Block 39

Question 1

Potter sequence

Answer 1

• Pulmonary hypoplasia with facial and lower limb deformities(flattened nose and bilateral club feet)
• is caused by renal anomaly that lead to decrease urine output by the fetus.
• bilateral renal agenesis is the classic finding.
• oligohydroamnios.
• fetal heart anomalies are common during labor as well as umbilical cord compression.

Question 2

Acute tubular necrosis

Answer 2

• due to decreased renal perfusion during his cardiac arrest.
• ischemic ATN is one of the most common causes of AKI in hospitalized patients.
• ATN pts present with increased serum creatinine, BUN, normal BUN/serum creatinine ratio, and oligouria.
• muddy brown cast are variant of granular pigmented casts that are pathogonomic for ATN.

Question 3

Hypoxia from COPD can lead to

Answer 3

increased EPO secretion.

Question 4

Sertoli leydig cell ovarian tumor

Answer 4

Typically present as a large adenexal mass with ammenorrha and virilization.

• virilization occurs secondary to increased testosterone secretion by this rare sex cord stromal tumor.
• patients with neoplasm are usually younger women and its histopathologically similar to sertoli cell testicular neoplasms.
• microscopic examination of these tumors show hallow or solid tubules lined by round sertoli cells and surrounded fibrous stroma.

Question 5

G protein coupled receptors

Answer 5

• it binds to glycoprotein hormones such as TSH,LH and FSH …
• it contain 3 domains, extracellular domain responsible for ligand binding, transmembrane domain and an intracellular domain coupled with heterotrimeric G proteins.
• the transmembrane domain is made up of nonpolar, hydrophobic amino acids (alanine, valine, leucine, isoleucine tryptophan, methionine …).
• these amino acids are arranged in an alpha helical fashion and project their hydrophobic core of the phospholipid bilayer.
• the transmembrane domain may also play important role in cellular signaling and transport.

Question 6

What is the most common etiology in right sided endocarditis secondary to IV drug use

Answer 6

S.aureus.
-it can cause perforation in the heart valve, rupture of chordae tendineae and send septic emboli to-the lung or the brain and systemic circulation.

Question 7

Golgi tendon organs

Answer 7

Sensory receptors located at the junction of the muscle and tendon that are innervated by group Ib sensory axons.

• GTOS are connected in series with the contracting extrafusal skeletal muscle fibers.
• when a muscle activity contracts against resistance, the increase in tension is transmitted through the tendon activating the GTOS in the process , however GTO are insensetive to changes in muscle length.
• the Ib sensory axons from the GTOS contact inhibitory interneurons in the spinal cord which in turn synapse with the a motor neurons that innervate the same muscle. Thus, the golgi tendon circuit is a negative feedback system that regulates and maintains muscle tension.

Question 8

Varicose veins is caused due to

Answer 8

Incompetence of the valves of veins

Question 9

Stapedius muscle

Answer 9

• it arises from the wall of tympanic membrane and insert into the neck of stapes.
• its innervated by stapedius nerve (CN VII).
• the stapedius muscle functions to stabilize the stapes, paralysis of the muscle causes the stapes to oscillate more widely producing hyperacusis.
• pts typically complains of increased sensetivity to overeday sounds and will often withdraw socially as a result.
• ipsilateral hyperacusis is common finding associated with bell’s palsy.

Question 10

Abetalipoprotenemia -histology and features

Answer 10

• histology shows normal intestinal mucosal archeticture, but the enterocytes contain clear or foamy cytoplasm which is more prominent at the tips of the villi. These findings occur due to accumulation of lipids in the absorptive cells of the intestinal epithelium and are typical of abetalipoproteinemia.
• during the synthesis of apoB containg lipoproteins, ,microsomal triglyceride transfer protein (MTP) functions as a chaperone protein necessary for proper folding of apoB and also participates in the transfer of lipids to newly formed chylomicrons and VLDL particles.
• abetalipoproteinemia is caused commonly due to mutation in MTP gene, it manifests during the first year of life with symptoms of malabsorption.
• Lab shows very low plasma triglyceride and cholesterol levels, chylomicrons, VLDLs and apoB are entirely absent from the blood.
• poor absorption causes ADEK vitamin deficiency with acanthocytes as well as multiple neurologic abnormalities due to vitamin E deficiency.

Question 11

Vomiting due to chemotherapy affect what in the brain

Answer 11

• its believed to be triggered by chemotherapy trigger zone (CTZ) located on the dorsal surface of the medulla at the caudal end of 4th ventricle in a region known as area postrema.
• the area postrema receives blood from fenestrated vessesls (no BBB) which means sample chemicals circulating in blood can enter to it such as chemotherapy.

Question 12

Giardia

Answer 12

• ellipsoidal cyst with smooth well defined walls and 2+ nuclei.
• its the most common enteric parasite in USA and canada.
• it can colonize duodenal and jejunal mucosal lining.
• it causes chronic diarrhea, malabsorption and flatulence, foul smelling stools.
• its caused due to water drinking from endemic areas without boiling it first.
• metranidazole is the treatment of choice.

Question 13

EHEC O157:H7 toxin mechanism of action

Answer 13

• it can cause hemorrhagic colitis , most characterstically following ingestion of inadequately cooked meat.
• it doesnt ferement sorbitol during overnight incubation, and also doesnt produce glucuronidase (unlike all other E.coli strains).
• shiga like toxin is the toxin (verotoxin). Its phage encoded, and its production is enhanced by iron deficiency. Both shiga and shiga like toxin inactivates the 60S ribosomal subunit in human cells leading to inhibition of protein synthesis and eventual cell death.
• infection with EHEC can lead to HUS (microangiopathic hemolytic anemia, thrombocytopenia and renal insuffeciency.)
• it doesnt invade intestinal mucosa (unlike EIEC) and doesnt produce HS and HL toxins.

Question 14

Hydatid cyst

Answer 14

• echinococcus granulosus is the most common cause.
• most cases occurs in individual from endemic regions from middle east, mediterranean, soutch america etc.)
• ppl residing in USA with sheep and dog exposure.
• the liver is most oftenly affected but other organs such as the lung and muscles can also be affected.
• when infection occurs, echinococcal larbae implant within capillaries, triggerin an inflammatory reaction invloving monocytes and eosinophils. Some larvae encyst. Some larvae encyst. Microscopic examination shows encapsulated and calcified cyst “eggshell calcification” containing fluid and budding cells that will eventually become daughter cysts.
• if death occurs while treating the condition the most common cause of death is anaphylaxis.

Question 15

Macrocytosis

Answer 15

Can also occur in the liver disease, hypothyroidism, and alcoholic liver disease.

Question 16

Why women present later than men in hemochromatosis presentaion

Answer 16

Because women losses blood every month thorugh menustration.

Question 17

Arsenic poisoning

Answer 17

Mechanism: binds to sulfhydryl groups, disrupts cellular respiration and gluconeogenesis.(arsenic binds to sulfhydryl groups, impairing cellular respiration via inhibition of pyruvate dehydrogenase and disruption of gluconeogenesis and gluthaione binding).
-source: pesticides/insecticides, contaminated water, pressure treated wood.
Manifestation:
-acute: garlic breath, vomiting,watery diarrhea, QTc prolongation, delirium, hypotension.
-chronic: hypo/hyperpigmentation, hyperkeratosis, stocking-glove neuropathy.
Treatment:
-dimercarpol (british-anti lewisite)(increase urinary excertion of heavy metals by forming stable, nontoxic soluble chelates.
-DMSA (meso-2, 3,dimercaptosuccinic acid, succimer).

Question 18

Clubbing causes

Answer 18

It can be primary(idiopathic)
Or secondary to following chronic conditions such as:
-lung disease: lung cancer(large cell ), TB,CF,bronchoectasis, PHT, empyema and other chronic disease with hypoxia.(not asthma)
-heart disease: cyanotic congenital heart disease(teratology of fallot, truncus arteriousus, transposition of greatvessels, tricuspid atresia and TAPVC), endocarditis.
-others such as IBD, hyperthyrodism and malabsorption.

Question 19

Human rabies

Answer 19

Pathogenesis: transmission of rabies virus by a bite from infected mammal
Reservoir:
USA-> bats, raccons, skunks, and foxes.
Worldwide->dogs
Clinical features:
1. Encephalitis : hydrophobia, aerophobia, pharyngeal spasm, spastic paralysis and agitation(painful spasms with swallowing or inspiration causing dysphagia, hydrophobia and aerophobia)
2. Paralytic: ascending flaccid paralysis.
Tx: postexposure prophylaxis: rabies immune globulin and rabies (inacvitaved vaccine) immediately after exposure to high risk animal bite.
Prognosi: coma, respiratory failure and death within weeks

Question 20

Serotonin syndrome

Answer 20

• Neuromuscular excitation (hyperreflexia, clonus, myoclonus, rigidity and tremor).
• autonomic stimulation (hyperthermia, tachycardia, diaphoresis and vomiting/diarrhea).
• altered mental status (agitation and confusion)

Question 21

Serotonin syndrome first line treatment

Answer 21

Serotonin receptor antagonist such as cryptoheptadine which is the first generation histamine antagonist with non specific 5-HT1 and 5-HT2 receptor antagonistic properties.

Question 22

Thyroid hormone inhibition drugs on various sites

Answer 22

1. Damage to the thyroid via radioactive material such as iodine 131 can be released into the envirnoment following nuclear reactor accidents. Potassium iodide is given prophylactically to protect the thyroid from excessive accumulation of radioactive I-131 .high serum levels of nonradioactive iodide (resent in potassium iodide) can competitevely inhibit radioactive I-131 from entering thyroid follicular cells.
2. Propylthiouracil and methimazole inhibit thyroid peroxidase and thyroid hormone synthesis.
3. Iodide inhibit sodium iodide symporter and iodide secretion
4. Propylothuraciil, beta blockers and ipodate inhibit conversion of T4 to T3

Question 23

Muscarinic antagonist adverse effect

Answer 23

-facial flushing and pupillary dilation are common finding in patients taking medications with anticholinergic effects. There are 2 main forms of cholinergic receptors, nicotinic and muscarinic.
-the toxic effect of anticholenergic medication occurs primarily due to blockage of muscarinic receptors.
For example inhibition of eccrine sweat gland secretion can result in fever and compensatory cutaneous vasodilation and inhibition of the pupillary constrictor and cilliary muscles can cause pupilary dilation.
-H1 receptor antagonist such as diphenydramine for this allergic rhinitis.

Question 24

Leptin mechanism of action

Answer 24

Leptin decreased food intake in the following important ways:

1. Leptin decreases the production of neuropeptide Y, a potent appetite stimulant, in the arcuate nucleus of the hypothalamus.
2. Leptin stimulate the production of POMC in the arcuate nucleus. Alpha MSH is produced by cleavage of POMC and inhibit food intake.

Question 25

Cornybacterium diphteriae ,features and toxin mechanism

Answer 25

-it coloNizes the respiratory tract and secrete diphteria toxin
-diphteria toxin is an AB exotoxin that inhibit protein synthesis by ADP-ribosylation of EF-2
-toxin acts locally, causing respiratory cell necrosis with formation of fibrinous coagulative necrosis.
-clinical symptoms:
Sore throat, fever, cervical lymphadenopathy and pharyngeal exudates with caolescing pseudomembrane.
-complication include: submucosal edema and psedumembrane aspiration (can cause suffocation)
-systemically absorbed diphtheria toxin has predilection for brain and heart tissue —> myocarditis/HF and neurologic toxicity.
-prevention is usually by toxoid vaccine.

Question 26

PBC vs PSC

Answer 26

• PBC commonly occurs insidiously in middle aged women. Fatigue and pruritus are normally the first symptoms. As the disease progresses hepatosplenomegaly and cholestasis (jaundice, pool stool and dark urine).hypercholesterolemia with xanthlasma formation is common.
• PSC presents usually with fatigue and high ALP in man with a long history of ulcerative colitis are suggestive of PSC. Classic histologic findings include diffuse inflammation/fibrosis of the large intra- and extrahepatic bile ducts with periductal concentric fibrosis and obstruction of the small ducts.

Question 27

Apoptosis in response to chemotherapy- which substances from mitochondria might be responsible

Answer 27

The initiation of apoptosis occurs via signals from 2 seperate pathways:

1. The intrinsic (mitochondrial) pathway : mitochondria ->more permeable -> pro-apoptotic substances are released —>the pro-apototic substances proteins —> increased permeability of the mitochondria —> release of caspase activating substances like cytochrome C.
2. the extrinsic pathway(death receptor pathway): requires engagment of death receptor on the cell surface (eg Fas binding, TNFR1)

Question 28

Carbon monoxide poisoning mechanism of toxicity and features

Answer 28

• dizzenes, headache ranging to convulsion and respiratory arrest depends on concentration and exposure.
• it occurs due the ability of CO to competitively bind iron oresent in heme proteins.
• the gas binds to heme iron with a much larger affinity than O2 forming carboxyhemoglobin.even if only 1 of the 4 heme sites is affected, the remaining three have increased O2 affinity, impeding O2 delivery to tissues.
• the PaO2 is unchanged in CO poisoning.
• treatment of CO posining is by administration of high-flow or hyperbaric O2 therapy.

Question 29

Folic acid pathway drugs

Answer 29

1. Sulfonamides : inhibit p-aminobenzoic acid (PABA)—> dehydropoteroic acid —> DHF
2. MTX, TMP, Pyerimethamine all inhibit DHT—>THF

Question 30

Thromboangiitis obliterans (buergers disease)

Answer 30

Vasculitis of medium and small sized arteries, principally the tibial and radial arteries.
-histologically there is acute and chronic inflammation of the arterial walls, often with thrombossis of lumen whcih can undergo organization and recanalization.
-this segmental thrombosis vasculitis often extends into contigous veins and nerves. A feature rarely seen in other types of vasculitis.
-it may result from direct endothelial cell toxicity from tobacco products or from hypersensitivity to them.
-is most commonly seen in heavy smokers with onset before age 35.
-calf, foot, or hand intermittent claudication may be seen, as well as superficial nodular phelbitis and cold sensitivity (raynaud phenomenon). Severe distal pain, even at rest, can result and may be due to neural involvement.
TX= smoking cessation.

Question 31

Reassortment of genomic segment of the human strain is common in what disease.

Answer 31

• Rotavirus

- infleuenza virus(orthomyxoviruses)