis.
• this can be seen as capillary wall thickening with sub endothelial and sub epithelial deposit formation.
• hypercellularity similar that seen in PSGN or MPGN

Question 8

Aplastic anemia

Answer 8

• fatigue,weakness, conjuctival pallor and decreased hemoglobin suggestive of anemia
• bruising not associated with trauma, suggest thrombocytopenia
• high lipid content of the bone marrow aspirate suggestive of hematopoietic cell aplasia or hypoplasia.
• as with most anemia, increased production of erythropoietin by the kidney would be expected.

Question 9

Tumor lysis syndrome(TLS)

Answer 9

Oncologic emergency. It often develops during chemotherapy for high grade lymphomas, leukemia and other tumors that have rapid cell turnover and high sensitivity to chemotherapy.

• when a lrage number of tumor cells are destroyed during chemotherapy, intracellular ions such as K+, uric acid, and phosphorus are released into serum and to kidney,
• uric acid at physiologic PH is soluble, but precipitates in acidic environment, the lowest PH in the nephron is found in the distal tubule and collecting ducts so these are the segments of nephron that may become obstructed by uric acid crystals.
• the risk of TLS can be reduced by urine alkalization and hydration.
• allupurinol is used to reduce uric acid production during breakdown of tumor cells.

Question 10

Sickle cell disease, spleen changes

Answer 10

• sickle cell disease leads to splenic infarctions, however repeated infarctions eventually leads to significant scarring, fibrosis and atrophy of the spleen which is likely to present in adults.
• in the long term sickle cell anemia can cause macrocytic anemia due to the fact that it needs high folate in erythrocytes turnover.

Question 11

Enterococcal endocarditis

Answer 11

Usually occur in elderly men who have recently undergone manipulation of areas colonized by this organism.

• the genitourinary tract is the most common portal of entry, GI or obstetric procedures are also risk factors.
• enterococci can also cause UTI, wound infection …
• enterococci are gamma hemolytic, catalase negative, PYR positive, lancified group D gram positive cocci that can grow in hypertonic saline and bile.

Question 12

Ivabradine mechanism of action

Answer 12

Its the only drug used in HF that can slow heartrate without any effect on contractility and relaxation.

• it slows the rate of sinoatrial node firing be selective inhibition of funny sodium channels, therapy prolonging the slow depolarization phase.
• ivabradine is used in certain patients with chronic HF with reduced ejection fraction and persistent symptoms despite appropriate medical therapy. It has been shown to reduce the risk of hospitalization due to HF.

Question 13

Marfan syndrome signs and symptoms

Answer 13

• taller slender body
• arachnodactyly
• breastbone dips inward or protrudes outward(sternum is inward)
• joint hypermobility
• increased arm to height ratio
• ectopic lens
• kyphosis and or scolisois

Question 14

Which substance is responsible for stimulation of the first step in gluconeogenesis

Answer 14

Pyruvate carboxylase —> oxaloacetate.

-its stimulated via increased Actyl-Coa

Question 15

Citrate is important in regulation of what enzyme in gluconeogenesis

Answer 15

-citrate is an important positive regulator of actyl-coa carboxylase and 1,6 bisphosphatase.

Question 16

Inhaled anasthesia leads to increase in

Answer 16

• increase in cerebral blood flow
• inhaled anesthetics have shown to affect K+ channels in the neuronal membrane and lock them in a state of hyperpolarization.
• in the brain these anasthetics lead to decrease vascular resistance and increase blood flow —> increased intracranial pressure.
• in kidneys they decrease GFR and RPF, and increase renal vascular resistance.
• they decrease hepatic blood flow
• all inhaled anesthetics except nitrous oxide are respiratory depressant, they decrease tidal volume and minute ventilation and causes hypercapnia, also they lead to decrease mucocilliary clearance -> postoperative atelectasis (halothone and sevoflurane -> bronchodilation, used in asthmatic patients)
• cardiovascular depression -> decreased CO and increase atrial and ventricular pressure

Question 17

Uretral circulation

Answer 17

• the proximal ureter is supplied via branches of the renal artery
• the distal ureter, arterial blood supply arises from superior vesical artery.
• in between (the middle ureter) the arterial supply is anasmotic and highly variable with possible afferent branches from gonadal, common and internal iliac, aorta and uterine arteries

Question 18

Aortocavitary fistula

Answer 18

• uncommon complication of infective endocarditis caused by extension of the infection from the valve to the adjacent myocardium.
• during normal cardiac cycle, central aortic pressure (120/80) is higher than right ventricular pressure (25/5) during systole and diastole, thus a fistula between the two will most likely lead to continuous flow from aorta to the right ventricle

Question 19

Ecchymosis

Answer 19

Cutaneous or subcutaneous collection of extravasated blood measuring at least 1 cm in diameter. They sometimes indicate a deep hemorrhage due to bony fracture, ligamentous rupture or muscular injury.
-petichiae are small (5mm in diameter)

Question 20

Nitrates mechanism of action

Answer 20

• metabolized within vascular smooth muscle cells to nitric oxide
• activates guanylate cylase and promote GTP —> cGMP.
• increased levels of cGMP —> decreased intracellular Ca+.
• this promotes myosin light chain dephosphorylation and vascular smooth muscle relaxation.

Question 21

Ribosomes function in the cell

Answer 21

They are cellular organelles that synthesize proteins.

• each ribosome consist of 2 subunits
• 40S is responsible for binding the mRNA
• 60S unit contains peptidyl transferase, the enzyme that catalyzes peptide bond formation between amino acids.
• all ribosomes begin protein translation in cytoplasm but some ribosomes translocate to the RER during protein synthesis depending on the proteins target destination,.
• attached ribosomes to the RER after protein tranlsation begins. They synthesize most secretory proteins, the integral membrane proteins of the nucleus and cell membrane and proteins within the ER, golgi network and lysosomes.
• the RER is particularly well developed in protein secreting cells. Ribosomes attach to the RER via translocon, a protein complex containing ribophorins that binds the large 60S subunit.

Question 22

Serratus anterior muscle injury

Answer 22

• this occurs due to long thoracic nerve injury, usually due to mastectomy with axillary lymph nodes removal.
• the function of serratus anterior is to stabilize and rotate the scapula upward.
• the deltoid and supraspinatous muscle abduct the arm up to the horizontal position, after ward trapizius and serratus anterior required to rotate the glenod cavity superiorly —> allowing complete abduction of the arm over the head.
• paralysis of serratus anterior causes scapular winging. (If a patient outstrechs the arm against a wall, the medial border of the scapula lifts off the thoracic wall and becomes prominent)

Question 23

Ventral posterior thalmus stroke

Answer 23

• thalamic stroke, the thalamic VPL nucleus recieves input from spinothalamic and dorsal coulms and VPM nucleus recieves input from trigiminal pathway. They send somatosensory projection to the cortex via thalamocortical fibers.
• damage to these nuclei may result in complete contralateral sensory loss.
• severe proprioceptive defects may cause unsteady gait.

Question 24

Lipohyalinosis and micratheromas are

Answer 24

• they are believed to be the primary cause of lacunar infarcts
• lipohyalinosis occurs secondary to leakage of plasma proteins through damaged endothelium and characterized by hyaline thickening of the vascualr wall, collagenous sclerosis and accumulation of mural foamy macrophages.
• microatheromas results from atherosclerotic accumulation of the lipid laden macrophages within the intimal later of a penetrating artery near its origin off the parent vessel.
• these changes predispose to small vessel occlusion and infarction of central nervous system tissue with liquefactive necrosis and formation of a fluid filled cavity.

Question 25

Lacunar infarcts

Answer 25

Lacunaes are small cavitary infarcts located within the basal ganglia, posterior limb of internal capsule,pons and cerbellum. - the infarcts results from occlusion of the small penetrating arteries that supply these deep brain structures most commonly in the setting of chronic uncontrolled hypertension or D.m

Question 26

Urinary Schistosomiasis

Answer 26

- its caused by schistosoma haematobium. - human acquire it via contact with infected freshwater. - the incubator animal is freshwater snails - once released the larvae can penetrate intact human skin -> liver -> mature into adults over weeks —> mesenteric venule of intestine (s.masnoni or s.japonicum) (diarrhea, abdominal pain, hepatomegaly )—> or the urinary bladder (s.haematobium)(urinary symptoms - dysuria and terminal hematuria )(hydronephrosis, pyelonephrosis and SCC of bladder )

Question 27

Cori disease

Answer 27

Debranchign enzyme deficiency -present at infancy , with hypoglycemia, ketosis, hepatomegaly. -hypotonia, muscle weaknsess, are characterestic and helps differntiating it from other diseases. -hepatic fibrosis is common but fat infiltration never seen, 0cytosolic accumulation of glycogen with abnormally short outer chains

Question 28

Aortic dissection presentation

Answer 28

- acute chest pain - hypertension is the primary risk factor - teat in the aortic intima - differences in BP in right and left arm

Question 29

Cholestatoma

Answer 29

Collection of squamous cell debris that form a round, pearly mass behind the tympanic membrane in the middle ear. - they can occur congenitally or develop in adults as either an aquired primary lesion or secondary to infection, trauma or surgery of the middle ear. - primary cholestatomas are the result of chronic negative pressure on the middle ear causing retraction prockets in the tympanic membrane that become cystic, as the squamous cell debris accumulates, a cholestatoma is fomed. - cholestatoma most commonly causes painless otorrhea. Also they can produce lytic enzymes and are often discovered when they erode throgh the auditory ossicle, causing conductive hearing loss.

Question 30

Smooth endoplasmic reticulum

Answer 30

It contains enzymes for steroid and phospholipid biosynthesis. - all steroid producing cells (adrenal cortex, liver and gonads) contains a well developed SER. - the SER also involved in detoxification of numerous drugs, especially in hepatocytes. In addition a specialized SER functions as the SR in striated muscle cells.

Question 31

Obesity related restrictive lung disease

Answer 31

Obesity alters respiratory compliance -> to compensate reduced compliance obese patients typically have increased respiratory rates with reduced tidal volumes (rapid-shallow breathing) - the most common indicator of obesity related disease is a reduction in expiratory reserve expiration. (ERV). - it has a minimal effect on RV, but FRV is reduced due to reduced ERV. - it can also reduce FVC, FEV1 and TLC .

Question 32

CSF pathway

Answer 32

Lateral ventricles -> foramen of monro -> third venticle -> aqueduct -> fourth ventricles -> foramina of lushcka and magendie -> subarachinoid space. -absorption by arachnoid granules —> venous sinuses.

Question 33

Urge incontinence is traeted using

Answer 33

Anti muscarinic 3 receptors. Like oxybutynin.

Question 34

Bone biopsy showing haphazardly oriented segment of lamellar bone with prominent cement lines

Answer 34

Pagets disease of bone -the disease have 3 stages 1. Osteoclastic (increased number of osteoclast that appears abnormally large with excessive number of nuclei) 2. Mixed 3. Osteoblastic (which resulted in biopsy shown above) Biopsy showing mosaic pattern of bone is highly suggestive of pagets

Question 35

Why oral isosorbide dinitrate is given in higher dose than sublingual nirtoglycerine

Answer 35

Due to the first pass metabolism effect

Question 36

Glaucoma drugs

Answer 36

1. latanoprost (prostaglandins agonist ) — > increase uveoscleral outflow 2. Muscarinic agoinst - > incraese meshwork outflow 3. Alpha agonists -> decrease production of aqueous humor via vasoconstriction of cilliary bodies 4. Beta blockers decrease aquoeus humor production 5. Carboni anhydrase inhibitor (dorzlamide) decrease formation of bicarbonate in the cilliary body leading to decreased sodium and fluid transport —> decrease production of aqueous

Question 37

Bioavaliabilty iv vs oral

Answer 37

-the bioavailability of a drug (non-iv) can only be determined after a study of pharmacokinetics of the drug. -the drug must plot the plasma drug concentration as a function of time for a given dose of drug administered by both the IV route and other route being studied (i.e PO,SQ, IM, PR , inhalation , SL and transdermal) . -oral bioavailabilty of a drug can be calculated by F= (area under oral curve X IV dose)/ (area under IV curve X oral dose)

Question 38

Pilocytic astrocytoma

Answer 38

Well demarcated lesion comprised of cystic and solid compoents. - piloctic astrocytes with bundles of GFAP positive hairlike process - and classic rosenthal fibers. - surgrical resection can be curative due to slow progression

Question 39

When an infant cant recieve Hib conjugate vaccine he’ll be prone to develop

Answer 39

Meningitis. Due to the fact that Hib vaccine protects normally against meningitis but the patient even if vaccinated can still develop otitis media and sinusitis.

Question 40

Phospholipid in amniotic fluid is used to test for

Answer 40

Lung maturity (L/S ratio)

Question 41

Alveolar hyaline membrane is seen in

Answer 41

ARDS.

Question 42

Coagulative necrosis

Answer 42

Its present in any ischemic injury in all organs except the brain.

Question 43

B19 virus vertical transmission

Answer 43

- fetal infection can lead to interruption of erythropoiesis causing profound anemia, congestive heart failure. Fetal heart failure can lead to pulmonary hypoplasia and ascitis. - B19 is SSDNA virus that can present in the mother with symmetric arthralgia and arthritis involving hands, knees and/or feet with or without a rash.

Question 44

Advanced malignancy signs on the heart

Answer 44

- sterile platelet rich thrombi attached to the mitral valve leaflets is charcterestic of nonbacterial thrombotic endocarditis(NBTE). - NBTE is most commonly associated with advanced malignancy as well as chronic inflammatory disorder like SLE (libman sacks endocarditis). - NBTE is seen in mucinous adenocarcinoma which may relate to procoagulant effect of circulating mucin. - pathogenesis is thought to begin with endothelial injury caused by circulating cytokines which triggers platelet deposition in the presence of hypercoagulabale state.

Question 45

Cell surface bound antibody bridging by antigen is found in

Answer 45

H.S type I