5.8.2015 Uworld Notes

Question 1

Opioid analgesic in ER–>Severe abdominal pain. Tender RUQ. Which is responsible for current condition?

Answer 1

Mu opioid analgesics like morphine cause contraction of smooth muscle cells in sphincter of Oddi=spasm; severe pain and cramping in RUQ.
Use NSAIDs like diclofenac or ketorolac for pain control.

Question 2

New ACE inhibitor in 65 yo woman. Concerned about side effect with initial dose. Which is important to do before starting treatment?

Answer 2

First dose hypotension can be limiting factor when starting ACE inhibitors. They reduce venous return to heart secondary to decrease in angiotensin II levels. Can activate reflex causing vagally mediated hypotension and bradycardia.

Hypovolemic secondary to diuretic therapy, low bp, high renin, hyponatremia, high aldosterone, renal impairment, heart failure=PREDISPOSING FACTORS

Check for thiazide or loop diuretics (hypovolemic and hyponatremic).

ACE inhibitor plus beta blocker (suppresses renin)=No additional antihypertensive effect since both work on RAAS. Nonselective beta blockers in combo with ACE inhibitors increase risk of HYPERKALEMIA

Question 3

15 yo: 3 mo of periodic sudden onset jerking of arms. Aggravated by sleep deprivation. What medication should he take?

Answer 3

Valproic acid

Has myoclonic seizures, form of generalized epilepsy. Jerking movements but preserved consciousness.

Broad spectrum anticonvulsants: Lamotrigine, levetiracetam, topiramate, valproic acid) treat most seizure types.

Narrow spectrum anticonvulsants: Carbamazepine, gabapentin, phenobarbital, phenytoin) are for focal onset seizures and avoided in generalized epilepsy.

Question 4

Turner syndrome patients can become pregnant?

Answer 4

Lack of X chromosome–>Ovaries of connective tissue and no follicles or few atretic follicles (streak gonads).

Puberty: Normal pubic hair but no breast development or menarche due to ovarian failure. Elevated levels of gonadotrophins (LH and FSH).

Can become pregnant using donor oocytes and require estrogen and progesterone supplements.

Possibility of aortic dissection or rupture in pregnant Turner syn women. All must undergo med eval.

Question 5

Half life of drug after single dose?

Answer 5

T1/2=(VdX ln2)/CL

Vd=Volume in distribution
CL=clearance
Ln=natural log of 2 (0.693=approx 0.7)

One half life: 50% of drug remains
Two half lives: 75% of dose is eliminated (50% plus half of 50%)

Question 6

IL2 stimulates what cells?

Answer 6

IL2 made by helper T cells and growth factor of antigen specific CD4 and CD8 T cells AND B cells AND activates natural killer cells and monocytes.

Anti-tumor effects of IL2: T cells and NK cells

Question 7

Diabetic ketoacidosis: Serum pH HCO3 and pCO2

Answer 7

Decreased serum pH, decreased serum HCO3, decrease in pCO2. Kidneys try to correct metabolic acidosis via:

1. Increased HCO3 reabsorption from urine to buffer extracellular pH.
2. Increased H+ secretion: Acidosis increases H+ secretion throughout nephron.
3. Increased acid buffer excretion: Kidney uses acid buffers to trap H+ and allow excretion of more acid without lowering urinary pH by a lot. Two most important acid buffers are HPO4 and NH3 (best) which go into urine to buffer excess H+ ions.

Question 8

H. H influenzae grows around streak of S. aureus why?

Answer 8

H. influenzae requires X factor (exogenous hematin) and V factor (NAD+) to grow. Sheep blood agar plates lack sufficient nutrients and are missing NAD+. Enzymes of beta hemolytic s. aureus lyse RBC then X factor is released and V factor is secreted by staphylococci into growth medium.

Catalase=enzyme in staphylococci but not in streptococi.

Lactose fermentation=E coli

Question 9

Potter syndrome

Answer 9

Pulmonary hypoplasia, limb deformities, characteristic facies (suborbital creases, depressed nasal tip, low set ears, retrognathia) as a result of oligohydramnios. Bilateral renal agenesis=no fetal urine. Amniotic fluid required for proper lung development.

Maternal megaloblastic anemia: Deficiency of Vit B12 or folate.

Question 10

Incontinence: Stress, urge, overflow?

Answer 10

Stress: Loss of urethral support and intrabdominal pressure exceeds urethral sphincter pressure. (Urethral sphincter=smooth muscle activity; symp.-contraction; parasymp.-relaxation). 2x as common in women because EUS trauma or pudendal nerve injury in vaginal child birth.Postmenopausal women=low E->Laxity and weakness of pelvic floor support.
Urge: Detrusor overactivity
Overflow: Impaired detrusor contractility; bladder outlet obstruction.

Question 11

Peroxisomal diseases

Answer 11

Rare errors of metabolism where peroxisomes are absent or nonfunctional. Very long chain and some branches chain fatty acids cannot undergo mitochondrial beta oxidation. Fatty acids metabolized by special beta oxidation (VLC FA) or alpha oxidation (branched FA like phytanic acid) in peroxisomes. VLC FA and branched FA cannot undergo beta oxidation in mitochondria.

Zellweger syndrome: Infants can’t form myelin in CNS: Hypotonia, seizures, hepatomegaly, MR, early death. Defect in peroxisomal alpha oxidation. Treat: Avoidance of chlorophyll in diet.

Mucopolysaccharidoses=Lysosomal dysfunction

Question 12

Pharyngeal arches

Answer 12

Muscular elements=mesoderm
Bony elements=neural crest cells

First arch: CN 5, maxilla, zygoma, mandible, vomer, palatine, incus and malleus. Muscles of mastication, ant belly of digastricm, mylohyoid, tensor tympani, tensor veli palatini.

Second arch: CN 7. Muscles of facial expression, stylohyoid, stapedius, posterior belly of digastric.

Fourth and sixth arches: Cartilaginous structures of larynx

Question 13

Adult lead poisoning:

Answer 13

1. Colicky abodminal pain, constipation, headaches, impaired concentration, short term memory
2. Bluish pigmentation at gum-tooth line
3. Wrist drop or foot drop due to perip. neuropathy
4. Microcytic hypochromic anemia and basophilic stippling on peripheral smear.

Question 14

Classic complement pathway

Answer 14

IgG and IgM trigger classical complement after binding C1 molecule. Cl binds to Fc portions of two different Ab. igM is more effective in starting complement cascade because IgM circulates in pentameric form.

Activatoin of complement by IgM is inhibited due to fact that C1 binding site on IgM is hidden while unbound IgM is circulating in planar form. Conformational change after Ag binding.

Question 15

Von Hippel Lindau:

Answer 15

Rare AD condition: Capillary hemangioblastomas in retina and/or cerebellum and congenital cysts and/or neoplasms in kidney, liver, and pancreas. Pts increased risk for renal cell carcinoma. CLUE: Cerebellar hemangioblastoma in association with congential cysts of kidneys, liver, and/or pancreas.

NF1: neurofibromas and optic nerve gliomas. Lisch nodules: pigmented nodules of iris and cafe au lait spots (hyperpigmented cutaneous macules).

NF2: AD nervous system tumor syndrome in which patients develop bilateral cranial nerve 8 schwannomas and multiple meningiomas

Sturge-Weber: Neurocutaneous disorder: Facial angiomas and leptomeningeal angioams. Ophtalmic and maxiallary divisions of trigeminal nerve=skin involvement is over these two areas. Associated with MR, seizures, hemiplegia, skull radiopacities.

Tuberous sclerosis: kidney, liver, pancreatic cysts. Cortical and subependymal hamartomas. AD. Cutaneous angiofibromas, visceral cysts, renal angiomyolipomas and cardiac rhabdomyomas. Seizures.

Osler-Weber-Rendu syndrome: Hereditary hemorrhagic telangiectasia. AD inheritance of congenital telangiectasias. Rupture of these==>GI bleeding, hematuria, epistaxis. NO CYSTS.

Question 16

Nonsense, missense, silent mutations, frameshift?

Answer 16

Nonsense: Mutations that introduce a stop codon.

Missense: Mutations that result in change of amino acid.

Silent: Mutations that result in same amino acid (single base substitutions that code for same aa).

Frameshift: Deletion or insertion of bases that are not a multiple of three.
Alter reading frame of genetic code.

Question 17

Lentivirus subgropu of retroviruses: HIV has what type of genome?

Answer 17

Single stranded positive sense RNA diploid genome.

HIV 1 provirus contains three genes (gag, pol, env) and six regulatory genes (tat, rev, vif, vpr, nef, vpu).

Gag encodes Ag in virion core such as nucleocapsid proteins p24 and p7.

Pol encodes proteins like reverse transcriptase, integrase, and protease.

Env gene indirectly encodes envelop glycoproteins gp120 and gp41.

Rev encodes protein that facilitates transport of unspliced viral transcripts out of nucleus.

HIV tat gene encodes protein that transcriptionally activates other viral genes. Virulence of HIV.

Question 18

Oxygen Hb dissociation curve
Left shift
Right shift

Answer 18

Left shift: Decreased H+ (increased pH)
Decreased 2,3 DPG
Decreased temperature
Thing LUNGS=Left shift
Hb has increased affinity for Hb (lower P50). O2 is less available to tissues. 

Right shift: Increased H+ (decreased pH)
Increased 2,3 DPG (chronic lung disease, heart failure, exposure to high altitudes)
Increased temperature
Allows release of more O2 in peripheral tissues (elevated levels of DPG decrease Hb O2 affinity).
Hypoventilation=Respiratory acidosis
Strenuous exercise=decreased tissue pH

Question 19

Angina pectoris: Nitroglycerin Why does it work?

Answer 19

NITRATES decrease cardiac preload (LV volume during diastole/LV filling volume) by VENODILATION. This decreases myocardial O2 demand and results in venodilation and retention of blood in venous system.

Nitrates have modest dilatory effect on coronary arterioles and can cause decrease in afterload through systemic arteriolar vasodilation. Significant systemic arteriolar dilation can REDUCE coronary blood flow so HIGH DOSES of nitrates are BAD for angina.

Coronary steal syndrome: Pharmacologic dilation of coronary vessels without decreasing cardiac work is BAD. Decrease in blood flow to area of ischemic myocardium because blood will flow though pharm dilated arteries of heart not obstructed by atherosclerotic coronary vessel narrowing (and these vessels are already maximally dilated by innate mechanisms).

Increase in coronary perfusion pressure would require increase in diastolic bp since leaflets of aortic valve are closed and aortic blood flows into coronary arteries. Increased diastolic bp would mean increased afterload against which LV must contract. This would increase cardiac work and myocardial oxygen demand.

ACE inhibitors, ARBs, CCB=Decrease arteriolar resistance and this decreases cardiac work due to decreased AL.

CCB and B-blockers decrease heart rate which is useful in ischemic heart. BUT nitrates actually increase HR due to decrease in arteriolar resistance induced by nitrates.

Question 20

How does vasodilation work in vascular endothelial cells?

Answer 20

Ach, bradykinin, serotonin, substance P, shear forces stimulate specific membrane receptors to increase cytosolic Ca levels. This causes activation of endothelial NO synthase which synthesizes NO from ARGININE, NADPH, and O2.

NO diffuses into adjacent smooth muscle cells and activates guanylyl cyclase and increases cGMP which activates protein kinase G which causes reduction in cytosolic calcium levels and relaxation of vascular smooth muscle cells.

Question 21

Minute ventilation: Lung elasticity vs. restriction

Answer 21

Work done against elastic resistance of lung is increased when tidal volume is increased. Work done against airflow resistance is increased when breathing frequency is increased.

Stiff lungs=Increased elastic resistance=Work of breathing is minimized when respiratory rate is high and tidal volume is low. Rapid shallow breaths: Pulmonary fibrosis, pulmonary edema, ARDS.

Diseases that cause high airflow resistance: Asthma, COPD, fixed upper airway obstruction (large goiter) cause patients to breath at lower rate to minimize work of breathing. Slow deep breaths.

Alpha1 anti-trypsin deficiency=panacinar emphysema a type of COPD.

Question 22

Celiac disease

Answer 22

Small intestinal mucosa become inflamed and atrophic in response to gluten which results in defective mucosal absorption of vitamins and nutrients. Malabsorption of vitamin D occurs due to excess excretion in bulky fatty stools. Resulting decrease in vitamin D levels causes rickets in kids and osteomalacia in adults.

Vitamin D deficiency: Ca and P absorption are decreased. Hypocalcemia causes increased PTH. High levels of PTH induce increase in urinary phosphate excretion.

Question 23

Oral thrush in adult

Answer 23

White patches on oral mucosa that can easily be scraped off revealing arythematous mucosal surface underneath. KOH treated scrapings will show pseudohyphae and Candida yeast.

Oral thrush=in denture wearers, diabetics, immunosuppressed, steroids, antibiotics, chemotherapy. Common presentation of HIV infection.

Tobacco use can cause leukoplakia (precancerous lesion that manifests as white patches or plaques on oral mucosa but these cannot be easily scraped off).

Question 24

Campylobacter species

Answer 24

Can be transmitted from domestic animals to humans. Campylobacter is curved Gram negative rod with filament that allows it to move in corkscrew fashion. Inflammatory diarrhea (watery then bloody), cramping, leukocytes in stool, abdominal pain that mimics appendicitis. ASSOCIATED WITH GUILLAIN BARRE.
Acute gastoenteritis in kids and adults. Fecal oral route. Acquired from domestic animals; contaminated food (unpasteurized milk and undercooked poultry).

S. aureus gastroenteritis: Preformed exotoxin associated with consumption of precooked foods, diary products, custard, mayonnaise. Vomiting and abdominal cramps>diarrhea.

Shigella: Fecal oral route; daycare; food contamination.

Bacillus cereus: Steamed/fried rice. Heat stable enterotoxin.

Vibrio parahemolyticus: Contaminated shellfish.

Giardia lamblia: Drinking contaminated water. Camping/hiking.

Question 25

Diphtheria

Answer 25

Corynebacterium diphtheriae.
Acute infection of naso and oropharynx which causes pseudomembranous pharyngitis. AB exotoxin specific for neural and cardiac tissue. Deactivates EF2 which inhibits human protein synthesis.
Sx: Sore throat, fever, lymphadenopathy, upper airway dyspnea, odynophagia. Respiratory droplets=transmission.
Cardiomyopathy is major cause of death.

Treatment:

1. Diptheria antitoxin
2. Penicillin or erythromycin (not that helpful in curing disease because sequelae from exotoxin)
3. DPT vaccine

Antitoxin inactivates all toxin but is ineffective against toxin already gained access to cardiac or neural cells. Rapid administration of antitoxin is essential. Antitoxin is PASSIVE IMMUNIZATION: Transfer of pre-existing neutralizing antibodies.

Acute immunization with DPT vaccine prevents future diphtheria infection.

Question 26

Blastomyces dermatitidis

Answer 26

Dimorphic fungus that can cause pulmonary infections in immunocompetent people. In states east of Mississippi and Ohio river valleys. Some overlap with histoplasmosis.
In mold form and found in soil/animals. Transmitted by respiratory route: Enters lungs and transforms into yeast form (thermal dimorphism).
Pulmonary blastomycosis: Granuloma formation, extrapulmonary disease in immunocompromised (skin and bones): Broad based budding.
Itraconazole is preferred treatment.

Pneumocystis jiroveci=Pulmonary disease in immunocompromised patients particularly those with HIV. Doesn’t cause problem in immunocompetent hosts.

Mucor species: Infects paranasal sinuses in patients with neutropenia, burns, DM. Mucormycosis associated with DKA.

Penicillium marneffei: Opportunistic infection of immunocompromised patients in SE Asia esp those with AIDS.

Question 27

Diuretics

Answer 27

Thiazide diuretics (HCTZ): Block Na/Cl symporters in DCT causing enhanced Na, Cl, H20 secretion. Small amount of filtered Na reaches distal tubules, thiazides not as effective as loop diuretics. Thiazides can cause hypercalcemia, hypokalemia, hyponatremia, hyperuricemia.

Loop diuretics (furosemide, bumetanide, torsemide): Can cause hypokalemia, hypomagnesemia, hypocalcemia, ototoxicity. Work in thick ascending limb.

Potassium sparing diuretics (triamterene): All can cause hyperkalemia. Spironolactone: Gyncomastia, antiandrogen effects. Work in CD where aldosterone and ADH make final adjustments to urine content.

Carbonic anhydrase inhibitors (acetazolamide): Metabolic acidosis is side effect. Block reabsorption of NaHCO3 and work in convoluted and straight PT.

Osmotic diuretics (mannitol): Hyponatremia, pulmonary edema. Work in PT and descending limb of loop of Henle to reduce Na and water reabsorption.

Question 28

Beta thalassemia minor

Answer 28

Mediterranean descent.
Microcytic anemia
Increased HbF concentration
Hypochromia and poikilocytes including target cells.
mRNA translation problem which results in increased formation of HbF and HbA2 and deficiency of Beta globin. Insoluble alpha chain tetramers precipitate in RBCs.

Alpha thalassemia is more common in SE Asia.

Porphyrias are disorders of heme production pathway.

Impaired intracellular oxidant detox occurs with G6P dehydrogenase deficiency: Hemolytic anemia.

Normal adult Hb contains 2 alpha chains and 2 beta chains.

Question 29

Intussusception

Answer 29

Invagination of portion of intestine into lumen of intestinal segment. Leads to impaired venous return from invaginated segment of bowel which leads to ischemia and necrosis.

Most typical location is at ileocolic junction. Most common in kids

Question 30

Haloperidol used in treatment of agitation associated with neuroleptic malignant syndorme

Answer 30

Cause of NMS: Specific anti-dopaminergic activity of antipsychotic meds: Antagonism of D2 receptor. Central dopaminergic systems involved in thermoregulation and regulation of muscle tone and movement.
Presentation: Hyperthermia, extreme generalized rigidity, autonomic instability, altered mental status. ABSENCE OF MYOCLONUS AND PRESENCE OF RIDIGITY.
Treatment: Dopamin agonists (bromocriptine) and/or direct muscle relaxants (dantrolene).

Acute dystonia: Associated with anti-psychotic use. Involuntary movements and abnormal postures.

Neuroleptic induced Parkinsonism results from excessive dopamine blockade in nigrostriatal tissues may manifest with rigidity, bradykinesia, tremor.

SSRIs plus MAOIs=Serotonin syndrome. Fatal complication arising from any pharm agent that increases serotoninergic tone in CNS.

Question 31

Portacaval anastomoses

Answer 31

Esophageal varices->Left gastric vein (portal); esophageal vein (systemic). Come from portal HTN associated with cirrhosis (hepatic fibrosis). Dilation of collateral vessels between portal and systemic circulation.

Treatment: Transjugular intrahepatic portosystemic shunt (TIPS) between portal vein and hepatic vein. Relives portal HTN by shunting blood to systemic circulation.

Hemorrhoids: Superior rectal vein (portal); middle and inferior rectal veins (systemic)

Cpaut medusae: Paraumbilical veins (portal); superficial and inferior epigastric veins (systemic)

Question 32

Poststreptococcal glomerulonephritis

Answer 32

Onset of malaise, fever, cola-colored urine, facial edema 2-4 wks after streptococcal infection of pharynx or skin in 6-10 yo child.
Urine has dysmorphic red cells, RBC casts, protein. Elevations of creatinine and BUN also present.

Light microscopy: Granular deposits of IgG, IgM, C3 on BM and mesangium of glomeruli. Electron micro: Electron dense deposits on epithelial side of BM. Humps=immune complexes.

Crescentic glomerulonephritis (RPGN)=Fibrin deposition.

Question 33

Intraventricular hemorrhage in premature infant?

Answer 33

Germinal matrix bleed (subventricular zone where neurons and glial cells migrate out during brain development. Lots of thin walled vessels)

Question 34

Severe beta thalassemia: Regular blood transfusions to maintain acceptable O2 carrying capacity of blood. Skeletal deformities and mongoloid face. Lymph node biopsy=phagocytic cells with golden yellow cytoplasmic granules composed of…

Answer 34

Hb derived marker of iron accumulaton: Hemosiderin=gold yellow brown bigment. Aggregation of ferritin micelles.
Pts with hemolytic anemias or repeated blood transfusions have excessive iron in circulation. Iron is deposited as HEMOSIDERIN in tissues. Iron chelation therapy can reduce iron load and should be performed if hemosiderin deposition.

Bilirubin=primary pigment in bile; derived from Hb but lacking in iron. Excess of biliruin associated with jaundice.

Lipofuscin is yellow brown pigment of lipids and phospholipids complexed with proteins. Associated with aging/wear and tear.

Melanin=Brown black pigment in melanocytes when tyrosine is oxidized to form dihydroxyphenylalanine.

Amyloid protein=Pink red extracellular substance that can cause damage by placing pressure on cells.

Glycogen=clear cytoplasmic vacoules and stains pinkish purple with acid Schiff reaction.

Question 35

Brief severe stabbing pains in extremities that occur several times a day. Stumbles frequently at night. CSF=VDRL positive. Degeneration of which spinal cord area?

Answer 35

Neurosyphillis. Spirochetes damage sensory nerves in dorsal roots: Demyelination and loss of axons in DORSAL COLUMNS. Pain, paresthesia, loss of vibration/position sensation. Loss of proprioception is compensated for by visual clues (but this won’t work at night because can’t see).
Accompanied by ataxia and Argyll Roberston pupils.

Question 36

Pacemaker cells in heart: Action potential

Answer 36

1. Phase 0 upstroke: Opening of Ca channels
2. Phase 3 repolarization: Opening of K channels and efflux of K+ from cell and closing Ca channels.
3. Phase 4 pacemaker potential: Slow influx of Na. K+ channels close slowly. Once membrane reaches -50mV, calcium channels open and allow Ca to enter cell and contribute to depolarization. -40mV: More Ca channels open until AP reached at -35 mV.

Adenosine and Ach act on Phase 4 reducing depolarizatoin. Adenosine activates K channels and prolongs flow causing membrane to be neagtive for longer. It also inhibits Ca channels prolonging time taken to reach threshold. DECREASE IN HR.

Ach opens K channels and decreases inward Ca and Na during phase 4.

Norepinephrine opens Ca channels and Na channels in phase 4 causing rapid depolarization.

Question 37

Kimmelstiel Wilson nodules

Answer 37

Nodular glomerulosclerosis: Located in peripheral mesangium. Ovoid or spherical in shape. Lamellated apperance. Eosinophilic on hematoxylin and eosin stain. Periodic acid Schiff. Hyaline arteriolosclerosis associated with nodular glomerulosclerosis.
Diabetic neuropathy: Type 1 and Type 2 DM is most common cause.
Presents: Glomerular BM thickening and increased mesangial matrix deposition. Compression of glomerular capillaries happens bc expanded mesangium. Progressive proteinuria that can lead to overt nephrotic syndrome: Peripheral edema, weight gain, HTN, renal failure. No red or white cell casts.
IRREVERSIBLE CONDITION.

Minimal change disease: Secondary to allergic reaction. Glomeruli appear normal on light microscopy and immunofluorescent. Electron micro shows podocyte foot process effacement.
Hep C assoc. with mebranoproliferative glomerulonephritis: Glomeruli appear hypercelullar with thickening and splitting of glomerular BM due to immune complex deposition.
Focal segmental glomerulosclerosis: Seoncdary to HIV, heroin, obesity. Sclerotic change.
Solid tumors assoc with membranous glomerulonephritis: Capillary wall thickening and membrane spikes on silver stain.

Conditions with NEPHRITIC PRESENTATION (hematuria, red cell casts, variable proteinuria):
Poststreptococcal glomerulonephritis: diffuse glomerular hypercellularity due to leukocyte infiltration and mesangial cell proliferation. IgG and C3 deposits as humps on electron microscopy.

Question 38

20 yo; episodes of jaundice; unprotected sex; mild splenomegaly/icterus/RBC in hypotonic saline=Hb is released. Pt at highest risk of?

Answer 38

Pigmented gallstones

This patient has high LDH and indirect bilirubinemia=>Hemolytic anemia
Lysis of RBC=osmotic fragility test (TEST FOR SPHEROCYTOSIS). Sexual history is distractor and not related to patient’s anemia.

Pigmented gallstones are complication of ANY hemolytic anemia. Increased bilirubin from lysted RBC preciptates as clacium bilirubinate forming pigmented stones in gallbladder.

Hereditary spherocytosis is AD condition that results from RBC cytoskeleton abnormalities. Spectrin and ankrin defects. Test is positive osmotic fragility test.

Question 39

23 yo frequent UTIs after intercourse and 1 case of pyelonephritis. Which caused the pyelonephritis?

Answer 39

Vesicoureteral urine flow

E coli, Klebsiella, Proteus, enteroccoci (pathogenic gram neg rods bacteria). Normal urine is bactericidal due to high urea content and high osmolarity and
urine flow washes bacteria downstream.

Frequent bladder infections may weaken vesicoureteral junction and facilitate reflux. Without vesicoureteral reflux, ascent of pathogens to kidneys is impossible and pyelonephritis does not occur.